CN202637103U - Catheter having renal nerve mapping function - Google Patents

Abstract

The utility model provides a catheter having renal nerve mapping function, which comprises a catheter head end with a plurality of electrodes. The catheter head end can be placed within a renal artery lumen. The electrodes are capable of delivering a direct current, an alternating current and RF energy. The above catheter can be used for mapping renal nerves and treating diseases caused by the systematic hyperexcitability of renal sympathetic nerves, such as hypertension, heart failure, renal failure and diabetes.

Description

Conduit with the neural mapping function of kidney

Technical field

The present invention relates to for mapping and the conduit system that melts the kidney nerve, in order to improve effectiveness and the safety of carrying out the neural ablation of kidney through catheterization procedure.

Background technology

Congestive heart failure, hypertension, diabetes and chronic renal failure have many different pathology causes of disease; But these diseases all will experience a common pathway in the process that develops into disease in latter stage at end, namely the kidney sympathetic nerve is overexcited.The kidney sympathetic nerve arrives the senior sympathetic nerve maincenter that is arranged in spinal cord and brain as the signal afferent pathway by afferent kidney neural activity is imported into, can increase system's sympathetic tone degree; Simultaneously the kidney nerve also can be used as efferent pathway and participates in the sympathetic nerve that senior sympathetic nerve maincenter causes and be overexcited, and further increases the sympathetic tension force of whole body (Dibona and Kopp, 1977).Originally orthosympathetic tension force increases is useful, but finally can become the pathologic activity.Under the overwrought state of sympathetic nerve, many pathology can occur change: hormone secretion is unusual, raises such as catecholamine, epinephrine and Angiotensin II level, and peripheral blood vessel shrinks and/or water-sodium retention, thereby causes elevation of the blood pressure; Glomerular filtration is impaired and thereby nephron reduces the renal failure that causes, thereby left ventricular hypertrophy and myocardial cell loss cause cardiac insufficiency and heart failure; Apoplexy, even diabetes.Therefore, to orthosympathetic be overexcited regulate (reduce/remove) and can slow down or stop these advancings of disease.Recently, use the high radio frequency that melts to remove a kind of accepted method that the kidney nerve has become treatment intractable hypertension (Esler et al., 2010 and Krum et al., 2009) and abnormal glucose metabolism (Mahfoud, 2011).Yet the method for the neural ablation of present employed kidney or other Renal denervation can't position the distribution of kidney nerve, the medical professional do not know whether will arteriorenal which partly carry out the neural art of removing of kidney, thereby operation is to carry out in mode blindly, and its therapeutic effect and safety all have much room for improvement and improve.The present invention attempts to address this problem.

The kidney sympathetic nerve is overexcited and hypertension

The kidney sympathetic nerve is overexcited and can be caused hypertension, to the research of this existed system.Although the existing hypertensive single medicine of various treatments and composition of medicine use clinically at present, and auxiliary to improve patient's life style, and hypertensive cure rate is still very low.Even approximately 1/3 hyperpietic adopts the prioritization scheme of multi-medicament treatment, its blood pressure still can not be controlled in normal range, and this phenomenon is called as intractable hypertension or Drug tolerance hypertension.In the hyperpietic, approximately its blood pressure of the patient of half is higher than generally acknowledged therapeutic goal level because of various former carrying on as before after treatment.There is research to think that present Drug therapy can not act on the pathophysiological mechanism of its morbidity effectively in " constitutional " hypertension (namely can not check the persistence hypertension of the clear and definite cause of disease) patient.In addition, hyperpietic's maincenter stimulates renin release to kidney Sympathetic Nerve nerve signal, increase renal tubules to the heavily absorption of sodium, reduce renal blood flow, and from the sympathetic outgoing mechanism of nervus centripetalis signal scalable maincenter of kidney, further regulate again water and sodium, vascular tone/vascular resistance and blood pressure.

Existing mass data confirms renal nerve blocking to reducing hypertensive effect, has confirmed simultaneously the relation between the increase of sympathetic nervous system irritability and the hypertension.For example there are some researches show that sympathetic nervous system that renal dysfunction causes is overexcited causes one of hypertensive mechanism (Campese, 2002; Ye S, 2002).Experiment showed, on the animal model of chronic renal insufficiency, retardance kidney neural activity can be controlled hypertension (Campese, 1995); Clinically, the multicystic kidney disease patient is implemented the Renal denervation art and can eliminate its intractable kidney strand pain and hypertension (Valente 2001).Further confirmation of other researchs, the norepinephrine that the sympathetic nervous system excitation time excessively is discharged in the renal veins is the main cause (Esler et al., 1990) of essential hypertension.Research also shows, can treat by excision kidney nerve and accept dialysis and taken multi-medicament simultaneously but still can not control its blood pressure patient's serious hypertension symptom (Converse 1992).In animal model, also confirmed, the hypertensive progress that Renal denervation can postpone or stop the kinds of experiments model (for example, spontaneous hypertensive rat (SHR), apoplectic spontaneous hypertensive rat, New Zealand's spontaneous hypertensive rat, borderline hypertension rat (BHR), Goldblatt hypertension 1K, the 1C rat, Goldblatt hypertension 2K, the 2C rat, the aortic stenosis dog, aortic nerve cuts off rat, the DOCA-NaCL rat, the DOCA-NaCL pig, the Angiotensin II rat, Angiotensin II rat and rabbit, the fat dog that high fat diet causes, the rat of row kidney parcel art) (DiBona and Kopp, 1997).

The method of research topical is absorbed in the in the past experiment of some reduction intractable hypertensions, for example gives antipsychotic drugs in some part, neural site, such as local anesthetic, ketamine, tricyclics or neurotoxin.

We confirm that in the research of using the dog experimental model the local blocking-up of use medicine kidney is neural, the imagination for the treatment of and the sympathetic tension force diseases related of kidney.In the acute experiment of this research, used 11 acute heart failure model dogs collection of inducing through microsphere thromboembolism heart arteria coronaria blood capillary: 8 dogs for the treatment of group with 10ml bupivacaine (Marcaine

) be injected in the Jie Shi fascia around the renal artery neurally with the retardance kidney, 3 dogs use normal saline to be injected at same area to organize in contrast in addition.Take per 15 minutes urine amount as a unit, relatively in the heart failure situation, the urine amount is in the variation of bupivacaine injection front and back.In treatment group, use the animal of bupivacaine blocking-up kidney nerve that the diuresis natriuresis is arranged; And at matched group, cause the oliguria behind the acute heart failure all not have to improve always.This result has confirmed that blocking-up kidney nerve is with the physiological and pathological basis for the treatment of with the too high diseases related of the sympathetic tension force of kidney.In the experiment of using other 6 micro-embolizations to induce the chronic heart failure dog to carry out, also obtained same result of study (Vigilance 2005).

Kidney sympathetic nerve be overexcited insulin sensitivity and glucose metabolism

The kidney nerve is overexcited and is thought equally with body sensitivity and the glucose metabolism of insulin also had suitable effect.The norepinephrine of for example following the kidney nerve to be overexcited and causing discharges and increases, and Oligemia and cell are reduced the picked-up of glucose.Shown that cell is impaired by the ability of its cell membrane transporter glucose.The orthosympathetic open quantity of blood capillary that has caused causing through nerve conduction of being overexcited of kidney reduces, thereby insulin is increased from the distance that vascular bed is transported to cell.Under the insulin resistant state, the muscle blood flow that insulin produces has reduced approximately 30%.This result has disclosed sympathetic excitability and the direct positive correlation of insulin resistant, the open quantity of insulin resistance and blood capillary be inversely proportional to (Mahfoud, et al., 2011).These the results shows sympathetic nerve be overexcited and diabetes and/or metabolic disease between pathological relation; Sympathetic nerve is overexcited and can be caused that insulin raises in insulin resistance and the blood, and this can cause further increasing of sympathetic tone again conversely.The effect of kidney nerve to diabetes assessed in now existing clinical research.

