Failure of erythropoietin to render jeopardized ischemic myocardium amenable to incremental salvage by early reperfusion.
OBJECTIVE
Erythropoietin (EPO) has been thought to be capable of potentiating protection of jeopardized myocardium by reperfusion in evolving myocardial infarction. However, diversity in study design and measurements of infarct size in studies evaluating EPO has led to inconsistent results. We sought to characterize the effect of EPO on infarct size after myocardial ischemia and reperfusion with the use of assessment of left-ventricular (LV) creatine kinase (CK) depletion and echocardiography.


METHODS
Acute coronary occlusion was induced in 10-week-old C57BL6 mice by left anterior descending coronary artery ligation for 3 h followed by 72 h of reperfusion. EPO (10,000 U/kg) or an equivalent amount of saline vehicle alone was injected intraperitoneally before ligation or immediately after the onset of reperfusion. Assays of residual LV CK activity and calculation of LV CK depletion were performed on LV homogenates harvested 72 h after onset of reperfusion for measurement of infarct size, and echocardiography was performed immediately before harvest of tissue for measurement of function.


RESULTS
Mice administered EPO before ligation had similar infarct size (37.1+/-4.1%) and echo scores (22.9+/-0.4) compared with those in corresponding control mice administered saline (35.29+/-1.9 and 21.3+/-1.1%, respectively). Mice administered EPO after reperfusion had similar infarct size (39.1+/-4.8%) and echo scores (19.5+/-1.0) compared with those in corresponding control mice administered saline (40.3+/-4.9 and 21.5+/-1.9%, respectively).


CONCLUSIONS
EPO does not protect ischemic myocardium such that reperfusion after 3 h can yield additional salvage.
Department of Medicine, Cardiovascular Research Institute, University of Vermont, Burlington, Vermont 05446, USA.
Christopher J
CJ
French
A K M Tarikuz
AK
Zaman
Burton E
BE
Sobel
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003402:Creatine Kinase / Q000378:metabolism; D004195:Disease Models, Animal; D015150:Echocardiography, Doppler; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology*; D011994:Recombinant Proteins; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects
D015415:Biomarkers; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa; D003402:Creatine Kinase