Coronary endothelial dysfunction increases the severity of ischaemia-induced ventricular arrhythmias in rat isolated perfused hearts

In order to determine the role of coronary vascular endothelial cells in generating cardioprotective substances during myocardial ischaemia, rat isolated hearts, perfused at constant flow by the Langendorff technique, were subjected to treatment with the detergent Triton X100 and the responses of these hearts to a 30 or 60 min period of coronary artery occlusion was determined. Endothelial damage or denudation was shown both by histological examination and by the altered vasodilator response to the endothelium-dependent vasodilator bradykinin (100 nM), which was reversed to vasoconstriction in hearts treated with Triton X100. In contrast, the responses to sodium nitroprusside (100 μM) were unimpaired in these hearts and were not different from control responses. Ventricular ectopic activity was much more pronounced in hearts with endothelial dysfunction (e.g., 3329±361 ventricular premature beats over a 30 min occlusion period compared to 243±34 in controls; P<0.01), and the duration of ventricular tachycardia was greatly increased (1162±391 s v 9±12 s in the controls; P<0.01). Ventricular ectopic activity was still marked when the occlusion was prolonged to 1 h and was still apparent at the end of this 1 h occlusion period. Reperfusion arrhythmias (ventricular tachycardia and ventricular fibrillation) were marked in endothelium-damaged hearts (50%); whereas there were no such arrhythmias after a 30 or 60 min occlusion period in control hearts. Hearts were also preconditioned by a 3 min coronary artery occlusion period 10 min prior to a 30 min coronary artery occlusion. This reduced ventricular ectopic activity in both control and endothelium-damaged hearts to about the same extent (between 80 and 90% suppression).