Avanti

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.

Anesthesia was induced with Telazol (4.4 mg/kg), Ketamine (2.2 mg/kg), and Xylazine (2.2 mg/kg), and was maintained with 1.5–2.5% Isoflurane (Highland Medical Equipment, Temecula, CA and Baxter, Deerfield, IL). Sheaths were placed (AVANTI®, Cordis Corporation, Miami Lakes, FL) in both femoral veins for intravenous adenosine and contrast administration. In three of the animals, an extra sheath was placed in the right carotid artery to pass a Judkins Right (JR) catheter (Cordis Corporation, Miami Lakes, FL) into the left coronary ostium. A pressure wire (PrimeWire PRESTIGE® Pressure Guide Wire, Volcano Corp, Rancho Cordova, CA) was then advanced into the distal LAD. A balloon was passed over the wire into the mid LAD and was used to generate several levels of sub-occlusive stenosis with FFR (ComboMap, Volcano Corp., Rancho Cordova, CA) severities of 0.7–0.9 under maximal vasodilation (240 µg adenosine/kg/min, Model 55-2222, Harvard Apparatus, Holliston, MA). Beta blockers were not administered for heart rate control and nitroglycerin was not administered during CTA.

An incision of approximately 3–5 cm was made bilaterally on the flanks of the sheep. After dissection of the subcutis and muscle layers, the peritoneum was opened carefully. In each opening, two 10 F access sheaths (Avanti^®, Cordis^® Corporation, Arrow Int. Inc., Reading, PA, United States) were inserted and positioned in each of the four different quadrants of the abdominal cavity. Catheters for cranial IAP (IAP_cr) and caudal IAP (IAP_cd) were inserted opposite each another into the right abdominal wall. Ventral IAP (IAP_ventr) and dorsal IAP (IAP_ds) were measured by inserting the catheters into the left abdominal wall in an opposing manner. Abdominal integrity was restored by closing the peritoneum and fascia continuously and the skin by making single-knots and purse-string sutures around the inserted catheters. Finally, the pressure transducers were fixated to the sheep’s skin via Backhaus clamps after connecting them to the catheters. Abdominal pressures were measured during ventilated and spontaneous breathing. Representative curves for abdominal pressures during spontaneous and ventilated breathing can be seen in Figures 3A,B.

Induction of anesthesia was achieved with Telazol (4.4 mg/kg), Ketamine (2.2 mg/kg), and Xylazine (2.2 mg/kg), and was maintained with 1.5–2.5% Isoflurane (Highland Medical Equipment and Baxter) [14 (link)]. Introducer sheaths were placed (5 Fr, AVANTI^®, Cordis Corporation) in each femoral vein and were used for contrast media injection, intravenous fluids, and adenosine administration.