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

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 mg·kg−1). Seven minutes later, sheep received intravenous BIMU-8 (1.5 mg·kg−1), vatinoxan (0.15 mg·kg−1), 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 minutes post-treatment to reverse immobilisation. Linear mixed-effects models were used for statistical analysis. Etorphine induced bradypnea, pulmonary hypertension, dysrhythmias, and tachycardia in sheep. BIMU-8 significantly reduced mean pulmonary arterial pressure (F2,91 = 4.17, p = 0.02) and mean arterial pressure (F2,89 = 6.01, p < 0.01) but was associated with severe tachydysrhythmia. Vatinoxan decreased respiratory rate (F2,91 = 4.13, p < 0.01), increased cardiac output (F2,91 = 10.88, p < 0.01), and reduced body temperature (F6,85 = 2.2, p = 0.05), while having no effect on pulmonary or systemic arterial pressures. 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.