title: Impact of alcohol intoxication on hemodynamic, metabolic, and cytokine responses to hemorrhagic shock.
abstract: BACKGROUND
  Alcohol intoxication is associated with a high incidence of traumatic injury, particularly in the young healthy population. The impact of alcohol intoxication on the immediate pathophysiologic response to injury has not been closely examined. We hypothesized that acute alcohol intoxication would aggravate the immediate outcome from hemorrhagic shock by impairing homeostatic counterregulation to blood loss.
  
  
  METHODS
  Chronically catheterized male Sprague-Dawley rats were randomized to receive an intragastric infusion of ethyl alcohol (1.75 g/kg followed by 250-300 mg/kg/h) or isocaloric dextrose (3-mL bolus + 0.375 mL/h) for 15 hours. Before initiating fixed-pressure hemorrhage followed by fluid resuscitation, an additional intragastric bolus of ethyl alcohol (1.75 g/kg) was administered. Hemodynamic, metabolic, cytokine, and acid-base parameters were assessed during the hemorrhage period and at completion of resuscitation. Lungs were obtained for cytokine determinations.
  
  
  RESULTS
  Basal mean arterial pressure was significantly lower in alcohol-intoxicated (blood-alcohol concentration, 135 +/- 12 mg/dL) animals than in controls during baseline (20%) and after the initial fluid resuscitation period (30%). Hemorrhage decreased arterial HCO3 and Pco2, and increased Po2 without significant alteration in arterial blood pH. Alcohol intoxication blunted the decrease in Pco2 and increase in Po2 and decreased blood pH during baseline and throughout the course of the hemorrhage period. Hemorrhage produced marked and progressive elevations in plasma glucose and lactate levels in controls, and this was inhibited by alcohol intoxication. Hemorrhage elevated plasma tumor necrosis factor-alpha (TNF-alpha) (686 +/- 252 pg/mL) and interleukin (IL)-10 (178 +/- 25 pg/mL), and did not alter IL-6 and IL-1 levels. Alcohol blunted the hemorrhage-induced rise in plasma TNF-alpha (142 +/- 48 pg/mL) and enhanced the hemorrhage-induced increase in IL-10 (678 +/- 187 pg/mL). Hemorrhage produced a two- to threefold increase in lung content of TNF-alpha, IL-1alpha, and IL-6 without significantly altering lung IL-10. Alcohol exacerbated the hemorrhage-induced increase in lung TNF-alpha, and did not alter the IL-1alpha, IL-6, and IL-10 lung responses.
  
  
  CONCLUSIONS
  These results indicate marked alterations in the hemodynamic and metabolic responses to hemorrhagic shock by alcohol intoxication. Furthermore, our findings suggest that alcohol modulates the early proinflammatory responses to hemorrhagic shock. Taken together, these alterations in metabolic and inflammatory responses to hemorrhage are likely to impair immediate outcome and predispose to tissue injury.
authors.affiliation: Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112-1393, USA.
authors.forename: Herbert
authors.initials: H
authors.lastname: Phelan
authors.forename: Paul
authors.initials: P
authors.lastname: Stahls
authors.forename: John
authors.initials: J
authors.lastname: Hunt
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Bagby
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Molina
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000435:Alcoholic Intoxication / Q000150:complications*; D000818:Animals; D001639:Bicarbonates / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002245:Carbon Dioxide / Q000097:blood; D016207:Cytokines / Q000378:metabolism*; D006439:Hemodynamics; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000097:blood; D008168:Lung / Q000378:metabolism; D008297:Male; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D001639:Bicarbonates; D001786:Blood Glucose; D016207:Cytokines; D002245:Carbon Dioxide; D019344:Lactic Acid; D000410:Alanine Transaminase; D010100:Oxygen