Intrathecal clonidine and the response to hemorrhage.
Intraspinally administered alpha 2-adrenergic agonists are being examined for postoperative analgesia, yet their effects on the hemodynamic response to acute hemorrhage have not been examined. In this study chronically prepared conscious sheep received thoracic intrathecal saline or clonidine 300 micrograms followed in 15 min by rapid removal of 1,000 ml blood. In saline-treated ewes blood pressure was maintained and heart rate steadily increased during hemorrhage of up to 700 ml blood, with further blood removal resulting in rapid decreases in both variables. In contrast, heart rate never increased and blood pressure was maintained only up to 400 ml blood loss in animals receiving intrathecal clonidine. Compared to saline controls, clonidine did not alter blood pressure or heart rate at the end of hemorrhage or during blood pressure restitution during the next hour. Clonidine inhibited the increase in plasma epinephrine at the end of hemorrhage without altering plasma norepinephrine, vasopressin, renin, or atrial natriuretic factor. Intrathecal idazoxan, a specific alpha 2-adrenergic antagonist, reversed clonidine's effect on blood pressure during hemorrhage. Intravenous DG-5128, a poorly lipid-soluble alpha 2-adrenergic antagonist, also reversed clonidine's effect and additionally completely blocked any reduction in blood pressure and heart rate during hemorrhage. These data suggest that intrathecal clonidine interferes with maintenance of blood pressure during hemorrhage, likely because of a spinal sympatholytic effect, but does not affect the ultimate decrease in blood pressure after rapid removal of 1,000 ml blood. This difference in effect during the two phases of hemorrhage can be explained by the relative importance of the sympathetic nervous system in each.
Department of Anesthesia, Wake Forest University Medical Center, Winston-Salem, North Carolina 27157-1009.
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D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002395:Catecholamines / Q000097:blood; D003000:Clonidine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004146:Dioxanes / Q000494:pharmacology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D019329:Idazoxan; D007093:Imidazoles / Q000494:pharmacology; D007278:Injections, Spinal; D012756:Sheep; D012769:Shock / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D002395:Catecholamines; D004146:Dioxanes; D007093:Imidazoles; C032368:midaglizole; D003000:Clonidine; D019329:Idazoxan