To test the hypothesis that pulmonary alterations are more important than hemodynamic changes in alpha2-agonist-induced
hypoxemia in ruminants, the cardiopulmonary effects of incremental doses of (4-[1-(2,3-dimethylphenyl)ethyl]-1H-imadazole)
hydrochloride (medetomidine; 0.5, 1.0, 2.0, and 4 micrograms/kg) and 2-(2, 6-diethylphenylamino)-2-imidazol (
ST-91; 1.5, 3.0, 6.0, and 12 micrograms/kg) were compared in five
halothane-anesthetized, ventilated sheep using a placebo-controlled randomized crossover design. Pulmonary resistance (RL), dynamic compliance, and tidal volume changes in transpulmonary pressure (DeltaPpl) were determined by pneumotachography, whereas cardiac index (CI), mean pulmonary artery pressure (Ppa), and pulmonary artery wedge pressure (Ppaw) were determined using thermodilution and a Swan-Ganz
catheter. The most important finding was the fall in partial pressure of
oxygen in arterial blood (PaO2) after administration of
medetomidine at a dose (0.5 micrograms/kg) 20 times less than the
sedative dose. The PaO2 levels decreased to 214 mm Hg as compared with 510 mm Hg in the placebo-treated group. This decrease in PaO2 was associated with a decrease in dynamic compliance and an increase in RL, DeltaPpl, and the intrapulmonary shunt fraction without changes in heart rate, CI, mean arterial pressure, pulmonary vascular resistance, Ppa, or Ppaw. On the other hand,
ST-91 only produced significant changes in PaO2 at the highest dose. After this dose of
ST-91, the decrease in PaO2 was accompanied by a 50% decrease in CI and an increase in mean arterial pressure, Ppa, Ppaw, and the intrapulmonary shunt fraction without significant alterations of RL and DeltaPpl. The study suggests that the mechanism(s) by which
medetomidine and
ST-91 produce lower PaO2 are different and that
drug-induced alterations in the pulmonary system are mainly responsible for the
oxygen-lowering effect of
medetomidine.