NEW STRATEGY FOR PROLONGING THE PRESERVATION TIME OF HEARTS FOR TRANSPLANTATION

Our study concerned the findings that rat and rabbit heart transplants do not survive after six hours. They become dark, hard and fail to co ntract within 2 min after reperfusion and never regain their function. We tested the supplementation of solutions for heart transplant prese rvation with tetrahydrobiopterin (H4B) and L-arginine (L-ARG) to maint ain the oxidative and reductive domains of the endocardial NO synthase . We decided to study the excised rabbit hearts preserved in Hank's ba lanced salt solution (HBSS) at 0 degrees C supplemented with different concentrations of H4B (0, 1, 5, 10 or 100 mu M). At desired time inte rvals, successive pieces stored in the above solutions were warmed to rabbit body temperature in 4 ml of HBSS and maximally agonized by dire ct application of 20 mu l of 200 mu M bradykinin (or other agonist) on to the exposed endocardium. Nitric oxide bursts were monitored with a porphyrinic NO sensor lying on the exposed endocardium. Our goal was t o find the lowest H4B concentration which would maximally agonize NO. and prolong the time of heart preservation to more than 6 hours. Ten m u M are a minimum H4B concentration which achieves maximum prolongatio n of heart preservation time up to 90 hours. This effect was based upo n maximal potentiation of NO. release and minimizing of superoxide pro duction.