Published online Dec 18, 2008.
https://doi.org/10.4068/cmj.2008.44.3.169
Effects of Propofol and Gabexate Mesilate (Foy) on Endotoxin-induced Acute Lung Injury in Rabbit
Abstract
This study was to clarify the effects of propofol and gabexate mesilate (foy), a synthetic protease inhibitor, on endotoxin induced-acute lung injury in rabbit. Animals were randomly assigned to one of five groups. Each group received intravenous infusion of saline only, saline and Escherichia coli endotoxin, propofol (4 mg/kg bolus, then 20 mg/kg/hr) and endotoxin, foy (2 mg/kg bolus, then 2 mg/kg/hr) and endotoxin and propofol (4 mg/kg bolus, then 20 mg/kg/hr) plus foy (2 mg/kg bolus, then 2 mg/kg/hr) and endotoxin. Infusion of saline, propofol or foy was started 30 minutes before the infusion of saline or endotoxin, and continued for 6 hours thereafter. At the end of infusion, animals were sacrificed and the wet to dry (W/D) weight ratio of lung, lung injury score, leukocyte counts, percentage of polymorphonuclear leukocyte (PMNL), and concentrations of albumin and interleukin-8 (IL-8) in bronchoalveolar lavage fluid (BALF) were evaluated. Endotoxin decreased the PaO2 and peripheral blood leukocyte and platelet counts. And it increased the W/D weight ratio of lung, the lung injury score, leukocyte counts, percentage of PNML, and concentration of albumin and IL-8 in BALF. Each propofol or foy attenuated all these changes except the leukocyte count in peripheral blood. These findings suggest that each propofol or foy attenuates endotoxin-induced acute lung injury in rabbit by inhibiting neutrophil, IL-8 and platelet responses which may play a central role in sepsis related lung injury. But both propofol and foy do not show synergic effect.
Fig. 1
Effect of propofol or foy or both of them on changes in arterial oxygen tension(PaO2) in endotoxin induced acute lung injury. Horizontal axis indicates time period after the start of saline or endotoxin infusion. Red circle, saline control group (S-S), blue diamond, endotoxin control group (S-E), black triangle, propofol treated group (P-E), brown square, foy treated group (F-E), propofol and foy treated group (P-F-E). Each point represents mean±SEM from seven rabbits. *p<0.05 versus time matched values in S-S group.
Table 1
Changes in pH, base excess, leukocyte and platelet counts in peripheral blood
Table 2
Analysis of bronchoalveolar lavage fluids (BALF), wet to dry (W/D) weight ratio and lung injury score (LIS)
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