Objective To investigate the safety of inhalation of isoflurane (ISO) or sevoflurane (SEVO) mixed with nitric oxide (NO) during mechanical ventilation.Methods Thirty-six healthy piglets of both sexes weighing 7-11 kg were randomly allocated to one of 6 groups ( n = 6 each): (1) control group was mechanically ventilated with O2; (2) NO group inhaled 20 ppm NO; (3) ISO group inhaled 1.3 MAC isoflurane; (4) ISO + NO group 1.3 MAC isoflurane + 20 ppm NO; (5) SEVO group inhaled 1.3 MAC sevoflurane and (6) SEVO + NO group inhaled 1.3 MAC sevoflurane + 20 ppm NO. The animals were mechanically ventilated with IPPV (VT 10 ml·kg-1 , RR 30-40 bpm, I: E 1:2) for 4 h in the all 6 groups. The animals were premedicated with atropine 0.02 mg·kg-1 i.m. . The Ⅳ line was established for fluid and drug administration. An additional dose of ketamine 10 mg·kg-1 was given i.v. before tracheostomy. 4F S-G catheter was placed in pulmonary artery via right internal jugular vein for hemodynamic monitoring. Femoral artery was cannulated for BP monitoring and collection of artrerial blood samples. MAP, HR, CVP, right ventricular pressure (RVP), PCWP, MPAP and total compliance of respiratory system (Crs), Paw, VT and PET CO2 were recorded before (T0 ) and at 1, 2, 3, 4 h of ventilation (T1-4). Blood samples were taken at T0 , T2 and T4 for determination of Met Hb and NO2- /NO3- .
The animals were killed at the end of 4 h mechanical ventilation and the lungs were removed for determination of wet/dry(W/D) lung weight ratio, broncho-alveolar lavage fluid (BALF) and microscopic examination. BALF was collected for determination of surface tension and concentrations of saturated phosphate (DSPC) , total phosphate (TPL) total protein (TP) and white cell count. Results Crs was significantly decreased at the end of ventilation (T4 ) as compared with the baseline (T0) in group 3,4,5 and 6, while there was no significant change in Crs in group 1 and 2. DSPC/TP was significantly lower in group 3,4,5 and 6 than in group 1 ( P < 0.05) , There were no significant changes in the level of MetHb and NO2- /NO3- at the end of ventilation (T4) as compared with the baseline (T0) in the all 6 groups. There was no significant difference in W/D ratio, WBC count in BALF, lung injury scores and alveolar expansion among the 6 groups ( P > 0.05 ) . Conclusion 1.3 MAC isoflurane or sevoflurane mixed with 20 ppm NO can be used safely during mechanical ventilation.