The Effect Of Posttreatment With Isoflurane Versus Propofol On Pulmonary Alveolar Capillary Barrier In Endotoxemic Rats

Objective In this study, we established a rat model with endotoxemia to observe the changes in pulmonary permeability and the expression of tight junction (TJ) molecules ZO-1 and occludin in lung tissues to explore the impacts and underlying mechanisms of posttreatment with isoflurane versus propofol on pulmonary alveolar capillary barrier (PACB) and to provide theoretical evidence for the choice of anesthetics in clinical setting. Methods Ninety-six male Sprague-Dawley rats (weighing 250 to 350 g) were administered with intravenous lipopolysaccharide (LPS, 4 mg/kg) or equivalent volume of normal saline (NS) to induce endotoxemic model. Two hours later, rats were randomly treated with intravenous pentobarbital (C, 20 mg·kg^-1·h^-1), inhaled isoflurane (I, 0.55%) or intravenous propofol (P, 10 mg/kg bolus, 40 mg·kg^-1·h^-1) to group as NS-C, NS-I, NS-P, LPS-C, LPS-I, LPS-P (n=16 per group). Rats were ventilated for 2h. Mean arterial pressure (MAP) and arterial blood gas were assessed hourly for 4h. One cohort (n=8 per group) was subjected to bronchial alveolar lavage in left lungs for determination of protein concentration in the bronchial alveolar lavage fluid (BALF) and the lung permeability index (LPI, BALF protein concentration/serum protein concentration). The right lungs were removed for light and electron microscopy observation and for measurement of wet wet-to-dry weight ratio (WW/WD). In a second cohort (n=8 per group), evans blue dye (EBD, 30 mg/kg) was injected 30 min before the end of the experiment to determine EBD concentration in the lung. The levels of mRNA and protein expression of ZO-1 and occludin were semi-quantified by reverse-transcription polymerase chain reaction (RT-PCR) and western blot, respectively. Immunohistochemistry was used to locate the protein expression of ZO-1 and occludin in pulmonary. Results (1) The MAP, pH, PaCO2 and PaO2 were not different significantly within three NS groups and three LPS groups. (2) WW/WD did not show any difference among all six groups. (3) The LPI and EBD concentration in lung were significantly higher in LPS-C group (8.1 ± 2.4× 10^-3, 0.628±0.082 absorption unit (AU)) than in NS-C group (3.3 ±2.2× 10^-3, 0.479±0.154 AU), and were higher in LPS-P group (9.1 ±2.2× 10^-3, 0.664±0.028 AU) than in LPS-I group (5.5±2.0× 10^-3, 0.517±0.048 AU). (4) Light microscopy showed more severe lung injury changes in LPS groups than in NS groups, which...