Haessler R, Kuzume K, Wolff R A, Kuzume K, Chien G L, Davis R F, Van Winkle D M
Department of Anesthesiology, Oregon Health Sciences University, Portland, USA.
Coron Artery Dis. 1996 Apr;7(4):305-14. doi: 10.1097/00019501-199604000-00007.
The aim of this study was to determine whether (1) adrenergic activation is cardioprotective, (2) adrenergic cardioprotection occurs via adenosine receptor activation, and (3) ischemic preconditioning requires alpha-adrenergic activation.
Anesthetised open chest rabbits underwent 30 min coronary occlusion and 3 h reperfusion. Ischemic preconditioning was elicited with 5 min coronary occlusion and 10 min reperfusion. Activation of adrenergic receptors with endogenous norepinephrine was achieved with tyramine (0.28 mg/kg/min intravenously for 5 min). Adenosine receptors were blocked with 8-p-sulfophenyl theophylline (10 mg/kg intravenously), alpha 1-adrenergic receptors were selectively blocked with prazosin (0.1 mg/kg intravenously), and alpha-adrenergic receptors were blocked with phentolamine (4 mg/kg intravenously).
Ischemic preconditioning reduced risk-adjusted infarct volume by 79% (P < 0.0005). This protection was attenuated by adenosine receptor blockade. Tyramine infusion resulted in a 1305% change from baseline plasma norepinephrine concentration (P < or = 0.01), and reduced infarct volume by 55% (P = 0.01). Adenosine receptor blockade abolished this protection. Blockade of alpha 1-adrenergic receptors with prazosin failed to abolish ischemic preconditioning (79 versus 89% reduction in infarct volume, without and with prazosin, respectively). Similarly, non-selective blockade of alpha-adrenergic receptors also failed to abolish ischemic preconditioning (79 versus 57% reduction without and with phentolamine, respectively).
We conclude that the cardioprotection of ischemic preconditioning and alpha-adrenergic activation both involve adenosine, but ischemic preconditioning does not require alpha-adrenergic activation.
本研究的目的是确定（1）肾上腺素能激活是否具有心脏保护作用，（2）肾上腺素能心脏保护作用是否通过腺苷受体激活发生，以及（3）缺血预处理是否需要α-肾上腺素能激活。
对麻醉开胸兔进行30分钟冠状动脉闭塞和3小时再灌注。通过5分钟冠状动脉闭塞和10分钟再灌注诱导缺血预处理。用酪胺（0.28毫克/千克/分钟静脉注射5分钟）实现内源性去甲肾上腺素对肾上腺素能受体的激活。用8-对磺基苯甲酰基茶碱（10毫克/千克静脉注射）阻断腺苷受体，用哌唑嗪（0.1毫克/千克静脉注射）选择性阻断α1-肾上腺素能受体，用酚妥拉明（4毫克/千克静脉注射）阻断α-肾上腺素能受体。
缺血预处理使风险调整后的梗死体积减少79%（P<0.0005）。腺苷受体阻断减弱了这种保护作用。输注酪胺导致血浆去甲肾上腺素浓度相对于基线变化了1305%（P≤0.01），梗死体积减少了55%（P=0.01）。腺苷受体阻断消除了这种保护作用。用哌唑嗪阻断α1-肾上腺素能受体未能消除缺血预处理（梗死体积减少分别为79%和89%，无哌唑嗪和有哌唑嗪时）。同样，α-肾上腺素能受体的非选择性阻断也未能消除缺血预处理（梗死体积减少分别为79%和57%，无酚妥拉明和有酚妥拉明时）。
我们得出结论，缺血预处理和α-肾上腺素能激活的心脏保护作用均涉及腺苷，但缺血预处理不需要α-肾上腺素能激活。
