WO1999045982A2

WO1999045982A2 - A catheter to be inserted into a blood vessel, and a method for detection of substances

Info

Publication number: WO1999045982A2
Application number: PCT/SE1999/000259
Authority: WO
Inventors: Jan Liska; Anders Franco-Cereceda
Original assignee: Jan Liska; Franco Cereceda Anders
Priority date: 1998-03-11
Filing date: 1999-02-24
Publication date: 1999-09-16
Also published as: SE9804081L; WO1999045982A3; SE9804081D0; EP1061969A2; SE511932C2; AU2863599A

Abstract

A catheter (1) to be inserted into and guided by a blood vessel, and a method for detecting substances in the coronary sinus. The catheter (1) comprises an elongate catheter body (2), having a distal end and a proximal end, and includes at least two channels (23, 24). A first and second channel (23, 24) for microdialysis solution are connected with each other so that microdialysis solution can flow from one channel to the other. An opening (25), in connection with which a microdialysis membrane (30) is arranged, is provided in the catheter body (2). A space (26) in the catheter body is formed by a part of the first channel in connection with said opening and forms a microdialysis chamber (26). The catheter is connectable to external means (10) for circulating and monitoring/analyzing the dialysis solution. In the method the concentration of at least one substance in a group, in a sample of a dialysis solution obtained by microdialysis of blood in the vascular system, e.g. in the coronary sinus, is measured and possibly compared with a reference concentration for the respective substance measured.

Description

A catheter to be inserted into a blood vessel, and a method for detection of substances .

FIELD OF THE INVENTION The invention relates to a catheter, to be inserted into and guided by a blood vessel, comprising an elongate catheter body, having a distal end and a proximal end, and an outer essentially cylindrical surface, limiting a wall structure, enclosing at least two channels, and to a method for detection of substances in a heart. Further it relates to a method for detection of at least one substance indicating metabolic changes in a heart.

BACKGROUND OF THE INVENTION The human heart represents a major organ with respect to morbidity and mortality among the population. In spite of increased knowledge and treatment of cardiovascular disorders myocardial infarction and coronary artery disease still represent major causes of death. Acute myocardial infarction was the primary cause of 25023 deaths during 1992 in Sweden (AFA, Arbetsmarknadens Fδrsakrings Aktiebolag, "Hjartinfarkt och samhalle", 1995.).

Microdialysis is used to monitor the interstitial fluid in various body organs with respect to local metabolic changes.

The technique is now also experimentally applied in humans for measurements in adipose tissue (H. Rosdahl, U. Ungerstedt and J. Henriksson, "Microdialysis in human skeletal muscle and adipose tissue at low flow rates is possible if dextran-70 is added to prevent loss of perfusion fluid", Acta Physiol Scand, 1997, 159, pp 261- 262), muscle (Rosdahl et al, as above, D.G. Maggs, .P. Borg and R.S. Sherwin, "Microdialysis techniques in the study of brain and skeletal muscle", Diabetologia, 1997, 40: pp 75- 82, Springer- Verlag and P. -A. Jansson, J. Fowelin, U. Smith, and P. Lonnroth, 1988, "Characterization by microdialysis of intercellular glucose levels in subcutaneous tissue in humans", Am J Physiol 255, E218-E220.) and brain (Maggs et al, as above and R. Kanthan, A. Shuaib, G. Goplen and H. Miyashita, " A new method of in-vivo microdialysis of the human brain", Journal of Neuroscience Methods 60 (1995) 151- 155) . Routine use of microdialysis in clinical settings is, however, not yet established. Traditionally microdialysis catheters are inserted into the tissue whereafter an equilibration period, measurements of metabolic changes within the local tissue area can be made.

