Method for treating an arterial wall injured during angioplasty

What is claimed is:

1. A method for treating a lesion in an arterial wall having plaque thereon and a luminal surface, the arterial wall having been injured during an angioplasty procedure, the arterial wall and the plaque including fissures resulting therefrom, the method comprising the steps of:

positioning an angioplasty catheter adjacent to the lesion being treated;

delivering a bioprotective material between the arterial wall and the angioplasty catheter so that the bioprotective material is entrapped therebetween and permeates into the fissures and vessels of the arterial wall during apposition of the angioplasty catheter thereto;

applying thermal energy to the lesion, thereby bonding the bioprotective material to the arterial wall and within the fissures and vessels of the arterial wall; and

removing the angioplasty catheter, the bioprotective material remaining adherent to the arterial wall and within the fissures and vessels thereof, thereby coating the luminal surface with an insoluble layer of the bioprotective material so that the insoluble layer provides at least semi-permanent protection to the arterial wall, despite contact with blood flowing adjacent thereto.

2. The method of claim wherein the angioplasty catheter utilized includes an inflatable balloon.

3. The method of claim 2 wherein the inflatable balloon is at least partially inflated before delivering the bioprotective material between the arterial wall and the inflatable balloon so that the layer of the bioprotective material may be formed therebetween.

4. The method of claim 1 wherein the bioprotective material utilized is macroaggregated albumin which bonds to the luminal surface and within fissures and vessels of the aterial wall as a result of the application of thermal energy.

5. The method of claim 1 wherein the bioprotective material utilized comprises platelets, injected as a suspension, which upon being trapped between the inflatable balloon and the luminal surface become adherent to the luminal surface and to tissues adjacent to fissures and vessels of the arterial wall as a result of the application of thermal energy.

6. The method of claim 1 wherein the bioprotective material comprises red blood cells, injected as a suspension, which upon being trapped between the inflatable balloon and the luminal surface become adherent to the luminal surface and to tissues adjacent to fissures and vessels of the arterial wall as a result of the application of thermal energy.

7. The method of claim 1 wherein the bioprotective material comprises liposomes, injected as a suspension, which upon being trapped between the inflatable balloon and the luminal surface become adherent to the luminal surface and to tissues adjacent to fissures and vessels of the arterial wall as a result of the application of thermal energy.

8. The method of claim 1 wherein the bioprotective material utilized is gelatin which upon being trapped between the inflatable balloon and the luminal surface bonds to the luminal surface and within fissures and vessels of the arterial wall as a result of the application of thermal energy.

9. The method of claim 1 wherein the bioprotective material utilized is a solution of fibrinogen which upon being trapped between the inflatable balloon and the luminal surface precipitates onto the luminal surface and within fissures and vessels of the arterial wall as a result of the application of thermal energy.

10. The method of claim 1 wherein the bioprotective material utilized is a solution of collagen which upon being trapped between the inflatable balloon and the luminal surface precipitates onto the luminal surface and within fissures and vessels of the arterial wall as a result of the application of thermal energy.

11. The method of claim 1 wherein the bioprotective material utilized is a solution of a high molecular carbohydrate which upon being trapped between the inflatable balloon and the luminal surface precipitates onto the luminal surface and within fissures and vessels of the arterial wall as a result of the application of thermal energy.

12. The method of claim 1 wherein the bioprotective material utilized entraps a useful pharmaceutical agent in order to provide local drug therapy directly to the luminal surface, and to deeper layers of the arterial wall.

13. The method of claim 12 wherein the useful pharmaceutical agent is an anti-coagulant.

14. The method of claim 12 wherein the useful pharmaceutical agent is a fibrinolytic agent.

15. The method of claim 12 wherein the useful pharmaceutical agent is a thrombolytic agent.

16. The method of claim 12 wherein the useful pharmaceutical agent is an anti-inflammatory agent.

17. The method of claim 12 wherein the useful pharmaceutical is an anti-proliferative compound.

18. The method of claim 12 wherein the useful pharmaceutical is an immunosuppressant.

19. The method of claim 12 wherein the useful pharmaceutical is a collagen inhibitor.

20. The method of claim 12 wherein the useful pharmaceutical is an endothelial cell growth promotor.

21. The method of claim 12 wherein the useful pharmaceutical is a sulfated polysaccharide.

22. The method of claim 1 wherein the bioprotective material includes a drug which is bound to albumin in solution prior to injection so that the drug is permanently affixed thereto by application of the thermal energy.