The research that Mahfoud etc. do (2011) estimated the Renal denervation art to take hypertension after at least 3 kinds of antihypertensive drug (comprising a kind of diuretic) treatment still 〉=the type ii diabetes patient's of 160mmHg (or 〉=150mmHg type ii diabetes patient) therapeutical effect.With month after operation with when following up a case by regular visits in 3 months, detect blood parameters, fasting glucose, insulin, C peptide and glycolated hemoglobin (HbA1c) in the preoperative, during simultaneously in the preoperative with 3 months after operation, carried out oral glucose tolerance test (OGTT).Detect plasma glucose concentration with glucose oxidase method, detect plasma insulin and C peptide concentration with chemiluminometry.Behind the Renal denervation 3 months, the index relevant with diabetes obtained obvious improvement.Before carrying out the Renal denervation art, 13 patients' for the treatment of group insulin level 〉=20 μ IU/mL.After the Renal denervation operation, its insulin level has reduced by 77%, and is then unchanged at the matched group insulin level.Behind the Renal denervation, patient's insulin sensitivity also significantly increases.In 34 patients (tested group, n=25; Matched group, n=9), the preoperative oral glucose tolerance test of Renal denervation shows (OGTT), and 8 patient's impaired fasting glucoses are arranged, 18 patient's impaired glucose tolerance, other 8 patients suffer from diabetes.Postoperative has 7 oral glucose tolerance test results to improve among 25 patients.Be that patient's quantity that standard is diagnosed as diabetes has reduced by 12% (n=3) according to the oral glucose tolerance test; Patient's quantity of normal glucose tolerance has increased by 16% (n=4).The matched group patient when following up a case by regular visits to glucose or insulin metabolism without significant change.

Mahfoud etc. studies confirm that, the kidney sympathetic nervous system is an important ring of regulating insulin resistance, and remove the kidney nerve and can obviously improve patient's insulin resistance and glucose metabolism situation.

Used distinct methods to carry out the research of Renal denervation art in the past

Nineteen thirties, before the hypertensive medicine of many treatments comes out, just there is the surgeon to utilize renal sympathectomy to treat severe hypertension (Smithwick and Thompson, 1953).But this operation wound and side effect are all very big, and operative process is also very complicated, and (DiBona, 2003) therefore are very limited in clinical practice.

Recently there is researcher to use blood vessel Wicresoft interventional technique that the hypertensive patient is carried out the neural ablative surgery of kidney.The kidney nerve mainly is distributed in the renal artery adventitial space on the blood vessel wall beyond the tunica media.Therefore, use radio-frequency (RF) energy, laser energy, high intensity focused ultrasound and ethanol energy to be delivered to the renal artery wall by the renal artery tube chamber and melt the removal nerve, use cryoablation technology equally also can be removed the kidney sympathetic nerve on the renal artery wall.

The first human research who has carried out in 2009 through the neural ablation hyperpietic of conduit kidney.Its study subject is for taking at least three kinds of antihypertensive drug (comprising diuretic) but the blood pressure of standing (SBP) still is greater than or equal to the patient of 160mmHg, or those patients that clearly can not tolerate antihypertensive drug (Krum et al., 2009).The front blood pressure of 45 tested patients' art is 177/101 ± 20/15 (mmHg) in this research, and wherein 89% patient blood pressure after carrying out the treatment of Renal denervation art significantly reduces.

Whether effective in order to estimate the Renal denervation art, also detected the excessive level of kidney norepinephrine at the neural ablation of kidney, as going whether one of successful index of sympathetic nerve art.In this research, measured blood pressure and postoperative 1,3,6 before the art, 9 and the blood pressure 12 months the time.Recorded the amplitude that each time point systolic pressure and diastolic pressure reduce, As time goes on research worker is observed blood pressure continuous downward trend.The result shows, is removing kidney sympathetic nerve postoperative, 45 excessive levels of experimenter's whole body norepinephrine, 28% (p=0.043) that descended, and wherein approximately 1st/3rd, by going kidney sympathetic nerve art to cause.Behind 45 patient treatments, wherein 43 whole body or local vascular complication do not occur.

Present employed Renal denervation art method

Krum etc. carried out making first spend kidney sympathetic nerve art treatment hypertension after, it is present that what pass through is to get involved the neural ablation method of kidney through conduit to remove the kidney nerve.Classical kidney nerve melts method and comprises that the use conduit carries out respectively 4-6 radio frequency (RF) ablation in the every side renal artery of patient, each lasting 2 minutes, radio frequency is produced by radio-frequency signal generator, radio-frequency signal generator be set to automatization, the built-in safe mode of low-power.Radio-frequency (RF) energy is generally 5-8 watt, during treatment in renal artery with conduit from nearly ventral aorta one side shifting of kidney far-end ventral aorta one side direction, the interval is approximately 5mm and carries out radio-frequency (RF) ablation.

In the research of observation Renal denervation art to diabetes that above-mentioned Mahfoud etc. carry out, concrete ablation method is as described below: the conduit that will be used for the treatment of is by using the guiding of kidney hyperbolic seal wire or left inside mammary artery seal wire to insert in every side renal artery; Radio-frequency (RF) ablation melts with 8 watts low-power, and each lasting 2 minutes at most, radio-frequency (RF) ablation finished to nearly kidney end opening place from the main renal artery bifurcated, and after melting each time, the position of rotary guide pipe head end in renal artery carried out at most radio-frequency (RF) ablation 6 times.Before melting, the pattern that presets is to regulate radio-frequency (RF) energy; Melt in the whole process impedance of omnidistance monitoring tube head end and temperature.

Above cited Research of Intravascular Catheterization ablation techniques, purpose be do not block renal artery blood flow simultaneously can be being down to minimum to may damaging of endothelium, the method that employing is melted along the renal artery intermittent can make wound area less, and melting the damage that brings can comparatively fast heal.This neural ablation method can block that kidney is orthosympathetic to be imported into and Efferent Activities, reduces the sympathetic tension force of whole body, keeps the effect clinically that continues.

The desirable renal artery art of going should be optionally to block kidney sympathetic (comprise import into and spread out of) nerve, and do not damage sympathetic nerve to the domination of other organs, its key point is ablation energy can be delivered to accurately position that the kidney sympathetic nerve distributes to remove nerve on renal artery.But at present the neural ablation of kidney is that mode with " blindly " operates, and namely carries out the doctor of the neural ablative surgery operation of kidney and does not know the particular location of kidney sympathetic innervation, just melts at whole section renal artery; In addition, the present result that melts only has and detects after surgery its possible effect, such as the excessive level of norepinephrine, could confirm whether the kidney nerve is melted removal really.The patient data who gets based on small sample and very strict inclusion criteria at present shows, Renal denervation art treatment is to about 89% patient (the Krum et al. that produces effect, 2009 and Esler et al., 2010), but by the blood pressure that detect patient could confirm after surgery by at least one month for this effect; The 2nd, in the clinical practice of reality, use the effective percentage of verified this method of doctor of the neural ablation method of present kidney probably between 50-60%.The not good reason of therapeutic effect may be the kidney nerve regeneration (Esler et al., Lancet 2010, p.1908); More possible reason is to fail the accurately particular location of labelling kidney nerve in renal artery, melts thereby carry out with a definite target in view the kidney nerve.Therefore, the method in the urgent need to can precise marking kidney nerve distributing at renal artery clinically, thereby melt accurately target for the doctor provides, simultaneously also the labelling kidney is neural and whether estimate ablation effective to be used in the urgent need to finding out Relevant clinical indexes that those can Real-Time Monitoring.As discussed above, it is the co-channel of whole body sympathetic nervous system excitement that kidney imports into efferent nervous system, so stimulation of renal nerve can cause elevation of the blood pressure and alteration in heart rate and muscle sympathetic excitability.Thereby can increase sympathetic tone by direct stimulation of renal nerve blood pressure and heart rate are raise, and the muscle sympathetic neural discharge increase; Experimental result shows that simultaneously pressoreceptor reflex also can regulate blood pressure and heart rate (DiBona, 2003).Although having been noted that in Physiologic Studies in the past, this phenomenon not yet have researcher that the neural labelling of this mechanism and kidney and Renal denervation art are connected.

