FR2637807A1 - Device for protection against disorders of the blood, in particular thromboses, embolisms, haemorrhages, haemopathies and the presence of abnormal elements in the blood - Google Patents

Abstract

The device, which can be totally implanted, comprises means 1, 14, 15 for automatic measurement of biological parameters of the blood, in particular those relating to the blood constitution and/or haemodynamics and/or the myocardium and/or the arteries and/or to elements present in the blood, implanted observation means, threshold means for a comparison of the measured parameter value, and means for automatically delivering an appropriate treatment, for example fibrinolysis. This device comprises means 4 for recording and treating the heart rate.

Description

 Device for protection against blood-related conditions, in particular thromboses, embolisms, hemorrhages, hemopathies and the presence of abnormal elements in the blood.

 The present invention describes a device implantable in humans and mammals capable of automatically analyzing the biological and chemical constitution of the blood and / or its hemodynamics, and of intervening selectively in the event of the detection of anomalies, as well as the methods of 'analysis and treatment implemented.

 The invention relates more specifically to an implanted device for protection against blood-related conditions.

 An object of the invention is in particular to provide a device for protection against thromboses, embolisms, and atheromatous or infectious narrowing of blood vessels and cavities, and in particular, the arteries irrigating the myocardium or the brain.

 The invention also aims to combat vascular hemorrhages when they result from a blood clotting disorder or excessive hypertension or abnormal permeability of small vessels or endotheliums of the capillaries.

 The invention also aims to selectively monitor in the blood vessels certain compositions and presences of chemical, biochemical and ionic molecules as well as the blood count and formula, functions which allow early detection and immediate treatment and constantly counter hemopathies even autonomous , and certain cancers, the appearance and treatment of which can be observed by the appearance of new molecules or by a different concentration of certain existing molecules.

 The invention also aims to protect against pollution of air, water and food by automatically monitoring in the blood and in the bone marrow, the molecules relating to the polluting agent, hematopoiesis and the blood count and formula.

 The invention is in particular intended to amplify and complete the device for protecting the heart which is the subject of the French Zacouto patents FR-A-2,082,703 and its additions US-A-3,857,399 and 4,052,991.

 The protection of the human body against arterial and venous thrombosis and embolism is often ineffective, storytelling ~ and is not free from side effects.

 Apart from permanent medical treatments, in particular chemical or biochemical anticoagulants in invariable doses between the hemostasis control intervals, which are long, or surgical repair treatments, protection against thrombosis consists, on the one hand, in trying to treat the thromboses and embolisms which have occurred, by immediate administration of very short duration and, preferably in situ in the vicinity of the blood coagulate, of thrombolytics such as streptokinase or urokinase and derivatives, tissue activators of plasminogen (TPA) and derivatives.

 Intravascular treatments must be carried out as quickly as possible to reduce the necessary dose and increase the efficacy and good tolerance against the risk of bleeding.

 An objective of the invention is therefore to provide a device for protection against thromboses and vascular embolisms installed or in the process of formation, which allows immediate, effective, rapid and selective treatment.

 Another objective of the invention is to provide preventive treatment on demand, adapting quickly and automatically to spontaneous physiological and pathological multi-day variations in blood crase and presenting reduced risks of side effects.

 Another objective of the invention is to provide a device for protecting against thrombosis of the arteries, in particular the cardiac coronaries and carotid or even cerebral arteries capable of treating, preferably in situ, an early thrombosis or embolism, notably of the pulmonary, and of preventing its occurrence. . In particular, the device according to the invention makes it possible to prevent re-obstruction after aortocoronary bypass or coronary, carotid or cerebral endoarterial angioplasty.

 Another object of the invention is to provide a device for protection against consumption coagulopathies (DIC).

 Another objective of the invention is to provide a device for protection against haemorrhages and to modulate an anticoagulant treatment according to the spontaneous variations in blood crase.

 The subject of the invention is a device for protection against affections linked to blood, characterized in that it comprises - implanted means for permanently or periodically measuring at least one biological parameter capable of preceding or accompanying the imminence or the occurrence of a blood-related condition, - means implemented to determine one or more thresholds to which the measured value of the parameter is compared, - and implanted means sensitive to the crossing of this (these) threshold (s) to automatically release in circulating an appropriate dose of one or more therapeutic agents, such as, for example, thrombolytics and / or anticoagulants and / or vasodilators, and / or beta-blockers and / or diuretics and / or calcium channel blockers and / or prostaglandins 1G2 and PG12 and / or coagulation factors.

 The parameters measured can be general parameters, that is to say parameters linked to general factors capable of causing, in a more or less short time, an accident such as thrombosis, for example, coronary, carotid or cerebral or embolism, for example, pulmonary, or else reflecting in the general circulation, the consequences of the occurrence of such an embolism or thrombosis, or of a hemorrhage or a hemopathy. Such general parameters can be, for example, parameters related to blood coagulability, the occurrence of hypertension or hypotension, the release of factors capable of influencing the circulatory state such as catecholamines, hypoxia or hypercapnia, imbalances ionic and pH, overload of chylomicrons, glucose, creatinine, volemia, etc.

 It is also possible to detect the respiratory rate and amplitude, in particular by measuring, in a known manner, the electrical chest impedance.

 The device according to the invention can be provided for detecting such general parameters at any point in the circulation, but it is advantageously possible to provide for these measurement means to be located in a cardiac cavity or else in the immediate vicinity of part of vascular, lymphatic, intraosseous or cardiac route presenting a risk or a particular diagnostic interest.

 In another embodiment of the invention, the parameters measured can be local parameters, the measurement means then being arranged near or even at the level of a blood or lymphatic vascular pathway or a crossroads presenting particular risks. These parameters can then, for example, reflect a local anomaly resulting from the imminence or the occurrence of an embolism or thrombosis in the monitored area, these parameters can be, for example, a concentration of ions or other elements released during '' tissue ischemia, or electrical abnormalities in the genesis, propagation or absorption of a spontaneous or artificial electrical current of measurement linked to a risk or occurrence of such ischemia, or other parameters reflecting the effect of ischemia on tissue, such as, for example, tissue hypoxia, modification of myocardial noises, fine variations in local temperature, elevations of transaminases, etc.

 It is also possible to detect, by measurements on the electrocardiogram, electrical parameters relating to arrhythmia which enter into a reduction in cardiac and coronary output, in particular in the event of cardiac arrhythmias such as ventricular tachycardias, tachyarrhythmias by atrial fibrillation, extrasystolias. ventricular, or ventricular fibrillation. The means for detecting such disorders, for example described in US patents Zacouto 3,857,399 and 4,052,991, can then cause, in addition to the automatic electrical treatment described, the administration of anticoagulants and / or fibrinolytics to reduce or eliminate the risks of thrombosis which are often the cause or an aggravating factor of arrhythmia.

 However, preferably, the device according to the invention will include means of detection and measurement sensitive, directly or indirectly, to the quality of the infusion such as peak speed or flow, average or minimum, flow, geometric variations, perfusion pressure or active contraction of the vascular pathway. A preferred parameter is constituted by an electrical impedance representative of these characteristics but it is also possible to use other parameters, for example pressures, geometric deformations, flow measurements, optical absorptions (spectrometry), natural resonance frequencies of the arterial tree, velocity of the arterial pulsation wave, etc.

 For the prevention of embolism, it is also preferable to measure local parameters related to the imminence or the occurrence of coagulation in a particularly adequate path, such as, for example, an atrium or a ventricular cavity.

 Preferably, the device according to the invention simultaneously comprises means for acquiring rhythms related to hemodynamics, in particular heart rate and possibly respiratory rate, for example, electrocardiogram, variations in electrical impedances, plethysmogram, phonogram, mechanogram or others, this detection can then be used either to define or interpret the measurements of parameters varying within a cycle, for example in the case of impedance, pressures or geometric deformations or optical absorption , or to interpret the results of the measurement according to the cardiovascular cycles detected and thus modify the thresholds or inhibit functioning.

