CARDIOPULMONARY AND BEHAVIORAL-RESPONSES TO COMPUTER-DRIVEN INFUSION OF DETOMIDINE IN STANDING HORSES

Cardiopulmonary and behavioral responses to detomidine, a potent alpha (2)-adrenergic agonist, were determined at 4 plasma concentrations in standing horses. After instrumentation and baseline measurements in 7 horses ((X) over bar +/- SD for age and body weight, 6 +/- 2 years, an d 531 +/- 48.5 kg, respectively), detomidine was infused to maintain 4 plasma concentrations: 2.1 +/- 0.5 (infusion 1), 7.2 +/- 3.5 (infusio n 2), 19.1 +/- 5.1. (infusion 3), and 42.9 +/- 10 (infusion 4) ng/ml, by use of a computer-controlled infusion system. Detomidine caused con centration-dependent sedation and somnolence. These effects were profo und during infusions 3 and 4, in which marked head ptosis developed an d all horses leaned heavily on the bars of the restraining stocks. Hea rt rate and cardiac index decreased from baseline measurements (42 +/- 7 beats/min, 65 +/- 11 ml.kg of bodyweight(-1).min(-1)) in linear rel ationship with the logarithm of plasma detomidine concentration tie, h eart rate = -4.7 [log(e), detomidine concentration] + 44.3, P < 0.01; cardiac index = - 10.5 [log(e) detomidine concentration] + 73.6, P < 0 .01). Second-degree atrioventricular block developed in 5 of 7 horses during infusion 3, and in 6 of 7 horses during infusion 4. Mean arteri al blood pressure increased significantly from 118 +/- 11 mm of Hg at baseline to 146 +/- 27 mm of Hg at infusion 4. Similar responses were observed for mean pulmonary artery and right atrial pressures. Systemi c vascular resistance (baseline, 182 +/- 28 mm of Hg.ml(-1).min(-1).kg (-1)) increased significantly during infusions 3 and 4 (to 294 +/- 79 and 380 +/- 58, respectively). Plasma atrial natriuretic peptide conce ntration was significantly increased with increasing detomidine concen tration (20.4 +/- 3.8 pg/ml at baseline to 33.5 +/- 9.1 at infusion 4) . There were few significant changes in respiration rate and arterial blood gas and pH values. We conclude that maintenance of steady-state detomidine plasma concentrations resuited in cardiopulmonary changes t hat were quantitativeIy similar to those induced by detomidine bolus a dministration in horses.