We propose the neural assignment test method of kidney at this, remove art in conjunction with kidney is neural, thereby have reformed the neural removal method of present kidney.In the method, use certain site or section in the galvanism renal artery, simultaneously the reaction of Monitoring of blood pressure, heart rate and muscle sympathetic excitability.If monitoring blood pressure, heart rate and muscle sympathetic excitability changes, increase such as hypertension, alteration in heart rate or muscle sympathetic neural discharge, then can reasonably expect, carry out the kidney nerve in this site and melt and to destroy more accurately the kidney nerve fiber, thereby improve clinical efficacy.The neural mapping method of this kidney and improvement conduit interventional technique can be optimized the neural removal operation of kidney best, and unnecessary melting in the operation reduced to minimum, melt thereby instruct the doctor to carry out the kidney nerve.The neural ablation of kidney of the neural mapping method of kidney and optimization can improve significantly the clinical effectiveness of its treatment hypertension, heart failure, renal failure and diabetes and further guarantee its safety.

The neural ablation middle kidney of kidney can be used the anatomy location of the kidney nerve location of neurectomy

On anatomical configurations, contain kidney spread out of with centripetal fiber from nerve rise in solar plexus (a/k/a solar plexus) and branch, lumbar vertebra splanchnic plexus and Auerbach's plexus (DiBona and Kopp, 1997, p.79).Solar plexus comprises adrenal gland's neuroganglion (being aorticorenal ganglia), solar plexus and greater splanchnic nerve.Solar plexus receives by Sympathetic nerve and does (intrathoracic visceral never) and vagus nerve (DiBona and Kopp, 1997, neural impulse p.79).

Adrenal gland's neuroganglion has many distributions to the adrenal gland, and wherein some branch arrives around arteriorenal blood vessel peripheral nerve clump along arteria suprarenalis and enters the hilus renalis; Other branches then enter the in addition kidney of part of hilus renalis zone.Greater splanchnic nerve is arranged the branch of leading to kidney again through adrenal gland's neuroganglion in leading to the way of ganglia coeliaca.Ganglia coeliaca also has branch to send to arrive the branch of kidney, these branches around renal artery blood vessel peripheral nerve clump enter into the hilus renalis (DiBona and Kopp, 1997, p.79).

The other sympathetic trunk of vertebra that waist and thoracic viscera nerve rise respectively and be positioned at chest and waist.These nerves are distributed to the kidney nerve again via the branch that arrives ganglia coeliaca, and via the branch that arrives the blood vessel peripheral nerve clump around the renal artery enter the hilus renalis (DiBona and Kopp, 1997, p.79).

Plexus nervorum comprises the dorsal mesentery plexus nervorum between mesentery, and it gathers the neural impulse that comes from lumbar splanchnic nerve, this nerve be distributed in arrive before the kidney usually along ovary or testicular artery send branch (DiBona and Kopp, 1997, p.79).On anatomical structure kidney neural with renal artery and renal veins together enter the hilus renalis (DiBona and Kopp, 1997, p.81).They subsequently in the medullary substance outside renal cortex and cortex along the renal artery vascularity, these arteries comprise interlobar arteries, arcuate artery, interlobular arteries and import into and spread out of the glomerule tremulous pulse (DiBona and Kopp, 1997, p.81).This shows, the distribution of kidney nerve is very complicated, has multiple variability, uses clinically the distribution of anatomical structure location kidney nerve very difficult.

Before the kidney nerve melted, arteriorenal structure was the factor that need at first consider, carrying out intervene operation, before the conduit denervation, must think over the arteriorenal structure of every side.As in the research of Krum etc. and Esler etc., mentioning, can carry out interposing catheter treatment, depend on to a great extent arteriorenal anatomical structure, renal artery have or not narrow, whether have in advance the kidney support to insert or angioplasty and the renovascular situation of bilateral.Not only deformity and unusual renal artery structure can hinder the insertion of conduit, even the normal variant of renal artery structure also can whether it has a significant impact to performing the operation, particularly its risk is larger when using non-dedicated conduits system (namely not being to melt custom-designed conduit as renal artery).Possible risk when carrying out the renal artery intervene operation with this class conduit system or the conduit of not considering the renal artery characteristic comprises, because catheter tip and artery diameter do not mate, thereby or if the energy that causes renal artery to break in operative process melting in intra-arterial distortion is excessive to cause breaking and/or damaging of renal artery wall or Endothelium of Renal Artery, even renal artery is peeled off.Therefore, the special conduit system that design meets renal artery structure and common variation is used for the neural art of removing of kidney and is very important, and this will make a large amount of many patients that suffer from the too high diseases related of kidney sympathetic tone obtain suitable treatment.

Conduit system

Some that uses clinically at present is as the conduit system of coronary artery system design and to can be used for the conduit system that the kidney nerve melts similar; The ablation catheter system that is used for the treatment of arrhythmia that special head end is arranged that particularly designs for coronary artery specially also can be applied to the neural ablation of kidney.The characteristics of these conduit systems are that its head end electrode can detect the abnormal current loop that causes arrhythmia in the heart tissue.Desirable Renal denervation conduit system should have dual-use function: existingly can come stimulation of renal nerve with the neural function that distributes of mapping kidney by electric current is provided, can conduct again energy and carry out the Renal denervation operation.Like this doctor just can Real-Time Monitoring when carrying out electricity irritation and the physiology of Renal denervation postoperative patient change, but this type of conduit system also is not developed at present.

Present existing conduit system has the several functions of diagnosis and treatment heart disease usually.The known catheters of using clinically comprises following several:

A) Medtronic Achieve ^TM The Electrophysiological mapping electrode

When being generally used for treating Paroxysmal Atrial Fibrillation, behind the isolation pulmonary vein, so that the arrhythmia ectopic sites is made labelling and evaluation, uses with the another kind of arctic front Cryoablation system of Medtronic Inc. is collaborative by this conduit.This mapping catheter head end of Medtronic Inc. has toroidal mapping electrode, and two kinds of diameters available (15mm and 20mm) are arranged.This conduit uses the arctic front seal wire, carries out diaphragm puncture in the room, inserts the relevant position.Being characterized as on the head end Circumferential catheter part of conduit has 8 even spaced electrodes so that the doctor can the mapping left atrium and pulmonary vein between the electrical impedance situation.This conduit can be used for before the labelling cryoablation and the pulmonary vein potential of postoperative in addition, and instant evaluation ablation effect in cryoablation also can assist a physician.Its specification is as follows:

Conduit head end diameter is 3.3Fr, i.e. 1.1mm (0.043 ")

Total length 165cm; Active length 146cm

Blunt end annular shape mapping electrode has two kinds of specification: 15mm and 20mm

Two electrode spacings also have two kinds of specification: 4mm and 6mm

Blunt end annular shape mapping partly has the electrode of 8 1mm

This electrode can be 3.8Fr with the internal diameter minimum, and namely (conduit of 0.049 ") can use with compatibility 1.3mm.

B) Northwest University/integrated cardiac electrophysiology the mapping in champagne branch school, University of Illinois and ablation catheter electrode

This catheter electrode system is the combined catheter that can be used for the cardiac electrophysiology mapping and melt.This foley's tube electrode system comprises temperature, pressure and electrocardiography transducer and LED (Light-Emitting Diode) display screen.This system is based on Pop-up and the interconnected conceptual design of electronic device.The electronic components such as described temperature, pressure and electrocardiography transducer all are assemblied on the sacculus part of conduit; the external diameter of sacculus part forms slight depression less than the diameter of conduit, like this so that the various sensing electronic elements that are positioned at female when the conduit head end passes blood vessel and enters heart, can be protected.When conduit arrives desired location, sacculus is strutted, place sacculus to make electrode and be in the sacculus position sensor can with the wall of the heart close contact.

