title: Effect of desflurane-induced preconditioning following ischemia-reperfusion on nitric oxide release in rabbits.
abstract: Nitric oxide (NO) is the mediator of ischemic preconditioning against myocardial infarction. Desflurane produces anesthetic preconditioning to protect the myocardium against infarction. In the model of myocardial ischemia-reperfusion injury in rabbits, we evaluated desflurane-induced ischemic preconditioning and studied its mechanism of NO synthesis. Thirty-two male adult New Zealand white rabbits were anesthetized with intravenous (IV) 30 mg/kg pentobarbital followed by 5 mg/kg/hr infusion. All rabbits were subjected to 30 minutes (min) long lasting left anterior descending coronary artery (LAD) occlusion and three hours (hr) of subsequent reperfusion. Before LAD occlusion, the rabbits were randomly allocated into four groups for preconditioning treatment (eight for each group). The control group did not receive any preconditioning treatment. The desflurane group received inhaled desflurane 1.0 MAC (minimal end-tidal alveolar concentration) for 30 min that was followed by a 15 min washout period. The L-NAME-desflurane group received L-NAME (NG-nitro-L-arginine methyl ester; non-selective Nitric Oxide Synthetase (NOS) inhibitor) 1 mg/kg IV 15 min before 1.0 MAC inhaled desflurane for 30 min. The L-NAME group received L-NAME 1 mg/kg IV. Infarct volume, ventricular arrhythmia, plasma lactate dehydrogenase (LDH), creatine kinase (CK) activity and myocardial perfusion were recorded simultaneously. We have found that hemodynamic values of the coronary blood flow before, during, and after LAD occlusion were not significantly different among these four groups. For the myocardial ischemia-reperfusion injury animals, the infarction size (mean +/- SEM) in the desflurane group was significantly reduced to 18 +/- 3% in the area at risk as compared with 42 +/- 7% in the control group, 35 +/- 6 in the L-NAME group, and 34 +/- 4% in the L-NAME-desflurane group. The plasma LDH, CK levels, and duration of ventricular arrhythmia were also significantly decreased in the desflurane group during ischemia-reperfusion injury. Our results indicate that desflurane is an anesthetic preconditioning agent, which could protect the myocardium against the ischemia-reperfusion injury. This beneficial effect of desflurane on the ischemic preconditioning is probably through NO release since L-NAME abrogates the desflurane preconditioning effect.
authors.affiliation: Department of Anesthesiology, College of Medicine, National Yang-Ming University and National Taiwan University, Taipei Veterans General Hospital, 201, Shih-Pai Road, Second, Taipei, Taiwan.
authors.forename: Shen-Kou
authors.initials: SK
authors.lastname: Tsai
authors.forename: Su-Man
authors.initials: SM
authors.lastname: Lin
authors.forename: Cheng-Hsiung
authors.initials: CH
authors.lastname: Huang
authors.forename: Wei-Chih
authors.initials: WC
authors.lastname: Hung
authors.forename: Chun-Lien
authors.initials: CL
authors.lastname: Chih
authors.forename: Shiang-Suo
authors.initials: SS
authors.lastname: Huang
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism; D000077335:Desflurane; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D011817:Rabbits; D017180:Tachycardia, Ventricular / Q000517:prevention & control; D014693:Ventricular Fibrillation / Q000473:pathology
chemical_list: D018685:Anesthetics, Inhalation; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D009569:Nitric Oxide; D000077335:Desflurane; D007530:Isoflurane; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D003402:Creatine Kinase; D019331:NG-Nitroarginine Methyl Ester