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

• Published in: Anesthesiology (Philadelphia) 2009-03, Vol.110 (3), p.516-528
• Main Authors: Lange, M, Redel, A, Lotz, C, Smul, T M, Blomeyer, C, Frank, A, Stumpner, J, Roewer, N, Kehl, F
• Format: Article
• Language: English
• ISSN: 0003-3022
• DOI: 10.1097/ALN.0b013e318197ff62

Background: Anesthetic preconditioning is mediated by beta - adrenergic signaling. This study was designed to elucidate the role of beta -adrenergic signaling in desflurane-induced postconditioning. 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 times kg super(-1) times h super(-1)) for the initial 30 min of reperfusion or throughout reperfusion, the beta sub(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 II, and phospholamban was measured by Western immunoblotting. Myocardial infarct size was assessed by triphenyltetrazolium staining. Results: Infarct size was 57 plus or minus 5% in control. Desflurane postconditioning reduced infarct size to 36 plus or minus 5%. Esmolol given during the initial 30 min of reperfusion had no effect on infarct size (54 plus or minus 4%) but blocked desflurane-induced postconditioning (58 plus or minus 5%), whereas esmolol administered throughout reperfusion reduced infarct size in the absence or presence of desflurane to 42 plus or minus 6% and 41 plus or minus 7%, respectively. ICI 118,551 and KN-93 did not affect infarct size (62 plus or minus 4% and 62 plus or minus 6%, respectively) but abolished desflurane-induced postconditioning (57 plus or minus 5% and 64 plus or minus 3%, respectively). H-89 decreased infarct size in the absence (36 plus or minus 5%) or presence (33 plus or minus 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.