 In a preferred embodiment, the device is provided with means making it possible to measure the electrical, acoustic or optical impedance or conductance in one or more sensitive areas of the vascular path to be protected.

 One can also have, in a location in or at the edge of the blood circulation, or even outside, for example in the bone marrow, for example, sternal, an endoscopic type optic with quartz fibers transmitting the image in colors and possibly with adjustable viewing angle, towards a miniaturized image analyzer, of a type also known, where the image is analyzed, digitalized, ordered and stored on a memory, this set being, for example, located in a implanted case also containing the other means of the device according to the invention. The detected images can be, on the one hand, compared, by known electronic comparison means, to stored standard images, for example, of blood cells or cells abnormal in their form, in their contents, or in their quantities, and on the other hand, transmitted to the outside by radio frequency emission on demand. The device can thus trigger, for example, an external alarm by radio frequency to signal the vision of an abnormal image. It can also cause the automatic delivery of doses of suitable medication programmed for this purpose. It is possible to carry out a punctual sample by transcutaneous needle, and an optical cleaning by irrigation, according to a known method.

 Preferably, the electrical impedance measurements are made simultaneously on at least two different frequencies, which allows more precise measurements and better adapted to the selective conductive variations of the tissue or liquid medium studied. A device for measuring impedances by modulation of emission frequency over at least one range of frequency variation, and possibly several frequency ranges, can be carried out using the same transmit and receive electrodes or by using, for example , several electrodes, in particular electrodes placed on two geometrical axes defining a geometrical plane, preferably perpendicular axes, to allow the detection of the impedance vector in this plane. Preferably, the measurement is also carried out simultaneously in an axis located outside of this plane, preferably perpendicular to this plane, in order to acquire the three-dimensional vectograms of the impedances. The measurement currents can, for example, be emitted in scanning pulses of simultaneous or offset frequencies from one measurement axis to another.

 The time offset of certain parts of the electrical impedance spectrum can also be used.

 These means may include electrodes arranged around the vascular routes to be protected, for example a coronary artery, or in the vascular route itself, in particular in an atrium or artery, these electrodes being connected to means making it possible to send measurement currents to them. electrical impedance.

 Local or regional electrodes for measuring the impedance can also be inserted into the myocardial tissue, in particular apical, septal or parietal, so as to measure the local impedance in a part of the myocardium monitored by the electrodes. The distance between the electrodes can be, for example, a few millimeters.

 It is thus possible to measure the values of the impedance or, which amounts to the same thing, of the conductance either intermittently or continuously.

 One can in particular measure the maximum difference in electrical impedance reflecting, for example, variations in blood volume in the route considered or those of capillary circulation and / or muscle contraction in the myocardium for example, at each cardiac cycle.

 It is also possible to measure on the courses of the acquired impedance curve, the shapes, peaks and other characteristics, including differential or integral, at each cardiac cycle.

 The current used for the measurement of the impedances can Between a direct current in pulses, for example in the case where the impedance is measured of very small and fairly homogeneous zones, such as for example a thin artificial or artificially caused layer of fibrin monomer or polymer or of fibrin precursors, fibrinogen, fibrinopeptides, in mixture or isolated, or of prothrombin mixed with prothrombinase to test the tendency to the production of thrombin, factor of fibrin formation while taking into account, preferably , of the local accumulation of calcium or magnesium ions compared to the same ions measured in the general circulation.

This current can also preferably be variable and it is possible, if necessary, to use one or more currents of variable or different shapes and frequencies depending on the type of impedance variation to be measured. For the measurement of an impedance of a blood volume, for example in a coronary artery or in a cardiac cavity, relatively low frequencies can be used, for example of the order of a few kilohertz. We prefer to use the higher frequencies for the measurement of tissue impedances, for example of the order of 100 kHz to a hundred megahertz.

 It is also possible to record simultaneously along two axes, for example between an intraauricular electrode and an electrode carried by the pacemaker housing, on the one hand, and an intraventricular or intramyocardial electrode and the same electrode on the case. go. We thus obtain a Lissajoux type curve in the plane formed by the two axes and we can reconstruct the three-dimensional vectogram of the variations of the electrical impedances of the heart if we add a measurement according to at least one additional axis outside the plane. can also use skin or subcutaneous electrodes for this purpose to reconstruct the three-dimensional image of the variation of the impedances in the heart and possibly to transmit corresponding signals outside the body to a three-dimensional viewing receiver.

 Preferably, the mono-, bi- or, preferably, three-dimensional electrocardiogram can be superimposed on the corresponding vectogram of variations in the electrical impedances of the mono-, bi- or, preferably three-dimensional, heart. In the event of coronary thrombosis which causes a clear modification of the electrovectocardiogram, the vectogram of the electrical impedances of the corresponding heart is clearly modified and makes it possible to validate, on the one hand, the electrocardiographic variation and to specify the repercussions on the myocardial contractions.

 As another biological parameter for the protection of the arteries or cavities of the heart, taken in isolation or combined with the measurement of the impedance, it is possible to use modifications of the electrocardiogram and in particular modifications of the vectocardiogram detected by sets of electrodes suitably arranged. in space, either epicardial, or simply endocavitary, or in a monopolar position alone, or with the addition of bipolar electrodes, preferably on an endocavitary catheter of a pacemaker. We can thus detect significant and selective changes in the propagation of cardiac electrogenesis in its depolarization and repolarization.

Instead of or in addition to the measurements of the aforementioned electrical parameter (s), it is also possible to provide means sensitive to phenomena related to the content of oxygen and / or C02 and / or CO and / or pH and / or rH (coefficient oxidation-reduction) and / or sodium, chlorine or phosphorus ions to measure the osmotic pressure and / or ischemia of the tissue irrigated by the arterial branch to be protected, and in particular a sensor sensitive to ionic variations such as those of the potassium ion or the H + ion in or in the vicinity of said territory and / or a sensor sensitive to the oxygen content in or near this territory, for example an optical sensor sensitive to oxyhemoglobin at a wavelength of 660 nm or with methemoglobin. (Karl STANGL et al. A New Multisensor Pacing
System ..., Pace, Vol. Il June 1988: 712-724).

 In another embodiment, it is also possible, to detect a threat arising from an internal hemorrhage, to place an optical detector, for example, a detector of red light or other sensitive to wavelength absorbed by hemoglobin and / or other colored substances, for example bilirubin, in the lymphatics draining the lymph from the body or the brain into the lymphatic canal. It is also possible to add to this metering device sensitive to small amounts of hemoglobins in the lymphatic vessels, at least one optical microcomputer of known type making it possible to count red blood cells or platelets capable of quantifying a passage of blood in the lymph and, if necessary, to distinguish between the brain origin or not of these elements. Thus, a hemorrhagic tendency by hypocoagulability or vascular fragility, toxic or infectious or caused by excessive blood pressure, can be detected and if necessary treated automatically by the delivery of a re-coagulating drug such as, for example, prothrombin in equilibrium with Stuart factor and calcium or hypotensive ions. This recoagulation infusion will be automatically stopped as soon as said detector for a trace of blood in the lymph indicates disappearance of the bleeding, or as soon as a measurement of a factor of blood crase indicates a tendency towards the onset of hypercoagulability.

 It is also possible to detect an intra-myocardial or intramuscular hemorrhage by the use of a selective optical detector discriminating between hemoglobin or its derivatives and myoglobin, such an optical cell, of the endoscopic silica fiber type, allowing an analysis of the local image and the observation of an ischemia and the follow-up of its evolution at rest and with effort, and which can be placed in an intra-myocardial part of a probe connected to a pacemaker.

 The use of a quartz fiber optical cell placed, for example, in the catheter, for example, in the chambers of the right heart also makes it possible to measure the blood concentration of red blood cells, platelets and white blood cells and to measure the hematocrit, a drop of which accompanies a hemorrhage, or measure an isolated drop in red blood cells or thrombocytes whether or not related to a hemorrhage.

