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 (mean +/- SD for age and body weight, 6 +/- 2 years, and 531 +/- 48.5 kg, respectively), detomidine was infused to maintain 4 plasma concentrations: 2.1 +/- 0.5 (infusion 1), 7.2 +/- 3.5 (infusion 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 concentration-dependent sedation and somnolence. These effects were profound during infusions 3 and 4, in which marked head ptosis developed and all horses leaned heavily on the bars of the restraining stocks. Heart rate and cardiac index decreased from baseline measurements (42 +/- 7 beats/min, 65 +/- 11 ml.kg of body weight-1.min-1) in linear relationship with the logarithm of plasma detomidine concentration (ie, heart 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 arterial 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. Systemic 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 concentration was significantly increased with increasing detomidine concentration (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 resulted in cardiopulmonary changes that were quantitatively similar to those induced by detomidine bolus administration in horses.

Ibuprofen treatment was compared with saline solution treatment in an endotoxin-induced experimental model of bovine mastitis. Acute mastitis was induced in healthy lactating Holstein cows (n = 12) by intrammamary inoculation of 1 mg of Escbericbia coli 026:B6 lipopolysaccharide in a single quarter per cow. Cows were assigned at random to ibuprofen (25 mg/kg of body weight, IV, n = 6) or 0.9% sodium chloride solution control (1.25 ml/kg, IV, n = 6) treatment groups. Ibuprofen or saline solution was administered once, 2 hours after endotoxin administration. The clinical course of endotoxin-induced mastitis and hematologic, clinical biochemical, and plasma mineral changes were monitored and compared between ibuprofen-treated and control cows. Clinical monitoring and blood sample collection were performed at 0, 2, 4, 6, 8, 12, 24, 48, 96, and 192 hours after endotoxin challenge. Rectal temperature and heart and respiratory rates were significantly (P < 0.05) increased in saline treated cows, compared with cows treated with ibuprofen, Blood eosinophil count and serum phosphorus, sodium, and total carbon dioxide concentrations were significantly (P < 0.05) decreased in saline-treated cows, compared with cows treated with ibuprofen. Ibuprofen treatment did not significantly change ruminations per minute, electrical conductivity of milk, quarter size, or quarter inflammation. The remaining hematologic, serum biochemical, plasma mineral, and coagulation values also were not changed significantly in response to ibuprofen treatment. Untoward effects attributed to ibuprofen administration were not observed. These results indicate that ibuprofen may provide empiric relief of clinical signs of coliform-induced mastitis.