Desflurane-induced Postconditioning Is Mediated by β-Adrenergic Signaling Role of β1- and β2-Adrenergic Receptors, Protein Kinase A, and Calcium/Calmodulin-dependent Protein Kinase II
Desflurane-induced Postconditioning Is Mediated by β-Adrenergic Signaling Role of β1- and β2-Adrenergic Receptors, Protein Kinase A, and Calcium/Calmodulin-dependent Protein Kinase II
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DOI：
10.1097/aln.0b013e318197ff62
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发表时间：
2009-03-01
期刊：
影响因子：
8.8
通讯作者：
Kehl, Franz
中科院分区：
文献类型：
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作者：
Lange, Markus;Redel, Andreas;Kehl, Franz
背景：麻醉预适应是由β-肾上腺素能信号介导的。方法：将戊巴比妥麻醉的新西兰白色兔冠状动脉闭塞30 min，再灌注3 h，随机分为对照组、1.0最小肺泡浓度的地氟烷组、艾司洛尔组（30 mg . kg（-1）。h（-1）），β（2）-肾上腺素能受体阻滞剂ICI 118，551（0.2 mg/kg），蛋白激酶A抑制剂H-89（250 μ g/kg），或钙/钙调蛋白依赖性蛋白激酶II抑制剂KN-93（300 μ g/kg），存在或不存在地氟烷。蛋白激酶B、钙/钙调蛋白依赖性蛋白激酶H和受磷蛋白的蛋白表达通过Western免疫印迹法测定。结果：对照组心肌梗死面积为57 ± 5%。地氟醚后处理使梗死面积减少36.5%。在再灌注的最初30分钟内给予艾司洛尔对梗死面积没有影响（54 +/- 4%），但阻断了地氟烷诱导的后处理（58 +/- 5%），而在不存在或存在地氟烷的情况下，在整个再灌注期间给予艾司洛尔将梗死面积分别降低至42 +/- 6%和41 +/-7%。ICI 118，551和K-N-93不影响梗死面积（62 +/- 4%和62 +/-6%）。但在地氟醚诱导的后处理中，分别为57 +/- 5%和64 +/-3%。H-89在无（36 +/- 5%）或有（33 +/- 5%）地氟醚的情况下均能减少梗死面积。结论：地氟醚诱导的后适应是由β-肾上腺素能信号传导介导的。然而，β-肾上腺素能信号在再灌注期间的心脏保护中显示出不同的作用。
Background: Anesthetic preconditioning is mediated by beta-adrenergic signaling. This study was designed to elucidate the role of beta-adrenergic signaling in desflurane-induced postconditionmig.Methods: Pentobarbital-anesthetized New Zealand White rabbits were subjected to 30 min of coronary artery occlusion followed by 3 h of reperfusion and were randomly assigned to receive vehicle (control), 1.0 minimum alveolar concentration of desflurane, esmolol (30 mg . kg(-1) . h(-1)) for the initial 30 min of reperfusion or throughout reperfusion, the beta(2)-adrenergic receptor blocker ICI 118,551 (0.2 mg/kg), the protein kinase A inhibitor H-89 (250 mu g/kg), or the calcium/calmodulin-dependent protein kinase II inhibitor KN-93 (300 mu g/kg) in the presence or absence of desflurane. Protein expression of protein kinase B, calcium/calmodulin-dependent protein kinase H, and phospholamban was measured by Western immunoblotting. Myocardial infarct size was assessed by triphenyltetrazolium staining.Results: Infarct size was 57 +/- 5% in control. Desflurane postconditioning reduced infarct size to 36 5%. Esmolol given during the initial 30 min of reperfusion had no effect on infarct size (54 +/- 4%) but blocked desflurane- induced postconditioning (58 +/- 5%), whereas esmolol administered throughout reperfusion reduced infarct size in the absence or presence of desflurane to 42 +/- 6% and 41 +/- 7%, respectively. ICI 118,551 and K-N-93 did not affect infarct size (62 +/- 4% and 62 +/- 6%. respectively) but abo%-hed desflurane-induced postconditioning (57 +/- 5% and 64 +/- 3%, respectively). H-89 decreased infarct size in the absence (36 +/- 5%) or presence (33 +/- 5%) of desflurane.Conclusions: Desflurane-induced postconditioning is mediated by beta-adrenergic signaling. However, beta-adrenergic signaling displays a differential role in cardioprotection during reperfusion.