 One can also use means sensitive to light radiation, including IR or UV, reflected or absorbed by the blood and / or myocardium or a vascular wall during a suitably oriented emission of monochromatic light or not, coherent or not, by continuous or in pulses, for example using a very thin optical conductor, for example silica fiber with a diameter less than or equal to 1 mm, one optical end of which looks at the color of the blood, or of the myocardium in which it is placed, means associated with the fiber being arranged to analyze the light spectrum which reflects oxygenation or another metabolic parameter of the blood or of the tissues, for example separately.

As another parameter, it is also possible to measure the geometric deformation of the vascular pathway or cardiac cavity, for example, by strain gauge, or measurement of transit time of ultrasound, for example of the TRITONsonomicrometer type, SL 5-2 with two crystals 2 mm in diameter, manufactured by TRITON Technology, Inc., San Diego,
California, United States of America.

 One or more of these piezoelectric sensors can also be used to detect variations in sound or ultrasound propagation and reflection or to search for variations in sound or ultrasound resonance or even sound and / or ultrasound absorption preferably related to cardiac cycles. , for example. Sensors such as microphones can also be used to detect the quality and the sound level of the noises produced by the myocardium, hemodynamics and / or heart valves.

 As a variant, such sensors can also emit sounds or ultrasounds in the blood and / or in the myocardium in order to detect a possible global or regional functional anomaly which can be determined by stenosis or obstruction or excessive hypertension. In a variant, the ultrasonic wave can be modulated by one or more sound frequencies. At the same time, sound modulations can be triggered in relation to the detected phonocardiogram.

Preferably, the sounds or ultrasounds are emitted with a rapid frequency variation scanning a programmed spectrum in order to detect the resonance and / or the sound absorption of the arterial or venous blood column, or of the myocardium, according to the position and the orientation. of the transmitter sensor. These emissions can be permanent or very close together so as to sweep the totality of the cardiac cycles, or on the contrary, they can be produced during one or more determined periods of the cardiac cycle by timing time each emission and sound or ultrasonic reception on a periodic phenomenon of the cycle, so as to cause the emission and the subsequent measurement in a significant instant for the pressures and volumes of the cardiac cavities, the venous or arterial columns or the myocardium. In particular, the emissions and measurement can be adjusted on selected sound phenomena, for example closing of a heart valve or noises accompanying the movements of the myocardium.

 One can also, for example, if one causes the emission and the measurement using a sensor-transmitter suitably placed oriented towards the venous or arterial blood tree, as the case may be, from a probe , for example endocavitary, measure the resonance and absorption of an arterial or venous blood tree, which gives an immediate indication of the state of the pressure of the blood mass and the rigidity of the arterial wall. For each maximum and minimum of the blood pressure corresponding respectively a resonance frequency for each subject.

This allows, for example, to detect the appearance or increase of hypertension likely to promote thrombosis, embolism or vascular hemorrhage so that the device can then immediately administer a dose of corrective medication. It is also possible, by suitably choosing the time of measurement, the arrangement and the orientation of the emitting sensor, to detect and quantify the possible blood volume, in particular ventricular, postsystolic or telediastolic. For example, the search and measurement of the resonance of the arterial shaft can be carried out using an ultrasonic or sound sensor-transmitter placed in or near the cavity of the left ventricle by a trans catheter. septal from the right ventricle.

 As a variant, instead of a temporal sweep of an audio or ultrasonic frequency, for example in amplitude modulation of a higher ultrasonic frequency, during transmission, it is also possible to simultaneously transmit several frequencies spanning the spectrum. desired. The sound or ultrasonic transmitter and receiver devices described can also be placed at the level of a peripheral vessel, for example the radial artery at the level of the arm or the wrist by being implanted so as to vibrate in resonance the corresponding arterial column from from this peripheral location, the detection of the resulting sound spectrum possibly being possible remotely from the transmitter.

 In a variant of the invention, it is possible, by remote control from the outside, to implement, by the programmed or programmable means implanted, the measurement of a particular substance present in the blood, for example, a substance toxic, the device adjusting a measuring means, for example optical molecular, to become sensitive to this substance. In the case of a toxic, for example, food, one can provide a device, known per se, for toxic and of its concentration in food, water or air and transmit the information by remote control to the implanted device to make it sensitive to this substance and, possibly in return, inform the external device or the user, of the degree intracorporeal concentration of this toxic and indicate the possibility or not to tolerate an additional incorporation of this toxic. It is also possible to implant, for example in the bone marrow, a radiation detector, or isotope.

 As another biological parameter, in a preferred embodiment, it is also possible to measure, in a vascular or lymphatic pathway, preferably upstream of a ganglion, or cardiac cavity, in particular atrium or ventricle, at least one parameter of the blood crase. , for example by using one or more sensors sensitive to one or more coagulation factors, either more generally by measuring a parameter related to the coagulability of the blood or liquefaction of the coagulates such as, for example, viscosity or tendency to deposit of fibrin. For example, the content of blood in at least one of the following substances can be measured: prothrombin, plasminogen, prothrombinase, plasmin, fibrinopeptide, protein C, endothelin, serotonin, catecholamines, neuropeptides Y, fibrinogen, plasminogen activators, etc.

 It is advantageous to use, for this purpose, an artificial presentation of one or more coagulation factors or their precursors used in a coagulability provocation test. This permanent or periodic presentation can be carried out in particular - by definitive fixing of this substance on an insoluble support unalterable in the blood, leaving free, in contact with the blood, the active sites of the factors, allowing them to locally solicit the corresponding factors of the blood crase; this fixing can be carried out in any known way, for example adsorption on the support, crosslinking using a usual crosslinking agent, usual chemical bond with the support, for example of the avidin-biotin type; the support can be a usual support in these techniques, for example polymer, cellulose acetate, nitrocellulose, - by slow diffusion of the substance, for example, through a porous membrane, - by local microperfusion, of the order of a few mm 3 per hour, allowing, for example a six-monthly refill of the corresponding subcutaneous reservoir.

 In a variant of the invention, at least two biologically opposite factors in the equilibrium of the blood crase can thus be simultaneously or successively monitored, for example the coagulating factors of fibrinogenesis and / or thrombogenesis, on the one hand, and anticoagulant factors such as plasmin activator, plasminogen, or heparin derivatives, on the other hand. Thus, it becomes possible to know a pathogenic mechanism in the event of an abnormality of blood crase and to intervene selectively. For example, in the event of CIYD (decreased intravascular coagulation), the insufficiency of the thrombin detected associated with a fall of fibrinogen will make it possible to make the diagnosis.

 These sensors or analysis means can be, for example, carried by a catheter. Thus, by way of example, the tendency for fibrin to be deposited can be measured from a thin layer or a fine wire or tube of fibrin in a receptacle or on a relief of a catheter or at the level of '' a small segment of venous autograft, fixed, for example, on the catheter and preferably surrounded by a protective grid or stop, by an optical means, for example sensitive to color and / or molecular absorption and / or thickness fibrin, or any other means, for example, by measuring the sound or ultrasonic resonance which depends on the mass of fibrin deposited or its detectable molecular mass, or by measuring at least one dimension of the fibrin layer by ultrasound ultrasound, for example in mode A. It is also possible to measure the electrical impedance, for example ohmic, and / or absorption of an alternating current of fixed or variable given frequency or of ultrasound by the resonance of macromolecules intervening in the coagulation or da ns thrombolysis. This receptacle or relief can be arranged in a V shape or flared to create a tendency to a minimal deposit of fibrin normally contained by blood washing and spontaneous fibrinolysis and the size of which depends on the state of the blood crase. It can be surrounded by a dike or a fence preventing the arrival of the figured elements of the blood and the extension of the fibrin layer.

