Neurologic Critical Care Erythropoietin is equally effective as fresh-blood transfusion at reducing infarct size in anemic rats Anargyros Xenocostas, MD; Houxiang Hu, MD, PhD; Nicolas Chin-Yee; Xiangru Lu, MD; Ian Chin-Yee, MD; Qingping Feng, MD, PhD A nemia is a common condition in patients suffering from acute myocardial infarction (MI). The estimated prevalence of anemia, defined as a hemoglobin (Hb) level of 120 g/L, is approximately 15– 40% in patients with acute MI. Elderly populations show increased rates with more severe anemia (Hb 100 g/L) pre- senting in approximately 5% of individu- als (1, 2). Anemia and the resulting de- crease in the oxygen-carrying capacity of the blood could increase the potential for tissue damage during acute MI, and a number of clinical studies suggest that anemia adversely affects clinical out- comes (2–5). In the largest of these stud- ies, Sabatine et al (2) found that the mor- tality rate increased in acute coronary syndromes as Hb levels decreased below 14 g/dL, and there was an adjusted odds ratio of 1.21 (95% confidence interval, 1.12–1.30) for each 10 g/L decrement in Hb. Given the prevalence of anemia and its direct adverse effects on cardiovascu- lar function, it is important to seek effec- tive therapeutic interventions to reduce myocardial damage after acute MI (6, 7). Presently, the most common method of treating anemic patients is by red blood cell (RBC) transfusion. The effects of transfusion on acute coronary syn- dromes have also been studied, and there have been conflicting results. In a study conducted by Wu et al (1), transfusion was shown to reduce short-term mortal- ity in elderly patients after MI; however, contradictory results associating transfu- sion with higher mortality rates were ob- served in the setting of acute coronary syndromes (8). A subsequent clinical study found that although transfusion with a nadir Hb level of 80 g/L was associated with an increased mortality rate in patients experiencing acute MI, transfusion in patients with a nadir Hb level of 80 g/L showed a protective ef- fect following MI (9). Our group recently found similar results in a rat model show- ing transfusion to a Hb level of 100 g/L to be cardioprotective, but transfusion to higher Hb levels did not seem to be ben- eficial (10). If blood transfusion is to be- come an accepted treatment for myocar- dial ischemia, then the optimal Hb level for transfusion must be determined and balanced against the risks such as volume overload, transfusion-related acute lung injury, infection, and immunosuppres- sive effects associated with this interven- tion. From the Centre for Critical Illness, Research Lawson Health Research Institute (AX, HH, XL, ICY, QF); Canadian Blood Services (IC-Y); Departments of Medicine (AX, HH, IC-Y, QF), Physiology and Pharmacology (NC-Y, QF), Uni- versity of Western Ontario, London, Ontario, Canada; North Sichuan Medical College First Affiliated Hospital, Nanchong, Sichuan, P.R. China (HH). This study was supported by the CIHR, Canadian Blood Services, Hema Quebec, Bayer Partnership Fund, and the Anemia Institute for Research and Education. Dr. Feng is a Heart and Stroke Foundation of Ontario Career Investigator. Dr. Xenocostas has been a consultant for and has received educational grants and honoraria from Ortho Biotech, Canada. Dr. I Chin-Yee is the recipient of a grant from Canadian Blood Services. The remaining authors have not disclosed any potential conflicts of interest. For information regarding this article, E-mail: qfeng@uwo.ca or Ian.Chin-Yee@lhsc.on.ca Copyright © 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI: 10.1097/CCM.0b013e3181f17d6e Objective: We recently demonstrated that transfusion of ane- mic animals up to 100 g/L hemoglobin with fresh blood protects the heart from ischemic injuries following myocardial infarction. Erythropoietin has cardioprotective effects independent of its erythropoietic activity. The objective of this study was to compare the cardioprotective effects of erythropoietin treatment to fresh- blood transfusion in anemic rats after acute myocardial infarc- tion. Design: Randomized animal study. Setting: University laboratory. Subjects: Male Sprague-Dawley rats weighing 200 –300 g. Intervention: Myocardial infarction was induced by coronary artery ligation in 76 rats, 55 of which were anemic (80 –90 g/L) and 21 of which had normal hemoglobin levels. Animals were randomized to erythropoietin (2000 units/kg), fresh-blood trans- fusion to 100 g/L hemoglobin, or saline-treatment groups imme- diately following myocardial infarction. Measurements and Main Results: At 24 hrs after myocardial infarction, cardiac function and infarct size were determined. Myocardial apoptosis was determined by caspase-3 activity and terminal deoxynucleotidyl transferase d-UTP nick end labeling (TUNEL) assay. Infarct size was significantly decreased in anemic rats treated with erythropoietin or blood transfusion compared to those in the saline-treatment group. Cardiac function, as mea- sured by maximal positive and minimal negative first derivatives of left ventricular pressure, was better preserved in the normal hemoglobin groups and the erythropoietin- or transfusion-treated anemic animals compared to saline-treated anemic animals. Myocardial caspase-3 activity and TUNEL-positive nuclei were significantly increased in anemic rats but were decreased by erythropoietin treatment or red blood cell transfusion. Conclusions: Erythropoietin treatment is equally effective as fresh-blood transfusion in anemic rats after acute myocardial infarction at reducing infarct size, myocardial apoptosis, and improving cardiac function. (Crit Care Med 2010; 38:2215–2221) KEY WORDS: anemia; blood transfusion; myocardial infarction; erythropoietin 2215 Crit Care Med 2010 Vol. 38, No. 11