23. The method of claim 1 wherein the bioprotective material includes a drug which is physically trapped within a precipitated layer of albumin after the drug is injected with a solution of albumin.

24. The method of claim 1 wherein the bioprotective material comprises microspheres.

25. The method of claim 1 wherein the bioprotective material includes a drug preparation having an encapsulating medium.

26. The method of claim 25 wherein the encapsulating medium comprises albumin.

27. The method of claim 25 wherein the encapsulating medium comprises carbohydrates.

28. The method of claim 25 wherein the encapsulating medium comprises platelets.

29. The method of claim 25 wherein the encapsulating medium comprises liposomes.

30. The method of claim 25 wherein the encapsulating medium comprises red blood cells.

31. The method of claim 25 wherein the encapsulating medium comprises gelatin.

32. The method of claim 25 wherein the encapsulating medium comprises fibrin.

33. The method of claim 25 wherein the encapsulating medium comprises a synthetic polymer.

34. The method of claim 25 wherein the encapsulating medium comprises a sulfated polysaccharide.

35. The method of claim 25 wherein the encapsulating medium comprises an inorganic salt.

36. The method of claim 25 wherein the encapsulating medium comprises a phosphate glass.

37. The method of claim 1 wherein the bioprotective material is a suspension of microspheres in a physiologic solution.

38. The method of claim 1 wherein the step of removing the angioplasty catheter is followed by the step of bonding the bioprotective material to the lesion so that the bioprotective material remains adherent to the arterial wall, and fills cracks and recesses therewithin, thereby providing a smooth, luminal surface.

39. The method of claim 1 wherein the bioprotective material is delivered from a sleeve thereof provided upon the angioplasty catheter, the sleeve being disposed adjacent the arterial wall during apposition of the angioplastic catheter thereto, so that the sleeve of bioprotective material is transferred therefrom to the luminal surface, thereby becoming persistently affixed thereto upon applying the thermal energy and removing the angioplasty catheter.

40. The method of claim 1 wherein microspheres are formed in situ at the luminal surface and within the arterial wall as a result of the thermal energy applied to the bioprotective material.

41. The method of claim 1 wherein a drug, simultaneously injected with the bioprotective material, is entrapped within microspheres.

42. The method of claim 1 wherein the bioprotective material functions as a physiologic glue, thereby enhancing thermal fusion of fissured tissues within the arterial wall.

43. The method of claim 1 wherein the bioprotective material includes a chromophore which enhances absorption of electromagnetic radiation.

44. The method of claim 1 wherein a photosensitive dye is entrapped within the bioprotective material.

45. The method of claim 25 wherein the encapsulating medium comprises a chromophore which enhances absorption of electromagnetic radiation.

46. The method of claim 45 wherein the encapsulating medium entraps a photosensitive dye.

47. The method of claim 1 wherein the angioplasty catheter is a metal probe.

48. The method of claim 1 wherein the applied thermal energy is electromagnetic radiation.

49. The method of claim 48 wherein the applied thermal energy is continuous wave electromagnetic radiation.

50. The method of claim 48 wherein the applied thermal energy is pulsed electromagnetic radiation.

51. The method of claim 48 wherein the electromagnetic radiation is laser radiation.

52. The method of claim 48 wherein the electromagnetic radiation is radio-frequency radiation.

53. The method of claim 48 wherein the electromagnetic radiation is microwave radiation.

54. The method of claim 48 wherein the electromagnetic radiation is generated from electrical resistance.

55. The method of claim 1 wherein the bioprotective material is injected into the artery through the angioplasty catheter which is placed proximal to the lesion being treated.

56. The method of claim 2 wherein the bioprotective material is injected through a channel within the angioplasty catheter to the arterial wall by exiting through ports located proximal to the inflatable balloon.