 For example, the device may comprise, on a catheter, a short tubular element having a diameter for example of the order of 2 to 3 millimeters disposed laterally on the catheter and having an axis substantially parallel thereto so to be crossed by part of the blood stream. The catheter has, inside this tubular element, or in a cavity, a sensor for detecting substances such as fibrin or fibrinopeptides, fibrin monomers, prothrombins and prothrombinases- and consisting of a slit or opening or interval of weak thickness between a first wall secured to the catheter and a second wall also secured to the catheter. The space between these two walls can be determined experimentally by looking, in a blood in the state of normal crase, the thickness leading to a fine spite of fibrin. On one of the two walls opens the end of an optical fiber connected to a light source and, opposite, on the other wall, opens the start of a second optical fiber. The two optical fibers are returned to the catheter and lead, the first, to a light emission source, the second to a light sensor. The assembly of these two walls or reliefs is surrounded by a grid or stop preventing the passage or agglomeration of the figured elements of the blood and preventing the exit of fibrin elements. At the level of this sensor, for example all around all of said two walls, there are arranged means for supplying a thrombolytic allowing, if necessary, to dissolve the fibrin likely to accumulate on the sensor. a thin spite of fibrin or its precursors is formed between the two optical ends on said walls, the optical transmission changes and the light intensity received is attenuated. In addition, the color is changed so that the means sensitive to optical reception can determine, when a certain threshold is crossed, that a layer of fibrin is being formed. The device can even be sensitive to the speed and direction of variation of the fibrin layer by studying the variation of the optical signal over time.

 A certain distance downstream, or on the same trendy presentation piece, can advantageously be found, on the catheter and in the same tubular element, an element detection sensor promoting blood liquefaction such as heparin detection. , plasminogen, protein C, etc.

 We can also detect the presence and concentration, and even the size of elements present in the blood, such as particles, corpuscles or molecules, in particular substances or factors, related to blood crase, some of which have been listed above. , including soluble fibrin or its predecessors or other proteins, including fibrinogen, plasminogen, prothrombin, etc. This can be done, for example, using an optical source whose wavelength is varied according to a microprocessor program, for example, using a rotating prism or a system of multiple reflection prisms and / or known optical networks and / or multiple monochromatic sources or modulated laser detection of absorption spectra of the molecules sought can be done for example by microthermocouples and / or very sensitive photoelectric or photovoltaic cells and / or field effect transistors (FET) or other operating in thermistor or local electrical charge detectors. We can also use a laser or maser and study these absorptions by detecting and studying interference. The emission frequency can either be fixed and determined according to the element sought, or variable by scanning certain frequency zones, for example in the case of elements such as fibrin or the factors or precursors of fibrino- or thrombino formation, the formation of which is effected by successive polymerizations or cleavages which modify the molecular mass.

In particular, the measurement by tests of provocation of the state of blood coagulability and incoagulability can be carried out not on a thin solid or semi-solid layer of the precursors of fibrin or thrombin, on the one hand, and heparins and plasminogen, on the other hand, but on the relative concentration in liquid form of these substances in the immediate vicinity of a focus of presentation of coaguloactive and / or anti-coagulant substances. These presentation foci can either be of the solid type with substances insolubilized on a support, or consist of a liquid diffusion as described above. This avoids causing fibrin deposits and it also avoids providing protective grids or stops. In a variant, the coagulation and anticoagulation factor molecules are fixed on an insoluble material, on a surface, for example , a rod in a small tube slowing down local blood circulation, so that the ratio of local and general detections of calcium, magnesium or H + ions, by itself, automatically assess the state of blood crase
In a variant of the invention, an ultrasonic emission or other means, pulsed laser or other can be used to destroy or dislocate the dangerous mass which can form on the sensor in the protected volume, the debris being destroyed by the fibrinolytic delivered .

 One can also use as a parameter, globular aggregation, in particular platelet aggregation by a suitable detection means, for example, of optical type.

 Means can also be provided for measuring hemoglobin and / or red blood cells in a volume of a few mm 3 and thus determining the hemotocrite and hemoglobin per liter. This last analysis makes it possible to detect and monitor certain haemorrhages, polycythemia and anomalies of the voemia. Sensors of this type are known and can be miniaturized.

The device according to the invention, suitably provided with means which have now become conventional for transmission / reception of programming and monitoring, can be provided for programming new wavelengths or new wave modulations for the detection transmissions, to be sought. new molecules or new concentration ratios of these, associate with orders given to the microprocessor to perform the new calculations. The device can also allow automatic telephone communication with emission of a selective alarm or of measured biological data, according to known modes
As has been seen, the various sensors and / or transmitters described above, whether they are electrodes, ion sensors, piezoelectric sensors, optical sensors with blood coagulation provocation test location , etc., can be arranged at or near various locations in the heart or vessels. One of the preferred localizations is the intracavitary localization on one or more catheters. Another advantageous localization can be carried out at the level of a coronary bypass or a valvular prosthesis if it must be placed in a patient so the valvular prosthesis can include one or more of the elements such as blood or local fibrin impedance measurement electrodes, pressure sensor, etc.

 When the measured parameter crosses a predetermined threshold, the device can then automatically and regularly or periodically cause the sending, in the blood, from an implanted pump and reservoir, of reduced quantities, for example of the drip type, fibrinolytic or anticoagulant or antihemorrhagic or other agent.

 On the contrary, if, during the measurement, the parameter falls below the determined threshold, all delivery of fibrinolytic or anticoagulant is stopped.

The frequency with which the device performs the measurements is adapted to the characteristics of the therapeutic agent and its effects, for example, the speed and duration of effectiveness, its half-life and, possibly, the particularities known to the patient. For example, the interval between two successive measurements can range from a fraction of a second to a few hours or the measurement can even be continuous, at least by periods.

 Of course, when the device is intended to selectively deliver several agents, for example complementary or antagonistic, or independent, one or more different parameters can be provided with one or more different thresholds associated with the respective detections.

In a particularly preferred manner, the device comprises one or more sensors capable of measuring at least one and preferably more of the following parameters - appearance or variation of a thin layer or mass of fibrin or containing fibrin or one or more of its precursors on a support suitably placed in the blood circulation, for example in the atrium or the ventricle, so that the increase in mass corresponds to a tendency to hypercoagulability of the blood while the decrease in mass to a tendency to thrombolysis; one can thus follow very quickly a variation of the state of the blood crase whereas the current methods require a discontinuous extra-corporeal sample and long to interpret. This layer can possibly be put at a low electric tension - measurement of the concentration in calcium and / or magnesium ions in the immediate vicinity of, or in this thin layer or film, using a sensor based on a selective membrane for calcium ions known per se, allowing instantaneous monitoring of variations in local concentration in calcium ion, related to the degree of coagulability of the blood compared to the general concentration of calcium ions measured elsewhere by another sensor in the blood;
The small layer may, for example, be formed on a surface, for example made of micro-scratch glass, carried by the catheter and charged with negative electricity of determined voltage, moreover known, causing the local formation of the activator complex of prothrombin and the tendency to clot.

 The value of this negative voltage can be varied, either in time, or spatially, along said surface, or a succession of such surfaces, the measurement means then taking into account The value of the voltage corresponding to the fastest growth of spite.

 The surface can, if necessary, present precursors or other factors influencing the formation of fibrin or precursors, suitably isolubilized or fixed, for example, on the electrically negated surface.

 The means for determining the threshold or thresholds to which the measured value of the parameter is compared allow manual adjustment and preferably automatic adjustment of the threshold value or values. Preferably, these means can advantageously be remotely controlled from outside the body as in the remote controls of pacemakers, and be displayed on an external monitor.

 The device comprises, associated with its threshold determination means, logical or analog comparison means, making it possible to compare the measured values with the programmed threshold value for actuating, If the threshold is crossed, the means making it possible to release the appropriate dose of medicinal substance in the circulation, preferably after authorization by means of control of the pathological or metabolic significance of this crossing.

 These release means may advantageously include one or more implanted pumps and reservoirs, containing the substance or substances to be administered and capable of delivering, by at least one intracardiac or intracorporeal conduit, a programmed quantity of substance.

