Excitation-contraction coupling in postischemic myocardium. Does failure of activator Ca2+ transients underlie stunning?
To elucidate the mechanism of contractile dysfunction in postischemic ("stunned") myocardium, time-resolved measurements of intracellular free Ca2+ concentration ([Ca2+]i) were made using gated 19F nuclear magnetic resonance in seven perfused ferret hearts loaded with the fluorinated Ca2+ indicator 5F-BAPTA. Left ventricular developed pressure decreased to 65 +/- 3% (mean +/- SEM) of control after 15 minutes of global ischemia at 37 degrees C. In stunned myocardium, diastolic [Ca2+]i (0.24 +/- 0.03 microM) was not changed from control (0.18 +/- 0.03 microM, p greater than 0.10), but peak [Ca2+]i (1.03 +/- 0.13 microM) was paradoxically higher than that in control (0.61 +/- 0.06 microM, p less than 0.02). The slope of the relation between developed pressure and Ca2+ transient amplitude in stunned myocardium was significantly lower than that in control (p less than 0.05), even after normalization by maximal Ca2(+)-activated pressure. These results indicate that contractile failure in stunned myocardium is due to a decrease in the myofilament sensitivity to Ca2+ as well as to the previously identified decrease in maximal Ca2(+)-activated force; failure of activator Ca2+ delivery cannot be implicated. The increase in the amplitude of Ca2+ transients would require that more ATP be spent in Ca2+ sequestration; thus, decreased efficiency of energy utilization in stunned myocardium would result.
Kusuoka
H
H
Division of Cardiology, Osaka University Medical School, Japan.
Koretsune
Y
Y
Chacko
V P
VP
Weisfeldt
M L
ML
Marban
E
E
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D003327:Coronary Disease / Q000503:physiopathology*; D005289:Ferrets; D006321:Heart / Q000503:physiopathology*; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D011312:Pressure
D002118:Calcium