In vivo models of myocardial ischemia and reperfusion injury - Applicationto drug discovery and evaluation

This review discusses the pharmacology of regional myocardial ischemia and reperfusion (I/R) injury and the utilization of in vivo animal models in th e preclinical development of novel therapeutic compounds. The manuscript ai ms to provide an overview of a number of different cardioprotective strateg ies that have been successful from a preclinical perspective and to also pr esent where possible results of clinical trials of the respective compounds . Myocardial ischemia reperfusion injury may be manifested as myocardial st unning, ventricular arrhythmias, coronary vascular dysfunction, or the deve lopment of a myocardial infarct. This review is principally concerned with preclinical studies related to reduction of infarct size. The pathophysiolo gy of the reperfusion injury process is complex, including primarily cellul ar and humoral components of inflammation, as well as myocellular ionic and metabolic disturbances. This review will discuss strategies directed at ox ygen-derived free radicals, neutrophils, adenosine, and the sodium-hydrogen exchanger (NHE). The results of preclinical cardioprotective studies are i nfluenced by the paradigm used therefore methodological considerations will also be presented where appropriate. (C) 2000 Elsevier Science Inc. All ri ghts reserved.