Oxygen wastage of stunned myocardium in vivo is due to an increased oxygen cost of contractility and a decreased myofibrillar efficiency

OBJECTIVE: We investigated whether an increased oxygen cost of contractility and/or a decreased myofibrillar efficiency contribute to oxygen wastage of stunned myocardium. Because Ca(2+)-sensitizers may increase myofibrillar Ca(2+)-sensitivity without increasing cross-bridge cycling, we also investigated whether EMD 60263 restores myofibrillar efficiency and/or the oxygen cost of contractility. METHODS: Regional fiber stress and strain were calculated from mesomyocardially implanted ultrasound crystals and left ventricular pressure in anesthetized pigs (n=18). Regional myocardial oxygen consumption (MVO(2)) was measured before contractility (end-systolic elastance, E(es)) and total myofibrillar work (stress-strain area, SSA) were determined from stress-strain relationships. Atrial pacing at three heart rates and two doses of dobutamine were used to vary SSA and E(es), respectively. After stunning (two times 10-min ischemia followed by 30-min reperfusion), measurements were repeated following infusion of saline (n=8) or EMD 60263 (1.5 mg.kg(-1) i.v., n=10). Linear regression was performed using: MVO(2)=alpha.SSA+beta.E(es)+gamma.HR(-1) (alpha(-1), myofibrillar efficiency; beta, oxygen cost of contractility; and gamma, basal metabolism/min). RESULTS: Stunning decreased SSA by 57% and E(es) by 64%, without affecting MVO(2), while increasing alpha by 71% and beta by 134%, without affecting gamma. From the wasted oxygen, 72% was used for myofibrillar work and 18% for excitation-contraction coupling. EMD 60263 restored both alpha and beta. CONCLUSIONS: Oxygen wastage in stunning is predominantly caused by a decreased myofibrillar efficiency and to a lesser extent by an increased oxygen cost of contractility. Considering that EMD 60263 reversed both causes of oxygen wastage, it is most likely that this drug increases myofibrillar Ca(2+)-sensitivity without increasing myofibrillar cross-bridge cycling.