title: Effects of therapeutic hypercapnia on mesenteric ischemia-reperfusion injury.
abstract: Hypercapnic acidosis protects against direct lung injury in in vivo and ex vivo models, however, lung injury/acute respiratory distress syndrome commonly occurs after a nonpulmonary etiology. We investigated whether therapeutic hypercapnia (TH)-deliberate elevation of carbon dioxide (CO2) tension-would protect against lung injury after splanchnic ischemia-reperfusion injury in an in vivo model. TH was associated with preservation of lung mechanics, attenuation of protein leakage, and improved oxygenation compared with control conditions. Lung protection was therapeutic as well as prophylactic. Protection was dose-dependent, but inspired CO2 concentrations above 5.0% were associated with little additional lung protection. Before lung injury, increasing FICO2 resulted in a dose-dependent increase in PaO2. Lung protection with hypercapnia occurred despite pulmonary artery pressures that were greater than observed with normocapnia. Reperfusion increased lipid peroxidation (tissue 8-isoprostane concentration) in the bowel, liver, and lung, and caused histologically apparent bowel injury; however, none of these effects was altered by TH. Therefore, TH-induced by adding CO2 to inspired gas-provides consistent protection against lung injury in terms of lung permeability, oxygenation, and lung mechanics after mesenteric ischemia-reperfusion. These data further support the emerging evidence for ongoing physiologic study of TH at the bedside.
authors.affiliation: Department of Critical Care Medicine, The Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: John G
authors.initials: JG
authors.lastname: Laffey
authors.forename: Robert P
authors.initials: RP
authors.lastname: Jankov
authors.forename: Doreen
authors.initials: D
authors.lastname: Engelberts
authors.forename: A Keith
authors.initials: AK
authors.lastname: Tanswell
authors.forename: Martin
authors.initials: M
authors.lastname: Post
authors.forename: Thomas
authors.initials: T
authors.lastname: Lindsay
authors.forename: J Brendan
authors.initials: JB
authors.lastname: Mullen
authors.forename: Alex
authors.initials: A
authors.lastname: Romaschin
authors.forename: Derek
authors.initials: D
authors.lastname: Stephens
authors.forename: Colin
authors.initials: C
authors.lastname: McKerlie
authors.forename: Brian P
authors.initials: BP
authors.lastname: Kavanagh
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002245:Carbon Dioxide / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006935:Hypercapnia; D008297:Male; D017538:Mesenteric Artery, Superior / Q000503:physiopathology; D008641:Mesenteric Vascular Occlusion / Q000150:complications* / Q000503:physiopathology; D011651:Pulmonary Artery / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications* / Q000503:physiopathology; D012128:Respiratory Distress Syndrome / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D002245:Carbon Dioxide