Compositions and methods for ex vivo preservation of blood vessels for vascular grafts using analogues of cAMP and cGMP
OwnerYoshifumi Naka, David Pinsky +1inventors
InventorsYoshifumi Naka, David Pinsky, David Stern
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Abstract
The present invention relates to ex vivo methods for preserving/maintaining blood vessels that are to be used as vascular grafts. The present invention also relates to compositions comprising an analogue of cAMP and/or an analogue of cGMP for use in the methods of the invention, which compositions are free of: (i) an inhibitor of Type I phosphodiesterase, (ii) an inhibitor of Type II phosphodiesterase, (iii) an inhibitor of Type III phosphodiesterase, (iv) an inhibitor of Type IV phosphodiesterase, and (v) an inhibitor of TNF-α.
Claims103
A method of using a blood vessel as a vascular graft comprising:
- (a) contacting an isolated blood vessel or functional portion thereof ex vivo with a solution comprising an analogue of cAMP and/or an analogue of cGMP, which solution is free of:
- (i) an inhibitor of Type I phosphodiesterase, (ii) an inhibitor of Type II phosphodiesterase, (iii) an inhibitor of Type III phosphodiesterase, (iv) an inhibitor of Type IV phosphodiesterase, and (v) an inhibitor of TNF-α;
- and;
- (b) inserting the blood vessel into a patient so as to form a vascular graft in the patient.
A solution comprising an analogue of cAMP and/or an analogue of cGMP and heparinized blood, which solution is free of:
- (i) an inhibitor of Type I phosphodiesterase, (ii) an inhibitor of Type II phosphodiesterase, (iii) an inhibitor of Type III phosphodiesterase, (iv) an inhibitor of Type IV phosphodiesterase, and (v) an inhibitor of TNF-α.
A solution consisting of an analogue of cAMP and/or an analogue of cGMP and heparinized blood, which solution is free of:
- (i) an inhibitor of Type I phosphodiesterase, (ii) an inhibitor of Type II phosphodiesterase, (iii) an inhibitor of Type III phosphodiesterase, (iv) an inhibitor of Type IV phosphodiesterase, and (v) an inhibitor of TNF-α.
An isolated ex vivo blood vessel or functional portion thereof in contact with a solution comprising an analogue of cAMP and/or an analogue of cGMP, which solution is free of:
- (i) an inhibitor of Type I phosphodiesterase, (ii) an inhibitor of Type II phosphodiesterase, (iii) an inhibitor of Type III phosphodiesterase, (iv) an inhibitor of Type IV phosphodiesterase, and (v) an inhibitor of TNF-α.
A method of preserving a blood vessel comprising contacting an isolated blood vessel or functional portion thereof ex vivo with a solution comprising an analogue of cAMP and/or an analogue of cGMP, which solution is free of:
- (i) an inhibitor of Type I phosphodiesterase, (ii) an inhibitor of Type II phosphodiesterase, (iii) an inhibitor of Type III phosphodiesterase, (iv) an inhibitor of Type IV phosphodiesterase, and (v) an inhibitor of TNF-α.
A method of preserving a blood vessel comprising contacting an isolated blood vessel or portion thereof ex vivo with a solution consisting of (i) a fluid;
- and (ii) an analogue of cAMP and/or an analogue of cGMP, which solution is free of:
- (i) an inhibitor of Type I phosphodiesterase, (ii) an inhibitor of Type II phosphodiesterase, (iii) an inhibitor of Type III phosphodiesterase, (iv) an inhibitor of Type IV phosphodiesterase, and (v) an inhibitor of TNF-α, said fluid selected from the group consisting of heparinized blood, buffered saline, the modified Columbia University solution, the Euro-Collins solution, the University of Wisconsin solution, the low-potassium dextran glucose solution and the CELSIOR™ solution.
A method for performing a coronary artery bypass graft in a patient comprising,
- (a) removing from contact with a blood vessel or functional portion thereof a solution comprising an analogue of cAMP and/or an analogue of cGMP, which solution is free of:
- (i) an inhibitor of Type I phosphodiesterase, (ii) an inhibitor of Type II phosphodiesterase, (iii) an inhibitor of Type III phosphodiesterase, (iv) an inhibitor of Type IV phosphodiesterase, and (v) an inhibitor of TNF-α;
- and
- (b) grafting the blood vessel or functional portion thereof into the patient so as to serve as a coronary bypass graft.
A method of using a blood vessel as a vascular graft comprising:
- (a) contacting an isolated blood vessel or functional portion thereof ex vivo with a solution comprising nitroglycerin, which solution is optionally free of:
- (i) an inhibitor of Type I phosphodiesterase, (ii) an inhibitor of Type II phosphodiesterase, (iii) an inhibitor of Type III phosphodiesterase, (iv) an inhibitor of Type IV phosphodiesterase, and (v) an inhibitor of TNF-α;
- and;
- (b) inserting the blood vessel into a patient so as to form a vascular graft in the patient.
A solution comprising nitroglycerin and heparinized blood, which solution is free of:
- (i) an inhibitor of Type I phosphodiesterase, (ii) an inhibitor of Type II phosphodiesterase, (iii) an inhibitor of Type III phosphodiesterase, (iv) an inhibitor of Type IV phosphodiesterase, and (v) an inhibitor of TNF-α.
A kit comprising:
- (a) in a first container, a blood vessel preservation solution;
- and
- (b) a first plurality of vials, each vial comprising a lyophilized aliquot of an analogue of cAMP and/or an analogue of cGMP.
A kit comprising:
- (a) in a first container, a blood vessel preservation solution;
- (b) a first plurality of vials, each vial comprising a lyophilized aliquot of an analogue of cAMP and/or an analogue of cGMP;
- (c) a second plurality of additional containers, equal in number to said first plurality, each additional container containing an amount of said blood vessel preservation solution sufficient to dissolve said lyophilized aliquot when added to each said vial containing said lyophilized aliquot;
- (d) an incubation dish large enough to hold a blood vessel or portion thereof immersed in said preservation solution of said first container;
- and
- (e) a third plurality of needles and syringes, wherein the number of needles and syringes is equal, and is the same as the number of vials in said first plurality.
Dependencies are inferred from the claim text.