TY - JOUR T1 - Cardiopulmonary Effects of the α<sub>2</sub>-Adrenoceptor Agonists Medetomidine and ST-91 in Anesthetized Sheep JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 712 LP - 720 VL - 289 IS - 2 AU - C. S. Celly AU - W. N. McDonell AU - W. D. Black Y1 - 1999/05/01 UR - http://jpet.aspetjournals.org/content/289/2/712.abstract N2 - To test the hypothesis that pulmonary alterations are more important than hemodynamic changes in α2-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 μg/kg) and 2-(2,6-diethylphenylamino)-2-imidazol (ST-91; 1.5, 3.0, 6.0, and 12 μg/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 (ΔPpl) 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 μg/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, ΔPpl, 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 ΔPpl. 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. The American Society for Pharmacology and Experimental Therapeutics ER -