Cardiovascular effects of a selective 5-HT4 agonist and an alpha-2 adrenoceptor antagonist in etorphine immobilised sheep (Ovis aries) - a randomised, prospective, and controlled trial.

Abstract

BACKGROUND: Etorphine, a highly potent opioid widely used in wildlife immobilisation, is known to cause cardiorespiratory compromise. This study aimed to investigate the effects of a serotonergic agonist, BIMU-8 and an alpha-2 adrenoreceptor antagonist, vatinoxan on pulmonary hypertension and cardiovascular function in etorphine-immobilised sheep, as a model for wild ungulates. Six sheep were immobilised three times in a randomised, prospective, controlled crossover design using intramuscular etorphine (0.05&#xa0;mg&#xb7;kg). Seven minutes later, sheep received intravenous BIMU-8 (1.5&#xa0;mg&#xb7;kg), vatinoxan (0.15&#xa0;mg&#xb7;kg), or sterile water (control). Respiratory rate, pulmonary arterial, systemic arterial and central venous pressures, electrocardiography, heart rate, and cardiac output were recorded. Data were collected at resting state, six minutes post-etorphine, and at six-minute intervals post-treatment. Naltrexone was administered 19&#xa0;minutes post-treatment to reverse immobilisation. Linear mixed-effects models were used for statistical analysis. RESULTS: Etorphine induced bradypnea, pulmonary hypertension, dysrhythmias, and tachycardia in sheep. BIMU-8 significantly reduced mean pulmonary arterial pressure (F= 4.17,&#x2009;=&#x2009;0.02) and mean arterial pressure (F= 6.01,&#x2009;<&#x2009;0.01) but was associated with severe tachydysrhythmia. Vatinoxan decreased respiratory rate (F= 4.13,&#x2009;<&#x2009;0.01), increased cardiac output (F= 10.88,&#x2009;<&#x2009;0.01), and reduced body temperature (F= 2.2,&#x2009;=&#x2009;0.05), while having no effect on pulmonary or systemic arterial pressures. CONCLUSION: BIMU-8 reduces etorphine-induced pulmonary and systemic hypertension, but causes tachydysrhythmias, requiring further evaluation. Vatinoxan improves cardiac output, without alleviating pulmonary hypertension in etorphine-immobilised sheep. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12917-026-05379-x.