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 < 0.001). Maximal Ca2+-activated pressure (MCAP), measured from tetani after exposure to ryanodine, was decreased after stunning (P < 0.05). Normalization of the DP-ICa]o relationship by corresponding MCAP (Cao sensitivity) revealed a shift to higher ICalb in stunned hearts. To test whether cellular Ca overload initiates stunning, we reperfused with low-[Cai6 solution (0.1-0.5 mM; n = 8). DP and MCAP in the low-[Cajo group were comparable to control (P > 0.05), and higher than in the stunned group (P < 0.05). Myocardial IATP] observed by phosphorus NMR 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.

No abstract