WO2003097151A1

WO2003097151A1 - Device for treating cardiovascular diseases

Info

Publication number: WO2003097151A1
Application number: PCT/EP2003/005028
Authority: WO
Inventors: Till Neumann; Anja Neumann
Original assignee: Till Neumann; Anja Neumann
Priority date: 2002-05-15
Filing date: 2003-05-14
Publication date: 2003-11-27
Also published as: AU2003269562A1; DE10222776A1

Abstract

The invention relates to a device for interrupting the bloodstream in the blood vessels, comprising a feed tube (4) that can be inserted into the blood vessel. Said feed tube is connected to one or several balloons (1) that can be expanded by introducing a fluid or a gas. The inventive device also comprises a pressure generating device (3) that generates pressure for expanding the balloon (1) by means of the fluid or gas. At given intervals, said pressure generating device provokes an expansion of the balloon (1) during a given period followed by a reduction of pressure. The invention is based on the knowledge that repeated, short-lasting interruption of the bloodstream can induce the new formation and growth of vessels and parenchymatous cells. Interruption of the bloodstream is carried out by short-lasting inflation of a balloon (1) that is connected to the feed tube (4) which is inserted in the blood vessel. Alternatively, the bloodstream can also be partially interrupted by partial expansion of the balloon (1). The invention also relates to a method for inducing the growth and new formation of vessels and parenchymatous cells with the aid of a device that has been inserted at least partially into the blood vessel, said device having means for temporarily interrupting the bloodstream by closing the blood vessels.

Description

DEVICE FOR TREATING HEART CIRCULAR DISEASES

The invention relates to a device for interrupting the blood flow in blood vessels with a feed tube which can be inserted into the blood vessel and which is connected to one or more balloons which are expandable by supplying a liquid or a gas, and a pressure generating device which applies the pressure to expand the balloon generated via the liquid or the gas. The invention further relates to a method for inducing the growth and new formation of vessels.

Cardiovascular diseases are one of the most common causes of death in the industrialized countries. The cause of cardiovascular morbidity and mortality is to a large extent the insufficient supply of organs with blood (ischemia).

Central organ systems such as the heart and brain are often affected. Irrespective of this, reduced supplies can also lead to damage in all other areas of the organism, including the abdominal and peripheral current areas.

The cause of the insufficient supply is usually arteriosclerotic changes in the vessels. Atherosclerosis is a systemic disease of the arteries with chronically progressive degeneration and changes in the vascular wall. The result is wall hardening and wall deformation with often constricting the vessel lumen. The cause of the formation of arteriosclerosis is considered to be the Gender and age, among other things, the way of life (e.g. blood lipid levels), toxic influences (e.g. smoking), high blood pressure and metabolic diseases (e.g. diabetes mellitus).

Atherosclerosis usually progresses slowly. However, growth is not regular or strictly continuous. If there is a rapidly progressive increase in arteriosclerosis in a vascular segment, this can result in a displacement of the vascular lumen and thus an obstruction of the blood flow. Alternatively, by rupturing an arteriosclerotic plaque in the vessel wall, a blood clot (thrombus) can be formed by activating the coagulation cascade, which also impairs the blood flow within the vessel.

A rapidly occurring low supply leads to an undersupply of the cells in the subsequent perfusion section. The result is often the destruction of tissue. Cardiac infarction (myocardial infarction) and stroke (apoplex) are common examples of tissue loss due to insufficient supply. However, other areas of the organism's current can also be damaged if there is insufficient supply as a result of a reduction in vascular lumen.

In recent years, the treatment of vascular changes has experienced an extraordinary boom. Using catheters and surgical instruments, it is possible to avoid complex operations that are stressful for the patient. The previously established methods for the therapy of ischemia are aimed at eliminating constrictions in pre-existing vessels and / or reopening closed vessels.

In the previous therapeutic methods, the catheter or microsurgical instrument used is advanced to the place of use via blood-carrying vessels. As a rule, there is an obstruction to the blood flow in the corresponding vessel during use. Occasionally, a reversible relocation of the vessel and thus an interruption of the blood flow is accepted. Disabilities or relocations of the blood flow that exist for longer lead to a reduced supply of the subsequent tissue and can cause complications such as tissue death.