In US-A-4 694 832, a dialysis probe is disclosed, which is primarily used for insertion in biological tissues, for example brain tissue. In such applications, the probe is located in the tissue through operation. It can also be inserted in a blood vessel or a tissue in the same manner as a canula and is then provided with a pointed, cutting edge. Consequently it is not suitable to be inserted into and guided by a blood vessel. Also the design of the dialysis chamber makes it unsuitable for insertion into and guidance by a blood vessel, since it is too fragile .

When admitted to a cardiac intensive care unit, patients with chest pain are routinely monitored by ECG and intermittent peripheral venous plasma markers (ASAT, ALAT, CK/CK-B, troponin-T and troponin-I ) for detection of cardiac damage. Regretfully though, the observed metabolic changes are usually detected late in the onset of myocardial infarction and angina pectoris. Those markers are monitored in peripheral venous plasma, and the response time is usually several hours. This halters the active treatment and intervention of ongoing myo- cardial ischaemia. Furthermore, a number of patients subjected to coronary surgery with CABG (coronary artery bypass grafting) or valve replacement have cardiac failure or associated diseases which increase the risk of the operation. These patients are post-operatively hemodynamically monitored at the intensive care unit but appropriate means of rapid detecting metabolic disturbances in the heart are still lacking.

A continuous, rapid and selective detection of metabolic disturbance of the heart during ischaemia would greatly enhance the possibilities of active intervention in the development of myocardial infarction with non-reversible damage of the heart in patients admitted to cardiac intensive care units as well as in patients undergoing cardiac surgery.

SUMMARY OF THE INVENTION

It is an object of the invention to provide a device which can be used for achieving an accurate and rapid response to the presence of certain substances in the blood of a blood vessel, and is robust, simple to insert, and has a simple construction.

It is also an object of the invention to provide an efficient device which can be used for accurate and rapid detection of substances in the coronary sinus related to metabolic changes in a heart.

These and other objects are attained by the features in the characterizing portion of claim 1.

Through the arrangement of a microdialysis chamber, a device is achieved, which can be used when measuring substances in blood, without the need of taking blood samples. Through the arrangement of a microdialysis chamber, further, a device is achieved, which has a short response time when used for measuring/monitoring substances in blood.

Through the specific design of the channels and the microdialysis chamber, a catheter, which is simple to manufacture is achieved.

By the features in claim 2 is further achieved a device that rapidly can obtain a reliable reference value.

By the features in claim 4 is further achieved a catheter, which is simple to manufacture.

By the features in claim 5 it is further achieved that the insertion of the catheter is facilitated, and that the catheter easier remains in the right position when once correct located.

By the features in claim 7 it is further achieved that the catheter can be used for taking samples from the coronary sinus and the right atrium of an adult.

By the features in claim 8 it is further achieved a catheter having a stiffness suitable for using Seldinger technique when inserting the catheter.

By the features in claim 9 it is further achieved that a guide wire can be used for facilitating the introduction of the catheter.

By the features in claim 11 it is further achieved that blood samples can be taken from the distal end of the catheter, in order to ensure correct position of the catheter. By the features in claim 12 it is further achieved a catheter, which is possible to place in a position where the patients blood easily can pass and get in contact with the both microdialysis membranes.

By the features in claim 13 it is further achieved a catheter which is robust, simple in its construction, cost-effective and easy to manufacture.

By the features in claim 15 it is further achieved a catheter having a stiffness suitable for insertion with Seldinger technique into the coronary sinus .

By the features in claim 16 it is further achieved a catheter, which is detectable with X-rays, and correct position of the catheter can be ensured by means of X-ray detection.

By the features in claim 17 it is further achieved a catheter for microdialysis having good long term capture and being prevented from clotting.

It is a further object of the invention to provide a method which can be used for achieving an accurate and rapid response to the presence of certain substances in the blood of a blood vessel, related to metabolic changes in a heart.

It is also an object of the invention to provide an efficient method which can be used for accurate and rapid detection of substances in the vascular system indicating reversible and non-reversible damage to the heart muscle.