 The determination of the dose to be released can be carried out by the doctor, in a completely usual manner, taking into account conventional factors, such as activity, clearance, half-life, etc., relating to the drug (s). choose). The implanted pump has, for this purpose, a usual dose adjustment device, remote control means, for example electromagnetic, being preferably provided to allow the doctor to adjust the dose by radio or other control from outside the body. .

 These means may for example be connected to the general vascular, venous or arterial system or to a local vessel, determined, for example, a coronary or carotid artery.

 In the case where the invention applies to a device for protecting the coronary arteries, it is preferable, for an in situ treatment, to unblock the conduit coming from the reserve of substance in the coronary artery, the conduit then preferably being a conduit contained in an endocavitary catheter or accompanying such a catheter, said conduit being able to cross the myocardium in its apical zone for example, to be connected, after its epicardial exit, to the coronary artery considered. However, the substance can also be delivered to another vessel, or to a heart cavity, atrium or ventricle, or even sometimes to tissue.

 Similarly, in such an embodiment, it is preferred that the conductors connected to electrodes for measuring impedance of coronary arteries, pass through the myocardium to preferably join the catheter of a pacemaker in the right ventricular cavity.

 In accordance with an important improvement of the device according to the invention, this device can comprise means sensitive to the cardiac and / or pulsating cycles of the arterial system being monitored, these sensitive means controlling the means for measuring the parameter so as to cause the measurements in determined or known moments of the cycle.

 It is also possible, in a particularly preferred form of the invention, to provide such means sensitive to cardiac cycles, for example to the duration of the cardiac cycle, and possibly the origin and the propagation of the electrical activation which determines it, of so as to be able to judge, in the event of crossing the threshold, of the pathological nature or not of this functioning, and decide, or not, the automatic intervention.

 This detection can also be used to automatically modify the thresholds and / or the treatments, according to a determined programming.

 In the case of peripheral arteries, implanted pulse detectors or endo- or peri-arterial pressure sensors or other known devices can be used.

 In the case of protection against hemopathies, such as leukemias, it is possible to place an optical cell or the optical end of a fibroscopic endoscope associated with means for measuring and / or counting blood cells, associated with means analysis of the detected images, the acquisition optic being arranged inside a lymph node or a bone marrow, for example the sternum. Intra or periosseous electrodes can also be used as electrocardiographic electrodes or for measuring variations in electrical impedances.

In the case of protection at the level of the heart and / or the cardiac coronary arteries, it is particularly useful to provide means sensitive to the duration, and preferably also to the quality of propagation of the electrical activation, at least of a previous cardiac cycle, and possibly several previous cycles, as described for example in patents
Zacouto US-A-3,857,399 and 4,052,991.

 It is thus possible, for example, in the case of extrasystoles, to automatically modify the thresholds with respect to the precocity of the extrasystole and to the extrasystolic potentiation resulting from the mechanical and metabolic parameters of the myocardium.

 For example, also, in the case of tachycardia, the reduction in the amplitudes of the mechanical phenomena and the modification of the metabolism, which can lead to an abrupt reduction, but without thrombosis, of the coronary flow, will not be considered as justifying the release of a dose of pure thrombolytic or coronary vasodilator, for example, unless coronary thrombosis is detected simultaneously by other means.

 It is also possible, and this embodiment is preferred in the case of the protection of the heart or of its coronary arteries, to provide means for acquiring the electrical phenomenon of the heart such as the electrocardiogram and / or at least one sensor sensitive to variations. pressure and / or volume of a cardiac cavity, to control the measuring means so as to carry out the measurement at a determined or known moment of the cycle, in particular systolic or diastolic.

 In such a device, the difference or variation of the parameter such as the electrical impedance between diastole and systole is compared with a threshold or threshold range which can be fixed or, if necessary, adjusted automatically, in particular as a function of the heart rate. andfor blood pressures and for example the detected level of blood or intramyocardial catecholamines.

 In addition to, or instead of measuring the difference in electrical impedance between diastole and systole, it is also possible to detect time shifts in this impedance and / or in blood or myocardial pressure relative to electrogenesis, by example acquired by the general or local electrocardiogram, and / or with respect to the local or general static or dynamic pressure cycles. The device can then be arranged to be sensitive to variations in the offsets. Preferably, the device is arranged to acquire the local electrocardiogram at the place where the impedance, and preferably the pressure, is simultaneously measured, in order to be free from modifications of the electrogenesis and of the mechanogram which are not obligatorily controlled nor significant compared to the phenomena locally measured.

 This offset is preferably studied by the device according to 1 invention in the myocardium, for example apical. It is also possible, in addition, to measure the variations and offset of the same parameters in a cardiac cavity such as for example the ventricle, preferably at a fairly short distance from the location where the detections of the same parameters are carried out in the myocardium. so as to compare the detections in this tissue and in the blood.

 Other characteristics of the invention will appear on reading the following description, given by way of nonlimiting example and referring to the attached drawing in which: - Figure 1 shows a schematic view of a device according to the invention , - Figure 2 shows a schematic view of the implanted means of measurement and comparison of this device, - Figure 3 shows a schematic view of the electrocardiogram and the curve for measuring electrical impedances.

- Figure 4 shows a schematic view of means for measuring myocardial parameters, - Figure 5 and 6 show schematic views in transverse and axial section of a sensor sensitive to the state of blood crase.

 Referring to FIG. 1, it can be seen that the device according to the invention, totally implanted in the organism, comprises, in an implantable housing 1, similar to that of an implantable pacemaker, an assembly which will be detailed by the after. From the casing 1, a complex venous catheter 2 penetrates into the right ventricle 3. In the ventricle, and possibly in the atrium, it has a certain number of detection and stimulation electrodes respectively connected by electrical conductors in the catheter 2 to a pacemaker contained in the boot 1. From the last electrode 4, the catheter 2 is continued by a tube 5 which, by transmyocardial route 6, joins the surface of the heart muscle to end with a cannula 7 penetrating into a coronary artery 9. The tube 5 is contained in a sheath which preferably contains a certain number of conductors, 10,11 which emerge from the sheath and which respectively join electrodes 14,15 carried internally by rings 16 , 17 preferably elastic which have been placed around the coronary artery 9 by thoracic surgical approach, the internal diameter of the rings 16,17 with the urs internal electrodes being large enough not to risk compressing or stenosing the artery. The establishment of the cannula 7 in the coronary 9 takes place during the same intervention.

 It is therefore understood that the catheter 2, which is a complex catheter, comprises all the electrodes and conductors of a conventional catheter for detection and stimulation by the right endocardial route and, in addition, the tube 5 with the conductors associated therewith. and which go to the electrode means 14,15. The end of the tube 5 is connected, by a suitable microvalve, to a miniaturized pump capable of delivering determined doses of a drug such as a thrombolytic, for example urokinase.

In another variant of the invention not requiring cardiac surgical intervention, but simply an endoartetrial intervention, the tube 5 can be omitted, as are the rings 16, 17, the catheter 4 being a conventional pacemaker catheter. In this embodiment, we just introduce, at one or more locations of the chosen coronary artery, using an arterial catheter introduced, for example, by the femoral artery, an endocoronary prosthesis, according to the existing method which is pressed against the internal wall of the coronary artery, this prosthesis, for example, of circular or tubular shape, having conducting elements forming electrodes so as to be able to determine at least two electrodes between which it will be possible to measure
The impedance of the blood from the artery segment disposed between the two electrodes. If necessary, more than two electrodes spaced along the artery can be provided and the impedance measured in several segments along the artery. The electrodes thus placed on the endocoronary prostheses are connected by respective very fine and flexible conductive wires, preferably grouped together, and extending along an arterial path to an exit point, for example at the level of the the femoral artery, to be connected, still remaining implanted, by subcutaneous route to the electronic means arranged in the case 1.

