Vol. 289, Issue 2, 712-720, May 1999

Cardiopulmonary Effects of the ₂-Adrenoceptor Agonists Medetomidine and ST-91 in Anesthetized Sheep¹

C. S. Celly, W. N. McDonell and W. D. Black

Departments of Biomedical Sciences and Clinical Studies (W.N.M.), Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada

To test the hypothesis that pulmonary alterations are more important than hemodynamic changes in ₂-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 (R_L), dynamic compliance, and tidal volume changes in transpulmonary pressure (Ppl) 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 R_L, Ppl, 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 R_L and Ppl. 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.