Depressed Ca2+ Activation of Contraction as a Consequence of Reperfusion-induced Cellular Calcium Overload in Ferret Hearts

Contractile dysfunction in stunned myocardium could result from a decrease in the intracellular free [Ca2+1 transient during each beat, a decrease in maximal Ca2+-activated force, or a shift in myofilament Ca2+ sensitivity. We measured developed pressure (DP) at several [Cal6 (0.5-7.5 mM) in isovolumic Langendoriperfused ferret hearts at 370C after 15 min of global ischemia (stunned group, n = 13) or in a nomnschemic control group (a = 6). At all ICal6, DP was depressed in the stunned group (P 0.05), and higher than in the stunned group (P < 0.05). Myocardial IATP] observed by phosphorusNMR failed to correlate with functional recovery. In conclusion, contractile dysfunction in stunned myocardium is due to a decline in maximal force, and a shift in Cao sensitivity (which may reflect either decreased myofilament Ca2+ sensitivity or a decrease in the [Ca2+j transient). Our results also indicate that calcium entry upon reperfusion plays a major role in the pathogenesis of myocardial stunning.