57. The method of claim 2 wherein the bioprotective material is injected through the angioplasty catheter to the arterial wall through microscopic perforations provided within the inflatable balloon.

58. A method for treating a lesion in an arterial wall having plaque thereon and a luminal surface, the arterial wall having been injured during an angioplasty procedure, the arterial wall and the plaque including fissures resulting therefrom, the method comprising the steps of:

positioning an angioplasty catheter adjacent to the lesion being treated;

delivering a bioprotective material between the arterial wall and the angioplasty catheter so that the bioprotective material is entrapped therebetween and permeates into the fissures and vessels of the arterial wall during apposition of the angioplasty catheter thereto;

applying thermal energy to the lesion, thereby bonding the bioprotective material to the arterial wall and within the fissures and vessels of the arterial wall; and

removing the angioplasty catheter, the bioprotective material remaining adherent to the arterial wall and within the fissures and vessels thereof, thereby coating the luminal surface with an insoluble layer of the bioprotective material so that the insoluble layer provides at least semi-permanent protection to the arterial wall, despite contact with blood flowing adjacent thereto.

59. A method for treating a lesion in an arterial wall having plaque thereon and a luminal surface, the arterial wall and the plaque including fissures resulting therefrom, the method comprising the steps of:

performing angioplasty;

positioning an angioplasty catheter adjacent to the lesion being treated;

delivering a bioprotective material between the arterial wall and the angioplasty catheter so that the bioprotective material is entrapped therebetween and permeates into the fissures and vessels of the arterial wall during apposition of the angioplasty catheter thereto;

applying thermal energy to the lesion, thereby bonding the bioprotective material to the arterial wall and within the fissures and vessels of the arterial wall; and

removing the angioplasty catheter, the bioprotective material remaining adherent to the arterial wall and within the fissures and vessels thereof, thereby coating the luminal surface with an insoluble layer of the bioprotective material so that the insoluble layer provides at least semi-permanent protection to the arterial wall, despite contact with blood flowing adjacent thereto.

60. The method of claim 1 wherein the step of applying thermal energy to the lesion comprises applying the thermal energy from the angioplasty catheter radially outwardly.

61. The method of claim 1 wherein the step of applying thermal energy to the lesion comprises delivering the thermal energy from a source thereof disposed outside the arterial wall radially inwardly.

62. The method of claim 1 wherein the step of applying thermal energy to the lesion comprises the step of applying thermal energy so that the temperature within the bioprotective material is raised to at least 50.degree. C.

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TECHNICAL FIELD

This invention relates to angioplasty, and more particularly to a method for treating an arterial wall injured during angioplasty.

BACKGROUND ART

Atherosclerosis is a progressive disease wherein fatty, fibrous, calcific, or thrombotic deposits produce atheromatous plaques, within and beneath the intima which is the innermost layer of arteries. Atherosclerosis tends to involve large and medium sized arteries. The most commonly affected are the aorta, iliac, femoral, coronary, and cerebral arteries. Clinical symptoms occur because the mass of the atherosclerotic plaque reduces blood flow through the afflicted artery, thereby compromising tissue or organ function distal to it.

The mortality and morbidity from ischemic heart disease results primarily from atheromatous narrowings of the coronary arteries. Although various medical and surgical therapies may improve the quality of life for most patients with coronary atherosclerosis, such therapies do not favorably change the underlying anatomy responsible for the coronary luminal narrowings. Until recently, there has not been a non-surgical means for improving the perfusion of blood through the lumina of coronary arteries compromised by atheromatous plaque.

Percutaneous transluminal coronary angioplasty has been developed as an alternative, non-surgical method for treatment of coronary atherosclerosis. During cardiac catheterization, an inflatable balloon is inserted in a coronary artery in the region of coronary narrowing. Inflation of the balloon for 15-30 seconds results in an expansion of the narrowed lumen or passageway. Because residual narrowing is usually present after the first balloon inflation, multiple or prolonged inflations are routinely performed to reduce the severity of the residual stenosis or tube narrowing. Despite multiple or prolonged inflations, a mild to moderately severe stenosis usually is present, even after the procedure is otherwise performed successfully.

