Influence of the diabetic state on digitalis-induced cardiac arrhythmias in rat

The present study was undertaken to determine the effect of diabetes on the manifestation of digitalis cardiotoxicity in whole animal model. Animals after 4, 8, 12 and 16 weeks of streptozotocin treatment (60 mg/kg i.v.) were anesthetized (45 mg/kg alpha-chloralose and 500 mg/kg urethane), chest opened and instrumented for the recording of EKG, carotid pressure, left ventricular pressure and dp/dt. Ouabain was infused at a fixed rate (0.4 mg/kg/min) via the femoral vein. Animals at all stages of diabetes had sinus bradycardia, but the basal mechanical function was found to be depressed only after 12 weeks of streptozotocin treatment. After 16 weeks of streptozotocin injection, 40% of the animals showed some spontaneous arrhythmic activity, which lasted only a few seconds, and prolonged QTc (QT interval corrected for heart rate). In response to ouabain infusion, diabetic animals showed less maximal inotropic effect (30-40% reduction from the weight-matched control rats) and required at least 3-fold more ouabain for the initiation of cardiac arrhythmias than the nondiabetic rats (24.031 +/- 1.52 mg/kg vs 8.05 +/- 1.3 mg/kg). The reduced sensitivity to ouabain could not be explained by the presence of bradycardia. Response to a toxic dose of ouabain was restored to the nondiabetic state on treatment with insulin. These observations suggest that the diseased diabetic myocardium shows diminished sensitivity to digitalis toxicity.