The preconditioning pulmonary protective effect of volatile isoflurane in acute lung injury is mediated by activation of endogenous iNOS
- 396 Downloads
There is still a lack of evidence to support the use of specific anesthetic agents during major operations that could affect the development of postoperative acute lung injury (ALI). This study determined the protective effect of inhaled isoflurane in a rat model of endotoxin-induced ALI.
Rats were exposed to volatile isoflurane (1.5 % in oxygen) or pure oxygen via a facemask for 2 h. After a 3-h recovery period, rats were reanesthetized and ALI was induced by intratracheal instillation of lipopolysaccharide (LPS, 1 mg/kg in 0.5 ml saline). In some animals, a specific inducible nitric oxide synthase (iNOS) inhibitor, 1400W, (10 mg/kg, i.p.) was administered before exposure to isoflurane. Animals were sacrificed 12 h later for analysis. Pulmonary artery vasomotor function and alveolocapillary permeability were assessed. Expression of iNOS and CD11b, and activity of myeloperoxidase in the lung were analyzed.
The maximal relaxation response to acetylcholine was significantly potentiated in rats pretreated with isoflurane. Lung wet-to-dry ratio was reduced in the lung of isoflurane-treated animals. Expression of iNOS and CD11b were attenuated in the lung tissue obtained from rats receiving isoflurane. Furthermore, enzymatic activity of myeloperoxidase was also reduced in the lung preexposed to isoflurane. However, these pulmonary protective effects of isoflurane were significantly abolished by pretreatment with 1400W.
Pretreatment with volatile isoflurane attenuated inflammatory process in the lung tissue of rats with LPS-induced ALI, and this preconditioning pulmonary protective effect was mainly mediated by activation of endogenous iNOS in the lung.
KeywordsInhaled anesthetics Endotoxin Myeloperoxidase Inflammation
This study was supported by research grants from the National Science Council, Taiwan (grant number NSC 100-2314-B-006-010 to Professor Tsai YC) and the Multidisciplinary Center of Excellence for Clinical Trial and Research (DOH101-TD-B-111-102), Department of Health, Executive Yuan, Taiwan.
- 6.Rivenes SM, Lewin MB, Stayer SA, Bent ST, Schoenig HM, McKenzie ED, Fraser CD, Andropoulos DB. Cardiovascular effects of sevoflurane, isoflurane, halothane, and fentanyl-midazolam in children with congenital heart disease: an echocardiographic study of myocardial contractility and hemodynamics. Anesthesiology. 2001;94:223–9.PubMedCrossRefGoogle Scholar
- 20.Miotla JM, Williams TJ, Hellewell PG, Jeffery PK. A role for the beta2 integrin CD11b in mediating experimental lung injury in mice. Am J Respir Cell Mol. 1996;14:363–73.Google Scholar
- 22.Khan R, Mohan IK, Kutala VK, Kotha SR, Parinandi NL, Hamlin RL, Kuppusamy P. Sulfaphenazole protects heart against ischemia–reperfusion injury and cardiac dysfunction by overexpression of iNOS, leading to enhancement of nitric oxide bioavailability and tissue oxygenation. Antioxid Redox Signal. 2009;11:725–38.PubMedCrossRefGoogle Scholar
- 26.Inagaki Y. Cardiac preconditioning by anesthetic agents: roles of volatile anesthetics and opioids in cardioprotection. Yonago Acta Med. 2007;50:45–55.Google Scholar