Abstract 4370: Intramyocardial Administration of Erythropoietin Promotes Cell Proliferation, Induces Early Angiogenesis and Attenuates Cardiac Remodeling
Erythropoietin (EPO) protects the ischemic myocardium from heart failure development after myocardial infarction (MI). However, little is known about its intracardiac cell proliferation and early angiogenesis. We hypothesize that EPO may contribute to cell proliferation, angiogenesis and eventually induce a beneficial remodeling process. Following permanent LAD ligation in rats, EPO (3000 U/kg; n=99) or saline (n=95) was delivered along the infarction border. In control animals without MI (n=55) saline was injected intramyocardially. After 6 weeks follow-up, left ventricle was catheterized and analyzed for cardiac performance. The level of eNOS mRNA was dramatically increased 9.3 fold in non-infarcted area of EPO treated rats at 24 h detected by real time PCR and confirmed by immunohistology. We found a 45 % enhancement in Ki-67+ cell numbers near the infarction at 48 h after EPO treatment (n=6, P<0.001). Hematopoietic cell lineages including c-Kit+ and CD34+ cells were augmented in the peripheral blood after 48h. Capillary density was enhanced by 17% as early as 1 week (n=6, P<0.001). Myocyte apoptosis was reduced by 41% and 37% at border zone after 1 and 6 weeks (n=6, P<0.05). Cardiac troponin T level, a highly sensitive and specific indicator of myocardial cell death, was significantly reduced in peripheral blood 2 weeks after EPO injection (n=5, P<0.05). Cardiomyocyte size and interstitial fibrosis at 6 weeks were decrease by 13% and 23% (n=6, P=0.015, P<0.001). Intramyocardial EPO delivery enhanced left ventricular performance at baseline and Dobutamine stress conditions compared with MI rats (cardiac output: 65% and 71% increase at baseline and stress; end-diastolic pressure: 51% and 53% reduction respectively, n=11–14, P<0.05). To conclude, intramyocardial EPO delivery induces early cell poliferation, angiogenesis and attenuates post MI remodeling.