Hypercapnic acidosis may attenuate acute lung injury by inhibition of endogenous xanthine oxidase.
Relative hypoventilation, involving passively-or "permissively"-generated hypercapnic acidosis (HCA), may improve outcome by reducing ventilator-induced lung injury. However, the effects of HCA per se on pulmonary microvascular permeability (Kf,c) in noninjured or injured lungs are unknown. We investigated the effects of HCA in the isolated buffer-perfused rabbit lung, under conditions of: (1) no injury; (2) injury induced by warm ischemia-reperfusion; and (3) injury induced by addition of purine and xanthine oxidase. HCA (fraction of inspired carbon dioxide [FICO2] 12%, 25% versus 5%) had no adverse microvascular effects in uninjured lungs, and prevented (FICO2 25% versus 5%) the increase in Kf,c following warm ischemia-reperfusion. HCA (FICO2 25% versus 5%) reduced the elevation in Kf,c, capillary (Pcap), and pulmonary artery (Ppa) pressures in lung injury induced by exogenous purine/xanthine oxidase; inhibition of endogenous NO synthase in the presence of 25% FICO2 had no effect on Kf,c, but attenuated the reduction of Pcap and Ppa. HCA inhibited the in vitro generation of uric acid from addition of xanthine oxidase to purine. We conclude that in the current models, HCA is not harmful in uninjured lungs, and attenuates injury in free-radical-mediated lung injury, possibly via inhibition of endogenous xanthine oxidase.
Shibata
K
K
Respiratory Research Unit, Department of Anaesthesia, and the MSICU, Toronto Hospital, Department of Anaesthesia, University of Toronto, Toronto, Ontario, Canada.
Cregg
N
N
Engelberts
D
D
Takeuchi
A
A
Fedorko
L
L
Kavanagh
B P
BP
D000138:Acidosis / Q000201:enzymology / Q000503:physiopathology*; D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002196:Capillaries / Q000503:physiopathology; D002199:Capillary Permeability / Q000502:physiology; D002245:Carbon Dioxide / Q000008:administration & dosage; D005609:Free Radicals / Q000037:antagonists & inhibitors; D006874:Hydrostatic Pressure; D006935:Hypercapnia / Q000201:enzymology / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply; D008297:Male; D008833:Microcirculation / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011651:Pulmonary Artery / Q000503:physiopathology; D011687:Purines / Q000009:adverse effects; D011817:Rabbits; D015427:Reperfusion Injury / Q000201:enzymology / Q000503:physiopathology; D012121:Respiration, Artificial / Q000009:adverse effects; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D014527:Uric Acid / Q000037:antagonists & inhibitors; D014655:Vascular Resistance / Q000502:physiology; D014969:Xanthine Oxidase / Q000009:adverse effects / Q000037:antagonists & inhibitors*
D005609:Free Radicals; D011687:Purines; D002245:Carbon Dioxide; D014527:Uric Acid; D019001:Nitric Oxide Synthase; D014969:Xanthine Oxidase