Pathophysiology and pathogenesis of contractile failure in stunned myocardium.
To investigate excitation-contraction coupling in stunned myocardium, intracellular free calcium concentration [( Ca2+]i) was measured before and after ischemia in perfused hearts using gated 19F NMR and the Ca2+ indicator 5F-BAPTA. Maximal Ca(2+)-activated force was also measured in parallel experiments. Stunned myocardium was created by reperfusion after 15 min global ischemia at 37 degrees C in isolated ferret hearts. In stunned myocardium, peak [Ca2+]i was paradoxically higher than that in control, but maximal Ca(2+)-activated pressure was lower in stunned hearts. These results indicate that contractile failure in stunned myocardium is due to a decrease in the myofilament sensitivity to Ca2+ as well as to a decrease in maximal Ca(2+)-activated force; failure of activator Ca2+ delivery cannot be implicated. The role of intracellular calcium overload in the pathogenesis of stunned myocardium was also investigated. Time-averaged 19F NMR measurements directly revealed the increase in [Ca2+]i during ischemia and in the early phase of reperfusion. The strategies to prevent Ca overload during reperfusion with modified reperfusate succeeded in preserving contractile function. Transient Ca overload without ischemia induced by different causes, i.e., high [Ca]0 perfusion, ventricular fibrillation or treatment with adriamycin, also produced contractile dysfunction that outlasted the interventions themselves. Thus, we propose that transient Ca overload during ischemia and early reperfusion initiates long-lasting contractile dysfunction in stunned myocardium.
First Department of Medicine, Osaka University Medical School, Japan.
H
H
Kusuoka
M
M
Kitakaze
Y
Y
Koretsune
M
M
Inoue
E
E
Marban
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003327:Coronary Disease / Q000503:physiopathology*; D005289:Ferrets; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D009200:Myocardial Contraction; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism
D010710:Phosphates; D002118:Calcium