Article

Increased myocardial oxygen consumption reduces cardiac efficiency in diabetic mice.

Department of Medical Physiology, Institute of Medical Biology, Faculty of Medicine, University of Tromsø, Norway.
Diabetes (impact factor: 8.29). 03/2006; 55(2):466-73. pp.466-73
Source: PubMed

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.

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Keywords

1.4-F pressure-volume catheter
 
Altered cardiac metabolism
 
cardiac work
 
contractile inefficiency
 
control db/+
 
db/db hearts
 
diabetic hearts
 
end-systolic pressure-volume relationships
 
ex vivo
 
fatty acids
 
first time documented
 
myocardial oxygen consumption
 
myocardial stiffness
 
oxygen waste
 
pressure-volume area [PVA]
 
STZ-administered hearts
 
Substrate oxidation
 
type 1 diabetes
 
type 2 diabetes
 
ventricular function