Differential effects of cyclo-oxygenase and thromboxane synthetase inhibition on ventilation-perfusion relationships in acid aspiration-induced acute lung injury.
Cyclo-oxygenase metabolites are important regulators of pulmonary vascular and airway tone and may act to regulate ventilation-perfusion (VA/Q) relationships. Hypoxemia that follows aspiration of gastric acid is associated with increased venous admixture, and plasma levels of thromboxane (TX) B2 and 6-keto-PGF2 alpha are increased after experimental acid-induced acute lung injury. The present study was designed to determine the effects of cyclo-oxygenase metabolites on VA/Q relationships in canine acid aspiration. Eighteen anesthetized dogs received 0.2 mL/kg 0.1 N HCl intratracheally; six were pretreated with ibuprofen (IBU), a cyclo-oxygenase inhibitor, 12.5 mg/kg IV, and six other dogs received OKY-046 (OKY), a TX synthetase inhibitor, 0.5 mg/kg IV. The remaining six animals (ACID) served as controls. Continuous distributions of ventilation and perfusion were evaluated with the multiple inert gas elimination technique. Within 30 minutes, acid injury resulted in significant (p < 0.05) decreases in PaO2 from baseline values by 44.7 +/- 5.4 and 47.6 +/- 4.8 mm Hg in the ACID and OKY groups, respectively. Although decreased, the change in PaO2 of 21.0 +/- 4.8 mm Hg in IBU animals was significantly (p < 0.05) attenuated in comparison with the other groups. Ibuprofen increased pulmonary vascular resistance, attenuated perfusion to shunt and low VA/Q areas, and reduced ventilation to unperfused areas for the first 2 hours after acid injury (all p < 0.05), whereas OKY exacerbated hypoxemia and VA/Q inequality.(ABSTRACT TRUNCATED AT 250 WORDS)
Wu
W
W
Department of Surgery, Cornell University Medical College, New York, New York.
Halebian
P H
PH
Hariri
R J
RJ
Cabrales
S X
SX
Shires
G T
GT
Barie
P S
PS
D000818:Animals; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D007052:Ibuprofen / Q000494:pharmacology*; D008689:Methacrylates / Q000494:pharmacology; D010100:Oxygen / Q000097:blood; D011015:Pneumonia, Aspiration / Q000097:blood / Q000201:enzymology / Q000503:physiopathology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D011652:Pulmonary Circulation / Q000187:drug effects; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors* / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects; D014692:Ventilation-Perfusion Ratio
D008689:Methacrylates; D011451:Prostaglandin-Endoperoxide Synthases; D013930:Thromboxane-A Synthase; C034364:ozagrel; D010100:Oxygen; D007052:Ibuprofen