The consequences of an interruption of the blood flow are known especially when using dilatation catheters. In order to reduce the side effects caused by reduced perfusion and to avoid serious complications, the blood flow is usually only interrupted for a short period of time. Repeated interruptions in the blood flow are only repeated until the goal of the intervention is reached.

The previously established methods of vascular intervention are characterized by the fact that they aim to preserve existing vessels. The problem that often arises here is that after comparatively short periods of time, restenosis occurs in many patients; H. a renewed narrowing of the vascular cavity, which makes it necessary to repeat the medical intervention.

A solution to the problem is made possible by induction of bypass circuits, so-called collateral circuits. Collaterals are vessels that branch off from the main blood vessel in the direction of the same supply area. If the blood flow in the original vessel is restricted, these vessels can act as a bypass blood path and thus prevent a reduced supply of the dependent tissue sections.

For this reason, processes have been developed which aim to form new vessels. In one of the developed methods, part of the vessel is separated from the perfusion by means of two or more balloons at the distal end of a catheter. Substances to promote the formation of new vessels (angiogenesis, arteriogenesis) can be injected in the space thus created between the two balloons and the vessel wall. Corresponding devices are documented in the publications WO 02/05887 A2 and US 4,824,436. So far, however, no process for the formation of new collateral circuits has been established.

Preformed collaterals occur in most organ systems in a healthy organism. These generally narrow, pre-formed collaterals are not sufficient for a functionally effective collateral cycle. The expansion of the preformed collaterals to further lumen vessels, which allow an effective collateral circulation, often only takes place under pathological conditions.

The induction of collateral circuits is induced, among other things, by hypoxia (undersupply of tissues with oxygen). Animal experiments have shown that the induction of collaterals can be induced by repeated two-minute hypoxia (Mohri M, Tomoike H, Noma M, Inoue T, Hisano K, Nakamura M. "Duration of ischemia is vital for collateral development: repeated brief coronary artery occlusions in conscious dogs ". Circulation Research 1989; 64: 287-96). In these experiments, an occlusion of the arteries was brought about by external pressure.

Based on this level of knowledge, the task is to develop a device that enables the induction of collateral circuits through the formation and growth of new vessels.

The object is achieved according to the invention by a device according to the preamble of claim 1, in which the pressure generating device causes the balloon to expand for a certain period of time followed by a release of the pressure, and by a method according to the preamble of claim 22 which a device is at least partially inserted into a blood vessel and has means for repeated, temporary interruption of the blood flow by closing the blood vessel.

The invention is based on the finding that recurrent ischemia

Induce the formation of new vessels or their growth. This can result in the division of existing cells as well as one Differentiation of new cells is coming. To cause this recurrent ischemia, active, repeated, short-term interruptions in the blood flow are carried out. The duration of the individual ischemia periods during therapy should be chosen so that permanent damage to the dependent tissue areas does not occur. The creation of new vessels is a long-term process that can take several weeks. Accordingly, the device according to the invention must be such that it expands the balloon for a certain, generally short period of several minutes, e.g. B. 2 min, which closes the blood vessel and then opens again by releasing the pressure. The device according to the invention is basically suitable for use in all vessel sections of the human or animal body.

The pressure to inflate the balloon is adjusted so that the balloon rests against the vessel wall, but does not irreversibly expand it. In this way, an effective occlusion of the blood vessel is effected during the expansion of the balloon without causing damage to the vessel, particularly the intima.

In contrast to the previously established catheter methods, in which the interruption or obstruction of the blood flow was regarded as an undesirable side effect, the interruption of the blood flow according to this invention is an essential part of the therapy. A side effect that is difficult to prevent is thus advantageously used.