 In a preferred variant, the arterial electrodes, such as 14, 15, can be powered by an autonomous energy source or powered by high frequency or radio transmission from an intracorporeal transmitter, for example located at the level of the pacemaker case. Likewise, the significant values of the impedance measurement will be sent to an intracorporeal receiver according to known methods.

Referring to FIG. 2, we can very schematically see the part of the device contained in the boot 1. This comprises an antitachycardial orthorythmic stimulator 20 which can advantageously be of the type described in US Pat. Nos. 3,857,399 and 4 052 991. With this stimulator 20 can, if necessary, be associated a fully automatic defibrillator as described in the French patent Zacouto of July 11, 1953 n ° 1 237 702 and implantable as described in the French patent
Zacouto no 74 01 383.

 The case 1 also incorporates a source of electrical energy, for example, lithium batteries and / or means for transcutaneous periodic transmission of energy to recharge batteries or accumulators or capacitors. Modern batteries used in implantable pacemakers and defibrillators allow coping for a period of time, enough for the patient to have independence between recharging or replacement periods, even in cases where the power consumption is high enough, for example , for actuating ultrasonic transmitters. It is also possible to use known implantable isotopic batteries.

 This stimulator 20 is articulated, in a known manner, around a logic member such as a microprocessor, associated with detection means and stimulation means according to the method described in the aforementioned US patents. These means make it possible, in particular, to acquire the electrocardiogram at the level of the right endocavitary electrodes 4 and an extracardial electrode, for example on the boot 1. One of the elements of the electrocardiograms (ECG) thus obtained is the instantaneous rhythm of the electrocardiogram, i.e. the period between two QRS complexes.

 The stimulator 20 includes the automatic anti-tachyarrhythmic means described in the said Zacouto patents and is sensitive to rhythm disturbances, by detecting their frequency and, preferably, the morphology of the spontaneous electrical signals collected in at least one heart cavity or wall. In the event of detection of signals recognized as dangerous, the stimulator 20 automatically delivers electrical stimulation in accordance with said patents, in particular by increasing the rhythm of the stimulation.

 According to an improvement of the invention, the catheter 2, apart from the tube 5 and the conductors which are associated with it and which are intended for justa- or endocoronary electrodes, can be designed like that described in US-A-4,754 753, with, in the case 1, the means described in this patent making it possible to acquire, at each heartbeat, 1 t electrovectocardiogram.

 In a schematic way, the device contained in the case 1 also has a generator or source 30 of square or sinusoidal or other pulses, or even a source of direct current capable of addressing in the circuits formed by the pairs of conductors 10, 11, a succession of square pulses. The duration of a pulse train is, for example, 30 ms, the frequency from 5 kHz to 25 MHz and the intensity of the order of 10 to 30 microamps. An impedance (or conductance) measuring circuit 40 is electrically associated with the pair of conductors coming from the pair of coronary electrodes 14, 15 so as to measure the impedance during current pulse emissions coming from source 30, circuit 40 being tuned to the corresponding frequency.

 The generator 30 and the circuit 40 can optionally be controlled from the pacemaker 20, depending on the frequency of the electrocardiogram.

 The circuit 40 includes means, which can moreover use a microprocessor, arranged so as to calculate the difference in the maximum and minimum impedances of a cycle and to send the result of this measurement to a comparison means, microprocessor or comparator 50 to the second input from which a threshold value or range is displayed from an adjustable threshold potentiometer 31.

The output of the comparator is addressed to a pump control circuit 60 which, when an impulse comes from the comparator 50, activates the motor of the pump contained in the case 1 and causes the delivery by the tube 5 of a dose of medicament in the coronary concerned.

In normal operation, operation is as follows and reference is made to FIG. 3
The source sends pulses to the electrodes 14, 15 and the corresponding circuit 40 measures the impedance between the electrodes 14, 15. This gives a curve C shown in the figure and showing the course of the impedance change. Circuit 40 is also sensitive to cardiac electrical cycles as detected by the pacemaker, these cycles being materialized by the succession of QRS complexes of the electrocardiogram which are transformed into pulses i by the pacemaker and addressed in this form. to the device 40. The circuit 40 is at the same time sensitive to the difference I between the largest value and the smallest value of the impedance measured during a cycle. The difference I between these two values in the same cycle is addressed by means of comparison 50 which compares it to the programmed thresholds and in the event of crossing of the threshold or thresholds, the circuit 60 for controlling the pump is actuated.

 The threshold value to which the difference in impedance I is compared can be fixed or, if necessary, programmed to take into account the duration and the origin of one or more previous cycles. As a replacement, if a fixed threshold or in any case independent of the cycles is maintained, it is advantageously possible to provide an inhibition circuit preventing actuation of the circuit 60 when, for example, the cycle preceding the current cycle was abnormally short. .

 Thus, for example, when the stimulator detection device detects a tachycardia exceeding a certain frequency threshold, for example 150 μm, the stimulator microprocessor inhibits the control device 60 of the pump so as to avoid the programmed dispatch of medication even if the difference between maximum and minimum impedance per cycle has dropped below the threshold.

 Similarly, these inhibition means can be arranged to inhibit the device for the duration of a normal cycle preceded by a short and / or ectopic cycle.

 As a variant, the device can be improved so as not to control the motor control circuit 60 on the first detection of a decrease in the difference I below the threshold value, but on the contrary it can be arranged to so as to activate these means only if this reduction is confirmed on one or more consecutive or successive cycles.

 The acquisition of the cycles, instead of being obtained by detection of the electrocardiogram, can also be obtained by other means for example by intracavitary and / or intramyocardial and / or arterial pressure sensor.

 Preferably, the device can be arranged so that it can be adjusted by the doctor who can choose either between sending a dose at each detection of crossing of threshold subject to the abovementioned inhibition conditions, which presents the advantage of instant medication, of particularly rapid action, i.e. after the acquisition of a certain number of successive lowerings below the threshold, which has the advantage of only intervening in the event of an anomaly practically certain of the coronary flow.

 The device according to the invention may also include means, made by the microprocessor suitably programmed, to be sensitive not only to the difference between the maximum and minimum values of impedance measured during a cycle but also to the offset maximum and minimum relative to the start of the cycle. It can also be sensitive to parameters related to this offset such as the integration or the mathematical derivation of the impedance measurement curve. In this embodiment, the device can advantageously include an offset threshold which, if crossed, that is to say if the time interval between the start of the cycle and the maximum and / or minimum of impedance exceeds this threshold value, activates the pump control circuit 60, unless this is inhibited for another reason. The start of the cardiac cycle can be determined by an electrical phenomenon, for example complex QRS or by a other cardiac phenomenon such as heart sounds or a specific point in the heart pressure mechanogram.

In another embodiment of
I invention, preferably combined with that which has just been described, one can also introduce into the coronary miniaturized piezoelectric sensors, namely at least one sensor, and preferably several sensors, for example, placed on an electrode ring-like, distributed along the coronary when possible. One can thus obtain, by cycle, the pressure curve in one or more places of the coronary and, in association with the measurement of impedance, if it is planned, obtain by carrying out the product of the impedance and the pressure, a quantity representative of the flow / pressure ratio in the coronaries.

 The pressure curve in the coronary artery can be used by the microprocessor in a similar way to that of the impedance curve. In particular, the device may be sensitive to changes in the course of the pressure curve or to time shifts in the course of the pressure curve relative to the electric cycle as well as the crossing of the pressure curves of blood flow and reflux in coronary arteries.

 Referring now to Figure 4, we see another embodiment of the invention in which the part of the device contained in the casing 1 is substantially identical to that described above. On the other hand, the catheter 2 does not extend by a tube passing through the myocardium to join one or more coronary arteries.

 The end 101 of catheter 2 penetrates a short distance into the myocardium at the bottom of the right ventricle towards the apex of the heart. The insertion distance can be of the order, for example, from 4 to 8 mm. This end 101 successively comprises, from the tip, a pressure sensor 102 then, on either side of the catheter, two electrodes 103, 104, coming slightly apart in the myocardium to form an anchoring point in the form of V. The catheter then presents potassium ion and H + ion sensors 105, 106 then again two electrodes 107, 108 opening in V for anchoring.

