Experimental Study Of The Influence Of Isoflurane On Acute Lung Injury Induced By Endotoxins In Rats

Objective: Isoflurane, a widly used inhalational anesthetic, has been demonstrated to increase alveolar-capillary permeability, to decrease alveolar epithelial fluid clearance, and inhibit Na+-K+-ATPase activity and pulmonary surfactant synthesis of alveolar type II cells in normal conditions. But the effects of isoflurane on injured lungs are not clear. Therefore, it is valuable to explore the effects of isoflurane on lung in pathological conditions. In our study, we observe the effects of isoflurane on lung in acute lung injury induced by endotoxin in rats. The aim of this research is to provide theory basis for clinical rational practice of isoflurane in patients with infectious shock . severe infection and acut lung injury.Methods:1. The study of preconditioning effect of isoflurane on lung injury induced by lipopolysaccharide (LPS) in ratsThe rats were divided into four groups: control group(group C,n=30); isoflurane control group(group Iso,n=30): rats inhaled 1.4% isoflurane for 15 minutes; LPS injured group(group LPS,n=30) : rats were intravenously administered LPS 5mg.kg-1; isoflurane preconditoning combined LPS injured group (group IPL,n=30): rats inhaled 1.4% isoflurane for 15 minutes, followed by intravenous LPS 5mg.kg-1. The histopathological samples were inspected, and total lung water content, pulmonary microvascular permeability, the ratio of neutrophils and protein content in bronchoalveolar lavage fluid were measured at 2, 4, 8 hours.2. The study of effect of isoflurane on acute lung injury induced byiiendotoxin in ratsThe rats were divided into four groups: control group(group C,n=30); isoflurane group(n=60): rats were exposed to isoflurane( 0.6% or 1.4% for 2,4,8h);LPS injured group(n=30): rats were intravenously administered LPS Smg.kg"1; LPS injured plus isoflurane exposed group(n=60): rats were intravenously administered LPS Smg.kg"1, followed by inhaled 0.6% or 1.4% isoflurane for 2,4,8h. The histopathological samples were inspected, and total lung water content, the ratio of neutrophils and protein content in bronchoalveolar lavage fluid(BALF) were measured. The change of SP-A hi bronchial lavage and serum was observed by Western Blotting, and TNFRi expression was analyzed using immuno-histochemistry.Results1. The study of preconditioning effect of isoflurane on lung injury induced by lipopolysaccharide (LPS) in ratsAfter LPS infusion in rats, lung water content, pulmonary micro vascular permeability, the ratio of neutrophils and content of protein in BALF were significantly increased (P<0.01) . But there was no significant difference between LPS group and IPL group ( PX).05 ) .2. The effect of isoflurane on acute lung injury induced by endotoxin in rats(1) After LPS infusion in rats, lung water content, the ratio of neutrophils and content of protein in BALF were significantly increased(PO.01) , with a decrease in SP-A of BALF and increase in SP-A of serum.(2) There was no significant difference between control group and 8h-0.6% isoflurane exposure group.(3) Compared with controls, 8h of exposure to 1.4% isoflurane caused a increase in the ratio of neutrophils and content of protein in BALF and SP-A ofserum, and a decrease in SP-A of BALF, with a rise in TNFRi expression ofinlung tissue.(4) LPS infusion plus isoflurane exposure caused greater increase in lung water content, the ratio of neutrophils and content of protein in BALF, SP-A of serum, with a decrease in SP-A of BALF when compared with the LPS infusion group.Conclusions:(1) Isoflurane preconditioning can not attenuate LPS-induced lung injury in rats.(2) Isoflurane might cause neutrophil collection and infiltration in the lung, increase alveolar-capillary membrane permeability, the SP-A level in serum and the expression of TNFRi, meanwhile isoflurane decrease the SP-A level in alveolus.(3) Isoflurane might aggravated the damage of ALI induced by LPS in rats. But the effect of isoflurane on LPS-induced lung injury needs to be further...