title: Mechanisms underlying the impaired contractility of diabetic cardiomyopathy.
abstract: Cardiac dysfunction is a well-known consequence of diabetes, with sustained hyperglycaemia leading to the development of a cardiomyopathy that is independent of cardiovascular disease or hypertension. Animal models of diabetes are commonly used to study the pathophysiology of diabetic cardiomyopathy, with the hope that increased knowledge will lead ultimately to better therapeutic strategies being developed. At physiological temperature, left ventricular trabeculae isolated from the streptozotocin rat model of type 1 diabetes showed decreased stress and prolonged relaxation, but with no evidence that decreased contractility was a result of altered myocardial Ca(2+) handling. Although sarcoplasmic reticulum (SR) Ca(2+) reuptake appeared slower in diabetic trabeculae, it was offset by an increase in action-potential duration, thereby maintaining SR Ca(2+) content and favouring increased contraction force. Frequency analysis of t-tubule distribution by confocal imaging of ventricular tissue labeled with wheat germ agglutinin or ryanodine receptor antibodies showed a reduced T-power for diabetic tissue, but the differences were minor in comparison to other models of heart failure. The contractile dysfunction appeared to be the result of disrupted F-actin in conjunction with the increased type I collagen, with decreased myofilament Ca(2+) sensitivity contributing to the slowed relaxation.
authors: Marie-Louise Ward, David J Crossman, Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand.
authors: Marie-Louise
authors: ML
authors: Ward
authors: Marie-Louise Ward, David J Crossman, Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand.
authors: David J
authors: DJ
authors: Crossman
keywords: Calcium homeostasis; Contractility; Diabetic cardiomyopathy; Excitation-contraction coupling; Heart failure; T-tubules