BUFLOMEDIL HYDROCHLORIDE REDUCES SYSTEMIC ACTIVATION OF POLYMORPHONUCLEAR LEUKOCYTES DURING HYPERDYNAMIC ENDOTOXEMIA

The purpose of the study was to examine the effects of buflomedil hydr ochloride (BFL) on the expression of adhesion molecules (beta 2-integr ins) and oxygen radical production of circulating and emigrated intra- abdominal polymorphonuclear leukocytes (PMNL) in a standardized porcin e model of hyperdynamic endotoxemia. A total of 20 anesthetized pigs w ere randomly assigned to one of the following groups: endotoxin group (endotoxin 5 mu g/kg.h, intravenously (i.v.), n = 7), BFL group (BFL ( 3 mg/kg initial i.v. bolus followed by a continuous infusion (.1 mg/kg .h) and endotoxin 5 mu g/kg.h, i.v., n = 7), and control group (NaCl . 9%; n = 6). Experiments were terminated at 330 min. Infusion of endoto xin alone resulted in the activation of circulating and emigrated PMNL as evidenced by neutropenia, functional and numerical up-regulation o f beta 2-integrins, and enhanced oxygen radical production. BFL was ab le to attenuate functional and numerical up-regulation of beta 2-integ rins as well as oxygen radical production of circulating and emigrated PMNL. An unexpected decrease in the plasma concentration of BFL durin g the experiments was associated with an increase in the oxygen radica l production of PMNL at the end of the experiments. In addition, BFL a ttenuated the fall in the intramucosal pH and the increase in plasma c oncentration of lactate observed in the late phase of endotoxemia. The se findings suggest that BFL is able to decrease systemic activation o f PMNL and to improve local tissue oxygenation during endotoxemia.