Effects Of The Different Concentrations Of Isoflurane Pretreatment On Respiratory Mechanics, Oxygenation And Hemodynamics With Endotoxin-induced Acute Lung Injury Of The Piglets

Objective:1. Establish an endotoxin-induced acute lung injury (ALI) animal model in piglets for ALI research.2. To investigate the three concentrations of isoflurane pretreatment effects on respiratory mechanics, oxygenation and hemodynamics in the model of ALI.Methods:Twenty-four piglets of 5-6 weeks old, weighing 9-14 kg were divided into 4 groups (n= 6 each group) in random:LPS control group (CON group, n=6),0.5 MAC (minimum alveolar concentration) isoflurane pretreatment group (0.5 MAC group, n=6),1.0 MAC isoflurane pretreatment group (1.0 MAC group, n=6),1.3 MAC isoflurane pretreatment group (1.3 MAC group, n= 6).The animals were anaesthetized, intratracheally intubated and subjected mechanical ventilation. After isolation of left carotid artery and left external jugular vein, catheters were placed respectively to monitor hemodynamic parameters and infusion fluid, meanwhile monitor the blood gas analysis of artery, life sign, and the related respiratory parameters. Each animal in CON group was treated by vein infusion with lipopolysaccharide (LPS) 20μg·kg-1 for 60min. After the establishment of ALI, the mechanical ventilation were maintained in each groups for 12 hours; in 0.5 MAC,1.0 MAC,1.3 MAC group, each animal was treated by three different concentrations of isoflurane for 30min respectively. Waited for 60min, each animal was treated by vein infusion with LPS 20μg·kg-1 for 60min. The mechanical ventilation were maintained for 12 hours after the establishment of ALI. The respiratory mechanism, oxygenation and hemodynamics parameters were measured at the time of baseline, LPS 1h, LPS 2h, ALI Oh, ALI 4h, ALI 8h, ALI 12h.Result:1. Twenty-seven piglets, in which three piglets died accidently during the experimental time, were treated by vein infusion with LPS 20μg·kg-1. After 3-6 h infusion of LPS, ALI was induced when PaO2/TiO2≤300 mmHg, a more than 30% reduction of dynamic compliance (Cdyn) compared to baseline.2. Hemodynamics:After LPS infusion, there was a greater change in 0.5 MAC isoflurane pretreatment group than 1.3 MAC isoflurane pretreatment group compared to baseline in heart rate (HR), mean arterial blood pressure (MABP), cardiac output (CO), systemic vascular resistance (SVR) and dp/dtmax. The differences were significant statistically compared with the two groups.3. Respiratory mechanics and gas change analysis:After LPS infusion, there was a less change in 1.0 MAC group than other groups at mean airway pressure (MAP), values of Vd/Vt, pH, PaP2/FiO2 compared to baseline among all groups.Conclusion:1.20μg·kg-1 LPS (E. coli 0111:B4) could successfully establish endotoxin-induced ALI in piglet for the research purposes.2. Compare to other two concentrations of isoflurane, the pretreatment of 1.3MAC isoflurane had better protection to keep the stable circulation.3. Inhalation of 1.0MAC isoflurane pretreatment for 30 min may improve respiratory mechanism, gas exchange and oxygenation.