Intravenous clonidine produces hypoxemia by a peripheral alpha-2 adrenergic mechanism.
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)
Eisenach
J C
JC
Department of Anesthesia, Wake Forest University Medical Center, Bowman Gray School of Medicine, Winston-Salem, North Carolina.
D000818:Animals; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D000860:Hypoxia / Q000139:chemically induced*; D007275:Injections, Intravenous; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D012119:Respiration / Q000187:drug effects; D012756:Sheep; D013997:Time Factors
D011942:Receptors, Adrenergic, alpha; D003000:Clonidine