Myocardial infarction: cardioprotection by erythropoietin

Abstract

Extensive research during the last decade demonstrated that a single systemic administration of -erythropoietin (EPO) lead to significant attenuation of myocardial infarction (MI) induced in animals, mostly small rodents, either by a myocardial ischemia followed by reperfusion or by a permanent ligation of a coronary artery. Both methods are critically reviewed with the aim of helping the reader in appreciating key issues in the translation of experimental results to the clinic. Results of several clinical trials in patients with acute MI completed to date failed to demonstrate beneficial effects of EPO, and thus put into question the validity of results obtained in animal models. Comprehensive review of design and results of animal experiments and clinical trials presented here allowed authors to postulate that therapeutic window for EPO during developing MI is very narrow and was possibly missed in negative clinical trials. This point was illustrated by the negative outcome of experiment in the rat model of MI in which timing of EPO administration was similar to that in clinical trials. The design of future clinical trials should allow for a narrow therapeutic window of EPO. Given current standards for onset-to-door and door-to-balloon time the optimal time for EPO administration should be just prior to PCI.

Fig. 1

Area of myocardium at risk (AAR) and size of myocardial infarction (MI) 24 h after permanent occlusion of the left descending coronary artery or after 2 h of occlusion followed by 22 h of reperfusion. rhEPO is administered at the time of reperfusion (IR-EPO-0 h) or 4 h after beginning of reperfusion (IR-EPO-4 h) or 6 h after permanent coronary occlusion (MI-EFO-6 h). Data presented as means± SEMI. AAR is presented as percent of left ventricle (LV). MI is presented as percent of AAR or percent of LV *p < 0.05 vs. all other group (Bonferroni post hoc comparison)