In order to control the expansion of the balloon at time-defined intervals, the device expediently has a control unit with a time-dependent circuit for initiating the generation of pressure. This control unit causes the repeated, periodically repeated expansion of the balloon to close the blood vessel over a period of time that lasts between several hours and several weeks, e.g. B. eight to twelve weeks. Such a period is usually necessary to ensure the effective formation of new vessels guarantee. It is important in therapy that the balloon is inflated frequently, but only for short periods of time, in order to induce the formation and growth of vessels without damaging tissue dependent on the blood supply. A typical program of the control unit therefore looks such that the vessel is closed for 2 minutes at intervals of 15 or 30 minutes.

According to an alternative embodiment of the invention, the blood flow is only partially interrupted by the device inserted into the blood vessel, in particular the balloon, in that the blood vessel is only partially closed. For this purpose, the balloon is not expanded to the wall of the vessel, but only to a certain percentage of the lumen of the vessel. The blood flow is severely restricted in this way to induce the formation of new vessels, but it is not completely interrupted. Typically, the expanded balloon should stop 50 to 90% of the blood flow.

Since the blood flow according to this alternative embodiment is not completely interrupted, the risk of the loss of tissue supplied by the blood flow is reduced, so that the blood flow can be interrupted for longer periods or also continuously partially. In the latter case, the balloon is accordingly not expanded at defined intervals. Finally, the expansion of the balloon or the strength of the interruption of the blood flow in the course of the treatment can also be increased, preferably to the extent that collateral circuits have already formed through the formation and growth of vessels, which ensure the adequate blood supply.

The ball or balloons are usually located at the distal end of the feed tube, where an easily deformable guide wire can also be provided for easier positioning of the device and stabilization of the position. A corresponding, easily deformable end is also used for conventional guidewires. In order to be able to bring the supply pipe to the desired location, it should also have a certain degree of flexibility. The device can be positioned in the target vessel via the lumen of an already positioned catheter (guide catheter). Alternatively, however, positioning is also possible via a guide wire previously inserted into the blood vessel. For this purpose, it makes sense that a lumen with a distal opening for receiving the guide wire runs through the interior of the feed tube, it being possible here to use both the actual inner lumen of the feed tube and an additional lumen placed therein. Alternatively, wire-guided positioning by means of an eyelet located on the outside of the feed pipe is also possible. The positioning of the device in the vessel is further facilitated in that the supply pipe is designed to be separable from the control unit or the pressure generating device at the proximal end.

For the position control of the balloon, radiopaque markings can be made in the area of the supply tube, particularly proximal and distal of the balloon, which makes positioning by means of X-ray radiation possible even without injuring contrast agents which are harmful to health. Such radiopaque markings are known per se and are widely used in the field of catheter technology.

The expansion of the balloon is effected by a liquid or a gas which is brought into the balloon via a pressure line by applying pressure. Both the supply pipe itself and another lumen located in the supply pipe can serve as the pressure line.

The control unit, which can be located intra- or extracorporeally during the treatment, advantageously not only controls the inflation and deflation of the balloon, but also serves to monitor various vital functions. In particular, an electrocardiogram (EKG) can be recorded during the therapy and / or the blood pressure can be measured and evaluated. Monitoring the blood pressure is particularly useful for therapy because the pressure to inflate the balloon can be adjusted to the prevailing blood pressure in order to ensure an effective occlusion of the blood vessel by expanding the balloon to its wall, but without, on the other hand application too high a pressure to cause an irreversible expansion of the wall and thus damage.

In order to further improve the comprehensive monitoring of the patient, the control unit can also be equipped with a telemetry function which forwards the measured data to other systems such as the central monitoring unit of a hospital. This forwarding can take place continuously or only if there are deviations from the setpoint in the form of an alarm system.

To control the blood flow, one or more ultrasound crystals can also be attached to the flexible supply tube. The ultrasound crystals make it possible to measure the blood flow rate (Doppler shift). This results in a good control of the blood flow in the corresponding vessel. In addition, changes in post-ischemic hyperperfusion can be detected using the ultrasound crystals.

Since the overall treatment usually takes a long period of time up to several weeks, it makes sense to leave the part of the device according to the invention inserted into the vascular system over the entire therapy period in the vascular system. In this way, the effort for positioning the feed pipe is kept low, which is all the more important since the individual treatment steps in the form of inflation of the balloon take place at comparatively short intervals. To prevent the device from remaining in the vascular system leading to the formation of thrombi, the parts of the device located intracorporeally during the treatment are advantageously provided with an antithrombotic coating. In addition, drug treatment with anticoagulant substances makes sense. Such coatings and substances for avoiding thrombosis are known to the person skilled in the field of medical technology.

