Inosine preserves ATP during ischemia and enhances recovery during reperfusion

The effects of exogenous inosine (IN) on high-energy phosphate metabolism and function in isolated, working rabbit hearts were monitored with 31P-nuclear magnetic resonance spectroscopy. Dynamic measurements of ATP and phosphocreatine (PCr) were made along with concomitant functional recordings during normal perfusion, global ischemia (IS), and reperfusion (RE). We found that 0.1 mM IN enhanced the rate of pressure development (dP/dt) within the left ventricle by 10 +/- 5% (n = 7). Although IN levels in treated hearts were elevated during normal perfusion, no effect was observed on ATP or PCr levels. However during IS, pretreatment with IN minimized ATP loss for the first 20 min relative to untreated controls (UNT, P less than 0.05). Both IN and UNT hearts that were ischemic for only 13.5 min regained function during a 60-min RE period. However, at the end of IS, IN hearts (n = 8) displayed 88 +/- 10% of the pre-IS ATP levels, whereas UNT hearts (n = 7) retained only 60 +/- 10%. With RE, ATP in IN hearts remained elevated over that of UNT hearts for the entire 60 min. IN treatment also increased the rate of recovery of dP/dt and maintained improved function over 60 min of RE. No correlation was found between post-IS ATP levels and dP/dt values during RE in either IN or UNT hearts. These data indicate that IN was protective against ATP loss during IS and improved functional recovery on RE.