Characterisation, utilisation and clinical relevance of isolated perfused heart models of ischaemia-induced ventricular fibrillation

Abstract

The isolated perfused heart has been used increasingly during the last decade as a model for identifying actions of drugs on ventricular fibrillation (VF) induced by myocardial ischaemia. In addition, it has been used to explore the mechanisms responsible for the initiation and maintenance of VF, the concept of endogenous myocardial protection and the phenomenon of preconditioning. This article is a review of the available data (effects of drugs, sources of variation, comparison with other models and man, etc.) and an attempt to evaluate the possible clinical relevance. For several reasons, it is not possible to make a precise judgement on the absolute value of the model in terms of its ability to accurately predict the effectiveness of drugs in the prevention of sudden cardiac death, the main reason being the lack of a positive control, i.e. a drug with proven effectiveness against sudden cardiac death caused by VF in man. Nevertheless, the means by which one may reliably and reproducibly generate ischaemia-induced VF in different isolated heart preparations, and the factors (such as species, heart rate, perfusion constituents and involved zone size) that determine the incidence of VF are now well documented. Careful selection of species and experimental conditions permits the isolated heart of smaller inexpensive animals to function as a first line model for detecting anti-VF activity of probable relevance to phase 1 arrhythmogenesis (i.e., arrhythmogenesis during the first 30 min of ischaemia). In view of the absence of a clinical template from which to evaluate how well it predicts drug effectiveness in man, this model's clinical relevance, like that of all other preparations and models, can yet be neither accepted nor dismissed. Recent publication patterns suggest an increasing use of the model. Therefore, recommendations are made to facilitate its effective use.