In vivo models of myocardial metabolism during ischemia: application to drug discovery and evaluation

This review examines the in vivo techniques that are available for evaluation of the metabolic effects and efficacy of agents intended for the treatment of myocardial ischemia. Energy substrate metabolism is complex, and requires simultaneous measurement of a variety of processes in order to obtain a thorough understanding of the biochemical mechanisms underlying any functional response. Small animals (from the mouse to the rabbit) are generally not very useful in the study of cardiac metabolism in vivo because it is not possible to sample the coronary venous drainage and measure the rate of substrate uptake or metabolite efflux. Anesthetized open-chest swine or dog models allows simultaneous serial measurement of myocardial substrate use, and repeated tissue sampling for the activities and contents of key enzymes and metabolites. The swine model is particularly good because pigs, like humans, lack innate collateral vessels, thus one can induce regional myocardial ischemia in the left anterior descending coronary artery and sample the venous effluent from the anterior interventricular vein. In this review the biochemical and physiological methods that can be used in conjunction with this preparation are described.