Altered Hemodynamic Counter-Regulation to Hemorrhage by Acute Moderate Alcohol Intoxication

Abstract

The incidence of traumatic injury, frequently associated with hemorrhagic shock, is higher in the alcohol-intoxicated individual. The outcome, as it pertains to both morbidity and mortality of this population, is partly dependent on duration of alcohol exposure and levels of blood alcohol at time of injury. In previous studies, we demonstrated that prolonged alcohol intoxication (15-h duration) produces marked hemodynamic instability and exacerbated early lung proinflammatory cytokine expression after hemorrhagic shock. The present study examines whether a shorter and more modest period of alcohol intoxication is sufficient to alter hemodynamic and proinflammatory responses to hemorrhagic shock. Chronically instrumented, conscious male Sprague-Dawley rats (250-300 g) received a single intragastric bolus of alcohol (1.75 g/kg) 30 min before the administration of fixed-volume (50%) hemorrhagic shock, followed by fluid resuscitation with Ringer lactate. Time-matched controls were administered on isocaloric dextrose bolus (3 g/kg). Alcohol (blood alcohol concentration, 152 +/- 10 mg/dL) produced a 14% decrease in basal mean arterial blood pressure and a more profound hypotensive response to equal blood loss. The 2-fold rise in circulating norepinephrine levels was similar in alcohol- and dextrose-treated hemorrhaged animals despite greater hypotension in alcohol-treated animals. Significant upregulation in lung and spleen interleukin (IL) 1, IL-6, IL-10, and tumor necrosis factor alpha expression was observed immediately after hemorrhage and fluid resuscitation, as previously reported. Only the hemorrhage-induced rise in lung IL-6 and tumor necrosis factor alpha was prevented by alcohol administration. In contrast, spleen cytokine responses to hemorrhage were not altered by alcohol administration. These results indicate that moderate acute alcohol intoxication results in significant modulation of hemodynamic and neuroendocrine responses to hemorrhagic shock.

Alcohol Binge Before Trauma/Hemorrhage Impairs Integrity of Host Defense Mechanisms During Recovery

“…In agreement with previous reports from our laboratory, TÂHem produced an early induction of lung and spleen cytokine (TNF-a and IL-1a) expression (Mathis et al, 2006;Phelan et al, 2002). Alcohol binge blunted the magnitude of the TÂHem-induced increase in lung TNF-a but did not produce significant alteration of the lung IL-1a response or of the spleen TNF-a and IL-1a response.…”

“…Alcohol binge blunted the magnitude of the TÂHem-induced increase in lung TNF-a but did not produce significant alteration of the lung IL-1a response or of the spleen TNF-a and IL-1a response. This is in contrast to our previous observations in animals that received a continuous 15-hour infusion in which tissue proinflammatory responses to hemorrhage were accentuated (Phelan et al, 2002) but similar to the effects produced by a single dose of alcohol administered before hemorrhage (Mathis et al, 2006). These apparently disparate effects of alcohol on immune responses have been attributed to differential duration of alcohol exposure, with acute alcohol resulting in most cases in suppression of proinflammatory responses (Boe et al, 2001;Szabo, 1999;Zhang et al, 2002) and chronic alcohol exposure favoring a proinflammatory response (Bautista, 1995;Diehl, 1998;Yang et al, 1998).…”

“…Alternatively, it is likely that the alcohol-induced blunting of sympathetic and sympathoadrenal responses to blood loss could have played a major role in the decreased tolerance to blood loss seen in the alcohol-treated animals. This suppression in neuroendocrine responses to blood loss in alcohol-treated animals has been consistently demonstrated by our studies investigating fixed-pressure as well as fixed-volume hemorrhage (Mathis et al, 2006;Molina et al, 2004a). Clearly, alcohol-induced impairment of these central neuroendocrine mechanisms involved in restoring blood pressure is likely to enhance susceptibility to tissue injury.…”

Central acetylcholinesterase inhibition improves hemodynamic counterregulation to severe blood loss in alcohol-intoxicated rats

“…Alcohol-intoxicated trauma patients enter the emergency department more hypotensive than their sober counterparts (41). Clinical data suggest that mean arterial blood pressure (MABP) at the time of admittance into the emergency department is one of the most critical indicators of a patient's outcome and survival from traumatic injury and blood loss (15); therefore, the greater hypotension noted in alcohol-intoxicated trauma patients is likely to contribute to their increased morbidity and mortality.Previously, we demonstrated that acute intoxication produced by intragastric administration of alcohol decreases baseline MABP, accentuates hypotension throughout hemorrhage, and blunts the pressor response to fluid resuscitation, regardless of the dose (1.75, 5, and 8 g/kg) and frequency (single dose, 3-day binge, and 15-h constant infusion, respectively) of alcohol administration (12,25,26,30,33). This impaired hemodynamic compensatory response to hemorrhage in alcohol-intoxicated rats is associated with suppression of catecholamine (epinephrine and norepinephrine) and AVP responses (30).…”

“…Previously, we demonstrated that acute intoxication produced by intragastric administration of alcohol decreases baseline MABP, accentuates hypotension throughout hemorrhage, and blunts the pressor response to fluid resuscitation, regardless of the dose (1.75, 5, and 8 g/kg) and frequency (single dose, 3-day binge, and 15-h constant infusion, respectively) of alcohol administration (12,25,26,30,33). This impaired hemodynamic compensatory response to hemorrhage in alcohol-intoxicated rats is associated with suppression of catecholamine (epinephrine and norepinephrine) and AVP responses (30).…”