CORONARY ENDOTHELIAL DYSFUNCTION INCREASES THE SEVERITY OF ISCHEMIA-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 tec hnique, were subjected to treatment with the detergent Triton X100 and the responses of these hearts to a 30 or 60 min period of coronary ar tery occlusion was determined. Endothelial damage or denudation was sh own both by histological examination and by the altered vasodilator re sponse to the endothelium-dependent vasodilator bradykinin (100 nM), w hich was reversed to vasoconstriction in hearts treated with Triton X- 100. In contrast, the responses to sodium nitroprusside (100 mu M) wer e unimpaired in these hearts and were not different from control respo nses. 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 contro ls; 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). Ve ntricular ectopic activity was still marked when the occlusion was pro longed to 1 h and was still apparent at the end of this 1 h occlusion period. Reperfusion arrhythmias (ventricular tachycardia and ventricul ar fibrillation) were marked in endothelium-damaged hearts (50 %); whe reas there were no such arrhythmias after a 30 or 60 min occlusion per iod in control hearts. Hearts were also preconditioned by a 3 min coro nary artery occlusion period 10 min prior to a 30 min coronary artery occlusion. This reduced ventricular ectopic activity in both control a nd endothelium-damaged hearts to about the same extent (between 80 and 90 % suppression). The results suggest that under normal conditions s ubstances generated from endothelial cells protect the myocardium agai nst ventricular arrhythmias both during ischaemia and reperfusion. How ever, in this species, preconditioning is still possible in hearts fro m which the coronary vascular endothelium has been removed. If these r esults can be extrapolated to the clinical situation, it suggests that in patients with endothelial dysfunction ventricular arrhythmias may be more pronounced following a period of ischaemia and especially of r eperfusion.