The physician will often prefer not to dilate lesions that are not severe because there is a good chance that they will recur. Because the occlusion recurs frequently, conventional angioplasty is often considered to be a suboptimal procedure. As a result, it is sometimes attempted only when a patient does not wish to undergo major cardiac surgery.

There are several reasons why the lesions reappear. One is that small clots form on the arterial wall. Tears in the wall expose blood to foreign material and proteins, such as collagen, which are highly thrombogenic. Resulting clots can grow gradually, or can contain growth hormones which are released by platelets within the clot. Additionally, growth hormones released by other cells, such as macrophages, can cause smooth muscle cells and fibroblasts in the region to multiply. Further, there is often a complete loss of the normal single layer of cells constituting the endothelial lining following angioplasty. This layer normally covers the internal surface of all vessels, rendering that surface compatible, i.e. non-thrombogenic and non-reactive with blood. Mechanically, when an angioplasty balloon is inflated, the endothelial cells are torn away. Combination of the loss of the endothelial layer and tearing within the wall often generates a surface which is quite thrombogenic.

Prior art angioplasty procedures also produce injuries in the arterial wall which become associated with inflammation. White cells will migrate to the area and will lay down scar tissue. Any kind of inflammatory response may cause the growth of new tissue. Restenosis or recurrence of the obstruction results because the smooth muscle cells which normally reside within the arterial wall proliferate. Such cells migrate to the area of the injury and multiply in response thereto.

It therefore appears that in order to combat problems associated with cumulating plaque, attention must be paid to: (1) the importance of thrombus; (2) inflammatory changes; and (3) proliferation. Any combination of these factors probably accounts for most cases of restenosis.

In order to address such problems, the cardiology community needs to administer drugs which are biocompatible and not induce toxic reactions. Therefore, it would be helpful to invoke a technique which allows localized administration of drugs that counteract clotting, interfere with inflammatory responses, and block proliferative responses. However, many such drugs when administered are toxic and are associated with potentially serious side effects which make the treatment and prevention of restenosis impractical. Accordingly, even though there is a number of potentially useful drugs, there is a tendency to avoid using them.

One of the other major problems with conventional methods of treatment is that the injured arterial wall exhibits a reduced hemocompatability compared to that associated with a normal arterial wall. Adverse responses which are associated with reduced hemocompatability include platelet adhesion, aggregation, and activation; potential initiation of the coagulation cascade and thrombosis; inflammatory cell reactions, such as adhesion and activation of monocytes or macrophages; and the infiltration of leukocytes into the arterial wall. Additionally, cellular proliferation results in the release of a variety of growth factors. Restenosis probably results from one or a combination of such responses.

Methods for treating atherosclerosis are disclosed in my U.S. Pat. No. 4,512,762 which issued on Apr. 23, 1985, and which is herein incorporated by reference. This patent discloses a method of injecting a hematoporphyrin into a mammal for selective uptake into the atheromatous plaque, and delivering light to the diseased vessel so that the light activates the hematoporphyrin for lysis of the plaque. However, one of the major problems with such treatments is that a flap of material occasionally is formed during the treatment which, after withdrawal of the instrumentation, falls back into the artery, thereby causing abrupt reclosure. This may necessitate emergency coronary artery bypass surgery. Accordingly, such techniques often provide only a temporary treatment for symptoms associated with arterial atherosclerosis.

My U.S. Pat. No. 4,799,479 was issued on Jan. 24, 1989 and is also herein incorporated by reference. This patent discloses a method used in percutaneous transluminal coronary angioplasty wherein a balloon is heated upon inflation. Disrupted tissues of plaque in the arterial wall are heated in order to fuse together fragmented segments of tissue and to coagulate blood trapped with dissected planes of tissues and within fissures created by the fracture. Upon subsequent balloon deflation, a smooth cylindrically shaped channel results.

Approaches such as those disclosed in U.S. Pat. Nos. 4,512,762 and 4,799,479, however, are directed mainly to producing an enhanced luminal result wherein a smooth luminal wall is produced. Problems of biocompatability, including thrombosis, and proliferation of cells tend to remain. Accordingly, the need has arisen to enable a physician to treat patients having atherosclerosis so that the problems of reduced hemocompatability and restenosis are avoided.

