13th International Congress
THE "NEW FRONTIERS"
OF ARRHYTHMIAS 1998

January 24-31, 1998
Marilleva, Trento, Italy

RT-133

Role of thrombus formation in arrhythmogenesis during acute ischaemia

Michiel J. Janse, Ruben Coronel, Francien J.G. Wilms-Schopman.
Department of Clinical and Experimental Cardiology, Academic Medical Center, University of Amsterdam, Interuniversity Cardiology Institute, The Netherlands (ICIN), Utrecht, The Netherlands

Introduction

The electrophysiological changes which occur during acute ischaemia and which result in lethal ventricular arrhythmias have been elucidated in studies on experimental animal models. Apart from species differences, these models vary considerably with respect to the methods used to produced ischaemia: sudden ligation of a coronary artery with or without simultaneously ligating collateral vessels, intracoronary balloon inflation, partial occlusion of a coronary artery preceding total occlusion, and coronary occlusion by the creation of a thrombus¹. The incidence of ischaemia-induced arrhythmias is dependent on many factors, such as the size of the ischaemic area, the degree of collateral flow, heart rate, activity of the autonomic nervous system, presence of a previous infarct, hypertrophy¹. Relatively little attention has been given to the question whether thrombus formation in itself could be an additional arrhythmogenic factor. In a recent paper, intracoronary thrombosis was reported to cause a greater incidence of ventricular fibrillation than ischaemia produced by intracoronary balloon inflation, despite a similar size of the ischaemic area². It was suggested that intracoronary thrombosis exerts arrhythmogenic effects above those of the arrest of coronary flow. One of the mechanisms involved could be that thrombin leads to release of lysophosphatidyl choline from endothelial cells, which causes electrophysiological alterations in distal ischaemic myocytes². One of the difficulties in interpreting the results of this study is that the onset of ischaemia during thrombotic occlusion was ill-defined because total occlusion of the artery was preceded by a period of gradually decreasing flow. Also, no electrophysiologic measurements were made. We therefore wanted to document the arrhythmogenic effect of thrombotic occlusion without preceding low flow ischaemia. In addition, we recorded local direct-current electrograms from 78 epicardial sites to determine activation patterns and the degree of ST-segment elevation in open-chested anaesthetised pigs during coronary ligation and during acute thrombotic occlusion. The details of this study are published elsewhere³. The pig was chosen because of the virtual absence of collateral vessels in this species. Thrombotic occlusion was produced by cannulating the left anterior descending coronary artery and by injecting a fresh thrombus into the artery. In addition to a single, prolonged period of ischaemia we also studied the effects of preconditioning by first clamping the coronary artery for two periods of 10 minutes, followed by 20 minutes of reperfusion. The third period of (prolonged) ischaemia was produced either by clamping the artery or by injection of a thrombus.