Anesthesia, monitoring and baseline measurements
Animals were acclimatized for at least 7 days. The night before
experiments, they were fasted. In all animals, premedication was
provided with an intramuscular injection of midazolam (0.3 mg/kg),
ketamine (20 mg/kg) and atropine (0.04 mg/kg). Anesthesia was induced
using inhalational isoflurane (end tidal concentration: 1-3%) and
maintained on the same concentration through an oral endotracheal tube
and mechanical ventilation was established with a tidal volume of 6-8
ml/kg. An arterial line was inserted through the right common carotid
artery and a central venous line was introduced into the left jugular
vein. A pulmonary artery catheter was inserted via the right jugular
vein and directed into position beyond the pulmonary artery bifurcation.
Standard monitoring consisted of: EKG, pulse oximetry, end tidal
CO2 and invasive arterial pressure. After a median
sternotomy and pericardiotomy, the heart and great vessels were exposed.
An umbilical tape was placed around the inferior vena cava and a
pressure-volume conductance catheter (Millar Instruments Inc, Houston,
TX, USA) was inserted into the left ventricular apex. Systemic
anticoagulation was achieved with an intravenous injection of heparin
(30 000 IU).