Cardiopulmonary effects of clonidine, diazepam and the peripheral α₂ adrenoceptor agonist ST‐91 in conscious sheep

Abstract

The cardiopulmonary effects of the intravenous administration of clonidine (15 micrograms/kg), ST-91 (30 micrograms/kg) and diazepam (0.4 mg/kg) were compared in five healthy sheep using a randomized cross-over design, to determine whether the hypoxaemic effects of alpha 2 adrenoceptor agonists are due to sedation, or to peripheral alpha 2 adrenoceptor stimulation. All three drugs significantly lowered arterial oxygen tension (PaO2) levels within 2 min of their administration; however, clonidine and ST-91 produced long lasting and severe hypoxaemia with mean PaO2 levels of approximately equal to 40 mm Hg and 50 mm Hg (5.3 kPa and 6.6 kPa), respectively. The fall in PaO2 was considerably less with diazepam (63 mm Hg or 8.4 kPa at 2 min) and by 15 min the values did not differ from placebo treated animals. None of the drugs increased arterial carbon dioxide tension (PaCO2) levels when compared to saline treatment and the acid base variables did not show any significant change. A significant increase was recorded in the packed cell volume of the ST-91 treated group throughout the study. Within 2 min of their administration, all drugs caused a significant increase in mean arterial pressure (MAP) as compared to the placebo treated group. The MAP remained significantly increased for 5 and 60 min after clonidine and ST-91 treatment, respectively. The study shows that ST-91 and clonidine produce a greater degree of hypoxaemia than occurs with diazepam sedation, and that the hypoxaemic effect of alpha 2 adrenoceptor agonists in sheep are mainly mediated by peripheral alpha 2 adrenoceptors.

The cardiovascular and respiratory effects of medetomidine and thiopentone anaesthesia in dogs breathing at an altitude of 1486 m

“…Lung oedema has been demonstrated in sheep following the administration of alpha2 agonists [3][4][5] . Lung oedema has not been demonstrated in dogs.…”

A pharmacokinetic study including some relevant clinical effects of medetomidine and atipamezole in lactating dairy cows

“…Different α 2 ‐agonists are known to induce hypoxaemia in sheep and cattle and the mechanism by which this effect occurs has been investigated in sheep by Celly et al . (1997a ), who found that both central and peripheral mechanisms were involved.…”

A2-agonists in sheep: a review

“…The heart rate decreased by 35% immediately after IV injection, but was attenuated and delayed after intrathecal and extradural administration (Castro & Eisenach 1989). An IV dose of 15 μ g kg −1 increased mean arterial blood pressure 30% within 2 minutes of injection and produced a prolonged decrease in heart rate (Celly et al. 1997a).…”

“…This α 2 ‐agonist has no central nervous activity and is used mainly in experimental studies as a model drug. When given to conscious sheep (30 μ g kg −1 IV) ST‐91 caused massive increases in arterial blood pressure and heart rate but did not produce sedation (Celly et al. 1997a).…”

“…1994). They also affect pleural pressures as measured by oesophageal balloon catheters (Celly et al. 1997a,b) that increases calculated respiratory resistance (Celly et al.…”