These and other objects are attained by the features of claims 18, 20, 22, 23 or 25. By the features of claims 18, 20, 22, 23 or 25 a method which can be used for continuous monitoring is also achieved.

By the features of claims 18, 20, 22, 23 or 25 a method for detection of substances in a heart of a patient with myocardial ischaemia, as one of a number of indications of development of myocardial infarction and failure is also achieved.

By the features of claims 18, 20, 22, 23 or 25 a method for detection of metabolic changes in a heart of a patient with myocardial ischaemia, as one of a number of indications of development of myocardial infarction is also achieved.

BRIEF DESCRIPTION OF THE DRAWINGS

Fig. 1 is a partly broken diagrammatic view of a first embodiment of a catheter according to the invention,

Fig. 2 is a cross sectional view taken at II-II in Fig. 1,

Fig. 3 is a cross sectional view taken at III-III in Fig. 1,

Fig. 4 is a longitudinal section taken at IV-IV in Figure 2,

Fig. 5 is a partly broken diagrammatic view of a second embodiment of a catheter according to the invention,

Fig. 6 is a cross sectional view taken at VI-VI in Fig. 5, and

Fig. 7 is a longitudinal section taken at VII-VII in Fig. 5. DESCRIPTION OF PREFERRED EMBODIMENTS

It is to be noted that like or corresponding parts are designated by like reference numerals throughout the drawings. Figure 1 is a partly broken diagrammatic view of a first embodiment of a catheter 1 according to the invention. The catheter comprises an elongate catheter body 2 having an essentially cylindrical outer surface, a distal end 21, and a proximal end 22, between which it preferably is continuous, except for the openings which will be explained below. The catheter body 2 is preferably made of radio opaque PVC or other suitable material, and its outer diameter is preferably in the range of 5- 7,5 Fr («1,5- 2,5 mm).

As seen in Figure 3, which is a cross section taken at III-III in Figure 1, the catheter body 2 includes a number of longitudinal channels. Two of the channels 23, 24 are designed for circulating dialysis solution, and at their proximal ends they are connectable to means 10 for circulating, monitoring or analyzing, and preferably collecting the dialysis solution. In the figure, the channels 23, 24 are shown to have the same inner diameters. However, the channels can have different inner diameters, and their cross sections can have different shapes than the shown. In the case of different inner diameters, channel 24 preferably has the smaller, and dialysis solution flows from the means 10 through channel 24 and back through channel 23.

At a distance from its distal end, the catheter body 2 has an opening 25, which is best seen in Figures 1 and 2. The form of the opening 25 in the outer surface of the catheter body 2 can for example be circular, oval or essentially rectangular. The length of the opening 25, in the longitudinal direction is preferably 10- 30 mm. The opening in the catheter body 2 can be formed by removing a part of its wall by cutting away a portion of the catheter body 2 in a wall region of channel 23, whereby a section of channel 23 is opened, and thus a space or chamber 26 is formed. As will be explained further below, the chamber 26 is provided with a wall formed by a microdialysis membrane 30, in order to provide a microdialysis chamber 26. Preferably the channel 26 is enlarged in this section by the removal of the wall part, as shown in the figures. A part of or the whole circumference to said region can be cut away to further enlarge the chamber 26 and thus enlarge the dialysis surface.

In Figure 4, which is a longitudinal section taken at IV-IV in Figure 2, it is shown that channels 23 and 24 are connected by a channel or opening 27 between the chamber 26 and channel 24, so that dialysis solution can flow between the channels. The channel or opening 27 is preferably arranged so as to connect a distal portion of the chamber 26 and the channel 24, but other placements could also be possible. Preferably the channels 23 and 24 are plugged or sealed between channel 27 and the distal end of the catheter body 2, by means of a plug or a seal 28, 29, in order to prevent dialysis solution from entering channels 23, 24 beyond channel 27. Further, channels 23 and 24 are plugged or sealed at the distal end 21 of the catheter body 2.

