Prosthesis (i.e. – artificial body members) – parts thereof – or ai – Arterial prosthesis
Reexamination Certificate
1999-06-30
2002-05-14
Willse, David H. (Department: 3738)
Prosthesis (i.e., artificial body members), parts thereof, or ai
Arterial prosthesis
C604S022000, C606S128000
Reexamination Certificate
active
06387116
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates generally to medical methods, systems, and kits. More particularly, the present invention relates to methods for treating vascular fistulas and grafts to inhibit hyperplasia and subsequent occlusion thereof.
Vascular fistulas and grafts are used in a wide variety of circumstances when it is desired to reconfigure or re-establish vascular circulation in a patient. For example, both fistulas and grafts are used to create access sites for blood withdrawal and return in patient's undergoing periodic kidney dialysis, hemofiltration, or other extracorporeal blood treatments. Usually, either a native artery and vein are connected together via a side-to-side anastomosis or a saphenous vein or synthetic graft is placed between an artery and a vein and attached at each end via an end-to-side anastomosis. Both natural grafts (usually a vein harvested from the patient being treated) and synthetic grafts are used in open and/or minimally invasive surgical procedures for treating vascular disorders, such as coronary artery bypass grafting for treating heart disease, surgical graft introduction for treating abdominal aortic aneurysms, peripheral vasculature repair, and the like. In all cases, at least two anastomotic connections are required for implanting the graft.
In many cases, it has been found that the anastomotic junction which is created at the fistula or between the blood vessel and the implanted graft is at significant risk of occlusion due to hyperplasia. In particular, intimal hyperplasia of the vascular smooth muscles cells will often occur as an injury response to the surgical creation of the anastomosis. Occlusion resulting from the hyperplasia is exacerbated by thrombosis which occurs as a result of the blood flow turbulence at the site of the anastomosis. The most troublesome lesions are formed at anastomotic junctions between a graft or artery and a vein.
At present, there are no effective treatments for hyperplasia at anastomotic junctions in any of the cases discussed above. When the anastomotic junction in an arterio-venous (A-V) fistula or graft fails in a dialysis patient, it is necessary create a new dialysis access site. After a time, there are no more new sites and kidney dialysis is no longer available to the patient. While it is possible for heart bypass patients having failed grafts to redo the procedure, second and later procedures are seldom as effective in treating the disease as in an initial bypass procedure. Moreover, the availability of autologous blood vessels for performing the procedure places a limit on the number of procedures that can be performed.
For all of these reasons, it would be desirable to provide methods, systems, and kits, for treating anastomotic junctions which are formed as the result of the creation of an arterio-venous fistula or the implantation of a bypass or other graft in a patient's vasculature. It would be particularly desirable to provide methods suitable for treating anastomotic junctions both at the time they are created as well as at subsequent times in order to effectively inhibit hyperplasia at the junctions. Preferably, the methods for inhibiting hyperplasia would require little or no modification to the implantation techniques themselves and would be suitable for use in a wide variety of procedures which rely on the formation of anastomotic attachments, including at least all of those described above. At least some of these objectives will be met by the inventions described hereinafter.
2. Description of the Background Art
The failure of vascular grafts and fistulas used for hemodialysis access is recognized to stem at least in part from neointimal hyperplasia. See, Taber et al. (1995) ASAIO J 41:842-846. Both pharmacological and mechanical solutions have been proposed. See, e.g., U.S. Pat. No. 4,840,940, which proposes systemic administration of fractionated heparin to inhibit restenosis, and Gray et al. (1995) Radiology 195:479-484 and Beathard (1993) Kidney Int. 43:872-877, which describe the use of stents for maintaining patency in arterio-venous access sites. Johnstone et al. (1994) Int. J. Radiat. Oncol. Biol. Phys. 29:1015-1025, observed the effects of intraoperative radiotherapy and external beam radiotherapy on prosthetic vascular grafts in a canine model and found that radiation could contribute to late occlusion of the graft.
Intravascular inhibition of hyperplasia by exposure to radioisotopes is described in a number of patents and publications, including U.S. Pat. Nos. 5,616,114; 5,302,168; 5,199,939; and 5,059,166. The therapeutic application of ultrasonic energy is described in a number of patents and publications including U.S. Pat. Nos. 5,362,309; 5,318,014; 5,315,998, WO 98/48711; and others. The application of intravascular ultrasound for inhibiting restenosis by decreasing the migration, viability, and adhesion of vascular smooth muscle cells via a cavitation mechanism is suggested in U.S. Pat. No. 5,836,896. See also, Rosenchein et al. (1990) JACC 15:711-717 and Siegel et al. (1991) J. Invasive Cardiol. 3:135 which describe thrombolysis via the cavitation mechanism. A high frequency ultrasonic catheter intended for tissue ablation which employs an air-backed transducer is described in He et al. (1995) Eur. Heart J. 16:961-966. Cell lysis of mammalian cell lines maintained in vitro is described in Kaufman et al. (1977) Ultrasound Med. Biol. 3:21-25. Catheters suitable for performing at least some methods according to the present invention are described in copending application Ser. Nos. 08/565,575; 08/566,740; 08/566,739; 08/708,589; 08/867,007, and 09/223,225, filed on Dec. 30, 1998, and assigned to the assignee of the present invention, the full disclosures of which are incorporated herein by reference.
SUMMARY OF THE INVENTION
The present invention provides methods and kits for inhibiting hyperplasia at an anastomotic junction of a vascular graft or fistula. By “hyperplasia,” it is meant that excessive cell proliferation occurs at the anastomotic junction (attachment site) between an artery and a vein in the case of a fistula, and an artery or vein and a tubular graft in the case of a graft connection. Hyperplasia can occur as the result of surgical creation of the anastomotic junction, and it has been found that the surgical attachment can damage cells lining the involved blood vessels in a manner which results in an injury response characterized by secretion of extracellular matrix and excessive proliferation of the smooth muscle cells lining the blood vessels which together form the neointimal layer lining the blood vessel wall adjacent the anastomotic junction.
Treatment according to the present invention is effected by exposing the anastomotic junction to vibrational energy at a mechanical index and for a time sufficient to inhibit hyperplasia of smooth muscle cells within the neointimal layer of the blood vessel. Surprisingly, it has been found that the strength of vibrational energy (as measured by the mechanical index) and the duration of the treatment (as measured by elapsed treatment time, duty cycle, and pulse repetition frequency (PRF)) can be selected to provide highly effective hyperplasia inhibition in the neointimal layer without significant damage to surrounding tissues or structures within the blood vessel(s) and/or the anastomotic junction itself. In particular, by exposing an anastomotic junction at risk of neointimal hyperplasia to a vibrational energy having a mechanical index in the range from 0.1 to 50, preferably from 0.2 to 10, and more preferably from 0.5 to 5, for a treatment time in the range from 10 seconds to 1000 seconds, preferably from 30 seconds to 500 seconds, and more preferably from 60 seconds to 300 seconds, the proliferation of vascular smooth muscle cells in the neointimal layer of the artery can be reduced by at least 2% (in comparison with untreated controls) after seven days, often at least 4% , and sometimes 6% or greater. The resulting reduction in hyperplasia
Brisken Axel F.
Corl Paul D.
McKenzie John R.
Zuk Robert F.
Pharmasonics, Inc.
Stewart Alvin
Townsend and Townsend / and Crew LLP
Willse David H.
LandOfFree
Methods and kits for the inhibition of hyperplasia in... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Methods and kits for the inhibition of hyperplasia in..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods and kits for the inhibition of hyperplasia in... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2863648