Abstract
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 (MVo(2)), 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 MVo(2). 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 MVo(2) in db/db and STZ-administered hearts, respectively. The slope of the PVA-MVo(2) 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.
Highlights
Altered cardiac metabolism and function has been observed in diabetes
Measurements of MVO2 and pressure-volume area (PVA) over a wide range of workloads are essential for a proper evaluation of cardiac efficiency
Reduced cardiac efficiency may be caused by an increase in unloaded MVO2, reflecting the oxygen cost of excitation-contraction coupling and/or basal metabolism
Summary
Characteristics of type 1 and type 2 diabetic mice. In accordance with previous results [9], db/db mice showed severe obesity and significantly elevated plasma concentrations of fatty acids and glucose, compared with nondiabetic controls (Table 1). The oxidation of fatty acids and glucose in hearts from STZ-administered mice was not different from control rates when perfused with low fatty acid supply (Fig. 2). The y-intercept (unloaded MVO2) was significantly higher in both db/db and STZ-administered hearts compared with control hearts, indicating reduced cardiac efficiency in unloaded type 1 and type 2 diabetic hearts. In all groups cardiac function was unaffected by the elevation of fatty acids in the perfusate, except for a minor reduction in contractility in db/db hearts, shown by the small reduction in Emax
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