As a result of problems remaining unsolved by prior art approaches, there has been a growing disappointment in the cardiology community that until now, no new technology or procedure has been available to dramatically reduce the rate of restenosis.

SUMMARY OF THE INVENTION

The present invention solves the above and other problems by providing a method for treating an arterial wall which has been injured during an angioplasty procedure. The method comprises the steps of positioning an angioplasty catheter adjacent to a lesion to be treated. A bioprotective material is delivered between the arterial wall and the angioplasty catheter so that the bioprotective material is entrapped therebetween and permeates into fissures in the arterial wall during apposition thereto of the angioplasty catheter. To bond the bioprotective material to the arterial wall and within the tissues, thermal energy is applied to the lesion. After removal of the angioplasty catheter, the bioprotective material remains adherent to the arterial wall and within the tissues, thereby coating the luminal surface of the arterial wall with an insoluble layer of the bioprotective material so that the insoluble layer provides at least semi-permanent protection to the arterial wall, despite contact with blood flowing adjacent thereto.

The objects, features, and advantages of the present invention are readily apparent from the following detailed description of the best modes for carrying out the invention when taken in connection with the accompanying drawings.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1A is a cross-sectional view of a lesion to be treated by a percutaneous transluminal angioplasty procedure, in which plaque is formed within an artery;

FIG. 1B is a cross-sectional view of the procedure disclosed by the present invention, in which a bioprotective material is delivered to a lesion during distention of an uninflated balloon;

FIG. 1C is a cross-sectional view of the procedure disclosed by the present invention, in which the balloon is inflated and the bioprotective material is entrapped between the balloon and the arterial wall, the bioprotective material also entering vessels of the arterial wall and fissures which result from previously administered angioplasty procedure;

FIG. 2 is a cross-sectional view of one embodiment of the anatomical environment and apparatus used to practice the subject invention, in which the area immediately surrounding the inflated balloon is permeated by the bioprotective material and bonded by thermal energy delivered to the bioprotective material within the arterial wall being treated;

FIG. 2A is an enlarged portion of the circled area depicted in FIG. 2; and

FIG. 3 is a cross-sectional view of the result of utilizing the procedure of the present invention, illustrating a smooth channel formed by the insoluble layer of bioprotective material at the luminal surface and within sealed fissures and sealed vessels of the arterial wall, thereby providing at least semipermanent protection to the arterial wall, despite contact with blood flowing adjacent thereto.

BEST MODES FOR CARRYING OUT THE INVENTION

FIG. 1A shows a guide wire 10 which is inserted along an artery and through a region 12 which is occluded primarily by plaque 14. Surrounding the plaque 14 are media 60 and adventitia 18. As is now known, the plaque 14 forms an occlusion. The guide wire 10 is usually a stainless steel wire having tightly coiled, but flexible springs. Conventionally, the catheter 20 is made of a plastic, or an elastomeric material and is disposed around the guide wire 10. Following conventional angioplasty, and before applying bioprotective material 26, the balloon section 22 is maneuvered so as to lie adjacent to the plaque 14.

FIG. 1B illustrates the positioning of the uninflated balloon 22 after conventional angioplasty has been performed. Expansion of the balloon 22 to position 22' (FIG. 1C) stretches out the lesion by tissue pressure. Larger balloons are capable of applying more pressure. Between about half an atmosphere and ten atmospheres may be necessary to dilate balloon 22' within the luminal surface 29. Before the balloon 22' is fully expanded, its pressure approximates the tissue pressure. However, once the balloon 22' cracks the plaque and is fully expanded, the outer layers of the tissue are somewhat elastic and the tissue pressure therefore no longer approximates the balloon pressure. The mild residual tissue pressure is helpful in applying the bioprotective material 26 to the arterial wall 28.

Referring again to FIG. 1C, the balloon section 22 having been placed adjacent to the plaque 14, is inflated to position 22', thereby opening the artery. At the same time, the fissures and dissected planes of tissue 24 are also opened.

