ozagrel and Pneumonia--Aspiration

Acid aspiration leads to increased neutrophil (PMN) oxidative metabolism, an event associated with lung leukosequestration and permeability increase. Neutropenia protected the vascular barrier function against acid injury. This study tests whether active oxygen species and elastase (which are presumably released by adherent PMNs) affect the microvascular barrier. Anesthetized rats underwent tracheostomy and insertion of a cannula into a lung segment. This was followed by localized instillation of 0.1 N HCl (n = 18) or saline (n = 18). Sequestration of PMNs in acid-aspirated and nonaspirated segments was 77 and 46 PMNs/high-power field (HPF), respectively, which was higher than control values of 11 and 8 PMNs/10 HPF in saline-aspirated and nonaspirated regions (P less than 0.05). Acid aspiration was associated with increased protein concentration in bronchoalveolar lavage (BAL) fluid to 3,550 and 2,900 micrograms/ml in the aspirated and nonaspirated lungs, respectively, which were higher than control values of 420 and 400 micrograms/ml (P less than 0.05). Acid aspiration also led to increased lung wet-to-dry weight ratios (W/D) of 6.6 and 5.4, which were higher than control values of 3.4 and 3.3 (P less than 0.05). Intravenous treatment of rats (n = 18) 90 min after aspiration with scavengers of reactive oxygen species, superoxide dismutase (1,500 U/kg), and catalase (5,000 U/kg), both conjugated to polyethylene glycol, did not reduce PMN sequestration but attenuated acid aspiration-induced increase in protein accumulation in BAL fluid in the aspirated and nonaspirated segments (990 and 610 micrograms/ml) as well as the increased lung W/D (4.6 and 4.0; all P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Catalase; Evans Blue; Hydrochloric Acid; Lung; Male; Methacrylates; Neutrophils; Pancreatic Elastase; Permeability; Pneumonia, Aspiration; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Superoxide Dismutase; Thromboxane B2; Thromboxane-A Synthase

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)

Topics: Animals; Dogs; Hemodynamics; Ibuprofen; Methacrylates; Oxygen; Pneumonia, Aspiration; Prostaglandin-Endoperoxide Synthases; Pulmonary Circulation; Thromboxane-A Synthase; Vascular Resistance; Ventilation-Perfusion Ratio

The systemic circulation to the lung is thought to be an important microvascular exchange region which may contribute to pulmonary edema resulting from airway injury. In a chronic sheep model, we have evaluated the flow through the bronchial artery after airway injury caused by the aspiration of 2.5 ml/kg of 0.1 N hydrochloric acid with and without inhibition of thromboxane synthetase and cyclooxygenase. Cyclooxygenase inhibition with ibuprofen resulted in no rise in bronchial artery blood flow associated with airway acid aspiration (9.8 +/- 1.72 ml/min to 63.7 +/- 8.9 ml/min in the control group versus 11.3 +/- 2.5 ml/min to 10.3 +/- 3.4 ml/min in the ibuprofen group). No difference in bronchial artery blood flow was noted between control acid aspiration and acid aspiration with thromboxane synthetase inhibition. Significant early reduction in lung lymph flow was noted in the cyclooxygenase inhibition group compared to control. These data suggest that inhibition of the cyclooxygenase pathway of eicosanoid production may lessen the injury caused by airway acid aspiration. The decrease in airway blood flow with associated reduction in lymph flow suggests that airway blood flow may be important in the generation of pulmonary edema in this model.

Topics: Animals; Bronchial Arteries; Cyclooxygenase Inhibitors; Eicosanoids; Hydrochloric Acid; Ibuprofen; Inhalation; Lymph; Methacrylates; Pneumonia, Aspiration; Pulmonary Circulation; Pulmonary Edema; Sheep; Thromboxane-A Synthase