Pathophysiology and pathogenesis of stunned myocardium. Depressed Ca2+ activation of contraction as a consequence of reperfusion-induced cellular calcium overload in ferret hearts.

H Kusuoka; J K Porterfield; H F Weisman; M L Weisfeldt; E Marban

doi:10.1172/JCI112906

Pathophysiology and pathogenesis of stunned myocardium. Depressed Ca2+ activation of contraction as a consequence of reperfusion-induced cellular calcium overload in ferret hearts.

H Kusuoka, J K Porterfield, H F Weisman, M L Weisfeldt, and E Marban

Published March 1, 1987 - More info

View PDF

Abstract

Contractile dysfunction in stunned myocardium could result from a decrease in the intracellular free [Ca2+] 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 [Ca]0 (0.5-7.5 mM) in isovolumic Langendorff-perfused ferret hearts at 37 degrees C after 15 min of global ischemia (stunned group, n = 13) or in a nonischemic control group (n = 6). At all [Ca]0, DP was depressed in the stunned group (P less than 0.001). Maximal Ca2+-activated pressure (MCAP), measured from tetani after exposure to ryanodine, was decreased after stunning (P less than 0.05). Normalization of the DP-[Ca]0 relationship by corresponding MCAP (Ca0 sensitivity) revealed a shift to higher [Ca]0 in stunned hearts. To test whether cellular Ca overload initiates stunning, we reperfused with low-[Ca]0 solution (0.1-0.5 mM; n = 8). DP and MCAP in the low-[Ca]0 group were comparable to control (P greater than 0.05), and higher than in the stunned group (P less than 0.05). Myocardial [ATP] 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 Ca0 sensitivity (which may reflect either decreased myofilament Ca2+ sensitivity or a decrease in the [Ca2+] transient). Our results also indicate that calcium entry upon reperfusion plays a major role in the pathogenesis of myocardial stunning.

Images.