Pyruvate-enhancement of post-ischemic cardiac function is not mediated by cyclic AMP

This study tested the hypothesis lhat pymvate-enhancement of post-ischemic cardiac function, like that of catecholamines, is mediated by cyclic AMP (cAMP). Isolated working guinea-pig hearts, perfused with 10 mM glucose-fortified Krebs-Henseleit, were subjected to 45 min low flow (20% of baseline) ischemia, then repcrfused for 35 min to produce reversible dysfunction (stunning). Four groups of 6 hearts were studied: 100 min nonischemic time control (TC); reperfusion without intervention (REP), or treatment with 50 nM isoproterenol OSO) or 5 mM pyruvate (PYR) at 15-35 min reperfusion. cAMP was measured in frozen myocardium by radio-immunoassay. Figure: Cardiac function (left ventricular stroke work, mj/g wet; filled bars) and cAMP content (nmol/g dry; open bars) were measured at 35 min reperfusion (P < 0.05 vs. TC. t: P < 0.05 vs. REP). In REP. cardiac function was scvcrclv imoaired. but cAMP was unchanged. As expected, ISO stimulated function and increased cAMP content. PYR also restored function to TC lclel, but did not increase cAMP content. Conclusions: Cardiac stunning is not acompanied by decreased cAMP content. PYR enhancement of post-ischemic ventricular performance is independent of cAMP. (NIH support: HL 50441).