When conduit arrived correct position, the pressure transducer that is positioned at the conduit head end can detect the heart internal pressure, electrocardiography transducer monitoring electrocardio situation; But LED element pickup image also can provide the required energy of ablation to treat.Injury-free to guarantee myocardium health tissues by temperature sensor monitors local ablation temperature.The precision of operation has been guaranteed in the design of whole conduit system, and its various transducer performance that are positioned at sacculus any change can not occur when sacculus part enlargement and contraction.

This system can provide important high quality information in real time to surgical team, such as local temperature, pressure, blood flow, and electrocardiogram and local electrical impedance.

C)?

Arctic front (Arctic Front

) be the freezing sacculus ablation system through U.S. food Drug Administration (FDA) authentication.This balloon system and FlexCath Can regulate and control sheath pipe (steerable sheath) together uses; Its refrigeration modes is to pump into liquid coolant by freezing control station control device.This device is generally used for treating Paroxysmal Atrial Fibrillation.Its specification is as follows:

Balloon diameter has two kinds of specifications: be respectively 23mm and 28mm

Two sacculus security systems

Two-way degree of deflection (maximum can reach 45 degree)

With 12F FlexCath

Can regulate and control the sheath pipe compatible

Active length is 102cm

D) The lasso trick annular mapping catheter

Head end is ring-type during LASSO 2515, is according to vein size, can 25 and 15mm between the variable annular mapping catheter of adjusting size.

E)?

This conduit system is the custom-designed conduit system that melts for the kidney nerve of Ardian Inc. company (California, the U.S.), is comprised of ablation catheter and radio-frequency signal generator, i.e. Symplicity Conduit system.But this Symplicity

Conduit only has ablation functionality, does not have the function of mapping; Be used for coronary artery and carotid conduit system (and be used for blood vessel through the tip protector of dermatoplasty and angioplasty etc.); also take this design (and be used for blood vessel through the tip protector of dermatoplasty and angioplasty etc.); therefore these conduit systems also can be used for the indicated indication of producer purposes in addition; melt to remove the kidney nerve as being used for the kidney nerve, treatment hypertension, heart failure, renal failure and diabetes and other diseases.

As mentioned above, except Ardian Simplicity

Beyond the system, this type of conduit of major part that uses clinically at present all aims at the heart disease design, rather than according to designing for the renal artery dissection structure; Even if Ardian is Simplicity

System can not for the mapping of kidney nerve, not mate with arteriorenal anatomical structure simultaneously yet.Therefore these conduit systems all can't be used for kidney sympathetic nerve mapping, to arrive best clinical effectiveness, melt even if be used for the kidney nerve, and the clinical efficacy of these conduit systems also is subject to great restriction.

The utility model content

The invention provides a kind of conduit with the neural mapping function of kidney, this conduit comprises the conduit head end that is provided with a plurality of electrodes, and described conduit head end can place in the renal artery tube chamber, and described electrode can be sent DC current, alternating current and radio-frequency (RF) energy.It is the conduit that designs for the renal artery dissection structure specially that the present invention also provides a kind of head portion shape, the conductor housing end parts has can be used for the kidney sympathetic nerve is carried out a plurality of electrodes of mapping, and this conduit has simultaneously the kidney of carrying out nerve and melts and angiographic function.In certain embodiments, at the head end of this conduit, several electrodes are spaced along the length of conduit head end, described be spaced both can be equally spaced also can be unequal interval, these electrodes can contact with the renal artery wall in the renal artery tube chamber.In certain embodiments, the conduit head end be shaped as single-screw, the shape of cross section that forms single-screw wire rod is circle or flat pattern (Figure 1A-J).In other embodiments, the conduit head end be shaped as Double helix, the shape of cross section that forms double-helical wire rod is circle or flat pattern (Fig. 2 A-F).In further embodiments, the conduit head end can be with the sacculus that is wrapped up by helix round part, and wherein a plurality of electrodes are spaced (uniformly-spaced or unequal interval all can) (Fig. 3 A) along the length direction of spiral winding; Have among some embodiment, the conduit head end can be with the sacculus that is wrapped up by umbrella part again, and this umbrella part is wrapped sacculus, and wherein a plurality of electrodes are spaced (uniformly-spaced or unequal interval all can) (Fig. 3 B) along the length of umbrella part.The variant of these two kinds of structures is shown in Fig. 3 A and 3B, and the shape of cross section that forms the wire rod of helix round or umbrella part can be circle or flat pattern; Therefore the shape of spaced electrode also is circle or flat pattern on the helix round of conduit head end or umbrella part, and this depends on the shape of cross section of the wire rod that forms helix round or umbrella part.

In further embodiments, the conduit head end can be umbrella-shaped structure or the framework (Fig. 4 A-B) of endcapped formula, or the umbrella-shaped structure of open-ended (Fig. 4 C-D).

In certain embodiments, above-mentioned conduit head end can be presented to the effect of playing support in the arterial lumen.

In one embodiment, the single-screw of these conduit head ends or bifilar helix round part, perhaps the diameter of umbrella part can change in the scope of 0.5mm-10mm; The length of conduit head end can change in the scope of 2.0mm-6.0mm.

Electrode on the conduit head end can solely be activated independently of one another, perhaps is activated in the combination in any mode, to send electricity irritation or radio-frequency (RF) energy.The dual-use function of the electricity irritation of providing or radio-frequency (RF) energy is provided each electrode.Electricity irritation is used for the kidney nerve that distributes along renal artery is identified and mapping.Apply one or more index of physiology and pathologies that cause after the electricity irritation by monitoring, such as blood pressure (systolic pressure, diastolic pressure and mean arterial pressure), heart rate, muscle sympathetic excitability (Schlaich et al., NEJM 2009) or the excessive level of kidney norepinephrine (Esler et al.2009, and Schlaich et al., J Htn.2009) change, carry out identification and the mapping of kidney nerve, apply variation that electricity irritation can cause above-mentioned physical signs and show that the kidney sympathetic innervation is applying near the electrode of electricity irritation.In another embodiment, each electrode of conduit also can activate according to the compound mode that operator is selected, to estimate maximum physiological reaction, the neural position of mapping kidney.The electrode of conduit head end not only can send enough strong electric current and come stimulation of renal nerve, can also send the thermal energy such as radio-frequency (RF) energy etc., and being used for result according to the neural mark of kidney side, to melt potential kidney neural.In other embodiments, each electrode of conduit head end can be by selective single or multiple activation, and to send the ablation energy such as the firing frequency energy, the selection that wherein active electrode is used for melting is based on the mapping result to nerve.In further embodiments, according to the result of the neural mapping of kidney, use the energy of other types to melt, such as laser energy, high density focus supersonic, perhaps the ablation techniques such as cryogenic ablation technology also can be applied on the renal artery wall, removes the kidney sympathetic nerve to melt.

In certain embodiments, these conduits can with at present with the existing employed radio-frequency signal generator Alternate of cardiac catheter ablation system clinically.

In one embodiment, aforesaid conduit system can be used with any kind, the suitable catheter guide wire of coupling, and these seal wires are to be placed in advance to be used for the guide catheter head end in the patient vessel and to arrive desirable position.These conduit systems also can together be used with the intervention apparatus that uses just clinically, is applied to cardiovascular and renal vascular, such as sheath pipe and dilator.Aforesaid conduit system also can be used with the traction seal wire, to help that the conduit head end is placed into suitable position.

