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ȣ - 490406 127 |
| Erythropoietin protects the myocardium against reperfusion injury with an Akt dependent manner. |
| ¹ 분당서울대학교병원 심장센터 ²서울대학교 의과대학 순환기내과 |
| 김은지¹, 강서영¹, 장혁재¹ ² , 조영석¹ ² , 정우영¹ ² , 연태진¹ ² , 채인호¹ ² , 최동주¹ ², 김철호¹ ², 구본권², 김효수², 오병희², 박영배², 최윤식² |
Background Erythropoietin (EPO), known to stimulate the production of red blood and be used to treat anemia in cancer and renal failure, has recently been shown to have a tissue protective effect on diabetic neuropathy, encephalomyelitis, and stroke. The goal of this study was to determine whether EPO could protect myocardium from ischemia/reperfusion injury. Methods In anesthetized open-chest male Sprague-Dawley rats, receiving 5,000U/kg of erythropoietin (EPO) intravenously or saline prior to reperfusion, area of necrosis (AN), the area at risk (AAR), % of infarct (AN/AAR and AN/LV), and Left ventricular hemodynamics were measured after 24 hours of reperfusion followed of 30-min coronary occlusion. LV hemodynamics were accessed by measuring the first derivative of left ventricular pressure (dP/dt and -dP/dt) and the end-systolic elastance (Ees) in pressure-volume loops with IV dobutamine infusion by using high fidelity microcatheter (Millar Mikro-Tip®). To examine the mechanistic pathways involved in EPO-mediated protection, Akt phosphorylation was estimated at 6 and 12 hours after EPO injection. Results EPO administration reduced infarct size by 31% by %AN/AAR and 37% by %AN/LV (p<0.01 versus control), whereas AAR was not different in both group by %AAR/LV. EPO also improved ischemia/reperfusion-induced myocardial contractile dysfunction and responsiveness to dobutamine. Basal state of LV function was increased in EPO (dP/dt; 8418.6±1521mmHg/sec vs. 6390±978mmHg/sec and -dP/dt; -6586.7±1128mmHg/sec vs. -5375.6±797mmHg/sec, p<0.05) and myocardial responsiveness dobutamine was also enhanced in EPO (Ees; 0.750±0.197 vs. 0.454±0.138, p<0.01). The phosphorylation of Akt was enhanced from 6 hour after injection of EPO by ≈3 folds compared to control. Conclusions EPO, administered prior to reperfusion, reduced infarct size and improved LV function in whole animal model with an Akt dependent manner. These results suggest that EPO may be able to directly protect the myocardium against ischemic-reperfusion injury and implicate the clinical usefulness.
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