Susceptibility of Diabetic Heart to Catecholamine-induced Arrhythmias is Independent of Contractile Dysfunction

Abstract

Background: Diabetes is associated with myocardial electrical instability and prolongation of action potential duration that result in disturbances in the rhythm of the heart. Objective: Th is study was undertaken to examine the role of circulating catecholamines in abnormal cardiac rhythm and contractility during diff erent stages of diabetes. Methods: Diabetes was induced in male Sprague-Dawley rats with streptozotocin (STZ; 65 mg/kg, i.v.). Epinephrine (4-128 μg/kg, i.v.) -induced arrhythmias and plasma levels of epinephrine (Epi) and norepinephrine (NE) were determined in control, 4- and 8-wk diabetic animals. Echocardiography was used to assess cardiac remodeling and contractile function. Results: Although diabetes induced cardiac dysfunction, there were no significant differences in cardiac output, ejection fraction, left ventricle (LV) dimensions, LV fractional shortening between the 4- and 8-wk diabetic animals. Th e electrocardiogram of both diabetic groups showed deep S wave as well as changes in T wave and ST segment. In addition, prolongation of the RR interval in the 4- and 8-wk diabetic animals was seen, while prolongation of the QT and PR intervals were only seen in the 8-wk diabetic animals. Th e severity of Epi-induced ventricular arrhythmias, as assessed by arrhythmia score, was significantly lower in the 8-wk diabetic rats, as compared to the 4-wk diabetic animals. Circulating Epi levels were significantly decreased in the 8-wk diabetic rats, whereas NE levels were increased in the 4-wk diabetic rats. Conclusions: Th e sensitivity of the diabetic heart to catecholamine- triggered arrhythmias may be dependent on circulating Epi rather than NE and thus it can be proposed that the increased incidence of sudden cardiac death in diabetics may not be associated with response to catecholamines.