Another way to prevent thrombosis is to provide a mesh or cage distal to the balloon, the detached thrombus intercept and prevent further negative consequences.

The process of forming new vessels is partly mediated via messenger substances. For vascular development, these messengers include VEGF (vascular endothelial growth factor), FGF-2 (fibroblast growth factor 2), IGF (insulin like growth factor) and nitrogen monoxide (NO), but also substances such as heparin (Fujita M. et al. , "Heparin potentiates collateral growth but not growth of intramyocardial endarteries in dogs with repeated coronary occlusion"; Int. J. Cardiol. (1999; 70: 165-170)). The formation of new vessels and where appropriate, cardiomyocytes are also promoted.

In order to be able to continuously apply messenger substances or other substances close to the tissue, the supply pipe can be provided with additional lumens. The messenger substances can be applied via an opening in front of or after the balloon (or at both locations). Alternatively, the intravascular application of a messenger substance or another substance close to the tissue can be achieved by means of a mass which is attached to the supply tube or to the balloon and dissolves over time.

In addition to the vessels, the invention also extends to the new formation of parenchymatous cells of other organ systems, which are newly formed or differentiated by the illustrated invention.

The invention is further illustrated by the attached drawing. It shows:

Figure 1 is a schematic representation of the device according to the invention in the form of a longitudinal section.

The device according to the invention comprises a flexible feed tube 4 which is inserted into the vascular system from proximal 5 to distal 5 '. At the distal end of the feed pipe 4 there is a balloon which is expanded Condition 1 extends to the vessel wall and in this way closes the blood vessel and interrupts the blood flow. The balloon 1 is expanded by supplying a liquid or a gas through the pressure line 2, which runs through the lumen of the supply pipe 4. At the opposite end of the pressure line there is a pressure generating device 3, which can generate a pressure for the expansion of the balloon 1 and can reduce this pressure after a certain period of time, so that the volume of the balloon 1 decreases accordingly. The considerably smaller volume of the balloon in the unexpanded state 1 ′ compared to the expanded state can be seen from the schematic illustration using the dashed line.

Claims

claims

1. Device for interrupting the blood flow in blood vessels with a feed tube (4) which can be inserted into the blood vessel, which is connected to one or more balloons (1) which can be expanded by supplying a liquid or a gas, and a pressure generating device (3), which generates the pressure to expand the balloon (1) via the liquid or the gas, characterized in that the pressure generating device (3) causes the balloon (1) to expand at a certain time interval, followed by a release of the pressure.

2. Device according to claim 1, characterized in that the balloon (1) is expandable up to the wall of the blood vessel and completely interrupts the blood flow in the expanded state.

3. Device for interrupting the blood flow in blood vessels with a feed tube (4) which can be inserted into the blood vessel, which is connected to one or more balloons (1) which can be expanded by supplying a liquid or a gas, and a pressure generating device (3), which generates the pressure to expand the balloon (1) via the liquid or the gas, characterized in that the balloon (1) partially closes the blood vessel in the expanded state and partially interrupts the blood flow.

4. The device according to claim 3, characterized in that the pressure generating device (3) in time-defined intervals causes an expansion of the balloon (1) for a certain period of time followed by a release of the pressure.

5. Apparatus according to claim 3 or 4, characterized in that the pressure generating device (3) increases the expansion of the balloon (1) in the course of treatment in order to bring about a greater interruption of the blood flow.

6. Device according to one of claims 1 to 5, characterized in that the pressure generating device (3) via a

Control unit with time-dependent circuit for initiation of pressure generation is regulated.

7. Device according to one of claims 1 to 6, characterized in that the balloon (1) at the distal end (5 ') of the feed pipe (4).

8. Device according to one of claims 1 to 7, characterized in that the device at the distal end (5 ^* ) of the feed pipe (4) has a deformable guide wire.

