An emerging need for developing new models for myocardial infarction as a chronic complex disease: lessons learnt from animal vs. human studies on cardioprotective effects of Erythropoietin in reperfused myocardium

Abstract

A large number of studies are currently focused on diagnosis, prevention, and treatment of complex disorders. Animal studies are generally utilized as basic models for in-vivo studies and support subsequent clinical trials. Although animal models have so far been fruitful in understanding the mechanism of several diseases and testing the likely prevention and treatment strategies; some of them do not appropriately mimic complex disorders. There is an emerging need for developing new models for chronic complex diseases. Simplifying a complex system is needed for studying the basis of a complex phenomenon (i.e., Gregor Johann Mendel studies on Pisum sativum to discover genetic inheritance roles); however, these models do not reflect all aspects of a complex system (i.e., epistasis or inter/intra-allelic gene suppression). When an animal model is used as the basis of a clinical trial, it is needed to mimic all complex features of the patients. Myocardial infarction (MI) as a leading cause of mortality and morbidity worldwide has been extensively studied in medicine. MI is an acute phenomenon; however usually it comes after a prolonged period of atherosclerosis which is accompanied by hypoperfusion, hypoxia, and probably degrees of heart failure. As a matter of fact acute MI is the final sequence of the atherosclerosis as a chronic process. Animal models of MI generally do not completely mimic MI process. Although atherosclerosis models are currently available (Fuster et al., 2012; Getz and Reardon, 2012), usually MI animal models are surgically mimicked by clumping-reperfusion process (Moon et al., 2003, 2006; Prunier et al., 2007; Doue et al., 2008; Roubille et al., 2013b). Here, as an example, I have tried to discuss the paradoxical positive results of animal studies on protective effects of Erythropoietin (EPO) administration in reperfused myocardium vs. negative consequences in clinical setting. It seems that the main fault has been occurred in MI modeling for EPO treatment at the level of animal experimental studies, and followed imprecisely without considering the nature of EPO as a cytokine which is naturally secreted in human, and the pathophysiologic state of EPO and EPO receptor in atherosclerotic patients. This article will emphasize on the need of developing new models for MI which mimic its complex character rather than criticizing studies on cardioprotective effects of EPO after percutaneous coronary intervention (PCI) in MI.