NEUTROPHIL ACCUMULATIONS DUE TO PULMONARY THROMBOXANE SYNTHESIS MEDIATE ACID ASPIRATION INJURY

Acid aspiration leads to lung injury associated with high levels of plasma thromboxane (Tx). This study tests the role of Tx synthesis by the aspirated lung segment in mediating local and remote neutrophil (PMN) sequestration, alveolar diapedesis, and permeability edema. Anesthetized rats underwent tracheostomy and insertion of a fine-bore cannula into the anterior segment of the left lung. This was followed by the installation of either 0.1 ml saline (n = 18) or the Tx synthase inhibitor OKY 046 (0.1 mg/kg in 0.1 ml, n = 18). Twenty minutes later either 0.1 ml 0.1 N HCl or 0.1 ml saline was similarly introduced (n = 18). Three hours later, in the saline-HCl group, the rise in Tx concentration in both plasma (1,340 pg/ml) and bronchoalveolar lavage (BAL) fluid (2,100 pg/ml) was higher than that in the saline-saline aspirated control group (350 and 115 pg/ml, respectively; both P < 0.05). In the acid-aspirated lung PMN sequestration [87 PMN/10 high-power fields (HPF)] and diapedesis (96 x 10(4) PMN/ml in BAL) were higher than control values of 7 PMN/10 HPF and 3 x 10(4) PMN/ml (both P < 0.05). Acid aspiration induced local permeability edema with a high protein concentration in BAL of 3,350-mu-g/ml and an increase in lung wet-to-dry weight ratio (W/D) of 6.6, both higher than control values of 482-mu-g/ml and 3.4, respectively (P < 0.05). Leukosequestration in the aspirated side started at 30 min and was progressive over a 3-h monitoring period. This was not true of PMN diapedesis, which began 2 h after aspiration, and TxB2 synthesis, noted after 2.5 h. At 3 h, a correlation was found (P < 0.05) between PMN accumulations and Tx concentration in BAL (r = 0.95). Pretreatment by aspiration with OKY 046 prevented the acid aspiration-induced rise in BAL Tx (140 pg/ml) but not plasma Tx (1,800 pg/ml). PMN sequestration in the aspirated segment was reduced to 27 PMN/10 HPF and diapedesis to 19 x 10(4) PMN/ml (P < 0.05). Permeability edema was attenuated with protein concentration of 1,475-mu-g/ml and lung W/D of 4.1 (P < 0.05). Leukosequestration and permeability edema in the nonaspirated lung segments were not altered by localized OKY 046. These data indicate that after acid aspiration local pulmonary Tx synthesis is required for local PMN sequestration and lung permeability.