Methods for minimizing spasticity in blood vessel grafts

Abstract

Methods for minimizing spasticity in blood vessels during transplantation, in both ex-vivo and in-vivo procedures are disclosed.

1 . A method for treating blood vessel grafts comprising: 
 harvesting a blood vessel suitable for use as coronary artery graft;    forming a solution including a spasticity minimizing agent;    combining the solution of a spasticity minimizing agent with at least one vasodilator agent and an anti-coagulating agent to form a spasticity minimizing agent solution; and    soaking the harvested blood vessel in the spasticity minimizing agent solution for a period of time sufficient to reduce vasoconstriction in the graft induced by inotropic agents for up to at least 48 hours.    
     
     
         2 . The method of  claim 1 , wherein an amount of a patient's blood is added during the combining step.  
     
     
         3 . The method of  claim 2 , wherein a physiologic crystalloid buffer solution is added during the combining step.  
     
     
         4 . The method of  claim 3 , further comprising removing the harvested blood vessel from the spasticity minimizing agent solution and implanting the harvested blood vessel as an arterial graft into the patient.  
     
     
         5 . A method for the pretreatment of coronary artery grafts comprising: 
 harvesting an artery for use as an arterial graft;    forming a solution including a diluent and phenoxybenzamine;    combining the solution including phenoxybenzamine with an amount of a patient's blood, at least one vasodilator agent, and an anti-coagulating agent to form a phenoxybenzamine pretreatment solution;    soaking the harvested artery in the phenoxybenzamine pretreatment solution for a period of time sufficient to reduce vasoconstriction in the graft induced by inotropic agents for up to at least 48 hours; and    removing the harvested artery from the phenoxybenzamine pretreatment solution.    
     
     
         6 . The method of  claim 5 , wherein the diluent is selected from the group consisting of normal saline and related physiological solutions and buffer solutions.  
     
     
         7 . The method of  claim 5 , wherein the harvesting of the artery includes the artery and the surrounding pedicle of the artery.  
     
     
         8 . The method of  claim 7 , wherein the pedicle has been modified to increase exposure of the arterial graft to the phenoxybenzamine pretreatment solution.  
     
     
         9 . The method of  claim 8 , wherein the pedicle is modified by a fasciotomy.  
     
     
         10 . The method of  claim 5 , wherein the harvesting of the artery includes only the skeletonized portion of the artery.  
     
     
         11 . The method of  claim 5 , wherein the harvested artery is selected from the group consisting of internal mammary arteries, gastroepiploic arteries, inferior epigastric arteries, radial arteries and any other artery designated for a vascular conduit.  
     
     
         12 . The method of  claim 11 , wherein the harvested artery is a radial artery.  
     
     
         13 . The method of  claim 5 , wherein the concentration of phenoxybenzamine in the phenoxybenzamine pretreatment solution ranges from about 10 −6  M to about 10 −1  M.  
     
     
         14 . The method of  claim 5 , wherein the concentration of phenoxybenzamine in the phenoxybenzamine pretreatment solution ranges from about 10 −6  M to about 10 −1  M.  
     
     
         15 . The method of  claim 5 , wherein the time period in which the harvested artery is soaked in the phenoxybenzamine pretreatment solution ranges from about 5 to about 60 minutes.  
     
     
         16 . The method of  claim 5 , wherein the harvested artery and the phenoxybenzamine pretreatment solution are placed into an enclosure capable of being sealed and pressurized, the enclosure is then sealed, and the enclosure is then pressurized to a pressure of 0.01 to 100 mm Hg for a period of time to assist the penetration of the phenoxybenzamine pretreatment solution into the harvested artery.  
     
     
         17 . The method of  claim 16 , wherein the time period in which the harvested artery is soaked in the phenoxybenzamine pretreatment solution ranges from about 5 to about 60 minutes.  
     
     
         18 . The method of  claim 5 , wherein the soaking step additionally comprises an intralumenal injection of the phenoxybenzamine pretreatment solution into the harvested artery or a companion vein that may empty into the harvested artery.  
     
     
         19 . The method of  claim 18 , wherein the harvested artery, after the intralumenal injection of the phenoxybenzamine pretreatment solution into the harvested artery or companion vein that may empty into the harvested artery, is pressurized to a pressure of 0.01 to 100 mm Hg for a period of time to assist the penetration of the phenoxybenzamine pretreatment solution into the harvested artery.  
     
     
         20 . The method of  claim 19 , wherein the harvested artery, after the intralumenal injection of the phenoxybenzamine pretreatment solution into the harvested artery or companion vein that may empty into the harvested artery, is clamped or otherwise closed at least one end prior to being pressurized.  
     
     
         21 . The method of  claim 5 , further comprising removing the harvested artery from the phenoxybenzamine pretreatment solution.  
     
     
         22 . A method for the in-vivo pretreatment and implantation of an internal thoracic artery conduit in patients undergoing coronary bypass surgery comprising: 
 harvesting the internal thoracic artery for use as one end of the conduit;    soaking the one end of the harvested artery conduit in a phenoxybenzamine solution for a period of time; and    removing the one end of the harvested artery conduit from the phenoxybenzamine solution and implanting the harvested artery conduit as an arterial graft into the patient.    
     
     
         23 . A method of minimizing spasticity in a blood vessel graft comprising: 
 providing the blood vessel graft by clamping a free end of a patient's internal thoracic artery at one end;    infusing a solution including an alpha-adrenergic blocking agent into the clamped internal thoracic artery and soaking for a period of time;    flushing the solution containing the alpha-adrenergic blocking agent from the internal thoracic artery; and    attaching the free end of the internal thoracic artery to a blocked artery.    
     
     
         24 . The method of  claim 23 , wherein the alpha-adrenergic agent includes phenoxybenzamine.  
     
     
         25 . The method of  claim 24 , wherein the solution further includes a vasodilator and an anti-coagulating agent.  
     
     
         26 . The method of  claim 23 , wherein the period of time for soaking is between about 5 minutes and 60 minutes.  
     
     
         27 . The method of  claim 23 , wherein the soaking time is for a period of time sufficient to reduce vasoconstriction in the graft induced by inotropic agents for up to at least 48 hours.  
     
     
         28 . The method of  claim 23 , wherein the method is effective to reduce the incidence of angina and/or myocardial infarction in the patient.