Faculty of Veterinary Medicine, Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.
4Pharma Ltd., Turku, Finland.
Equine Vet J. 2019 Sep;51(5):646-652. doi: 10.1111/evj.13085. Epub 2019 Mar 14.
Medetomidine suppresses cardiovascular function and reduces gastrointestinal motility in horses mainly through peripheral α -adrenoceptors. Vatinoxan, a peripheral α -antagonist, has been shown experimentally to alleviate the adverse effects of some α -agonists in horses. However, vatinoxan has not been investigated during constant-rate infusion (CRI) of medetomidine in standing horses.
To evaluate effects of vatinoxan on cardiovascular function, gastrointestinal motility and on sedation level during CRI of medetomidine.
Experimental, randomised, blinded, cross-over study.
Six healthy horses were given medetomidine hydrochloride, 7 μg/kg i.v., without (MED) and with (MED+V) vatinoxan hydrochloride, 140 μg/kg i.v., followed by CRI of medetomidine at 3.5 μg/kg/h for 60 min. Cardiorespiratory variables were recorded and borborygmi and sedation levels were scored for 120 min. Plasma drug concentrations were measured. The data were analysed using repeated measures ANCOVA and paired t-tests as appropriate.
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 min HR (mean ± s.d.) was 26 ± 2 and 31 ± 5 beats/minute (P = 0.04) and MAP 129 ± 15 and 103 ± 13 mmHg (P<0.001) respectively. At 10 min, cardiac index was lower (P = 0.02) and systemic vascular resistance higher (P = 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 min (6.8 ± 0.8 and 4.5 ± 1.5 with MED and MED+V, respectively, at 10 min, P = 0.001). Plasma concentration of dexmedetomidine was significantly lower in the presence of vatinoxan (P = 0.01).
Experimental study with healthy, unstimulated animals.
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 min.. The Summary is available in Portuguese - see Supporting Information.
美托咪定主要通过外周 α-肾上腺素能受体抑制马的心血管功能并降低胃肠道蠕动。Vatinoxan 是一种外周 α-拮抗剂，已在实验中证明可减轻马的一些 α-激动剂的不良反应。然而，在马站立时美托咪定恒速输注（CRI）期间尚未研究过 vatinoxan。
评估 vatinoxan 在美托咪定 CRI 期间对心血管功能、胃肠道蠕动和镇静水平的影响。
实验性、随机、盲法、交叉研究。
六匹健康马静脉注射盐酸美托咪定，7μg/kg（无 Vatinoxan）和静脉注射盐酸 Vatinoxan，140μg/kg（有 Vatinoxan），随后以 3.5μg/kg/h 的速度 CRI 美托咪定 60 分钟。记录心肺变量并评分 120 分钟的肠鸣音和镇静水平。测量血浆药物浓度。使用重复测量方差分析和配对 t 检验适当分析数据。
与 MED+V 相比，MED 初始时心率（HR）明显降低，平均动脉血压（MAP）明显升高。例如，在 10 分钟时，HR（平均值±标准差）分别为 26±2 和 31±5 次/分钟（P=0.04），MAP 分别为 129±15 和 103±13mmHg（P<0.001）。在 10 分钟时，心脏指数较低（P=0.02），全身血管阻力较高（P=0.001）。用 MED 后肠鸣音减少；这种作用被 vatinoxan 减弱（P<0.001）。所有马都用美托咪定镇静，但 MED+V 的平均镇静评分在 20 分钟内降低（分别为 6.8±0.8 和 4.5±1.5，在 10 分钟时，P=0.001）。静脉注射 vatinoxan 后，右美托咪定的血浆浓度明显降低（P=0.01）。
对健康、未受刺激的动物进行的实验研究。
在健康马中美托咪定静脉注射负荷剂量加用 vatinoxan 可改善美托咪定 CRI 期间的心血管功能和胃肠道蠕动。镇静作用在最初 20 分钟内略有但显著降低。总结提供葡萄牙语版本-见支持信息。
