ADENOSINE-DEAMINASE INHIBITORS ATTENUATE ISCHEMIC-INJURY AND PRESERVEENERGY-BALANCE IN ISOLATED GUINEA-PIG HEART

We investigated the effect of the adenosine deaminase inhibitors eryth ro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and coformycin on high-energy p hosphate metabolism, tissue nucleotides and nucleosides, and recovery of contractile function in isolated, perfused guinea pig hearts. EHNA and coformycin (10 muM) improved postischemic recovery of contractile function approximately 85% and enhanced coronary flow rate in reperfus ed tissue approximately 40%. The protective effect of EHNA on recovery of contractile function was concentration dependent. Although adenosi ne (10 muM) increased coronary flow rate on reperfusion approximately twofold over vehicle, it failed to improve post-ischemic recovery of c ontractile function. EHNA and coformycin preserved cardiac ATP levels and increased endogenous tissue adenosine during ischemia. During repe rfusion, these agents enhanced recovery of high-energy phosphates appr oximately twofold and potentiated adenosine release into the perfusate with concentration dependency. Furthermore, EHNA and coformycin reduc ed the extent of myocardial ischemia-reperfusion injury, as indicated by the approximately 55% reduction in creatine phosphokinase release. We conclude that inhibitors of adenosine deaminase attenuate myocardia l ischemic injury and improve postischemic recovery of contractile fun ction and metabolism through endogenous myocardial adenosine enhanceme nt and ATP preservation.