The present invention also provides with the neural mapping of the described kidney of this invention and ablation catheter and has come the neural method that distributes of mapping kidney, it may further comprise the steps: implement electricity irritation in renal artery, the reactions change of physiologys such as blood pressure and heart rate of synchronous monitoring clinical indices, with the ablation points in the neural distribution of the kidney on the mapping renal artery and identification and the decision renal artery, with the neural ablation of the kidney that is optimized.These methods comprise: activate separate electrode on the described conduit head end, stimulate potential kidney neural, monitor simultaneously the reaction such as the physical signs such as blood pressure and heart rate; Cause the stimulation location that the physiological reactions such as blood pressure and heart rate change, showing has sympathetic innervation herein, is the optimum position of melting.Gather and analyze the neural mapping data of kidney, can provide kidney the neural information that distributes, effectively instruct the clinician to carry out the kidney nerve and melt and remove operation.

Description of drawings

Figure 1A shows the axonometric chart of the end portion (conduit head end) of single-screw ablation catheter according to an embodiment of the invention, wherein electrode 1 is spaced by 90 ° on spiral along the length direction of spiral, the cross section that wherein forms the wire rod 3 of spiral coil is circle, and wherein " L " expression catheter tip is with the length of electrode part, " l " then represents the length of unicoil one circle, namely in spiral coil each the circle between apart from the interval.

Figure 1B shows the sectional elevation according to the end portion of the single-screw ablation catheter of the embodiment shown in Figure 1A, wherein shows electrode 1, and visible four electrodes are spaced by 90 ° at the sectional elevation face of spiral.

Fig. 1 C shows the end-view of observing from the propelling movement transmission direction (tail end) of conduit according to the end portion of the single-screw ablation catheter of the embodiment shown in Figure 1A, wherein demonstrated three electrodes 1 in four electrodes.

The axonometric chart of the end portion of the single-screw ablation catheter of an embodiment during Fig. 1 D shows according to the present invention, wherein electrode 5 is along on the length direction of spiral, sectional elevation face at spiral is spaced by 120 °, and the cross section that forms the wire rod 7 of spiral coil is circular.

Fig. 1 E shows the sectional elevation according to the end portion of the single-screw ablation catheter of embodiment shown in Fig. 1 D, wherein shows electrode 5, and visible three electrodes are spaced by 120 ° at the sectional elevation face of spiral.

Fig. 1 F shows the end-view of observing from the propelling movement transmission direction (tail end) of conduit according to the end portion of the single-screw ablation catheter of embodiment shown in Fig. 1 D, wherein shows electrode 5.

Fig. 1 G shows the axonometric chart of the end portion of single-screw ablation catheter according to an embodiment of the invention, and wherein electrode 9 is spaced by 90 ° on spiral along the length direction of spiral, but the cross section of the wire rod 11 of formation spiral coil is flat pattern.

Fig. 1 H shows the sectional elevation according to the end portion of the single-screw ablation catheter of embodiment shown in Fig. 1 G, wherein shows electrode 9, and visible four electrodes are spaced by 90 ° at the sectional elevation of spiral.

The axonometric chart of the end portion of the single-screw ablation catheter of this embodiment during Fig. 1 I shows according to the present invention, wherein electrode 13 is spaced by 120 ° on spiral along the length direction of spiral, and the cross section that wherein forms the wire rod 15 of spiral winding is flat pattern.

Fig. 1 J shows the sectional elevation according to the end portion of the single-screw ablation catheter of embodiment shown in Fig. 1 I, wherein shows electrode 13, and visible three electrodes are spaced by 120 ° at the sectional elevation of spiral.

Fig. 2 A shows the axonometric chart of the end portion of Double helix ablation catheter according to an embodiment of the invention, wherein electrode 17 is spaced by 90 ° on spiral along each single-screw length direction, the cross section that wherein forms the wire rod 19 of spiral winding is circle, and wherein " L " expression is with the length of the catheter tip of electrode, and " l " represent the length of each spiral winding one circle, namely in spiral coil between each circle apart from the interval.

Fig. 2 B shows the end-view of observing from the propelling movement transmission direction (tail end) of conduit according to the end portion of the Double helix ablation catheter of embodiment shown in Fig. 2 A, wherein shows electrode 17.

Fig. 2 C shows the axonometric chart of the end portion of Double helix ablation catheter according to an embodiment of the invention, wherein electrode 21 is spaced by 120 ° on spiral along each single-screw length direction, the cross section that wherein forms the wire rod 23 of spiral winding is circle, " L " expression is with the length of the catheter tip part of electrode, and " l " represents the length of each spiral winding one circle, namely in spiral coil each the circle between apart from the interval.

Fig. 2 D shows the end-view of observing from propelling movement transmission direction (tail end) direction of transfer of conduit according to the end portion of the Double helix ablation catheter of embodiment shown in Fig. 2 C, wherein shows electrode 21.

Fig. 2 E shows the axonometric chart of the end portion of Double helix ablation catheter according to an embodiment of the invention, wherein electrode 25 is spaced by 90 ° on spiral along each single-screw length direction, and the cross section that wherein forms the wire rod 27 of spiral winding is flat pattern.

Fig. 2 F shows the axonometric chart of the end portion of Double helix ablation catheter according to an embodiment of the invention, wherein electrode 29 is spaced by 120 ° on spiral along each single-screw length direction, and the cross section that wherein forms the wire rod 31 of spiral winding is flat pattern.

The axonometric chart of the end portion of the sacculus ablation catheter of an embodiment during Fig. 3 A shows according to the present invention, wherein sacculus 33 is in swelling state, and wherein evenly to be spaced, wherein the cross section of wire rod 37 is circular and surrounds around the sacculus electrode 35 along the wire rod 37 that forms spiral winding.

Fig. 3 B shows the axonometric chart of the end portion of sacculus ablation catheter according to an embodiment of the invention, it comprises the umbrella part 39 that is wrapped in outside the sacculus 41, wherein sacculus is in swelling state, and wherein electrode 43 partly is spaced along the umbrella of wrapping up sacculus.

Fig. 4 A shows the axonometric chart of the end portion of ablation catheter according to an embodiment of the invention, and it comprises one with the umbrella framework 45 of closed type terminal, and wherein electrode 47 is arranged along this umbrella frame space.

Fig. 4 B shows the end-view of observing from the propelling movement transmission direction (tail end) of conduit according to the end portion of the ablation catheter of the embodiment as shown in Fig. 4 A.

The axonometric chart of the end portion of the ablation catheter of an embodiment during Fig. 4 C shows according to the present invention, it comprises one with the umbrella frame part 49 of open end, wherein electrode 51 is arranged along this umbrella frame space.

Fig. 4 D shows the end portion of an ablation catheter from the end-view of propelling movement transmission direction (tail end) observation of conduit.

The minimum and maximum variation of caused systolic arterial pressure (ASP is take mmHg as unit) after Fig. 5 A shows and carry out electricity irritation in left renal artery (LRA).The base line measurement control value is the systolic arterial pressure before the electricity irritation.

Fig. 5 B shows and carry out the minimum and maximum variation that caused auterial diastole after the electricity irritation is pressed (ADP is take mmHg as unit) in left renal artery.The base line measurement control value is that the auterial diastole before the electricity irritation is pressed.

Fig. 5 C shows the minimum and maximum variation of carrying out caused mean arterial pressure (MAP is take mmHg as unit) after the electricity irritation in left renal artery.The base line measurement control value is the mean arterial pressure before the electricity irritation.

Fig. 5 D shows the minimum and maximum variation of carrying out caused heart rate (HR, the per minute heart beating is unit) after the electricity irritation in left renal artery.The base line measurement control value is the heart rate before the electricity irritation.

Fig. 6 A shows the minimum and maximum variation of carrying out caused systolic arterial pressure (ASP) after the electricity irritation in right renal artery.The base line measurement control value is the systolic arterial pressure before the electricity irritation.

Fig. 6 B shows and carry out the minimum and maximum variation that caused auterial diastole after the electricity irritation is pressed (ADP) in right renal artery.The base line measurement control value is that the auterial diastole before the electricity irritation is pressed.

Caused mean arterial pressure (MAP) changed after Fig. 6 C showed and carry out electricity irritation in right renal artery (RRA).The base line measurement control value is the systolic arterial pressure before the electricity irritation.

