Abstract 3612: Myocardial Protection With a Novel Organ Preservation Solution Containing Deuterium Oxide for Prolonged Cold Ischemia of the Heart
Objective: Cold preservation of the heart using UW solution is limited to 4 – 6 hours. This is mainly due to ischemia and subsequent reperfusion injury that result in cardiomyocyte destruction by breaking-down or dysregulating the actin and ATP. We examined the effect of a new solution, Dsol containing deuterium oxide (D2O), which has properties to inhibit actin deploymerization and cytosolic Ca2+ overload, and to stimulate glycolysis.
Method: Lewis rat heart was immersed in either UW or Dsol at 4°C for 24 or 36 hours, and was transplanted to Lewis rat. Non-preserved hearts served as control. Graft survival, left ventricular (LV) function (examined by UCG), blood biochemistry and graft histology were assessed. H9c2 cardiomyocyte cells were subjected to 24-hour cold hypoxia in either solution, and the Ca2+-dependent protease, calpain activity was measured following 1-hour warm normoxia.
Results: After 24-hour ischemia, 7-day graft survival was 5/5 and 4/5, whereas, when cold ischemia was prolonged to 36 hrs, graft survival was 6/8 and 1/7 in Dsol and UW groups, respectively (Fig. 1⇓). LV function of the Dsol group was significantly preserved when compared to that of UW group (Fig. 2⇓). This was accompanied with reduced serum GOT (262 vs. 1144 IU/L) and LDH (526 vs. 1283 IU/L) levels at 24 hours after reperfusion. Dsol ameliorated LV necrosis (11.7 vs. 67.8%), cellular infiltrates, vacuolization and fibrosis of the cardiac grafts. Calpain activity of preserved H9c2 cells was significantly suppressed by the Dsol.
Conclusion: Supplementation of D2O suppresses calpain activity and myocardial injury, and improves cardiac function and survival of prolonged cold-preserved hearts.