Hypoperfusion-induced contractile failure does not require changes in cardiac energetics

Decreasing coronary perfusion causes an immediate decrease in contractile f unction via unknown mechanisms. It has long been suspected that this contra ctile dysfunction is caused by ischemia-induced changes in cardiac energeti cs. Our goal was to determine whether changes in cardiac energetics necessa rily precede the contractile dysfunction as one would expect if a causal re lationship exists. In 14 isolated rat hearts, we gradually decreased corona ry perfusion using a coronary perfusate with a normal hematocrit and normal concentrations of the major metabolic substrates. Using P-31 NMR spectrosc opy to measure ATP, phosphocreatine (PCr), P-i, and ADP concentrations ([AT P], [PCr], [P-i], [ADP]), pH, and amount of free energy released from ATP h ydrolysis (\Delta G(ATP)\), we found that none of these variables changed s ignificantly until several minutes after systolic pressure had significantl y decreased. Even when developed pressure had decreased by over one-third, only very slight changes in [P-i], pH, and \Delta G(ATP)\ had occurred, wit h no significant changes in [ATP], [PCr], or [ADP]. Additionally, the rate of high-energy phosphate transfer between ATP and PCr did not decrease enou gh during hypoperfusion to explain the contractile dysfunction. We conclude that nonenergetic factors are the dominant cause of the initial decrease i n systolic function when myocardial perfusion is decreased.