The effect of sympatholytics on uncontrolled hemorrhage

Crit Care Med. 1999 Sep;27(9):1856-61. doi: 10.1097/00003246-199909000-00025.

Abstract

Objective: To assess the possible benefits of sympatholytics on uncontrolled hemorrhage in unanesthetized rats.

Design: A randomized laboratory study using rats to test the effects of sympatholytics on uncontrolled hemorrhage.

Setting: Research laboratory.

Subjects: Forty female Sprague-Dawley rats, randomly assigned into four groups according to the treatment: untreated (Control); alpha-adrenergic blockade with phenoxybenzamine (Alpha); beta-adrenergic blockade with propranolol (Beta); and a combined alpha- and beta-adrenergic blockade by phenoxybenzamine and propranolol (Alpha/Beta).

Intervention: After cannulation under light ether, the rats were allowed to awaken. A baseline blood sample was withdrawn. The uncontrolled hemorrhage was initiated by tail resection and allowed to continue without intervention for the duration of the experiment. After 15 mins, 80 mL/kg isotonic saline fluid was infused at 4.4 mL/min. At 60 mins, another blood sample was drawn; changes in mean arterial pressure, hematocrit, blood loss, and mortality were observed for up to 180 mins.

Main outcome measure: Survival, mortality, blood loss (amount, prevalence, and rate), and hemodynamic variables (mean arterial pressure, pulse rate, hematocrit).

Results: In the Alpha group, there was a reduction in spontaneous blood loss compared with the control group (2.9 vs. 10.6 mL/kg, respectively) and 100% survival. In contrast, the Beta group exhibited an increase in tail blood loss (21.1 mL) and a decreased survival (10%). Despite the enhanced hemorrhage in the Alpha/Beta group (17.0 mL/kg) compared with controls, the survival rate in both of these groups was 60%. In all groups, no significant increase in tail blood loss was observed after 60 mins.

Conclusions: An alpha-adrenergic blockade increased survival in uncontrolled hemorrhage by significantly reducing spontaneous blood loss. Conversely, a beta-adrenergic blockade significantly decreased survival and increased blood loss, whereas a combined blockade significantly increased blood loss without affecting survival.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic alpha-Antagonists / pharmacology*
  • Adrenergic beta-Antagonists / adverse effects*
  • Animals
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Female
  • Hemodynamics / drug effects
  • Hemorrhage / drug therapy*
  • Hemorrhage / mortality
  • Phenoxybenzamine / pharmacology*
  • Propranolol / adverse effects*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Survival Rate
  • Sympatholytics / pharmacology*
  • Time Factors

Substances

  • Adrenergic alpha-Antagonists
  • Adrenergic beta-Antagonists
  • Sympatholytics
  • Phenoxybenzamine
  • Propranolol