Fig. 6 D shows the minimum and maximum variation of carrying out caused heart rate (HR) after the electricity irritation in right renal artery.The base line measurement control value is the heart rate before the electricity irritation.

Fig. 7 A shows and carries out respectively four diabetes involving the kidney when melting in left renal artery (LRA) tube chamber, the variation of caused systolic arterial pressure (ASP) when melting each time.

Fig. 7 B shows and carries out respectively four diabetes involving the kidney when melting in left renal artery (LRA) tube chamber, and caused auterial diastole is pressed the variation of (ADP) when melting each time.

Fig. 7 C shows and carries out respectively four diabetes involving the kidney when melting in left renal artery (LRA) tube chamber, the variation of caused mean arterial pressure (MAP) when melting each time.

Fig. 7 D shows and carries out respectively four diabetes involving the kidney when melting in left renal artery (LRA) tube chamber, the variation of caused heart rate (HR) when melting each time.

Fig. 8 A shows and carries out respectively four diabetes involving the kidney when melting in right renal artery (RRA) tube chamber, the variation of caused systolic arterial pressure (ASP) when melting each time.

Fig. 8 B shows and carries out respectively four diabetes involving the kidney when melting in right renal artery (RRA) tube chamber, and caused auterial diastole is pressed the variation of (ADP) when melting each time.

Fig. 8 C shows and carries out respectively four diabetes involving the kidney when melting in right renal artery (RRA) tube chamber, the variation of caused mean arterial pressure (MAP) when melting each time.

Fig. 8 D shows and carries out respectively four diabetes involving the kidney when melting in right renal artery (RRA) tube chamber, the variation of caused heart rate when melting each time.

Fig. 9 shows acute pig research experiment design drawing.

The specific embodiment

Please note that the term " conduit " of mentioning in this description instructs the whole length of pipe device in the whole text, the interior part of body that is used for carrying out mapping and the head portion that melts, conduit, the outer body of conduit have been comprised, until the bound fraction of connecting duct and radio-frequency signal generator.The term of mentioning in this description " conduit head end " refers to be distributed with the catheter tip part of electrode, has in vivo that the position of target organ stimulates, mapping and the function that melts.Term " conduit head end " can Alternate with " end portion " of another term conduit of mentioning.

The invention provides a kind of method of the mapping kidney nerve for the kidney ablation, this ablation is used for the treatment of the disease that systemic kidney nerve is overexcited and is caused, said method comprising the steps of: (a) guide the conduit with mapping and ablation process function to enter renal artery; (b) before the site demarcation is carried out in the use electricity irritation, detect index of physiology and pathology, to obtain the base line measurement control value; (c) by the specific site in this electrosurgical catheter stimulation of renal arterial lumen, neural with distribution of stimuli potential kidney on renal artery; (d) optionally move the head end of conduit according to specified scheme, it is contacted with the desirable position of renal artery intracavity; (e) carry out detecting index of physiology and pathology after the electricity irritation at each specific site, and record it with respect to the variation of base line measurement control value before stimulating; And (f) after a certain position stimulates in the renal artery tube chamber, detect the variation of index of physiology and pathology, and according to the variation of described index of physiology and pathology judge this position whether with the neural distribution correlation of kidney, thereby mapping goes out the particular location of the kidney nerve of renal artery intracavity.

Anatomical structure and its distribution on renal artery of finding out the kidney nerve are the keys of achieving success and melting; Therefore, successfully carrying out before the neural ablation of conduit kidney, must carefully find out or the neural structure of the individual kidney of mapping.Because kidney neuro anatomy structure exists the normal individual variation, add the lopsided or unusual of some patient's kidney neuro anatomy structure, so that all need mapping to go out the neural residing position of kidney before melting Renal denervation.In other words, melting denervation in the renal artery does not have fixing site, may be different to the best site that each patient is melted, and the best site of namely melting is between the different people and all different between the different tremulous pulsies.Therefore the ablation that will obtain optimum efficiency just needs identification or the distribution sites of mapping kidney nerve on renal artery.

The conduit that uses in above method can be carried out stimulation and melt two functions.In one embodiment, the conduit that uses is the present invention's conduit described below.In another embodiment, conduit can be the ablation catheter that is used for the treatment of clinically cardiac arrhythmia at present.

In one embodiment, the detection index described in the above method comprise the hematodinamics index relevant with hypertension, with the diabetes index of correlation or with congestive heart failure relevant index.Relevant hematodinamics index comprises systolic arterial pressure, diastolic pressure, mean arterial pressure, heart rate, muscle sympathetic excitability and urine output.The index relevant with diabetes or the index of being correlated with congestive heart failure comprise hormone such as epinephrine, norepinephrine, dopamine and angiotensin in blood sugar level, the blood.

In one embodiment, use the scheme of mobile conduit head end in the above method to comprise from a close side of kidney in the renal artery, with the stimulation of conduit head end or melt part and move to renal artery near a side of ventral aorta, carry out the one or many electricity irritation at renal artery.

In another embodiment, the scheme of mobile conduit head end comprises in the following order in renal artery the stimulation of steering nozzle head end or melts part: the rear wall that (a) turns to tremulous pulse from the antetheca of tremulous pulse; (b) forward the upper wall of tremulous pulse to from the rear wall of tremulous pulse; And the lower wall that (c) forwards tremulous pulse from the upper wall of tremulous pulse to, wherein each angle of rotating is 90 ° or less.In one embodiment, in renal artery, can carry out the one or many electricity irritation behind the steering nozzle head end at every turn.

In one embodiment, electricity irritation is carried out according to following parameter: (a) voltage is between the 2-30 volt; (b) impedance is between 100-1000 ohm; (c) electric current is between the 5-40 milliampere; (d) apply the 0.1-20 millisecond.

The neural ablation method of kidney of the disease that causes that the present invention also provides a kind for the treatment of because systemic kidney nerve is overexcited, the method may further comprise the steps: (a) come mapping kidney nerve with above-mentioned assignment test method; (b) through conduit radio-frequency (RF) energy is applied to the specific site of renal artery intracavity, neural to melt the kidney that has been gone out by mapping.In other embodiments, based on the neural mapping of kidney, employed other ablation techniques in this area can be applied on the renal artery wall to remove the kidney sympathetic nerve, for example use the ablation techniques of other energy, such as laser energy, high density focus supersonic or cryogenic ablation technology.

The present invention also provides a kind of mapping and has melted the method for kidney nerve, and with the disease that treatment is overexcited and is caused by systemic kidney nerve, the method may further comprise the steps: (a) guide catheter enters desirable position in the renal artery, keeps motionless at this place; (b) in the situation that the motionless guide current of maintenance conduit is passed through supravasal each electrode, and the monitoring index of correlation, to carry out the neural mapping of kidney according to method described here; And (c) when keeping conduit motionless the guiding radio-frequency (RF) energy by each electrode of conduit, neural to melt the kidney that has been gone out by mapping.As previously discussed, except radio-frequency (RF) energy, also can use other energy to melt.

The present invention also provides a kind of energy to be used for the conduit of the neural assignment test method of kidney described here, wherein this conduit has comprised the conduit head end with a plurality of electrodes, described electrode can be positioned at the renal artery intracavity, and wherein said electrode can be sent DC current and alternating current and radio-frequency (RF) energy.In one embodiment, these electrodes had both had stimulatory function and had also had ablation functionality.Electrode is single being activated and stimulate or melt independently of one another, perhaps is activated in the mode of combination in any and stimulates or melt.In one embodiment, the long 1.0-2.0m of whole conduit, the long 2.0-6.0cm of conduit head end wherein, the diameter of conduit head end is 2.0-10.0mm.

In another embodiment, the shape of conduit head end can be single-screw or Double helix, the shape of cross section that wherein forms single-screw or double-helical wire rod is circle or flat pattern, a plurality of electrodes are spaced along the length direction of wire rod, if wherein the cross section of wire rod is circular, electrode on the conduit head end also is circular, if the cross section of wire rod is flat pattern, the electrode on the conduit head end also is flat pattern.In one embodiment, electrode evenly is spaced along single-screw or double-helical length direction, apart 60 °, 90 °, 120 ° or 180 ° of the sectional elevations of spiral.

