Increased myocardial oxygen consumption reduces cardiac efficiency in diabetic mice.
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.
How
Ole-Jakob
OJ
Department of Medical Physiology, Institute of Medical Biology, Faculty of Medicine, University of Tromsø, Norway. ole-jakob.how@fagmed.uit.no
Aasum
Ellen
E
Severson
David L
DL
Chan
W Y Anna
WY
Essop
M Faadiel
MF
Larsen
Terje S
TS
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology; D006321:Heart / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008929:Mitochondria, Heart / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology*; D016276:Ventricular Function / Q000502:physiology