In a region around the opening 25 the catheter body 2 is provided with microdialysis membrane 30 having a socket-like shape, and surrounding a portion of the catheter body 2. In Figure 1 the microdialysis membrane 30 is partly broken up, so that the opening 25 and the chamber 26 can be seen. The microdialysis membrane 30 can be slid on to the catheter body 2 over the distal end 21. At regions of its edges 301, 302 the microdialysis membrane 30 is further bonded or fastened with a glue or adhesive, or by other suitable means to the catheter body 2, in order to prevent any liquid to enter or exit between the microdialysis membrane 30 and the catheter body 2 from or to the outside.

Possibly, the catheter body 2 can be provided with an annular recess, for receiving the microdialysis membrane 30, in said region surrounding the opening 25.

Depending on the substances to be detected at the micro- dialysis, a microdialysis membrane 30 of cuprophane, polycarbonate or PES (molecular cut-off between 1- 200 kD) can be used. In order to prevent trigging of coagulation when in contact with blood, the microdialysis membrane 30 may be surface heparinized.

To facilitate the insertion of the catheter 1 into a certain blood vessel, a guide wire channel 50, for receiving a guide wire 51, can be arranged in the catheter body 2. The distal end of the catheter body 2 is closed or sealed except for an opening 52. This opening 52 forms a continuation of the inner surface of the guide wire channel 50. The guide wire 51 is used during insertion of the catheter, to increase the stiffness of the catheter 1, and to make it possible to bend the catheter 1 into a desired curve, in order to facilitate its insertion. After insertion of the catheter 1 the guide wire 51 is removed, and a blood sample can be taken out at the proximal end of the catheter 1 through the opening 52 and the guide wire channel 50. To prevent the guide wire 51 from passing through the opening 52 the guide wire 51 is provided with a stop 53.

The catheter body 2 can advantageously be manufactured from an extruded continuous profile body. The profile body is cut to a desired length, and the channels, except the guide wire channel, are sealed or plugged at their distal ends. Further the microdialysis chamber is formed by cutting, the channel between the channels (microdialysis chamber and channel) are formed, and the blind ends of the channels are sealed or plugged. Thereafter the catheter body 2 is provided with a microdialysis membrane, and connections or connection tubes at the proximal end.

The distal portion of the catheter may be preformed into a desired curvature so that by torquing the catheter about its longitudinal axis, the catheter can be manipulated to the desired location.

To provide sufficient control over the movement of the catheter, it is necessary that its structure is somewhat rigid. However, the catheter must not be so rigid as to prevent navigation of the catheter through blood vessels to arrive at the precise location where the microdialysis procedure will be performed. In addition it is necessary that the catheter is not so rigid as to cause damage to the blood vessels through which it is being passed.

While it is important that the catheter not is so rigid as to cause injury to blood vessels, it is also important that there is sufficient rigidity in the catheter to accommodate torque control, i.e. the 'ability to transmit a twisting force along the length of the catheter. Sufficient torque control enables controlled manoeuvrability of the catheter by the application of a twisting force at the proximal end of the catheter that is transmitted along the catheter to its distal end. The preform is also advantageous in that, it helps the catheter to remain in the right position when once correctly located.

In figure 5 a second embodiment of a catheter according to the invention is shown. This catheter includes a first microdialysis chamber 26, with associated channels 23,24, a first opening 25 and a first microdialysis membrane 30, as described in connection to the first embodiment according to figure 1. At a centre distance of about 100- 120 mm from the first opening 25 in the catheter body 2, in the direction towards the proximal end 22, a second opening 45 is provided in the catheter body 2, located on the opposite side to the first opening 25. As seen in Figures 5 and 7, a second microdialysis chamber 46 with associated second microdialysis membrane 31, and channels 43, 44, is arranged in connection with the second opening 45, in the same manner as in the first embodiment. Channels 43, 44 are connected by means of a channel 47, preferably at the distal portion of the second microdialysis chamber, and the channels 43, 44 are preferably sealed or plugged 48, 49 to prevent dialysis solution to enter the portions of the channels between channel 47 and the distal end of the catheter body 2, in the same manner as in the first embodiment. The two channels 43, 44 are connected at their proximal ends to the same means 10, for circulating, monitoring or analyzing, and preferably collecting the dialysis solution, as the two channels 23, 24, or to separate means.

