O. Casis and E. Echevarria Pages 237 - 248 ( 12 )
Diabetic patients show a higher incidence of cardiac arrhythmias, including ventricular fibrillation and sudden death. However, although diabetic cardiomyopathy is a frequent and important complication of diabetes mellitus, its physiological basis is not completely known. The electrocardiogram of diabetic patients shows several alterations from normal patterns, most of them related to the QT interval and T wave. Recently, different alterations in cardiac ionic currents have been described in myocytes isolated from diabetic hearts, mainly a reduction in potassium repolarizing currents. Three different mechanisms could be involved in these alterations. First, direct metabolic alterations of the cardiac myocyte, such as impaired activity of protein kinases and phosphatases, intracellular pH regulation, intracellular calcium handling, and others. Second, impaired support of extra cardiac factors regulating cardiac activity, such as sympathetic regulation of heart rate and contractility. Thus, diabetic autonomic neuropathy leads to diminished noradrenaline release in cardiac ventricle in response to standing, exercise or cold stress. Besides, diabetic cardiomyopathy reduces cardiac myocyte response to acute noradrenaline exposure and finally, impairs support of different trophic factors responsible for the regulation of ionic channel expression. Thus, basal noradrenaline release in the ventricles, necessary to maintain adequate potassium channel expression, is reduced by sympathetic neuropathy. Moreover, the levels of insulin and other trophic factors required for the maintenance of adequate ionic channel expression are also altered in diabetic patients. Therefore, different physiopathological mechanisms are involved in diabetic cardiomyopathy. Thus, further research is needed in order to prevent the development of this long-term complication, and to improve the pharmacological management of diabetic patients.
diabetes, heart, contractility, ionic channels
Department of Physiology,School of Pharmacy, University of the Basque Country, P.O. Box 699,48080 Bilbao, Spain