Myocardial Infarction: Cardioprotection by Erythropoietin

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