Erythropoietin Is Equally Effective as Blood Transfusion at Reducing Infarct Size in Anemic Rats.

In acute myocardial infarction (MI), anemia may exacerbate ischemia, increasing tissue injury. Red blood cell (RBC) transfusion is currently the only therapeutic intervention to acutely correct anemia. Erythropoietin (EPO) has previously been shown to be cardioprotective, independent of its erythropoietic effects, during ischemic injury in non-anemic hosts. The goal of this study was to measure the cardioprotective effect of EPO compared to that of RBC transfusion in anemic rats after acute MI.

MI was induced by ligation of left descending coronary artery in 62 male Sprague-Dawley rats, 47 of which were anemic (Hb 80-90 g/L), and 15 with normal Hb levels (140-150 g/L). To compare the effects of EPO treatment and RBC transfusion (stored <4 hours in CPDA-1), animals were randomized and either treated with EPO (2,000 U/kg), transfused with RBC to a Hb level of 100 g/L, or received control treatment with saline instead of EPO, or pentastarch (PS) instead of transfusion, immediately following MI. Anemic and normal Hb animals were randomized into 6 treatment groups: 1. Normal Hb, saline treatment; 2. Normal Hb, EPO treatment; 3. Anemic, saline treatment; 4. Anemic, EPO treatment; 5. Anemic, PS infusion; 6. Anemic, transfusion to Hb 100 g/L. At 24 hours post-MI, hemodynamic measurements were obtained, and infarct size was determined.

Both normal Hb groups (EPO and saline treated) had significantly improved 24-hour survival compared to the anemic groups treated with saline and PS (100% and 90% vs. 54% and 50%, respectively; P<0.05). There was a non-significant trend of higher survival in anemic animals treated with EPO or transfusion (70% and 75%, respectively; P=NS) compared to the saline and PS groups. Twenty-four hours post-MI, the infarct size to area at risk ratios were significantly increased in the anemic saline and PS groups compared to the normal Hb group (P<0.05). Infarct size was significantly decreased in both the EPO treated and transfused groups compared to the anemic saline and PS groups (P<0.05). Cardiac function as measured by LVSP, dP/dt_max(contractility), and–dP/dt_min(diastolic function) was better preserved 24 hours post-MI in the normal Hb groups and the EPO or transfusion treated anemic animals compared to PS or saline treated anemic animals. No statistically significant differences were observed in infarct size or cardiac function between the EPO and transfusion treated anemic groups.

EPO treatment was as effective as RBC transfusion in anemic animals after acute MI in reducing infarct size and improving cardiac function. The acute cardioprotective effects of EPO treatment occurred in the absence of any changes in Hb concentration.

(This study was supported by the Canadian Institutes of Health Research, Canadian Blood Services, Bayer Partnership Fund, and the Anemia Institute of Research and Education).

Xenocostas:Ortho Biotech, Canada: Consultancy, Honoraria, Research Funding.