Modification of inflammatory response to aspiration with ibuprofen

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Abstract
Acid injury of the lungs provokes thrombocytopenia and an inflammatory infiltrae that appears to be influenced by prostacyclin (PGI2) and thromboxane A2 (TXA2). Previous experiments with acid aspiration demonstrated that an infusion of the cyclooxygenase inhibitor, ibuprofen, alone or in combination with PGI2, is an effective therapy to restore cardiopulmonary function and decrease pulmonary edema. The present study was designed to clarify the significance of PGI2 and TXA2 in acid inflammation of the lungs in dogs. Within 30 min, acid injury led to a significant increase in platelet lung entrapment; there was an increase in plasma thromboxane B2 (TXB2), the stable hydrolysis product of TXA2, apparently due to platelet TXA2 production. Leukocyte (WBC) synthesis of TXB2 increased 2 h after acid injury; at this time WBC were entrapped by the lungs. Starting 1 h after aspiration, continuous infusion of PGI2 for 1 h at 100 ng .cntdot. kg-1 .cntdot. min-1 had no effect on thrombocytopenia or WBC sequestration in the lungs. PGI 2 infusion enhanced platelet production of TXB2 and increased plasma TXB2 levels. A bolus ibuprofen infusion of 12.5 mg/kg, 1 h after aspiration, inhibited the generation of TXB2 by platelets and WBC, lowered plasma TXB2 levels, and, although failing to restore circulating platelet counts, prevented WBC sequestration and edema in the lungs. The combination of an ibuprofen bolus (12.5 mg/kg) with a PGI2 infusion (10 ng .cntdot. kg-1 .cntdot. min-1) reduced TXB2 production, restored the number of circulating platelets, stimulated leukocytosis, reversed platelet entrapment, and prevented WBC sequestration by the lungs. Evidence of inflammation and pulmonary edema, as determined by histological examination, was minimized by ibuprofen alone or in combination with PGI2. Evidently, edema of acid injury is in large part mediated by WBC aggregation and sequestration by the lungs. Secretory activity, following platelet and leukocyte adhesion/aggregation, appears to be accentuated by circulating PGI2.