INTRAVENOUS CLONIDINE PRODUCES HYPOXEMIA BY A PERIPHERAL ALPHA-2 ADRENERGIC MECHANISM

  • 1 January 1988
    • journal article
    • research article
    • Vol. 244  (1) , 247-252
Abstract
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 .mu.g/kg) and ST-91 (3-30 .mu.g/kg) produced arterial hypoxemia, clonidine was more effective (arterial PO2 was 91 .+-. 4 mm Hg after saline, 30 .+-. 3 mm Hg after 15 .mu.g/kg of clonidine and 43 .+-. 6 mm Hg after 30 .mu.g/kg of ST-91; mean .+-. S.E., P < .0001). ST-91 increased mean arterial blood pressure in a dose-dependent manner (P < .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 < .0001), the hydrophilic alpha-2 adrenergic antagonist DG-5128 (0.1-10 mg/kg, 62 .+-. 7% inhibition after 10 mg/kg; P < .0005) and by infusion of prostacyclin (0.15-0.5 .mu.g/kg/min, 57 .+-. 7% inhibition after 0.5 .mu.g/kg/min; P < .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. Clonidine decreased arterial PO2 (from 497 .+-. 57 mm Hg to 35 .+-. 7 mm Hg; mean .+-. S.E., P < .001) and increased intrapulmonary shunt (from 11 to 4% to 72 .+-. 10% of total flow; P < .001) and deadspace ventilation (from 41 to 4% to 71 .+-. 3% of total ventilation; P < .001). These data suggest that i.v. clonidine produces hypoxemia in sheep by a peripheral alpha-2 adrenergic mechanism. Hypoxemia is not due to changes in blood pressure or prostaglandin synthesis. Clonidine-induced hypoxemia may be due to transient platelet aggregation and pulmonary embolism.

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