Nucleotide degradation and functional impairment during cardioplegia: amelioration by inosine

The degradation of adenine nucleotide levels and impairment of functional recovery associated with exposure to hypothermic (20 degrees C) cardioplegia was studied in 84 isolated working rat hearts. After a 1-hour control period, hearts were exposed to 1 hour of cardioplegia that consisted of increasingly longer periods of cardioplegic solution (CPS) infusion (30 seconds and 10, 30 and 60 minutes), followed by increasingly shorter periods of global ischemia (591/2 minutes and 50, 30 and 0 minutes). Hearts were then reperfused for 1 hour with control perfusate, during which recovery of cardiac output was monitored. Additional hearts were freeze-clamped at various points in the protocols to determine adenine nucleotide levels (ATP, ADP, AMP and their sum TAN). Exposure to increasingly longer periods of CPS perfusion resulted in proportionally greater degradation of nucleotides and poorer recovery of cardiac output. Addition of inosine to the recovery perfusate as well as the CPS further improved nucleotide levels and recovery of cardiac output. These results suggest that washout of nucleotide degradation products in the CPS or reperfusion prevents their salvage for nucleotide resynthesis and impairs functional recovery from cardioplegia.