Effects of Propofol and Gabexate Mesilate (Foy) on Endotoxin-induced Acute Lung Injury in Rabbit

Sung-Su Chung; Hong-Beom Bae; Seok-Jae Kim; Cheol-Won Jeong; Hye-Jin Chung; Mai Li; Sang-Hyun Kwak

doi:10.4068/cmj.2008.44.3.169

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Chung, Bae, Kim, Jeong, Chung, Li, and Kwak: Effects of Propofol and Gabexate Mesilate (Foy) on Endotoxin-induced Acute Lung Injury in Rabbit

Original Article

Chonnam Medical Journal

Chonnam Medical Journal 2008; 44(3): 169-176.

Published online: 18 December 2008

DOI: 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

Sung-Su Chung¹, Hong-Beom Bae, Seok-Jae Kim, Cheol-Won Jeong, Hye-Jin Chung, Mai Li, Sang-Hyun Kwak

Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, Korea.

¹Department of Anesthesiology and Pain Medicine, School of Dentistry, Gwangju, Korea.

Corresponding author (shkwak@jnu.ac.kr)

Accepted 19 November 2008

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.

Keywords: Acute lung injury, Endotoxin, Gabexate mesilate (foy), Propofol

Figures and Tables

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

Values are mean±SEM. S-S, saline only; S-E, saline+endotoxin; P-E, propofol+endotoxin; F-E, foy+endotoxin: P-F-E, propofol+foy+ endotoxin. ^*p<0.05 versus group S-S; ^†p<0.05 for group P-E, F-E and P-F-E versus group S-E.

Table 2

Analysis of bronchoalveolar lavage fluids (BALF), wet to dry (W/D) weight ratio and lung injury score (LIS)

Values are mean±SEM. S-S, saline only; S-E, saline+endotoxin; P-E, propofol+endotoxin; F-E, foy+endotoxin; P-F-E, propofol+foy+ endotoxin. PMN, polymorphoneuclear neutrophil; IL-8, Interleukin-8; TxB2, Thromboxane B2. ^*p<0.05 versus group S-S; ^†p<0.05 for group P-E, F-E or P-F-E versus group S-E; ^‡p<0.01 for group P-E, F-E or P-F-E versus group S-E versus group S-E.

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