Preserving cardiac output with beta-adrenergic receptor blockade and inhibiting the Bezold-Jarisch reflex during resuscitation from hemorrhage

J Trauma. 2007 Jul;63(1):26-32. doi: 10.1097/TA.0b013e31806864e2.

Abstract

Background: Successful fluid resuscitation after severe hemorrhage may be limited by activation of the Bezold-Jarisch reflex. We postulated that pharmacologic inhibition of this reflex would restore cardiovascular hemodynamics more effectively than would volume repletion alone during resuscitation for hemorrhagic shock.

Methods: We measured mean arterial pressure (MAP), heart rate (HR), and cardiac output (CO) during fluid resuscitation after hemorrhaging laboratory rats until their CO had decreased by 90% to 95%. To block distinct components of the Bezold-Jarisch reflex, animals received capsazepine, yohimbine, or propranolol before iso-osmotic volume repletion.

Results: Hemorrhage decreased MAP and CO; despite an initial tachycardia, HR fell significantly in response to this large volume blood loss. The degree of hemorrhage-induced bradycardia mediated by the Bezold-Jarisch reflex predicted resuscitation MAP. Capsazepine-treated animals had greater resuscitation-induced increases in MAP (values in mm Hg +/- SEM), 130 +/- 12, when compared with the saline-only animals, 90 +/- 7 (p = 0.004). The capsazepine group also had a greater increase in systemic vascular resistance over baseline values during resuscitation (86% +/- 19%) compared with vehicle-treated animals (26% +/- 14%, p = 0.02). Capsazepine had no effect on cardiac dynamics. On the other hand, yohimbine increased HR and diminished CO, and propranolol dramatically increased stroke volume by 30%.

Conclusion: Inhibition of the Bezold-Jarisch reflex may aid fluid resuscitation after hemorrhage only if stroke volume is restored. Beta-adrenergic receptor antagonists such as propranolol may prove the most salutary of these agents in enhancing fluid resuscitation in patients with severe hemorrhage.

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology*
  • Animals
  • Blood Pressure / drug effects*
  • Blood Pressure / physiology
  • Bradycardia / physiopathology
  • Cardiac Output*
  • Disease Models, Animal
  • Fluid Therapy*
  • Heart Rate / drug effects*
  • Heart Rate / physiology
  • Heart Ventricles / innervation
  • Hemorrhage / physiopathology*
  • Hemorrhage / therapy
  • Male
  • Myocardial Contraction / drug effects
  • Myocardial Contraction / physiology
  • Propranolol / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Reflex / drug effects*
  • Sensory Receptor Cells / drug effects
  • Sensory Receptor Cells / physiology
  • Stroke Volume
  • Vagus Nerve / physiology
  • Vascular Resistance

Substances

  • Adrenergic beta-Antagonists
  • Propranolol