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Background <p>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·kg<sup>−1</sup>). Seven minutes later, sheep received intravenous BIMU-8 (1.5&#xa0;mg·kg<sup>−1</sup>), vatinoxan (0.15&#xa0;mg·kg<sup>−1</sup>), 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.</p> Results <p>Etorphine induced bradypnea, pulmonary hypertension, dysrhythmias, and tachycardia in sheep. BIMU-8 significantly reduced mean pulmonary arterial pressure (F<sub>2,91</sub> = 4.17, <i>p</i> = 0.02) and mean arterial pressure (F<sub>2,89</sub> = 6.01, <i>p</i> &lt; 0.01) but was associated with severe tachydysrhythmia. Vatinoxan decreased respiratory rate (F<sub>2,91</sub> = 4.13, <i>p</i> &lt; 0.01), increased cardiac output (F<sub>2,91</sub> = 10.88, <i>p</i> &lt; 0.01), and reduced body temperature (F<sub>6,85</sub> = 2.2, <i>p</i> = 0.05), while having no effect on pulmonary or systemic arterial pressures.</p> Conclusion <p>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.</p>

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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

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  • 发表日期：

    2026年3月6日

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  • Hathaipat Rattanathanya,
  • Anna Binetti,
  • Friederike Pohlin,
  • Susana C.M. Ferreira,
  • Christina Braun,
  • Johannes Schramel,
  • Leith C.R. Meyer,
  • Anna Haw,
  • Marja Raekallio,
  • Stefan Böhmdorfer,
  • Szilvia Kalogeropoulu,
  • Martina Mosing,
  • Gabrielle Stalder

摘要

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 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.

Results

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.

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.