title: Role of the beta1-adrenergic pathway in anesthetic and ischemic preconditioning against myocardial infarction in the rabbit heart in vivo.
abstract: BACKGROUND
  Anesthetic and ischemic preconditioning share similar signal transduction pathways. The authors tested the hypothesis that the beta1-adrenergic signal transduction pathway mediates anesthetic and ischemic preconditioning in vivo.
  
  
  METHODS
  Pentobarbital-anesthetized (30 mg/kg) rabbits (n = 96) were instrumented for measurement of systemic hemodynamics and subjected to 30 min of coronary artery occlusion and 3 h of reperfusion. Sixty minutes before occlusion, vehicle (control), 1.0 minimum alveolar concentration desflurane, or sevoflurane, and esmolol (30.0 mg x kg(-1) x h(-1)) were administered for 30 min, respectively. Administration of a single 5-min cycle of ischemic preconditioning was instituted 35 min before coronary artery occlusion. In separate groups, the selective blocker esmolol or the protein kinase A inhibitor H-89 (250 microg/kg) was given alone and in combination with desflurane, sevoflurane, and ischemic preconditioning.
  
  
  RESULTS
  Baseline hemodynamics and area at risk were not significantly different between groups. Myocardial infarct size (triphenyltetrazolium staining) as a percentage of area at risk was 61 +/- 4% in control. Desflurane, sevoflurane, and ischemic preconditioning reduced infarct size to 34 +/- 2, 36 +/- 5, and 23 +/- 3%, respectively. Esmolol did not alter myocardial infarct size (65 +/- 5%) but abolished the protective effects of desflurane and sevoflurane (57 +/- 4 and 52 +/- 4%, respectively) and attenuated ischemic preconditioning (40 +/- 4%). H-89 did not alter infarct size (60 +/- 4%) but abolished preconditioning by desflurane (57 +/- 5%) and sevoflurane (61 +/- 1%). Ischemic preconditioning (24 +/- 7%) was not affected by H-89.
  
  
  CONCLUSIONS
  The results demonstrate that anesthetic preconditioning is mediated by the beta1-adrenergic pathway, whereas this pathway is not essential for ischemic preconditioning. These results indicate important differences in the mechanisms of anesthetic and ischemic preconditioning.
authors.affiliation: Department of Pharmacology, Bayerische Julius Maximilians-Universität, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Lange
authors.forename: Thorsten M
authors.initials: TM
authors.lastname: Smul
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Blomeyer
authors.forename: Andreas
authors.initials: A
authors.lastname: Redel
authors.forename: Karl-Norbert
authors.initials: KN
authors.lastname: Klotz
authors.forename: Norbert
authors.initials: N
authors.lastname: Roewer
authors.forename: Franz
authors.initials: F
authors.lastname: Kehl
mesh_terms: D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D006339:Heart Rate; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000517:prevention & control*; D015221:Potassium Channels / Q000502:physiology; D011412:Propanolamines / Q000494:pharmacology; D011817:Rabbits; D018342:Receptors, Adrenergic, beta-1 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D000777:Anesthetics; D015221:Potassium Channels; D011412:Propanolamines; D018342:Receptors, Adrenergic, beta-1; D017868:Cyclic AMP-Dependent Protein Kinases; C036604:esmolol