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

Objective: We investigated whether an increased oxygen cost of contractilit y and/or a decreased myofibrillar efficiency contribute to oxygen wastage o f stunned myocardium. Because Ca2+-sensitizers may increase myofibrillar Ca 2+-sensitivity without increasing cross-bridge cycling, we also investigate d whether EMD 60263 restores myofibrillar efficiency and/or the oxygen cost of contractility. Methods: Regional fiber stress and strain were calculate d from mesomyocardially implanted ultrasound crystals and left ventricular pressure in anesthetized pigs (n=18). Regional myocardial oxygen consumptio n (MVO2) was measured before contractility tend-systolic elastance, E-es) a nd total myofibrillar work (stress-strain area, SSA) were determined from s tress-strain relationships. Atrial pacing at three heart rates and two dose s of dobutamine were used to vary SSA and E-es, respectively. After stunnin g (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 = alpha .SSAbeta .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 MVO2, while increa sing alpha by 71% and beta by 134%. without affecting gamma. From the waste d oxygen. 72% was used for myofibrillar work and 18% for excitation-contrac tion coupling. EMD 60263 restored both alpha and beta. Conclusions: Oxygen wastage in stunning is predominantly caused by a decreased myofibrillar eff iciency 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. (C) 2001 Elsevier Science B.V . All rights reserved.