Figure 6 is a cross sectional view taken at VI-VI in Fig. 5, showing a possible placement of the two channels 23, 24, the two channels 43,44, the guide wire 51, and the guide wire channel 50 inside the catheter body 2. When used, the catheter is inserted with the help of the guide wire into a blood vessel of a patient, e. g. the jugular vein or the subclavian vein by Seldinger technique. The catheter is thereafter guided in the vein and advanced into the right atrium of the patient's heart and positioned into for example the coronary sinus, so that the first microdialysis chamber will be located in the coronary sinus. By preforming the catheter into an optimal curvature and/or by bending the guide wire, the achievement of the right position is facilitated. The correct position is ensured by blood sampling through the opening 52 and the guide wire channel 51, with measurement of oxygen saturation, or alternatively by X-ray or ultra sonic detection. Using the catheter with two microdialysis chambers, the distance between the two chambers is selected so that the second chamber then will be located in the right atrium, so that microdialysis can be performed in both the coronary sinus and the right atrium. This distance is about 100- 120 mm for an adult. In the case of two microdialysis chambers it is important that the openings in the catheter body 2 are located at substantially diametrically opposed sides of the catheter body 2 , so that it is possible to place the catheter in a position where the patients blood easily can pass and get in contact with the both microdialysis membranes. In order to use the Seldinger technique the catheter must have a suitable flexibility. This is achieved by selecting the thickness of the parts thereof with respect to the properties of the respective material. However, this is common knowledge for a person skilled in the art.

Alternatively, the catheter 1 could be tunulated through the skin of the patient, and placed directly into the coronary sinus during cardiac operations. The insertion hole is sealed with a suture to enable removal of the catheter 1 through the skin during post operative monitoring. When the catheter 1 is positioned in a blood vessel to be monitored, the proximal ends of the two channels 23, 24 and possibly the two channels 43, 44 are connected to external means 10. This means include container for dialysis solution, container for collecting microdialysis solution that has passed a microdialysis chamber 26, 46, and pumps for circulating the microdialysis solution through the respective pair of channels 23, 24 and 43, 44. Further it includes means or apparatus for monitoring or analyzing the microdialysis solution having passed a microdialysis chamber. For example the concentration of substances, having passed from the blood in the vein through a microdialysis membrane 30, 31 to the microdialysis solution in the microdialysis chamber 26 ,46 by microdialysis and transported to the monitoring or analyzing apparatus, can be measured. Such substances could be metabolic markers, such as ASAT, ALAT CK/CK-B, troponin-T and troponin-I, or substances such as lactate, pyruvate, glucos, glycerol, urea, aspartate, glutamate, myoglobin, hypoxanthines or peptides .

In the embodiment with two microdialysis chambers 26 ,46, the concentration of the monitored substances can be measured in e.g. both the coronary sinus and the right atrium. The measurement from the right atrium is then used as a reference value, when detecting changes in the coronary sinus. The values so obtained, with either of the two embodiments of a catheter, can be used for detection of metabolic changes in a heart of a patient with myocardial ischaemia, as one of a number of indications of development of myocardial infarction. Other indications are received from ECG-monitoring and monitoring of hemodynamic changes, arrythmias and blood pressure changes. By using the catheter and the method according to the invention, a quick response to metabolic changes in a heart is achieved. The response time is about 15- 20 minutes, which is to be compared with several hours, which is the response time for the methods used today.

