The Effects Of Isoflurane Administration Before Ischemia On Ischemia-Reperfusion Injury In Rat Lung

Objective In this study, we established a rat model of lung ischemia-reperfusion injury to observe the changes of pulmonary function, vascular permeability, the content of MDA and SOD, MPO activity, pulmonary histology, the gene expressions of intercellular adhesion molecule-1 (ICAM-1) and cytokine-induced neutrophil chemoattractant (CINC), the expression of CD18 and the DNA binding activity of nuclear factor-κB (NF-κB) in rat lung in order to explore the effects of isoflurane administration before ischemia on ischemia-reperfusion injury in rat lung and offer the experimental and theoretical evidence for the choice of anesthetics in clinical practice. Methods The rat ischemia model with occlusion of left pulmonary hilum for 45min was used in this experiment. One hundred and twenty male Sprague-Dawley rats were randomly divided into four groups. Group C (n=30): continuous perfusion without ischemia; group IR (n=30): interruption of perfusion and ventilation for 45min, followed by reperfusion; group ISO-IR (n=30): 1MAC isoflurane inhalation for 30min before ischemia, followed by ischemia-reperfusion; group ISO-C (n=30): 1MAC isoflurane inhalation for 30min, followed by continuous perfusion. The changes of arterial blood gas analysis, the lung wet-to-dry weight ratio (W/D), malondialdehyde (MDA), superoxide dismutase (SOD) and myeloperoxidase (MPO) of lung were studied at 45 min after pulmonary ischemia and 30min, 60min, 120min of reperfusion. The gene expressions of ICAM-1 and CINC were detected by reverse-transcription polymerase chain reaction (RT-PCR) , the expression of integrin subunit CD18 was determined by the method of flow cytometry and the DNA binding activity of NF-κB in rat lung was measured by electrophoretic mobility shift assay (EMSA ) at the same time above-mentioned. The cell counts, percentage of polymorphonuclear neutrophil (PMN) and total protein (TP) content in left bronchoalveolar lavage fluid (BALF) was performed at 120min of reperfusion. MAP was continuously monitored. Results (1) The change of PaO2: In IR and ISO-IR groups, PaO2 decreased gradually and was obviously lower than that in C and ISO-C groups during reperfusion (P<0.05).There was no significant difference in PaO2 between IR and ISO-IR groups, but there was a tendency of the improvement in PaO2 of ISO-IR group during reperfusion compared with IR group. (2) The lungW/D: At 45min after ischemia, there was no significant difference in the lung W/D among groups. During reperfusion the lung W/D in IR and ISO-IR groups increased progressively and was evidently higher than that in C and ISO-C groups (P<0.05)；but compared with IR group, preadministration of isoflurane could inhibit the increase in the lung W/D after 60min of reperfusion (P<0.05). The lung W/D in ISO-C group was no obvious change compared with C group during the experiment. (3) The cell counts, percentage of PMN and TP content in BALF: There was no marked difference in the cell counts among groups, but the percentage of PMN in IR group was obviously increased compared with the other groups at 120min of reperfusion (P<0.05). IR significantly increased the content of TP in BALF of IR and ISO-IR groups, but the degree of increase in TP content of ISO-IR group was decreased markedly compared with IR group (P<0.05). (4) The lung contents of MDA and SOD: Little change in lung contents of MDA and SOD was measured in C and ISO-C groups during the perfusion and there was no marked difference between the two groups, too. In IR and ISO-IR groups, MDA increased and SOD decreased significantly compared with C group during reperfusion (P<0.05), but the inhalation of isoflurane could attenuate the increase in MDA after 60min of the reperfusion (P<0.05) and not inhibit the decrease in SOD. (5) Lung MPO activity: The marked change of MPO activity was not observed in C and ISO-C groups during the perfusion. After the reperfusion, lung MPO activity in IR and ISO-IR groups increased gradually, especially after 60min of reperfusion and was higher than that in C group (P<0.0...