Cardiopulmonary effects of clonidine, diazepam and the peripheral alpha 2 adrenoceptor agonist ST-91 in conscious sheep.

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.