 In the ventricle, the catheter can advantageously include, in addition to different electrodes, a pressure sensor 109 as well as other sensors 110, 111, 112 for example for detecting, in the blood, potassium ions, H + ions and at minus a parameter relating to blood coagulability, in particular of blood plasma and / or of figured elements of blood.

 The two electrodes 103 and 107, separated from each other by a distance of a few millimeters, are connected to a pulse generator such as the generator 30 and an impedance measurement means between these electrodes 103 and 107 such as the circuit 40 The electrodes 104 and 108 are intended to detect between them the local electrocardiogram in this area of the myocardium. We. can thus obtain locally both the electrical impedance, the electrocardiogram and the myocardial pressure mechanogram.

 In the part of the catheter penetrating into the myocardium, it is also possible to place a selective optical detector discriminating hemoglobin from myoglobin to detect a possible hemorrhage.

 The device can then be arranged, as before, so as to compare with the programmed thresholds the difference between the minimum and maximum impedances during a cardiac cycle determined by the local bipolar electrocardiogram, and / or the shape of the curve. corresponding impedance and / or time shift of the peak or minimum impedance. It can also provide thresholds at which it compares the maximum and minimum pressure values during a cardiac cycle, the progress of the pressure curve as well as the possible offset of a peak or minimum pressure with respect to the cardiac cycle.

 It may also be sensitive to the abnormal diffusion of potassium ions or to an abnormal change in pH.

 The invention can of course be the subject of a number of variants. In particular, the means allowing at the level of an artery, such as for example a coronary or a coronary collateral, to detect the passage or the stagnation of the blood flow can be different.

 By staying in the field of electrical impedance measurements, intra-arterial electrodes can be used instead of being arranged around the artery. These electrodes can, for example, consist of simple conductive wires introduced into the artery, for example at the time of making a coronary bypass or by endarterial probe.

In the event of implantation of an artificial heart, (performed for the first time successfully in
I animal by the inventor in 1953), the protection of the arteries, in particular carotid and cerebral can be particularly important and the tests of provocation of the coagulability and the incoagulability of the blood as well as the tests of vascular hemorrhage and of formula blood will be monitored by the device.

 One can also use electrical means sensitive to blood flow other than the impedance measurement and, in a nonlimiting way, one could for example provide a transmitter and an ultrasonic sensor operating for example on Doppler effect or means of duration measurement ultrasonic transit, or even an optical sensor with a light source.

 Instead of using a detection means sensitive to the blood flow immediately in place, it is also possible to use means for detecting the vectocardiogram as described in US Pat. No. 4,754,753 so as to acquire the origin and the vectors of the electrical propagation. both in depolarization and in repolarization. It is known that the study of the variation of these vectors makes it possible to determine, at least approximately, the myocardial zone in which an ischemia occurs. In the event of variations in the vectors relating to this zone beyond a certain threshold of variation, the device produces a release of a dose of medicament in the endocavitary circulation, or directly in a coronary vessel or in the three main coronaries which can be linked for a selective shipment of medication.

 Referring to Figures 5 and 6, there is shown an embodiment of a sensor such as the sensor 112, intended to measure optically the thickness variations of a fibrin spite. The sensor 112 is placed in a cavity 150 of the catheter 2. In the drawing, the catheter 2 has a diameter of the order of 4 mm. The cavity 150, suitably profiled, is closed on the outside by a perforated steel grid of thickness, for example 3/10 and whose mesh holes preferably have a diameter greater than 1/10 mm and less 1 or 2 mm. A good size can be, for example of the order of 0.8 mm. This grid is periodically subjected to an ultrasonic beam allowing it to be released from the elements of the blood which would tend to clog it.

 In the central part of the cavity 150, the bottom of the cavity has an arm 152 containing a bundle of optical fibers terminating in a conventional optical device terminating a bundle of fibers 153 elongated lengthwise of the catheter. Opposite, and separated from a space 154, is an optic 155 ending in a bundle of fibers contained in an arm 156. The optical beam passing through 152 and joining the oblique 153 is connected to a light source capable of addressing in the space 154, an optical radiation which will be picked up by the optics 155 and retransmitted by the optical fibers of the beam 165 towards measurement means. In the space 154, there is disposed midway between the optics 153 and 155, a grid 157, preferably electrically conductive and which can be periodically subjected to ultrasonic vibrations to remove clogging elements. This grid is supported in this space by an arm 158. At the lower part of the gate 157, there is a field effect transistor 159 preferably associated with a small electrode (not shown) capable of being brought to a negative voltage. The assembly of the gate and of the transistor 159 is contained in a very fine mesh 160, the meshes of which have an opening dimension of 3 microns, this gate being able for example to be produced from son of fiber such as carbon fiber having a diameter, for example from 1 to 3 microns.

 When the catheter is placed in the blood, the latter, in its flow, crosses the grid 151 and circulates, to a certain extent in the cavity 150. The blood penetrates through the fine screen 160 into the space 154, the elements shown however, blood is unable to enter this space due to the diameter of the screen 160 which may, if necessary, also be brought to a negative potential repelling the figured elements. The fibrin which may possibly form will preferably be deposited on the grid 157 which can, for this purpose, be provided beforehand with a layer of fibrin or presented in association with fibrin or separately, products capable of inducing fibrin formation , such as in particular precursors or insolubilized factors on the grid. The light crossing the space 154 will see its intensity decrease, and its spectrum, if necessary, be modified, according to the presence or absence of fibrin on the 157 mesh and the thickness of the fibrin layer. Transistor 159 is sensitive to the concentration of calcium ions. Advantageously, the lower part of the grid 160 can be brought to a negative potential facilitating the formation of fibrin so that one can, if necessary, observe a spite of decreasing thickness upwards, the spatial variations thickness can then also be analyzed by analysis of the different pixels received in the different fibers of the beam 156. Advantageously, one or more conduits can be provided in the arm 158 to bring into space 154, if there is place, a fibrinolytic agent, for example, plasminogen, heparin, etc., and limit the amount of fibrin likely to form there. The grid 151, for its part, prevents, in the event of break-in of the grid 160, the passage into circulation of fibrin elements having a dangerous size.

 The various parameter measurement means, such as laser and maser transmitters and / or receivers, optionally modulated, ultrasonic, audible, electrical impedance measurement or EKG can preferably be spatially oriented in by remote control from the 'outside. In this case, the energy necessary for the mechanical movement can be supplied by remote transmission, for example high frequency, the energy source of the device according to the invention being able, for example, to comprise, on the one hand, a battery, nuclear or no, and on the other hand, a receiver implanted with energy from the outside, either for overconsumption linked to particular maneuvers or interventions of the device, or to recharge all or part of the source.

 Thus, for example, the intra or justacardiac ultrasonic receiver detector may include a mobile or rotating transmitter-receiver head monotorized by remote control, making it possible to record on a memory of the implanted device, an echocardio- or echediediastinogram of central origin, capable of be retransmitted outside by remote control.

 The endoscopic optical means can also be orientable, for example to explore bone structures or cells.

