Intravenous injection of the alpha-2
adrenergic agonists,
clonidine and
xylazine, have been previously shown to produce
hypoxemia in sheep. To characterize this effect further,
clonidine and
ST-91, a
clonidine analog that does not cross the blood-brain barrier, were injected i.v. in 10 conscious ewes. Although both
clonidine (3-15 micrograms/kg) and
ST-91 (3-30 micrograms/kg) produced arterial
hypoxemia,
clonidine was more effective (arterial PO2 was 91 +/- 4 mm Hg after saline, 30 +/- 3 mm Hg after 15 micrograms/kg of
clonidine and 43 +/- 6 mm Hg after 30 micrograms/kg of
ST-91; mean +/- S.E., P less than .0001).
ST-91 increased mean arterial blood pressure in a dose-dependent manner (P less than .0001), whereas
clonidine did not affect blood pressure.
Clonidine-induced
hypoxemia was inhibited in a dose-dependent manner by the alpha-2
adrenergic antagonist idazoxan (0.01-1 mg/kg, complete inhibition after 1 mg/kg; P less than .0001), the hydrophilic alpha-2
adrenergic antagonist DG-5128 (0.1-10 mg/kg, 62 +/- 7% inhibition after 10 mg/kg; P less than .0005) and by infusion of
prostacyclin (0.15-0.5 microgram/kg/min, 57 +/- 7% inhibition after 0.5 micrograms/kg/min; P less than .05).
Hypoxemia was not inhibited by the
opiate antagonist
naloxone (1 mg/kg), the alpha-1
adrenergic antagonist prazosin (1 mg/kg) or the
prostaglandin synthetase inhibitor
ibuprofen (12.5 mg/kg). To characterize pulmonary vascular effects,
clonidine was injected i.v. in four anesthetized, mechanically ventilated ewes.(ABSTRACT TRUNCATED AT 250 WORDS)