Pell T J, Baxter G F, Yellon D M, Drew G M
The Hatter Institute for Cardiovascular Studies, University College London Hospitals and Medical School, London WC1E 6DB, United Kingdom.
Am J Physiol. 1998 Nov;275(5):H1542-7. doi: 10.1152/ajpheart.1998.275.5.H1542.
Brief renal ischemia-reperfusion is reported to precondition the myocardium; however, the underlying mechanisms are unknown. This phenomenon was, therefore, investigated using an in vivo rabbit model of acute myocardial infarction. Characterization of the mechanisms involved was performed using the nonselective adenosine receptor antagonist 8-(p-sulfophenyl)theophylline (8-SPT) and the ATP-sensitive potassium (KATP) channel blocker sodium 5-hydroxydecanoate (5-HD). Pentobarbital-anesthetized rabbits underwent a left thoracotomy and pericardiotomy. A laparotomy was then performed to expose the left renal artery. Animals were either preconditioned with a 10-min occlusion of the renal artery followed by 10 min of reperfusion or underwent a 20-min sham period of anesthesia. Subsequently, the left coronary artery was then occluded for 30 min and reperfused for 2 h. Infarct-to-risk ratio was limited from 32.7 +/- 4.0% (n = 12) in controls to 17.8 +/- 3.0% (n = 9; P = 0.002) in preconditioned hearts. Protection was abolished by 7.5 mg/kg iv 8-SPT (36.7 +/- 3.7%; n = 6) or 5 mg/kg iv 5-HD (33.1 +/- 4. 4%; n = 6) administered before preconditioning. 8-SPT (40.0 +/- 4. 4%; n = 6) or 5-HD (40.5 +/- 4.2%; n = 6) did not affect infarct-to-risk ratio in sham controls. Thus activation of both adenosine receptors and KATP channels appears to be involved in acute renal preconditioning of the myocardium.
据报道,短暂性肾缺血再灌注可对心肌起到预处理作用;然而,其潜在机制尚不清楚。因此,本研究使用急性心肌梗死的体内兔模型对此现象进行了研究。使用非选择性腺苷受体拮抗剂8-(对磺基苯基)茶碱(8-SPT)和ATP敏感性钾(KATP)通道阻滞剂5-羟基癸酸钠(5-HD)对相关机制进行了表征。用戊巴比妥麻醉的兔子接受左胸切开术和心包切开术。然后进行剖腹手术以暴露左肾动脉。动物要么接受肾动脉10分钟闭塞加10分钟再灌注的预处理,要么经历20分钟的假麻醉期。随后,左冠状动脉闭塞30分钟并再灌注2小时。梗死与危险心肌比值从对照组的32.7±4.0%(n = 12)限制到预处理心脏的17.8±3.0%(n = 9;P = 0.002)。在预处理前静脉注射7.5 mg/kg的8-SPT(36.7±3.7%;n = 6)或5 mg/kg的5-HD(33.1±4.4%;n = 6)可消除保护作用。8-SPT(40.0±4.4%;n = 6)或5-HD(40.5±4.2%;n = 6)对假手术对照组的梗死与危险心肌比值没有影响。因此,腺苷受体和KATP通道的激活似乎都参与了心肌的急性肾预处理。