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Effects of MK-467 hydrochloride and hyoscine butylbromide on cardiorespiratory and gastrointestinal changes induced by detomidine hydrochloride in horses

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  • 1 Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, 00014 Helsinki, Finland.
  • | 2 Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, 00014 Helsinki, Finland.
  • | 3 Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, 00014 Helsinki, Finland.
  • | 4 Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523.
  • | 5 Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, 00014 Helsinki, Finland.
  • | 6 Admescope Ltd, Typpitie 1, 90620 Oulu, Finland.
  • | 7 Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, 00014 Helsinki, Finland.

Abstract

OBJECTIVE To compare the effects of MK-467 and hyoscine butylbromide on detomidine hydrochloride–induced cardiorespiratory and gastrointestinal changes in horses.

ANIMALS 6 healthy adult horses.

PROCEDURES Horses received detomidine hydrochloride (20 μg/kg, IV), followed 10 minutes later by MK-467 hydrochloride (150 μg/kg; DET-MK), hyoscine butylbromide (0.2 mg/kg; DET-HYO), or saline (0.9% NaCl) solution (DET-S), IV, in a Latin square design. Heart rate, respiratory rate, rectal temperature, arterial and venous blood pressures, and cardiac output were measured; blood gases and arterial plasma drug concentrations were analyzed; selected cardiopulmonary variables were calculated; and sedation and gastrointestinal borborygmi were scored at predetermined time points. Differences among treatments or within treatments over time were analyzed statistically.

RESULTS With DET-MK, detomidine-induced hypertension and bradycardia were reversed shortly after MK-467 injection. Marked tachycardia and hypertension were observed with DET-HYO. Mean heart rate and mean arterial blood pressure differed significantly among all treatments from 15 to 35 and 15 to 40 minutes after detomidine injection, respectively. Cardiac output was greater with DET-MK and DET-HYO than with DET-S 15 minutes after detomidine injection, but left ventricular workload was significantly higher with DET-HYO. Borborygmus score, reduced with all treatments, was most rapidly restored with DET-MK. Sedation scores and pharmacokinetic parameters of detomidine did not differ between DET-S and DET-MK.

CONCLUSIONS AND CLINICAL RELEVANCE MK-467 reversed or attenuated cardiovascular and gastrointestinal effects of detomidine without notable adverse effects or alterations in detomidine-induced sedation in horses. Further research is needed to determine whether these advantages are found in clinical patients and to assess whether the drug influences analgesic effects of detomidine.

Abstract

OBJECTIVE To compare the effects of MK-467 and hyoscine butylbromide on detomidine hydrochloride–induced cardiorespiratory and gastrointestinal changes in horses.

ANIMALS 6 healthy adult horses.

PROCEDURES Horses received detomidine hydrochloride (20 μg/kg, IV), followed 10 minutes later by MK-467 hydrochloride (150 μg/kg; DET-MK), hyoscine butylbromide (0.2 mg/kg; DET-HYO), or saline (0.9% NaCl) solution (DET-S), IV, in a Latin square design. Heart rate, respiratory rate, rectal temperature, arterial and venous blood pressures, and cardiac output were measured; blood gases and arterial plasma drug concentrations were analyzed; selected cardiopulmonary variables were calculated; and sedation and gastrointestinal borborygmi were scored at predetermined time points. Differences among treatments or within treatments over time were analyzed statistically.

RESULTS With DET-MK, detomidine-induced hypertension and bradycardia were reversed shortly after MK-467 injection. Marked tachycardia and hypertension were observed with DET-HYO. Mean heart rate and mean arterial blood pressure differed significantly among all treatments from 15 to 35 and 15 to 40 minutes after detomidine injection, respectively. Cardiac output was greater with DET-MK and DET-HYO than with DET-S 15 minutes after detomidine injection, but left ventricular workload was significantly higher with DET-HYO. Borborygmus score, reduced with all treatments, was most rapidly restored with DET-MK. Sedation scores and pharmacokinetic parameters of detomidine did not differ between DET-S and DET-MK.

CONCLUSIONS AND CLINICAL RELEVANCE MK-467 reversed or attenuated cardiovascular and gastrointestinal effects of detomidine without notable adverse effects or alterations in detomidine-induced sedation in horses. Further research is needed to determine whether these advantages are found in clinical patients and to assess whether the drug influences analgesic effects of detomidine.

Contributor Notes

Address correspondence to Dr Tapio (heidi.tapio@helsinki.fi).