In another embodiment, the conduit head end comprises the sacculus that is wrapped up by helix round or umbrella part, and wherein electrode is spaced along the length direction of helix round or umbrella part.In one embodiment, umbrella partly has open or closed type terminal.

The present invention is summarized, can more easily understand the present invention by the reference following instance, following example only is in order to further specify some concrete aspect and details of the present invention, embodiment and concrete experimental result, and non-limiting the present invention.

Example 1

The neural mapping of kidney

Use the design implementation scheme of following acute pig experiment, to verify the present invention and to reach following purpose:

1. detect conduit (7F, Type B, interval 2-5-2mm, the CELSIUS that is used for clinically at present cardiac ablation

RMT diagnoses/melts and can regulate and control conduit, Biosense Webster, Diamond Bar, California 91765, the U.S.) and a kind of radio-frequency signal generator (STOCKERT 70 RF Generator, Model Stockert GmbH EP-SHUTTLE ST-3205, STOCKERT GmbH, Freiburg, Germany), whether can be used for the neural mapping of kidney and melt.

2. the variation of blood pressure and heart rate comes the mapping kidney neural when acting on left renal artery chamber and right renal artery intracavity different loci by the monitoring electricity irritation.

3. by variation and the histological examination of macroscopy renal artery wall, determine to put on the safety range of the firing frequency energy that melts for the kidney nerve in the renal artery.

4. the sign that melts as the effective kidney nerve of evaluation with the variation of blood pressure and heart rate in the neural ablation procedure of kidney.

Acute pig is used for carrying out the neural mapping experiment of kidney.With pentobarbital sodium (15mg/kg, intravenous injection) anesthesia 3 pigs (body weight 50-52kg).Monitoring systolic arterial pressure, diastolic pressure, mean arterial pressure and heart rate.Experimental design and scheme are as shown in Figure 9.

Carry out electricity irritation in renal artery before, monitoring systolic arterial pressure, diastolic pressure, mean arterial pressure and heart rate obtain the base line measurement control value.Then electricity irritation is carried out in some sites in the renal artery; Begin after 5 seconds in 2 minutes time, to detect systolic pressure, diastolic pressure, mean arterial pressure and heart rate carrying out electricity irritation, to estimate the effect that stimulates.The result shows, when electricity irritation acted on arteriorenal some site (there are differences between different animals), blood pressure and heart rate can obviously raise; And the stimulation of parameter is when arteriorenal other sites equally, and blood pressure and heart rate only have atomic little variation.

Stimulate respectively in the site of renal artery near ventral aorta (" ventral aorta side ") or close kidney (" kidney side ").In order to prove that the renal artery different loci is carried out electricity irritation can produce Different Effects to blood pressure and heart rate, also for further proof can be by the site of different loci electricity irritation in the renal artery being come mapping have the kidney nerve to distribute, the present embodiment has adopted multiple stimulating method.Table 1 has shown the design parameter of electricity irritation and blood pressure and the changes in heart rate of No. 1 pig.

Table 1. is used for the neural kidney nerve stimulation that distributes of mapping

No. 1 animal:

No. 1 pig (table 1) carries out respectively four different stimulations in left renal artery, carry out twice different stimulation in the right renal artery.According to experimental program, apply respectively twice different electricity irritation in left renal artery ventral aorta side: direct action is in the tremulous pulse antetheca, and another time acts on the tremulous pulse rear wall.Antetheca and rear wall in left renal artery kidney side: apply respectively once different electricity irritation, direct action is in the tremulous pulse antetheca, and another time acts on the tremulous pulse rear wall.Observe these stimulations to the Different Effects of blood pressure and heart rate.In right renal artery, arteriorenal ventral aorta side and kidney side are applied respectively an electricity irritation.No. 2 pigs and No. 3 pigs are adopted same stimulating method (electricity irritation acts on the ventral aorta side, and another time electricity irritation acts on the kidney side).Table 2 and table 3 have been concluded respectively concrete stimulus parameter, and blood pressure and heart rate are to the reactions change of these stimulations.

Table 2. is used for the neural kidney nerve stimulation that distributes of mapping

No. 2 animals:

Table 3. is used for the neural kidney nerve stimulation that distributes of mapping

No. 3 animals:

Above these results have clearly shown for every test and have used pig, and the diverse location in the renal artery is carried out the different variations that electricity irritation can cause systolic pressure, diastolic pressure, mean arterial pressure and heart rate.For example in No. 1 animal and No. 3 animals, it is respectively 19.5mmHg and 29mmHg that the maximum that causes systolic pressure in the left renal artery after the electricity irritation changes; The minimum change of systolic pressure is respectively 2mmHg and 1mmHg.But for No. 2 animals, the variation that electricity irritation acts on the systolic pressure that ventral aorta side or kidney rear flank cause is consistent.In addition, to produce the stimulation sites of maximum effect and least action be different in the electricity irritation of same parameter between different animals, and this illustrates that the kidney sympathetic innervation is inconsistent between different animals.These results conclude out in table 4A.

When left renal artery is carried out electricity irritation, can observe the phenomenon that systolic arterial pressure, diastolic pressure, mean arterial pressure and heart rate produce similar reaction, table 4B, 4C and 4D have concluded respectively the above results.

The variation of systolic arterial pressure (SBP) during the table 4A. electricity irritation left renal artery

The variation of diastolic pressure (DBP) during the table 4B. electricity irritation left renal artery

The variation of table 4C. electricity irritation left renal artery period average arterial pressure (MAP)

The variation of heart rate (HR/min) during the table 4D. electricity irritation left renal artery

When carrying out electricity irritation in right renal artery, can observe the phenomenon that systolic pressure, diastolic pressure, mean arterial pressure and heart rate produce similar reaction, table 5A, 5B, 5C and 5D have concluded respectively the above results.

The variation of systolic pressure (SBP) during the table 5A. electricity irritation right renal artery

The variation of diastolic pressure (DBP) during the table 5B. electricity irritation right renal artery

The variation of table 5C. electricity irritation right renal artery period average arterial pressure (MAP)

The variation of heart rate (HR/min) during the table 5D. electricity irritation right renal artery

These experimental datas provide the evidence of verifying this concept for the distribution of mapping kidney nerve, when namely the ad-hoc location by a large amount of kidney nervous ramification that distributes in to renal artery through conduit carries out electricity irritation, can cause that obvious physiologic index reaction occurs, such as peaked hypertension, these sites are the best site of melting.By this method, just can identify the ad-hoc location that goes out kidney nervous ramification with mapping.The mean values that use calculates from table 4 and table 5 (average ± standard deviation) (comprises its all subgraphs) and represents with the form of chart in Fig. 5 and Fig. 6.

After the electricity irritation research of carrying out the neural mapping of kidney, carried out the kidney nerve same experiment pig and melted.In left and right renal artery, carry out respectively melting for four times, from the kidney side press antetheca, rear wall, upper wall, then the ordinal shift of lower wall is to the ventral aorta side; Melt and previous ablation locations interval≤5mm, and the electrode tip of ablation catheter (conduit head end) rotates 90 ° at every turn after melting at every turn.According to document (Krum 2009,2010), should adopt mental retardation magnitude (5-8 watt) to carry out the kidney nerve and melt; Therefore adopt 5 watts and 8 watts to carry out the kidney nerve and melt.Energy level with 5 watts melts left renal artery, melts duration 120 seconds; Energy level with 8 watts melts right renal artery, melts duration 120 seconds.The temperature that melts the site is 40-50 ℃ after testing.Detect systolic arterial pressure, diastolic pressure, mean arterial pressure and heart rate in the ablation procedure.Data clearly show the different variations that cause blood pressure and heart rate of melting at the interior diverse location place of renal artery, confirm that further the kidney nerve is not equally distributed along renal artery, the change of hemodynamic parameter such as blood pressure and heart rate can be used as and estimate the index that effective diabetes involving the kidney melts when melting.