Claims (57)

CLAIMS.  1. Device for protection against affections linked to blood, characterized in that it comprises: - implanted means (14, 15, 103, 106) for permanently or periodically measuring at least one biological parameter capable of preceding or support the imminence or the occurrence of a blood-related condition, - implanted means (40, 50, 51) to determine one or more thresholds to which the measured value of the parameter is compared, - and implanted means (60) sensitive on crossing this (these) threshold (s) to automatically release into the circulation an appropriate dose of one or more therapeutic agents.  2. Device according to claim 1, characterized in that it comprises means (14, 15) for measuring the impedance of a vascular path.  3. Device according to claim 2, characterized in that said means (14, 15) are arranged in or around an artery, in particular coronary.  4. Device according to claim 2, characterized in that said means are arranged in a cardiac cavity.  5. Device according to claim 2, characterized in that said means are arranged in the myocardium.  6. Device according to any one of claims 2 to 5, characterized in that it comprises an electrical source (30) connected to electrode means (14, 15) for an emission intended for the measurement of an electrical impedance , at least at a frequency between a few kHz and one or a few MHz.  7. Device according to any one of claims 2 to S, characterized in that the device comprises means (40) sensitive to the difference of the measured impedances.  8. Device according to claim 7, characterized in that said means (40) are sensitive to the difference between the maximum impedance and the minimum impedance measured in the same cardiac cycle.  9. Device according to any one of claims 2 to 8, characterized in that it comprises means (40) sensitive to the offset of the course of the impedance measurement curve likely to occur between two cycles.  10. Device according to any one of claims 2 to 9, characterized in that it comprises electrode means disposed in and / or at a distance from the heart muscle to form separate measurement axes and acquire the vectogram of the variations d electrical impedance of the heart.  11. Device according to any one of claims 1 to 10, characterized in that it comprises at least one pressure sensor sensitive to blood or myocardial pressure.  12. Device according to claim 11, characterized in that it comprises at least two pressure sensors spaced along a vascular or cardiac path and means sensitive to the value of the pressures sensed and / or to the offset between the establishment of the pressures sensed by said sensors.  13. Device according to any one of claims 2 to 12, characterized in that it comprises one or more sensors sensitive to the geometric deformation of a cardiac or vascular pathway.  14. Device according to claim 13, characterized in that said sensor is a strain gauge arranged on a vessel.  15. Device according to claim 13, characterized in that said sensor comprises an ultrasonic transmitter.  16. Device according to claim 15, characterized in that it comprises sensor means capable of measuring the duration of the ultrasonic transit in the vascular or cardiac path.  17. Device according to any one of claims 13 to 17, characterized in that it comprises means connected to said sensors and sensitive to the amplitude of the geometric deformation during a cycle.  18. Device according to any one of claims 13 to 17, characterized in that it comprises means sensitive to the offset of the course of the geometric deformation curve between two cycles.  19. Device according to any one of claims 1 to 18, characterized in that it comprises at least one sensor sensitive to an ionic concentration and disposed in the vicinity of a risk zone.  20. Device according to claim 19, characterized in that said ions are chosen from potassium, H +, sodium, chlorine, calcium, magnesium, phosphorus ions.  21. Device according to any one of claims 1 to 20, characterized in that it comprises at least one sensor sensitive to a parameter such as oxygen content, C02, CO in hemoglobin or derivatives, arranged in the vicinity of a risk area.  22. Device according to any one of claims 19 to 21, characterized in that said sensors are arranged in the myocardium and / or a cardiac cavity.  23. Device according to any one of claims i to 22, characterized in that it comprises at least one temperature sensor sensitive to the differential temperature in the vicinity of a risk zone.  24. Device according to any one of claims 1 to 23, characterized in that it comprises means for acquiring the electrocardiogram.  25. Device according to claim 24, characterized in that it comprises means sensitive to the heart rate.  26. Device according to any one of claims 24 and 25, characterized in that it comprises means sensitive to the shape of the cardiac electrogenesis.  27. Device according to any one of claims 24 to 26, characterized in that it comprises means of endocavitary and / or intramyocardial electrodes for the acquisition of the electrocardiogram.  28. Device according to any one of claims 24 to 27, characterized in that it comprises means sensitive to an electric heart anomaly exceeding a threshold value to cause the delivery of a medicament.  29. Device according to any one of claims 22 to 28, characterized in that it comprises electric detection electrodes arranged on several geometric axes for the acquisition of the vectocardiogram and means sensitive to a modification of the vectocardiogram au- beyond a threshold to cause the release of a dose of drug.  30. Device according to any one of claims 1 to 29, characterized in that it comprises at least one sensor sensitive to the spontaneous noises of the heart valves and / or of the myocardium.  31. Device according to any one of claims 1 to 30, characterized in that it comprises means for generating sounds or ultrasound in the heart or in a vascular pathway, as well as means sensitive to propagation, or the absorption of said sensitive sounds or ultrasound.  32. Device according to claim 31, characterized in that it comprises means generating sounds or ultrasound with a rapid frequency variation over a frequency range.  33. Device according to claim 31, characterized in that it comprises means sensitive to the resonant frequency.  34. Device according to any one of claims 1 to 33, characterized in that it comprises means sensitive to the deposition of fibrin in a vascular or cardiac pathway at risk.  35. Device according to any one of claims 1 to 34, characterized in that it comprises means sensitive to the state of blood crase.  36. Device according to claim 35, characterized in that it comprises at least one hearth provided with presentation means facilitating the local accumulation of factor of blood crase.  37. Device according to claim 36, characterized in that it comprises, at said focal point, a sensor sensitive to calcium ions, and / or H +.  38. Device according to one of claims 36 and 37, characterized in that it comprises, at said hearth, means for presenting at least one factor of blood crase.  39. Device according to any one of claims 36 to 38, characterized in that it comprises, to said focus, means sensitive to optical absorption by at least one factor of blood crase.  40. Device according to one of claims 35 to 39, characterized in that it comprises means sensitive to a spite of fibrin or its precursors.  41. Device according to claim 40, characterized in that it comprises a support, surface or cavity facilitating a local spite of fibrin or its precursors and means for measuring the thickness or the mass of said dep8t.  42. Device according to claim 41, characterized in that it comprises, in the vicinity of said support, surface or cavity, electrode means supplied with a current for measuring the impedance of the layer or mass of the deposit.  43. Device according to any one of claims 40 to 42, characterized in that it comprises, in the vicinity of said support, surface or cavity, light emission and reception means sensitive to the thickness of the mass of the deposit .  44. Device according to one of claims 40 to 42, characterized in that it comprises, in the vicinity of the support or cavity, means of sound or ultrasonic emission and means of sound or ultrasonic sensors sensitive to the resonance of the layer or mass of deposit.  45. Device according to any one of claims 35 to 39, characterized in that it comprises means of ultrasonic emission and ultrasonic reception sensitive to the resonance corresponding to the factor in the blood.  46. Device according to any one of claims 1 to 45, characterized in that it comprises means of sound or ultrasonic emissions and a sound or ultrasonic sensor, oriented in a vascular or cardiac path for emitting sounds or ultrasound with rapid frequency variation and detect resonance of the blood column.  47. Device according to claim 46, characterized in that it comprises means for causing the emission and the measurement at determined moments of the cardiovascular cycle, in particular during a systole or a diastole.  48. Device according to any one of claims 1 to 47, characterized in that it comprises optical means for acquiring a color or image in the circulating blood or a cardiac or arterial wall or the bone marrow.  49. Device according to claim 48, characterized in that it comprises means allowing the counting of figured elements of the blood.  50. Device according to one of claims 48 and 49, characterized in that it comprises means for analyzing the image.  51. Device according to any one of claims 1 to 50, characterized in that the measurement of the parameters is carried out periodically in association with the cardiac or arterial cycles.  52. Device according to any one of claims 1 to 50, characterized in that the parameters are measured several times during a cycle and that the variation in parameter during the cycle is compared with said threshold means.  53. Device according to any one of claims 51 and 52, characterized in that a parameter is measured at least once during a cycle and that the measurements are compared between two or more cycles.  54. Device according to any one of claims 1 to 53, characterized in that it includes means sensitive to the rhythm and / or to cardiac electrogenesis, said means being connected to threshold determination means for modifying the thresholds .  55. Device according to any one of claims 1 to 54, characterized in that it comprises means sensitive to the rhythm and / or the cardiac electrogenesis, connected to the dose release means for authorizing or inhibiting said release.  56. Device according to any one of claims 1 to 55, characterized in that it comprises a pacemaker and / or defibrillator.  57. Device according to claim 56, characterized in that said stimulator is provided with anti-tachyarrhythmic means.