After the catheter 20 is removed, following the teachings of conventional angioplasty procedures, the plaque 14 can collapse into the center of the artery, thereby resulting in an abrupt reclosure of the artery and the possibility of an acute myocardial infarction.

Following prior art techniques, even less severe disruptions in the arterial wall commonly result in gradual restenosis within three to six months after conventional balloon angioplasty. This occurs in part because platelets adhere to exposed arterial tissue surfaces. FIG. 1C is helpful in illustrating the fissures or dissected planes of tissue 24 which result from conventional angioplasty procedures. The presence of regions of blood flow separation and turbulence within the arterial lumen 36 predispose to microthrombi deposition and cellular proliferation within the arterial wall 28.

To overcome these and other problems resulting from prior art approaches, the method of the present invention applies the bioprotective material 26 to a lesion 27 of the luminal surface 29 of the arterial wall 28 and to deeper surfaces lining fissures and vessels of the arterial wall. The angioplasty catheter 20 is first positioned adjacent to the lesion 27 being treated. Next, the bioprotective material 26 is delivered between the arterial wall 28 and the angioplasty catheter 20. Before completing inflation of the balloon, the bioprotective material 26 lies within fissures and vessels of the arterial wall and between the arterial wall 28 and the angioplasty catheter 20, and downstream thereof. During apposition of the angioplasty catheter 20 to the arterial wall 28, a layer of the bioprotective material 28 is entrapped therebetween. Because of capillary action and pressure exerted radially outwardly by the balloon, the bioprotective material 26 further enters and permeates the vessels of the arterial wall as well as the fissures and dissected planes of tissue 24. As a result, localized delivery of the bioprotective material 26 is made possible.

Turning now to FIG. 2, it may be seen that thermal energy generated from an optical diffusing tip 32 is represented schematically by radially emanating wavy lines. The thermal energy bonds the bioprotective material 26 to the arterial wall 28 and within the tissues 24.

The guide wire 10 may be replaced with an optical fiber 30 having an optical diffusion area or tip 32 located within the inflated balloon 22'. The catheter 20 is inserted around the optical fiber in lumen 36. Expansion of the balloon 22 is produced by a transparent fluid through inflation port 38 in termination apparatus generally located at 40. The fluid utilized for inflation of the balloon may be a contrast medium or crystalloids, such as normal saline, or five percent dextrose in water. Each is relatively transparent to such thermal energy as radiation. After passing through the catheter wall 42, the fluid continues through a channel 44 in the outer catheter sheath, thereby inflating the balloon 34. After inflation, for example, laser radiation 46 is introduced into the optical fiber 30 for transmission to the optical diffusion tip 32. The laser radiation is then diffused therefrom and impinges upon the bioprotective material 26 and the arterial wall 28 after fracture or dissection of the plaque 14 has occurred following prior angioplasty. It will be apparent that there exist a variety of ways to deliver thermal energy to the area to be treated. Microwave, radio-frequency, or electrical heating of the fluid each are possible techniques.

The invention disclosed contemplates injection of the bioprotective material 26 through the guiding catheter 20, the tip of which lies near the origin of, for example, a coronary artery before passage of a small balloon catheter through an inner channel of the guiding catheter. The bioprotective material may be injected through the guiding catheter along with flowing blood. Alternatively, the physician may use a small tube that fits over the shaft of the balloon catheter 20 and inject drugs proximal to or upstream from the balloon's location. If the physician wishes, a separate channel within the angioplasty catheter could be used to inject the bioprotective material through exit holes located in the shaft of the catheter, proximal to the balloon.

In practicing the invention, the guide wire 10 may extend through a central channel in the balloon and extend down the arterial lesion path. Alternatively, the guide wire 10 can be fixed to a central channel in the balloon or be freely movable with respect thereto.

Unlike conventional approaches which may require repeated application of the angioplasty procedure with intermittent inflation of the balloon to avoid prolonged interruption of blood flow, the procedure taught by the present invention does not require multiple inflations, and is applied only once for about a twenty second period of thermal treatment followed by about a twenty second period of cooling before balloon deflation. If thicker layers of bioprote