Carry out four different kidney nerves in the renal artery of left kidney when melting, the change of systolic arterial pressure, auterial diastole pressure, mean arterial pressure and heart rate is respectively shown in Fig. 7 A, 7B, 7C and 7D.

Carry out four different kidney nerves in the renal artery of right kidney when melting, the change of systolic arterial pressure, auterial diastole pressure, mean arterial pressure and heart rate is respectively shown in Fig. 8 A, 8B, 8C and 8D.

During off-test, cut respectively left and right renal artery.Arterial endothelium and arterial wall are not all found the naked eyes visible damage; Histological data has confirmed these macroscopic results, and it is safe confirm adopting energy level and each 120 seconds ablation of 5 watts and 8 watts.

Example 2

The design of kidney mapping catheter

What disclosed herein is new design has stimulation, mapping, melts the conduit with angiographic function.

This pipe guide comprises a slender conduit, and the far-end of this slender conduit has the conduit head end, and it will remain on fixing position once inserting renal artery in renovascular structure; Also has a near-end; And a plurality of ablating electrodes.In one embodiment, ablating electrode can evenly be spaced on the conduit head end along the length direction of slender conduit head end.Above-mentioned a plurality of ablating electrode is spaced apart by the part of electric insulation to far-end from the near-end of slender conduit.Stimulation benchmark when in one embodiment, conductor housing first electrode distolateral or the catheter tip side can be used as any other electrodes transfer electricity irritation; As an alternative, any one in these electrodes is all as any benchmark of other electrodes.

In one embodiment, the slender conduit head end is spiral-shaped.

In another embodiment, one or more wire links to each other with a plurality of electrodes, and by one or more wire direct current or alternating current is offered a plurality of electrodes.When the conduit head end remained on the fixed position in renal artery, controller was configured in mode independently or controls to the electric current of a plurality of electrodes in mode simultaneously.

In another embodiment, one or more wire links to each other with a plurality of electrodes, and by one or more wire radio frequency (RF) energy is offered a plurality of electrodes, and described RF energy is single-stage RF energy or bipolar RF energy.Radio-frequency signal generator offers a plurality of electrodes by one or more wire with energy.When the conduit head end remained on the fixed position in renal artery, controller was configured to control energy source with mode independently, continuous mode or mode simultaneously and provides energy to a plurality of electrodes.

The radio-frequency (RF) energy that sends to electrode can be controlled as so that electrode only produces low-level electrical energy pulse, only to stimulate potential nervous tissue, and kidney nervous tissue especially.As an alternative, the radio-frequency (RF) energy that sends to electrode can be controlled as so that electrode produces higher electrical energy pulse, melts potential nervous tissue, especially kidney nervous tissue.Electrode on conduit head end, especially the conduit head end, be designed to stimulate with the whole process that melts in keep in touch in identical position and renal artery chamber all the time.

In another embodiment, conduit can use with the radio-frequency signal generator that is used at present the heart tissue ablative surgery.These radio-frequency signal generators can be including but not necessarily limited to the radio-frequency signal generator of the companies such as present Medtronic, Cordis/ Johnson ﹠ Johnson, Sheng Zhude medical treatment and Biotronic production.

Following exemplary embodiment of the present invention in greater detail provides the device that is used for Renal denervation.

Fig. 1 to 4 is example and diagrams of these ablation catheters and electrode.Be depicted as axonometric chart, viewgraph of cross-section and end-view according to the ablation catheter head end in the different embodiments of the invention.

In one embodiment, conduit has elongated helical form head end.A plurality of electrodes are arranged to the far-end of conduit head end from the near-end of conduit head end, are evenly spaced apart by the part of electric insulation.

In certain embodiments, the conductor housing end parts of ablation catheter comprises single-screw; In other embodiments, the conductor housing end parts of ablation catheter comprises Double helix.The formation single-screw of conduit head end or the cross section of double-helical wire rod can be circle or flat pattern.The electrode along the line length direction of material is evenly distributed; For example, on the projection plane of spiral, apart electrode can be spaced by 60 °, 90 ° or 120 °, but also can arrange or arrange with different angle intervals according to other forms.

If forming the cross section of the wire rod of spiral winding is flat pattern, then electrode can be flat rectangle or square.As an alternative, be circular if form the cross section of the wire rod of spiral winding, then electrode then can be circle.In one embodiment, the length of conduit head end is 2.0cm-6.0cm, and diameter is 0.5mm-10.0mm; Conduit total length 1m-2.0m.

In another embodiment, the conductor housing end parts of ablation catheter comprises sacculus.In one embodiment, electrode is that the wire rod that circle or flat pattern, formation are wrapped in the helix round part outside the sacculus evenly is spaced along cross section; In other embodiments, electrode is that circle or flat pattern, formation are spaced along the wire rod of the umbrella part of length of balloon direction parcel sacculus along cross section.In certain embodiments, described umbrella partly has an open end, and in other embodiments, described umbrella partly has a closed type terminal.Electrode and renal artery interior wall construction good contact when balloon-system expands.In one embodiment, length was not 2.0cm-6.6cm when the conduit head end expanded, and diameter is 0.5mm-10.0mm; The conduit total length is 1m-2.0m.In one embodiment, the diameter of conduit head end can change in the scope of 0.5mm-10mm when inflation.

In one embodiment of the invention, provide the neural mapping of a kind of kidney and ablation method (at left kidney or right kidney, perhaps the two), it comprises one of above-mentioned conduit is inserted in left renal artery (LRA) or the right renal artery (RRA), neural according to the method mapping kidney that describes in detail before subsequently, carry out the neural site of kidney target by each electrode afterwards and melt.

In one embodiment, the kidney nerve electric stimulation carries out according to following parameter: 0.1ms-0.2ms, 2V-30V, 5mA-40mA, 100 ohm-1000 ohm.In one embodiment, the kidney nerve melts and can be undertaken by following parameter: be lower than 8 watts, melted 30 seconds-180 seconds.

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Claims (8)

1. the conduit with the neural mapping function of kidney is characterized in that, this conduit comprises the conduit head end that is provided with a plurality of electrodes, and described conduit head end can place in the renal artery tube chamber, and described electrode can be sent DC current, alternating current and radio-frequency (RF) energy.

2. conduit as claimed in claim 1, it is characterized in that, one or more wire links to each other with described a plurality of electrodes, and by described one or more wire direct current or alternating current or radio-frequency (RF) energy are offered described a plurality of electrode, wherein said electrode had both had the mapping function and had also had ablation functionality.

3. conduit as claimed in claim 1 is characterized in that, wherein the conduit total length is 1.0-1.5m, and the long 2.0-6.0cm of conduit head end, the diameter of conduit head end are 2.0mm-10.0mm.

4. conduit as claimed in claim 1, it is characterized in that, wherein the conduit head end is shaped as single-screw or Double helix, the cross section that wherein forms single-screw or double-helical wire rod is circle or flat pattern, a plurality of electrodes are spaced along the length of described wire rod, if wherein the cross section of described wire rod is circular, then described electrode is circular; If the cross section of described wire rod is flat pattern, then described electrode is flat pattern.

5. conduit as claimed in claim 4 is characterized in that, described electrode is uniformly-spaced arranged with 90 ° or 120 ° along single-screw or double-helical length.

6. conduit as claimed in claim 1 is characterized in that, wherein the conduit head end comprises the sacculus that is wrapped up by helix round or umbrella part, and wherein a plurality of electrodes are spaced along the length of helix round or umbrella part.

7. conduit as claimed in claim 6 is characterized in that, wherein said electrode is uniformly-spaced arranged.

8. conduit as claimed in claim 6 is characterized in that, wherein the umbrella of conduit head end partly has open or closed type terminal.

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