Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.17.3.2 (xanthine oxidase)
 8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Hypercapnic acidosis may attenuate acute lung injury by inhibition of endogenous xanthine oxidase. 981 11

Hypoventilation, associated with hypercapnic acidosis (HCA), may improve outcome in acute lung injury (ALI). We have recently reported that HCA per se protects against ALI. The current study explored whether the mechanisms of protection with HCA were related to acidosis versus hypercapnia. Because CO(2) equilibrates rapidly across cell membranes, we hypothesized that (1) HCA would afford greater protection than metabolic acidosis. We further hypothesized that (2) buffering HCA would attenuate its protection. Forty isolated perfused rabbit lung preparations were randomized to: control (normal pH, PCO(2)); HCA; metabolic acidosis; or buffered hypercapnia. After ischemia-reperfusion (IR) injury wet:dry ratio was greatest with control and buffered hypercapnia, and rank order of capillary filtration coefficient was: control approximately buffered hypercapnia > metabolic acidosis > HCA. Isogravimetric pressure reduction was greatest with buffered hypercapnia. Despite comparable injury, pulmonary artery pressure elevation was less with buffered hypercapnia versus control. In vitro xanthine oxidase (XO) activity depended on pH, not PCO(2). We conclude that: (1) HCA and metabolic acidosis are protective, but HCA is the most protective; (2) buffering HCA attenuates its protection; (3) buffering HCA causes pulmonary vasodilation; (4) because metabolic acidosis and HCA similarly inhibit in vitro XO activity, the differential effects cannot be explained solely on the basis of extracellular XO activity.
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PMID:Buffering hypercapnic acidosis worsens acute lung injury. 1061 11