Ex Vivo and In Vivo Approaches to Study Mechanisms of Cardioprotection Targeting Ischemia/Reperfusion (I/R) Injury: Useful Techniques for Cardiovascular Drug Discovery

摘要

The last few decades have seen significant advancement in the therapy of Ischemic Heart Diseases (IHD). This is a direct outcome of the increasing knowledge of the molecular mechanisms involved during an ischemic insult of the myocardium. Even then there is still a major unmet need for better strategies or drug therapies to reduce ventricular remodeling and improve post-ischemic myocardial function. The ex-vivo isolated working heart model and the in vivo myocardial infarction model are the best known techniques to elucidate the contribution of a drug therapy to confer cardioprotection in the event of an ischemic insult/reperfusion. Our review aims to provide an insight into the state of the art techniques that lay the foundations for cardiovascular drug discovery and present the prospects for further development from a preclinical perspective. The first section of the review provides an overview of the rat/mouse ex-vivo and in vivo models of myocardial ischemia. The following section will then present various applications of these clinically relevant models in characterizing cardiac functions, screening for drugs and identifying the drug induced changes in cardiac functions. Finally the role of these models in drug development is discussed with respect to functional relevance of drug treatment on heart rate, aortic flow, coronary flow, infarct size and the mechanisms by which these drugs promote myocardial protection. This review may serve as a basic knowledge for researchers who intend to study the efficacy of a drug in the treatment of ischemic heart diseases.