Sevoflurane MAC and hemodynamics in pigs Otsuki DA et al. the approval of ANVISA, Brazil’s Regulatory Agency. Propylene glycol is a product utilized in several medications, via different routes, and has been considered a GRAS product (Generally Recognized as Safe) by the US Food and Drug Administration.3 It can be used as an antimicrobial preservative, disinfectant, humectant, solvent, vitamin stabilizer and water-miscible co-solvent. Given this information, we conducted a comparative study of sevoflurane with water additive versus with propylene glycol additive under experimental conditions in pigs. We compared the MAC, hemodynamic and metabolic effects and relevant lung histopathological analyses. MATERIALS AND METHODS The study protocol and design were approved by the Ethics and Animal Investigation Committee at our institution and were performed according to the recommendations of the National Institutes of Health guidelines for ethical animal research. Sixteen young male Large White x Landrace pigs weighing 30 to 35 Kg (31.6±1.8 Kg) were fasted overnight with free access to water and were randomly assigned to the Sevo A or Sevocris groups. After induction of anesthesia via mask with the assigned sevoflurane (6% in 100% oxygen), animals were orally intubated (7 mm internal diameter cuffed endotracheal tube, Hi-Lo, National Catheter, Argyle, NY). The lungs were mechanically ventilated (Primus, Dräger Medical, Lubeck, Germany) using volume-controlled ventilation, 40% FiO2, tidal volume of 8 mL/kg, PEEP of 5 cmH2O, which was the respiratory frequency adjusted to keep end-tidal CO2 between 35 and 45 mmHg. Anesthesia was maintained with 5% sevoflurane in 40% oxygen. A continuous infusion of lactated Ringer (Baxter, São Paulo, Brazil) was provided at a rate of 5 mL.kg-1.h-1 throughout all experiments. The temperature was maintained within normal limits for pigs (38.7-39.9°C) using warm blankets (Medi-therm II, Gaymar Industries, Orchard Park, NY, USA). Instrumentation After local anesthetic infiltration (10 mL 2% lidocaine with vasoconstrictor), the right femoral artery was surgically exposed and catheterized for arterial pressure measurements and blood collection. The right jugular vein was also catheterized with a pulmonary artery catheter (7.5 F Edwards CCO catheter connected to Edwards Vigilance CCO Monitor; Edwards Lifesciences Corp., Irvine, CA, USA). The position of the pulmonary artery catheter was confirmed by typical waveforms. All intravascular catheters were zeroed to atmospheric pressure. The midpoint between the 532 CLINICS 2010;65(5):531-7 anterior and posterior chest walls was taken as the zero reference point for pressure measurements. The STAT-Mode of the Edwards Vigilance CCO Monitor was used in each experiment, which displayed the actual cardiac output values registered over the past 60 seconds. The last five measurements of CO were averaged. The electrocardiogram and intravascular pressures, mean arterial pressure (MAP), mean pulmonary artery pressure (MPAP), pulmonary artery wedge pressure (PAWP) and central venous pressure (CVP) were monitored continuously (MP40, Philips). Numerical values of intravascular pressures from the monitor screen were recorded at established points of the protocol. After instrumentation, animals were allowed to stabilize for 60 minutes. Hemodynamic indices The derivative indexes were recorded directly from monitors during the experiment: the pulmonary vascular resistance index (PVRI), systemic vascular resistance index (SVRI), right and left ventricular stroke work index (RVSWI and LVSWI), right stroke volume index, (RSVI), right ventricle ejection fraction (RVEF) and right ventricular end-diastolic volume (RVEDV). The cardiac index (CI) was calculated according to calculated body surface (k.BW2/3, where k = 0.09, BW=body weight).4, 5 Venous admixture and oxygenation indices Arterial and mixed venous blood samples were collected for pH, partial pressure of arterial oxygen (PaO2), partial pressure of arterial carbon dioxide (PaCO ), arterial 2 oxygen saturation (SaO2), partial pressure of mixed venous oxygen (PvO2) and mixed venous saturation (SvO2) (ABL 555; Radiometer, Copenhagen, Denmark). The oxygen delivery index (DO2I), oxygen consumption index (VO2I) and extraction ratio (O2ER) were calculated utilizing conventional formulas. Determination of MAC The method for the determination of MAC in this study has been described elsewhere.6,7 The end-tidal concentration of sevoflurane was maintained at the intended level for a 15 min equilibration period. After 15 min of equilibration, the pig was stimulated on a dew claw with a hemostat clamped to a full ratchet lock for 60 s. The leg was moved back and forth. If there were no purposeful movements in response to the stimulus (withdrawal of the clamped foot or gross movements of either legs or head), the end-tidal sevoflurane was Copyright © 2010 CLINICS