9. Device according to one of claims 1 to 8, characterized in that a lumen with a distal opening for receiving a positioning wire is used through the interior of the supply tube (4).

10. Device according to one of claims 1 to 8, characterized in that on the outside of the supply pipe (4) or the balloon (1) is an eyelet for positioning the supply pipe (4) with the aid of a guide wire.

11. The device according to one of claims 1 to 10, characterized in that the supply pipe (4) at the proximal end of the control unit and / or the pressure generating device (3) is separable.

12. Device according to one of claims 1 to 11, characterized in that the feed pipe (4) is provided with one or more radiopaque markings.

13. Device according to one of claims 1 to 12, characterized in that a lumen for passing on the expansion of the balloon (1) serving pressure passes through the feed pipe (4).

14. Device according to one of claims 6 to 13, characterized in that the control unit carries out an electrocardiographic monitoring.

15. Device according to one of claims 6 to 14, characterized in that a measurement of the blood pressure is carried out via the control unit and the pressure for the expansion of the balloon (1) is adjusted as a function thereof.

16. The device according to one of claims 6 to 15, characterized in that the control unit has a telemetry function.

17. The device according to one of claims 1 to 16, characterized in that one or more ultrasonic crystals are attached to the feed pipe (4) for determining the flow rate of the blood.

18. Device according to one of claims 1 to 17, characterized in that the part of the device which can be inserted into the patient's body has an antithrombotic coating in whole or in part.

19. Device according to one of claims 1 to 18, characterized in that a net or a cage for trapping thrombi is located distal of the balloon (1).

20. Device according to one of claims 1 to 19, characterized in that in the interior of the supply pipe (4) there is a lumen with an opening for the application of medicaments or messenger substances for the formation of new vessels or parenchymatous cells.

21. Device according to one of claims 1 to 20, characterized in that the feed pipe (4) and / or the balloon (1) is coated with intravascularly dissolving substances.

22. A method for inducing the growth and new formation of vessels and parenchymatous cells, because the device is inserted at least partially into a blood vessel which has means for repeated, temporary interruption of the blood flow by occluding the blood vessel.

23. The method according to claim 22, characterized in that the blood flow is completely interrupted.

24. A method for inducing the growth and new formation of vessels and parenchymatous cells, so that a device is inserted at least partially into a blood vessel which has means for partially interrupting the blood flow by partially occluding the blood vessel.

25. The method according to claim 24, characterized in that the

The blood flow is interrupted repeatedly and temporarily.

26. The method according to any one of claims 22 to 25, characterized in that the means for interrupting the blood flow are one or more expandable balloons (1) by supplying a liquid or a gas.

27. The method according to claim 26, characterized in that the

Expansion of the balloon (1) is intensified in the course of the treatment in order to cause a greater interruption of the blood flow.

28. The method according to any one of claims 22 to 27, characterized in that the interruption of the blood flow is carried out over a period of several hours to several weeks.

29. The method according to any one of claims 22 to 23 or 25 to 28, characterized in that each interruption of the blood flow takes place for a period of <10 min, preferably 2 min.

30. The method according to any one of claims 22 to 29, characterized in that the device is positioned in the blood vessel via the lumen of an already positioned guide catheter or via a guide wire.

31. The method according to any one of claims 22 to 30, characterized in that the correct positioning of the device is monitored by radiopaque markings.

32. The method according to any one of claims 22 to 31, characterized in that the blood pressure is measured during the treatment and the pressure for the expansion of the balloon (1) is adjusted as a function thereof.

33. The method according to any one of claims 22 to 32, characterized in that the flow velocity of the blood is measured on the device inserted into the blood vessel with the aid of ultrasound crystals.

34. The method according to any one of claims 22 to 33, characterized in that the device remains at least partially in the blood vessel over the entire period of treatment.

35. The method according to any one of claims 22 to 34, characterized in that medication or messenger substances for the formation of new vessels or and parenchymatous cells are applied via the at least partially inserted device into the blood vessel.

36. The method according to claim 35, characterized in that VEGF, FGF-2, IGF NO and / or heparin are applied as messenger substances.