Since the substance (s) to be detected and/or measured are produced in the heart, the concentration thereof is highest in the heart. Therefore, in order to achieve the most accurate and rapid response it is preferred to take the sample for measurements in the heart, preferably in the coronary sinus. Some of the substances to be detected and/or measured have a very short lifetime in the blood since they are absorbed and metabolized, e.g. by the red blood cells (erythrocytes) . It is therefore very advantageous to isolate these substances from the blood by the microdialysis process. In the microdialysis solution they will remain constant (i.e. not metabolized), which is advantageous for the measurement, especially when they can be isolated already in the heart.

Although it is preferred that the samples to be analysed are obtained by microdialysis of blood in the coronary sinus, they can also be obtained by microdialysis of blood in other parts of the vascular system, e.g. in an artery. Especially advantageously the concentration of the substance (s) , e.g. glutamate, can be measured in samples taken by microdialysis in the pulmonary artery. Further the blood from the myocardium will be mixed and diluted, in the blood stream, which leads to a lower concentration of the substances to be measured. The metabolism and absorption in the blood of some of the substances also cause a decreased concentration at a distance from the heart. Some of the substances have a long lifetime, i.e. will not be metabolized in the blood or tissue, and can very advantageously be measured also in the venous system. Although the response is not that fast and the concentrations are lower compared to measurements from the coronary sinus, a satisfactory and reliable result can be obtained in most cases. The substances which can be obtained, monitored and/or measured (e.g. the concentration of) in an artery are the same as for the coronary sinus, i.e. at least one substance in a group consisting both of metabolic markers, such as ASAT, ALAT CK/CK- B, troponin-T and troponin-I, and substances such as lactate, pyruvate, glucos, glycerol, urea, aminoacids, myoglobin, purines and peptides . As in the case of samples obtained from the coronary sinus, the substances can be continuously monitored when the microdialysis process is continuous, also when the samples are obtained from other parts of the vascular system.

Myocardial ischemia i.e., quantitative deficiency of oxygenated blood delivered to the myocardial tissue produced by local obstruction to the arterial flow, is a serious condition which ultimately will lead to permanent irreversible myocardial cell damage (myocardial infarction) . Myocardial infarction is responsible for 25023 deaths during 1992 in Sweden, as mentioned above. The development of myocardial infarction is strongly dependent of ischemic duration, thus a complete obstruction of arterial blood flow to a defined area (area at risk) starts to produce irreversible damage within 10 to 15 minutes, after 60 minutes 80-90% of the area at risk comprises of myocardial infarction. It is therefore of great importance to detect metabolic changes and substances indicating ischemia, so that appropriate intervention to restore blood flow can be performed before permanent damage develops . These interventions includes dilatation of an obstructed vessel, dissolving a thrombus or performing acute coronary artery bypass surgery.

The detection of myocardial ischemia is today mainly dependent of alterations of the electrocardiogram (ECG) , however with an approximate sensivity and specificity of only 70%. Other means by which a myocardial infarction can be detected comprise of analyzing enzymes and other substances in venous blood, released from irreversible damaged myocardial cells. The disadvantages of these analyses are the duration time for the analysis itself, often several hours, and the time lag (3-6hrs) between the irreversible myocardial damage and the emergent of the specific markers. Ischemia in a heart produces an immediate shift in metabolism from aerobic to anaerobic, which is reflected by for example a rapid transient production of lactate instead of consumption. This production of lactate and certain substances related to ischemia such as glutamate, asparate, taurine, hypoxanthine and adenosine are released to the blood compartment with a maximal concentration in venous blood of the heart i.e., contained in the coronary sinus and the thebesian veins, the substances are further quickly dispersed into the main blood stream pumped by the heart, also the half-life of the substances are short due to metabolic consumption of the blood itself and the peripheral tissue, thus a transient detection is possible only in the pulmonary artery and possibly in systemic arteries but not in systemic venous blood.

