title: Preserving cardiac output with beta-adrenergic receptor blockade and inhibiting the Bezold-Jarisch reflex during resuscitation from hemorrhage.
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%.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, Naval Medical Center, San Diego, California 92134, USA.
authors.forename: Gordon
authors.initials: G
authors.lastname: Wisbach
authors.forename: Steven
authors.initials: S
authors.lastname: Tobias
authors.forename: Ryan
authors.initials: R
authors.lastname: Woodman
authors.forename: Aaron
authors.initials: A
authors.lastname: Spalding
authors.forename: Warren
authors.initials: W
authors.lastname: Lockette
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D001919:Bradycardia / Q000503:physiopathology; D002302:Cardiac Output; D004195:Disease Models, Animal; D005440:Fluid Therapy; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006352:Heart Ventricles / Q000294:innervation; D006470:Hemorrhage / Q000503:physiopathology* / Q000628:therapy; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects*; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology; D013318:Stroke Volume; D014630:Vagus Nerve / Q000502:physiology; D014655:Vascular Resistance
chemical_list: D000319:Adrenergic beta-Antagonists; D011433:Propranolol