期刊
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
卷 49, 期 6, 页码 337-345出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FJC.0b013e318040cf81
关键词
infarction; ischemia; receptors; MAP kinases; potassium channel
资金
- NHLBI NIH HHS [HL 54075, HL 08311] Funding Source: Medline
Erythropoietin is known to stimulate red cell production and has recently been shown to protect the heart against injury from ischemia/reperfusion. However, it is unknown whether darbepoetin alfa (Dpa), a long-acting analog of erythropoietin, can play a protective role against myocardial infarction. We assessed the potential protective role of Dpa in an in vivo rat model of myocardial ischemia/reperfusion and the underlying mechanisms. We found that a single intravenous Dpa treatment immediately before 30 minutes of regional ischemia reduced myocardial necrosis following 120 minutes of reperfusion in a dose-dependent manner. Optimal protection with Dpa against myocardial infarction was manifest at a dose of 2.5 mu g/kg. Dpa conferred cardioprotection when administered after the onset of ischemia and at the start of reperfiision. Dpa (2.5 mu g/kg) also reduced infarct size and Troponin I leakage 24 hours after reperfusion. Inhibition of p42/44 MAPK (PD98059), p38 MAPK (SB203580), mitochondrial ATP-dependent potassium (KATp) channels (5-HD), sarcolemmal KATp channels (HMR 1098), but not phosphatidylinositol-3 (PB) kinase/Akt (Wortmannin and LY 294002) abolished Dpa-induced cardioprotection. Dpa confers immediate and sustained cardioprotection in rats, suggesting a potential therapeutic role of this long-acting erythropoietin analog for the treatment of acute myocardial infarction.
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