Microdialysis has been used to monitor the interstitial fluid in various body organs with respect to local metabolic changes, as mentioned above. The present invention relates to a method of continuos detection of transient or more long-lasting production or release of substances from the heart related to metabolic changes in a heart and a specially designed microdialysis catheter to be used in the method. The method has the advantage compared to the traditional metabolic analysis of markers related to myocardial ischemia, that it is not limited to the analysis of substances with a long life time (e.g. half- life being hours-days) , and requires no sampling of blood and thereby continuos analysis is possible with a short time for analysis. The method can indicate ischemic changes in a heart in an early stage prior to development of extended permanent myocardial damage, it will therefore be very useful for the guidance of intervention. A disadvantage with conventional blood sampling is that it is limited to momentary situations.

With a continuous technique according to the invention it is possible to follow the development of metabolic changes, whereby an ominous condition can be detected.

Although the invention has been described in conjunction with a number of preferred embodiments, it is to be understood that various modifications may still be made without departing from the spirit and scope of the invention, as defined by the appended claims. For example the dimensions can vary, depending on the specific use. Although the catheter has been described for use in special parts of a human body, especially a human heart, it can be used in other parts of a body for detection of substances indicating metabolic changes, or other substances.

Claims

1. A catheter, to be inserted into and guided by a blood vessel, comprising an elongate catheter body, having a distal end and a proximal end, and an outer essentially cylindrical surface, limiting a wall structure, enclosing at least two channels, characterized in

said at least two channels including a first and a second channel for microdialysis solution, each channel having a proximal and a distal end,

the first and second channel being connected with each other at a first distance from the distal end of the catheter body so that microdialysis solution can flow from one channel to the other,

an opening, in connection with which a microdialysis membrane is arranged, being provided in the catheter body at a second distance from its distal end,

a space in the catheter body formed by a part of the first channel in connection with said opening forming a microdialysis chamber, having at least a portion of the microdialysis membrane as a part of its walls,

the proximal end of each of said first and second channel being connectable to external means for circulating and monitoring/analyzing the dialysis solution.

A catheter according to claim 1, wherein a third and a fourth channel for microdialysis solution are formed in the catheter body, each channel having a proximal and a distal end,

the third and a fourth channel being connected with each other at a third distance from the distal end of the catheter body so that microdialysis solution can flow from one of the third and a fourth channels to the other,

a second opening, in connection with which a second microdialysis membrane is arranged, being provided in the catheter body at a fourth distance from its distal end,

a second space in the catheter body formed by a part of the third channel in connection with said second opening forming a second microdialysis chamber, having at least a portion of the second microdialysis membrane as a part of its walls,

the proximal end of each of said third and fourth channel being connectable to external means for circulating and monitoring/analyzing the dialysis solution.

3. A catheter according to claim 1 or 2, wherein

each microdialysis membrane covers the respective opening.

4. A catheter according to any preceding claim, wherein each microdialysis membrane has a socket-like shape.

5. A catheter according to any preceding claim, wherein

the catheter is preformed into a desired curvature.

6. A catheter according to any preceding claim, wherein

each dialysis membrane is glued, adhered, bonded or fastened by other suitable means to the catheter body at regions in the vicinity of their respective edges, said edges being located at opposite sides of the respective openings .

7. A catheter according to any of claims 2-6, wherein

- the fourth distance is approximately 100-120 mm longer than the second distance.

8. A catheter according to any preceding claim, wherein

the catheter has a flexibility enabling it to be inserted into and guided in a blood vessel e.g. according to Seldinger technique.

9. A catheter according to any preceding claim, wherein

a guide wire channel, for reception of a guide wire, is formed in the catheter body.

10. A catheter according to any preceding claim, wherein

the catheter body is closed at its distal end.

11. A catheter according to claim 9, wherein

the catheter body is closed at its distal end except for an opening being a continuation of the guide wire channel .

