Effects of vatinoxan on cardiorespiratory function and gastrointestinal motility during constant-rate medetomidine infusion in standing horses.

Abstract

BACKGROUND: Medetomidine suppresses cardiovascular function and reduces gastrointestinal motility in horses mainly through peripheral &#x3b1;-adrenoceptors. Vatinoxan, a peripheral &#x3b1;-antagonist, has been shown experimentally to alleviate the adverse effects of some &#x3b1;-agonists in horses. However, vatinoxan has not been investigated during constant-rate infusion (CRI) of medetomidine in standing horses. OBJECTIVES: To evaluate effects of vatinoxan on cardiovascular function, gastrointestinal motility and on sedation level during CRI of medetomidine. STUDY DESIGN: Experimental, randomised, blinded, cross-over study. METHODS: Six healthy horses were given medetomidine hydrochloride, 7&#xa0;&#x3bc;g/kg i.v., without (MED) and with (MED+V) vatinoxan hydrochloride, 140&#xa0;&#x3bc;g/kg i.v., followed by CRI of medetomidine at 3.5&#xa0;&#x3bc;g/kg/h for 60&#xa0;min. Cardiorespiratory variables were recorded and borborygmi and sedation levels were scored for 120&#xa0;min. Plasma drug concentrations were measured. The data were analysed using repeated measures ANCOVA and paired t-tests as appropriate. RESULTS: Initially heart rate (HR) was significantly lower and mean arterial blood pressure (MAP) significantly higher with MED compared with MED+V. For example at 10&#xa0;min HR (mean&#xa0;&#xb1;&#xa0;s.d.) was 26&#xa0;&#xb1;&#xa0;2 and 31&#xa0;&#xb1;&#xa0;5 beats/minute (P&#xa0;=&#xa0;0.04) and MAP 129&#xa0;&#xb1;&#xa0;15 and 103&#xa0;&#xb1;&#xa0;13&#xa0;mmHg (P<0.001) respectively. At 10&#xa0;min, cardiac index was lower (P&#xa0;=&#xa0;0.02) and systemic vascular resistance higher (P&#xa0;=&#xa0;0.001) with MED than with MED+V. Borborygmi were reduced after MED; this effect was attenuated by vatinoxan (P<0.001). All horses were sedated with medetomidine, but the mean sedation scores were reduced with MED+V until 20&#xa0;min (6.8&#xa0;&#xb1;&#xa0;0.8 and 4.5&#xa0;&#xb1;&#xa0;1.5 with MED and MED+V, respectively, at 10&#xa0;min, P&#xa0;=&#xa0;0.001). Plasma concentration of dexmedetomidine was significantly lower in the presence of vatinoxan (P&#xa0;=&#xa0;0.01). MAIN LIMITATIONS: Experimental study with healthy, unstimulated animals. CONCLUSIONS: Vatinoxan administered i.v. with a loading dose of medetomidine improved cardiovascular function and gastrointestinal motility during medetomidine CRI in healthy horses. Sedation was slightly yet significantly reduced during the first 20&#xa0;min.. The Summary is available in Portuguese - see Supporting Information.