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Increased Myocardial Oxygen Consumption Reduces Cardiac Efficiency in Diabetic Mice

¹ Department of Medical Physiology, Institute of Medical Biology, Faculty of Medicine, University of Tromsø, Tromsø, Norway
² Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
³ Hatter Institute for Cardiology Research, Faculty of Medicine, Cape Town, South Africa

Address correspondence and reprint requests to Ole-Jakob How, Department of Medical Physiology, Institute of Medical Biology, Faculty of Medicine, University of Tromsø, N-9037 Norway. E-mail: ole-jakob.how{at}fagmed.uit.no

Key Words: KHB, Krebs-Henseleit buffer • MVO₂, myocardial oxygen consumption • PVA, pressure-volume area • STZ, streptozotocin

Altered cardiac metabolism and function (diabetic cardiomyopathy) has been observed in diabetes. We hypothesize that cardiac efficiency, the ratio of cardiac work (pressure-volume area [PVA]) and myocardial oxygen consumption (MVO₂), is reduced in diabetic hearts. Experiments used ex vivo working hearts from control db/+, db/db (type 2 diabetes), and db/+ mice given streptozotocin (STZ; type 1 diabetes). PVA and ventricular function were assessed with a 1.4-F pressure-volume catheter at low (0.3 mmol/l) and high (1.4 mmol/l) fatty acid concentrations with simultaneous measurements of MVO₂. Substrate oxidation and mitochondrial respiration were measured in separate experiments. Diabetic hearts showed decreased cardiac efficiency, revealed as an 86 and 57% increase in unloaded MVO₂ in db/db and STZ-administered hearts, respectively. The slope of the PVA-MVO₂ regression line was increased for db/db hearts after elevation of fatty acids, suggesting that contractile inefficiency could also contribute to the overall reduction in cardiac efficiency. The end-diastolic and end-systolic pressure-volume relationships in db/db hearts were shifted to the left with elevated end-diastolic pressure, suggesting left ventricular remodeling and/or myocardial stiffness. Thus, by means of pressure-volume technology, we have for the first time documented decreased cardiac efficiency in diabetic hearts caused by oxygen waste for noncontractile purposes.

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