Buflomedil hydrochloride reduces systemic activation of polymorphonuclear leukocytes during hyperdynamic endotoxemia.
The purpose of the study was to examine the effects of buflomedil hydrochloride (BFL) on the expression of adhesion molecules (beta2-integrins) and oxygen radical production of circulating and emigrated intra-abdominal polymorphonuclear leukocytes (PMNL) in a standardized porcine model of hyperdynamic endotoxemia. A total of 20 anesthetized pigs were randomly assigned to one of the following groups: endotoxin group (endotoxin 5 microg / kg x h, intravenously (i.v.), n = 7), BFL group (BFL (3 mg/kg initial i.v. bolus followed by a continuous infusion (.1 mg / kg x h) and endotoxin 5 microg / kg x h, i.v., n = 7), and control group (NaCl .9%; n = 6). Experiments were terminated at 330 min. Infusion of endotoxin alone resulted in the activation of circulating and emigrated PMNL as evidenced by neutropenia, functional and numerical up-regulation of beta2-integrins, and enhanced oxygen radical production. BFL was able to attenuate functional and numerical up-regulation of beta2-integrins as well as oxygen radical production of circulating and emigrated PMNL. An unexpected decrease in the plasma concentration of BFL during the experiments was associated with an increase in the oxygen radical production of PMNL at the end of the experiments. In addition, BFL attenuated the fall in the intramucosal pH and the increase in plasma concentration of lactate observed in the late phase of endotoxemia. These findings suggest that BFL is able to decrease systemic activation of PMNL and to improve local tissue oxygenation during endotoxemia.
Holzer
K
K
Institute for Surgical Research, Klinikum Grosshadern, Ludwig-Maximilians-University Munich, Germany.
Thiel
M
M
Kreimeier
U
U
Moritz
S
S
Messmer
K
K
D000818:Animals; D018821:CD18 Antigens / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000378:metabolism*; D019446:Endotoxemia / Q000188:drug therapy* / Q000378:metabolism; D004731:Endotoxins / Q000097:blood; D005753:Gastric Mucosa / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000097:blood; D007958:Leukocyte Count / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010100:Oxygen / Q000097:blood / Q000378:metabolism; D011759:Pyrrolidines / Q000097:blood / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013552:Swine
D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D004731:Endotoxins; D011759:Pyrrolidines; D017382:Reactive Oxygen Species; D019344:Lactic Acid; D010100:Oxygen; C010651:buflomedil