Isoflurane produces delayed preconditioning against myocardial ischemia and reperfusion injury: role of cyclooxygenase-2. Anesthesiology 2004 Mar;100(3):525-31
Date
04/28/2004Pubmed ID
15108964DOI
10.1097/00000542-200403000-00010Scopus ID
2-s2.0-1442332839 (requires institutional sign-in at Scopus site) 105 CitationsAbstract
BACKGROUND: Whether volatile anesthetics produce a second window of preconditioning is unclear. The authors tested the hypothesis that isoflurane causes delayed preconditioning against infarction and, further, that cyclooxygenase (COX)-2 mediates this beneficial effect.
METHODS: Rabbits (n = 43) were randomly assigned to receive 0.9% intravenous saline, the selective COX-2 inhibitor celecoxib (3 mg/kg intraperitoneal) five times over 2 days before coronary artery occlusion and reperfusion, or isoflurane (1.0 minimum alveolar concentration) 24 h before acute experimentation in the absence or presence of celecoxib pretreatment. Two additional groups of rabbits received a single dose of celecoxib either 30 min before or 21.5 h after administration of isoflurane. Rabbits were then instrumented for measurement of hemodynamics and underwent 30 min of coronary occlusion followed by 3 h of reperfusion. Myocardial infarct size was measured using triphenyltetrazolium staining. Western immunoblotting to examine COX-1 and COX-2 protein expression was performed in rabbit hearts that had or had not been exposed to isoflurane.
RESULTS: Isoflurane significantly (P < 0.05) reduced infarct size (22 +/- 3% of the left ventricular area at risk) as compared with control (39 +/- 2%). Celecoxib alone had no effect on infarct size (36 +/- 4%) but abolished isoflurane-induced cardioprotection (36 +/- 4%). A single dose of celecoxib administered 2.5 h before coronary occlusion and reperfusion also abolished the delayed protective effects of isoflurane (36 +/- 4%), but celecoxib given 30 min before exposure to isoflurane had no effect (22 +/- 4%). Isoflurane did not alter COX-1 and COX-2 protein expression.
CONCLUSIONS: The results indicate that the volatile anesthetic isoflurane produces a second window of preconditioning against myocardial ischemia and reperfusion injury. Furthermore, COX-2 is an important mediator of isoflurane-induced delayed preconditioning.
Author List
Tanaka K, Ludwig LM, Krolikowski JG, Alcindor D, Pratt PF, Kersten JR, Pagel PS, Warltier DCAuthor
Paul S. Pagel MD, PhD Professor in the Anesthesiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Anesthetics, InhalationAnimals
Blood Pressure
Blotting, Western
Celecoxib
Coronary Circulation
Cyclooxygenase 1
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Heart Rate
In Vitro Techniques
Ischemic Preconditioning, Myocardial
Isoenzymes
Isoflurane
Male
Myocardial Infarction
Myocardial Ischemia
Myocardial Reperfusion Injury
Prostaglandin-Endoperoxide Synthases
Pyrazoles
Rabbits
Sulfonamides
Ventricular Function, Left