title: Effect of an opiate antagonist (naloxone) and an agonist/antagonist (nalbuphine) in primate hemorrhagic shock: relationship to catecholamine release.
abstract: Recent evidence has suggested a relationship between the endogenous opioid peptides and the pathophysiology of various shock states. In the present study, we investigated the relationship between the effectiveness of naloxone (an opiate antagonist) and nalbuphine (an opiate agonist/antagonist), and the changes in circulating levels of catecholamines in the nonhuman primate subjected to hemorrhagic shock. Plasma levels of catecholamines were measured using high-performance liquid chromatography (HPLC) during hemorrhagic shock in 15 female baboons. Plasma levels of both epinephrine and norepinephrine increased significantly during hemorrhagic shock (p less than 0.05), which correlated with an increase in heart rate. Bolus administration of naloxone (5 mg/kg) significantly increased both plasma epinephrine (p less than 0.01) and norepinephrine (p less than 0.05) over shock levels along with a transient but significant increase in cardiac output (p less than 0.05) and mean arterial pressure (p less than 0.05), and a significant decrease in heart rate (p less than 0.05). Improvements in hemodynamics were maintained with a constant infusion of naloxone (5 mg/kg/hr), which also caused a further significant increase in plasma epinephrine (p less than 0.01). Administration of a single bolus of the opiate agonist/antagonist nalbuphine (5 mg/kg) dramatically decreased cardiac output and mean arterial pressure and had no effect on circulating catecholamines. Our results suggest that (1) the beneficial action of high-dose naloxone in primate hemorrhagic shock may be attributable in part to a drug-induced increase in circulating endogenous catecholamines; and (2) the failure of high-dose nalbuphine to improve cardiovascular function may be related to its partial agonist (cardiodepressant) properties at higher doses.
mesh_terms: D000818:Animals; D002395:Catecholamines / Q000097:blood*; D004195:Disease Models, Animal; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D009019:Morphinans / Q000494:pharmacology*; D009266:Nalbuphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology*; D010215:Papio; D012771:Shock, Hemorrhagic / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*
chemical_list: D002395:Catecholamines; D009019:Morphinans; D009270:Naloxone; D009266:Nalbuphine