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, Markus, Redel, Andreas, Lotz, Christopher, Smul, Thorsten M, Blomeyer, Christoph, Frank, Anja, Stumpner, Jan, Roewer, Norbert, Kehl, Franz
• Format: Article
• Language: English
• Subjects: Animals; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - physiology; Cyclic AMP-Dependent Protein Kinases - physiology; Isoflurane - analogs & derivatives; Isoflurane - pharmacology; Isoflurane - therapeutic use; Male; Myocardial Infarction - enzymology; Myocardial Infarction - physiopathology; Myocardial Infarction - prevention & control; Rabbits; Receptors, Adrenergic, beta-1 - physiology; Receptors, Adrenergic, beta-2 - physiology; Signal Transduction - drug effects; Signal Transduction - physiology; Time Factors
• ISSN: 1528-1175
• DOI: 10.1097/ALN.0b013e318197ff62

Anesthetic preconditioning is mediated by beta-adrenergic signaling. This study was designed to elucidate the role of beta-adrenergic signaling in desflurane-induced postconditioning. 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 x kg(-1) x h(-1)) for the initial 30 min of reperfusion or throughout reperfusion, the beta2-adrenergic receptor blocker ICI 118,551 (0.2 mg/kg), the protein kinase A inhibitor H-89 (250 microg/kg), or the calcium/calmodulin-dependent protein kinase II inhibitor KN-93 (300 microg/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. 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 KN-93 did not affect infarct size (62 +/- 4% and 62 +/- 6%, respectively) but abolished 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. Desflurane-induced postconditioning is mediated by beta-adrenergic signaling. However, beta-adrenergic signaling displays a differential role in cardioprotection during reperfusion.