Desflurane-induced Postconditioning Is Mediated by beta-Adrenergic Signaling Role of beta(1)- and beta(2)-Adrenergic Receptors, Protein Kinase A, and Calcium/Calmodulin-dependent Protein Kinase II

作者：Lange Markus^*; Redel Andreas; Lotz Christopher; Smul Thorsten M; Blomeyer Christoph; Frank Anja; Stumpner Jan; Roewer Norbert; Kehl Franz

来源：Anesthesiology, 2009, 110(3): 516-528.

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.

• 出版日期2009-3