Servo ventilator 900c

All 64 animals were anesthetized with an intramuscular dose of telazol (Wyeth Animal Health, Madison, NJ). Anesthesia was maintained by an IV infusion of propofol (2–9 mg/kg, AstraZeneca Pharmaceuticals, Wilmington, England) and 60% inhaled nitrous oxide. Upon sedation, the pigs were orally intubated and ventilated to maintain a PO₂ of 70–120 torr and a PCO₂ of 35–45 torr (SERVO Ventilator 900C, Siemens, Malvern, PA). Peripheral intravenous lines were placed in the surgically exposed right femoral artery and right jugular vein. A catheter was placed in the right femoral artery for continuous measurement of blood pressure and blood sampling. An introducer (7 French Avanti, Cordis Corporation, Miami Lakes, FL) was placed into the right jugular vein and a Swan-Ganz catheter (5 French, Edwards Lifesciences, Irvine, CA) was placed for measurements of pulmonary artery pressure, pulmonary wedge pressure, cardiac output, and mixed venous blood sampling. Animals then underwent a midline laparotomy and splenectomy. A Foley catheter was placed in the urinary bladder via stab cystostomy for collection of urine. The inferior vena cava (IVC) was cannulated for blood removal. After surgical preparation, animals were allowed to stabilize until plasma lactate levels reach a value of 2.0 mmol/L or less.

The animals were intubated as previously described^{45 (link)}. Briefly, under general anesthesia provided by ketamine 20 mg/Kg (Panpharma, France) and xylazine 1,5 mg/Kg (Rompun®, Bayer, Germany), a cuff tube of 2.5 mm (Mallinckrodt™, Covidien®, U.S.A.) was orally introduced into the trachea under view control. The animal was put in the supine position and connected to a volume-controlled respirator (Servo ventilator 900 C, Siemens®, Germany) (12 mL/kg of tidal volume with zero end-expiratory pressure [ZEEP], a respiratory rate of 30 bpm and an 0.5 inspired fraction of O₂), since it has been shown that VILI features are obtained with such settings^{46 (link),47 (link)}. Only ventilated rabbits were kept anesthetized and paralyzed throughout the experiment with midazolam (0.2 mg/Kg/h) (Hypnovel®, Roche, Switzerland) and cisatracurium besilate (0.8 mg/Kg/h) (Nimbex®, GlaxoSmithKline, U.K). The animals were placed on a heating blanket, and isotonic serum was infused. Non-invasive monitoring was used to monitor heart rate (Hewlett Packard 78353B Monitor). Arterial blood lactate and gases were measured just after intubation to ascertain the safety of our “adverse” MV and at 48 hours (or immediately before death, when bradycardia prior to asystole occurred).

Twenty-four sheep (24 [22 - 27] kg, median [25^th-75^thpercentiles]) were anesthetized with 30mg.kg^-1 sodium pentobarbital,
intubated and mechanically ventilated with a Servo Ventilator 900C (Siemens -
Elema AB, Solna, Sweden) with a tidal volume of 10mL/kg, an FiO₂ of
0.21 and a positive end-expiratory pressure of 6cmH₂O. The initial
respiratory rate was set to keep the arterial PCO₂ between 35 -
40mmHg. This respiratory setting was maintained during the rest of the
experiment. Neuromuscular blockade was performed with pancuronium bromide
(0.06mg.kg^-1). Additional pentobarbital boluses (1mg/kg) were
administered hourly and when clinical signs of inadequate depth of anesthesia
were evident. Analgesia was provided by fentanyl as a bolus of 2µg/kg,
followed by 1µg/kg/h. These drugs were administered intravenously.

Sixteen sheep (20 ± 2 kg, mean ± SEM) were anesthetized with 30 mg/kg of sodium pentobarbital, intubated, and mechanically ventilated with a Servo Ventilator 900C (Siemens-Elema AB, Solna, Sweden) with a tidal volume of 15 mL/kg, a FiO₂ of 0.21 and a positive end-expiratory pressure of 6 cm H₂O. The initial respiratory rate was set to keep the arterial PCO₂ between 35 and 40 mmHg. This respiratory setting was maintained during the rest of the experiment. Neuromuscular blockade was performed with pancuronium bromide (0.06 mg/kg). Additional pentobarbital boluses (1 mg/kg) were administered hourly and when clinical signs of inadequate depth of anesthesia were evident. Analgesia was provided by fentanyl as a bolus of 2 µg/kg, followed by 1 µg/h/kg. These drugs were administered intravenously.

Six Göttingen minipigs (2 females, 4 males, 27.8 ± 3.6 kg body weight) were examined in a 1.5-T clinical whole-body MRI. The animals were handled in compliance with the German animal welfare legislation and approval of the state animal welfare committee. All studies were performed under general anesthetic induced with ketamine, 30 mg/kg body weight intramuscular (Pharmacia, Karlsruhe, Germany); azaperone, 2 mg/kg body weight intramuscular (Stresnil; Janssen-Cilag, Neuss, Germany); and atropine, 0.025 mg/kg body weight (Eifelfango Chem.-Pharm. Werke, Bad Neuenahr-Ahrweiler, Germany). After intravenous application of 1.4 mg/kg propofol (Propofol-ratiopharm; Ratiopharm, Ulm, Germany), the animals were orally intubated (Roesch tube 6.0; Teleflex Medical, Kernen, Germany) and mechanically ventilated with an oxygen-air-mixture using an anesthesia workstation (Servo Ventilator 900C; Siemens, Erlangen, Germany). Anesthesia was maintained by intravenous injection with propofol (0.8 mg/kg/h). Animals were placed in a prone position, and the heart rate was monitored before each contrast administration. Test bolus and MRA imaging was performed during end-expiratory breath hold.

The animals underwent surgery under sterile conditions. Anesthesia was induced by intramuscular injections of pentobarbital (25 mg/kg). Sedation and analgesia were maintained through the continuous intravenous infusion of pentobarbital (2-3 mg/kg/h) combined with fentanyl (0.3-0.4 μg/kg/h) until the animals were euthanized. Intravascular catheters were placed in the femoral arteries and external jugular veins. The animals were orally intubated with a 7.5 ID tracheal tube for mechanical ventilation (Servo Ventilator 900C, Siemens-Elema; ventilation setting: pressure control; Pi: 12-16 cm H₂O; respiratory rate: 12-14/min; FiO₂: 23%-25%), in order to maintain SpO₂ > 95%, pO₂ > 80 mmHg, and pCO₂ = 35 ± 5 mmHg. A heating pad was used to maintain the core body temperature at 36.5 ± 1.0°C. Cystostomy was performed with a urethral catheter for adults (14F) fixed to the abdominal wall through a paramedian incision. Additionally, a gastric tube was orally placed for gastrointestinal decompression. Jejunostomy was performed over a length of 15-20 cm from the Treitz ligament, and the orificium fistulae were fixed at the lateral abdomen for intestinal microcirculation observation.