Animal models of myocardial ischaemia.

Abstract

The objective of any satisfactory model of myocardial ischaemia in experimental animals must be to reproduce, as accurately as possible, the spectrum of ischaemic heart disease as seen in man. Since we are still, to a very considerable extent, ignorant of the pathophysiology of angina pectoris and of sudden death causally associated with coronary atherosclerosis and thrombosis, it is, in my view, impossible to construct valid models for these important clinical expressions of ischaemic heart disease. This brief review is, therefore, exclusively concerned with myocardial necrosis. In human disease, the various patterns ofischaemic myocardial necrosis (Davies, 1977) occur for the most part against the background of a coronary circulation widely compromised by stenosing atherosclerosis. In regional infarction arterial occlusion, either by thrombus or by a mixture of thrombus and atheromatous debris, is present in the majority of cases (Davies et al, 1976) and the occlusions are usually related to splits or tears in the connective tissue caps of atherosclerotic plaques. These pathogenetic factors should certainly be subsumed in any experimental model which attempts to mimic the human disease. At present, it must be admitted that we cannot economically devise models which meet these requirements. Nevertheless our attitude, though critical, need not be totally nihilistic. Although the models we have are inherently unsatisfactory, they can provide some useful information on a variety of matters such as mapping infarcts, metabolic and structural changes in underperfused regions of the myocardium and the effects of various forms of intervention on these changes.