12. A catheter according to any of the claims 1-11, wherein

the openings in the catheter body are located on substantially diametrically opposed sides of the catheter body.

13. A catheter according to any preceding claim, wherein

the catheter body is formed by extrusion.

14. A catheter according to any preceding claim, wherein

each opening has an extension in axial direction of 10- 30 mm.

15. A catheter according to any preceding claim, wherein

the catheter has a flexibility enabling it to be inserted into and guided in the coronary sinus e.g. according to Seldinger technique.

16. A catheter according to any preceding claim, wherein

the catheter body is radio opaque.

17. A catheter according to any preceding claim, wherein

the microdialysis membrane (s) is (are) heparinized.

18. A method for detection of substances in a heart, characterized in that the concentration of at least one substance in a group consisting both of metabolic markers, such as ASAT, ALAT CK/CK-B, troponin-T and troponin-I, and substances such as lactate, pyruvate, glucos, glycerol, urea, aspartate, glutamate, myoglobin, hypoxanthines and peptides, in a sample of a dialysis solution obtained by microdialysis of blood in the coronary sinus, is measured and possibly compared with a reference concentration for the respective substance measured.

19. A method according to claim 18, wherein

- the reference concentration is obtained by measuring the concentration of said at least one substance in a second sample of a dialysis solution obtained by microdialysis in the right atrium.

20. A method for detection of metabolic changes in a heart, characterized in that the concentration of at least one substance in a group consisting both of metabolic markers, such as ASAT, ALAT CK/CK-B, troponin-T and troponin-I, and substances such as lactate, pyruvate, glucos, glycerol, urea, aspartate, glutamate, myoglobin, hypoxanthines and peptides, in a sample of a dialysis solution obtained by microdialysis of blood in the coronary sinus, is measured and possibly compared with a reference concentration for the respective substance measured.

21. A method according to claim 20, wherein

the reference concentration is obtained by measuring the concentration of said at least one substance in a second sample of a dialysis solution obtained by microdialysis in the right atrium.

22. A method for detection of at least one substance indicating metabolic changes in a heart, characterized in that the concentration of at least one substance in a group consisting both of metabolic markers, such as ASAT, ALAT CK/CK-B, troponin-T and troponin-I, and substances such as lactate, pyruvate, glucos, glycerol, urea, aminoacids, myoglobin, purines and peptides, in a sample of a dialysis solution obtained by microdialysis of blood in the vascular system, preferably in an artery, is measured and possibly compared with a reference concentration for the respective substance measured.

23. A method for detection of substances in a heart, characterized in that the concentration of at least one substance in a group consisting both of metabolic markers, such as ASAT, ALAT CK/CK-B, troponin-T and troponin-I, and substances such as lactate, pyruvate, glucos, glycerol, urea, aspartate, glutamate, myoglobin, hypoxanthines and peptides, in a sample of a dialysis solution obtained by microdialysis of blood in the coronary sinus, is measured and possibly compared with a reference concentration for the respective substance measured.

24. A method according to claim 23, wherein the reference concentration is obtained by measuring the concentration of said at least one substance in a second sample of a dialysis solution obtained by microdialysis in the right atrium.

25. A method for detection of metabolic changes in a heart, characterized in that the concentration of at least one substance in a group consisting both of metabolic markers, such as ASAT, ALAT CK/CK-B, troponin-T and troponin-I, and substances such as lactate, pyruvate, glucos, glycerol, urea, aspartate, glutamate, myoglobin, hypoxanthines and peptides, in a sample of a dialysis solution obtained by microdialysis of blood in the coronary sinus, is measured and possibly compared with a reference concentration for the respective substance measured.

26. A method according to claim 25, wherein

27. A method according to any of claims 18-26, wherein the concentration of the substance (s) to be detected is continuously measured in a sample of a dialysis solution obtained by continuous microdialysis of blood.