In a previous study, we demonstrated a significant release of
adenosine,
inosine and
hypoxanthine during
hypoxia and subsequent reoxygenation. The present study was designed to determine whether or not exogenous
adenosine,
inosine and
hypoxanthine are beneficial for the recovery of
hypoxia-induced loss of cardiac contractile force. Hearts were perfused for 20 min under hypoxic conditions, followed by 45 min-perfusion under reoxygenated conditions, and changes in contractile force, resting tension and metabolic parameters of the perfused heart were examined. When either
adenosine,
inosine or
hypoxanthine were exogenously infused during
hypoxia at the rate of 3 mumol/min, remarkable recovery (61 to 68%) of cardiac contractile force was observed upon reoxygenation. The recovery was accompanied by a significant restoration of myocardial
ATP (90 to 100%) and CP contents (80 to 86%), suggesting that exogenous metabolites are utilized for the restoration of myocardial
ATP during reoxygenation, which may lead to a beneficial recovery of
hypoxia-induced loss of cardiac contractile force upon reoxygenation. Infusion of exogenous metabolites also resulted in an almost complete inhibition of
hypoxia- and reoxygenation-induced release of
creatine phosphokinase from the perfused heart as well as a significant depression of
hypoxia-induced
calcium accumulation in the cardiac tissue. Since these phenomena are considered to represent increases in cell membrane permeability, protection of the myocardium against
hypoxia- and reoxygenation-induced changes in cell membrane permeability may be an alternative mechanism for the beneficial effect of
adenosine,
inosine and
hypoxanthine on the hypoxic myocardium.