title: Pathophysiology and pathogenesis of stunned myocardium. Depressed Ca2+ activation of contraction as a consequence of reperfusion-induced cellular calcium overload in ferret hearts.
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.
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D009202:Cardiomyopathies / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D002335:Carnivora / Q000502:physiology*; D003331:Coronary Vessels / Q000503:physiopathology; D005289:Ferrets / Q000502:physiology*; D006352:Heart Ventricles / Q000503:physiopathology; D007511:Ischemia / Q000150:complications*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000473:pathology; D010477:Perfusion
chemical_list: D000255:Adenosine Triphosphate; D002118:Calcium