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 Ca2+-sensitizers may increase myofibrillar Ca2+-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 (MVO2) was measured before contractility (end-systolic elastance, Ees) 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 Ees, 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: MVO2=α·SSA+β·Ees +γ·HR-1 (α-1, myofibrillar efficiency; β, oxygen cost of contractility; and γ, basal metabolism/min). Results: Stunning decreased SSA by 57% and Ees by 64%, without affecting MVO2, while increasing α by 71% and β by 134%, without affecting γ. From the wasted oxygen, 72% was used for myofibrillar work and 18% for excitation-contraction coupling. EMD 60263 restored both α and β. 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 Ca2+-sensitivity without increasing myofibrillar cross-bridge cycling.

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