Evidence for a role of endorphins in the cardiovascular pathophysiology of primate shock.
Using the opiate receptor antagonist naloxone, we tested the hypothesis that endorphins act on opiate receptors to cause cardiovascular depression in primate shock. Mean arterial pressure (MAP), cardiac output, and left ventricular contractility (LV dP/dtmax) were measured in 34 anesthetized cynomolgus monkeys. Hemorrhagic shock was induced by bleeding into a heparinized reservoir to achieve (t = 0) and maintain MAP at 45 mm Hg. At t = 60 min, the reservoir was clamped and the animals were treated with 2 mg/kg plus 2 mg/kg.h naloxone (n = 5) or 0.9% NaCl as a control (n = 5). There were no significant differences in the cardiovascular responses to naloxone and saline when acid-base balance and core body temperature were not controlled. Pressor responses to naloxone, however, were present in proportion to arterial pH and body temperature. When these factors were controlled, naloxone (n = 6) significantly increased MAP and LV dP/dtmax by 48% and 83%, respectively, whereas saline (n = 6) had no significant effect. Blood was reinfused at t = 120 min, and survival rate at 72 h was significantly (p = .01) higher with naloxone (3/6) than saline controls (0/6). In the endotoxic shock model, cynomolgus monkeys were treated with 2 mg/kg plus 2 mg/kg.h naloxone (n = 6) or 0.9% NaCl (n = 6) when MAP reached 75 mm Hg or its nadir 60 to 90 min after Escherichia coli endotoxin, 5 mg/kg iv. Naloxone significantly increased MAP and LV dP/dtmax by 24% and 22%, respectively, whereas saline had no effect. Survival rate at 48 h was significantly (p = .01) higher with naloxone (6/6) than saline (1/6). Plasma beta-endorphin and beta-lipotropin concentrations rose three to five-fold in both shock models and were not affected by treatment. We conclude that endorphins are activated in primate shock and act on opiate receptors to contribute to the cardiovascular depression found with hemorrhage and endotoxemia.
Gurll
N J
NJ
Surgical Service, Veterans Administration Medical Center, Iowa City, IA.
Reynolds
D G
DG
Holaday
J W
JW
D000138:Acidosis / Q000503:physiopathology; D000818:Animals; D003080:Cold Temperature; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008252:Macaca fascicularis; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D001615:beta-Endorphin / Q000097:blood / Q000502:physiology*; D008083:beta-Lipotropin / Q000097:blood / Q000502:physiology
D009270:Naloxone; D001615:beta-Endorphin; D008083:beta-Lipotropin