Consequences of alcohol-induced early dysregulation of responses to trauma/hemorrhage

Acute alcohol intoxication is a frequent underlying condition associated with traumatic injury. Studies from our laboratory have been designed to examine the early hemodynamic, proinflammatory, and neuroendocrine alterations in responses to hemorrhagic shock in surgically catheterized. conscious, unrestrained, male Sprague-Dawley rats during acute alcohol intoxication (1.75-g/kg bolus, followed by a constant 15-h infusion at a rate of 250-300 mg/kg/h). With both fixed-pressure (40 mm Hg) and fixed-volume (50%) hemorrhagic shock, followed by fluid resuscitation with Ringer's lactate, acute (15 h) alcohol intoxication has been shown to impair significantly the immediate hemodynamic, metabolic, and inflammatory counterregulatory responses to hemorrhagic shock. Alcohol intoxication enhanced hemodynamic instability during blood loss and impaired the recovery of mean arterial blood pressure during fluid resuscitation. Activation of neuroendocrine pathways involved in restoring hemodynamic stability was significantly attenuated in alcohol-intoxicated hemorrhaged animals. The hemodynamic and neuroendocrine impairment is associated with enhanced expression of lung and spleen tumor necrosis factor, and it suppressed circulating neutrophil function. In addition, neuroimmune regulation of cytokine production by spleen-derived macrophages obtained from alcohol-intoxicated hemorrhaged animals was impaired when examined in vitro. We hypothesize that impaired neuroendocrine activation contributes to hemodynamic instability, which, in turn, prolongs tissue hypoperfusion and enhances risk for tissue injury. Specifically. the early dysregulation in counterregulatory responses is hypothesized to affect host defense mechanisms during the recovery period. We examined host response to systemic (cecal ligation and puncture) and localized (pneumonia) infectious challenge in animals recovering from hemorrhage during acute alcohol intoxication. Increased morbidity and mortality from infection were observed in alcohol-intoxicated hemorrhaged animals. Our results indicate that alcohol-induced alterations in early hemodynamic and neuroimmune responses to shock have an impact on susceptibility to an infectious challenge during the early recovery period. (C) 2004 Elsevier Inc. All rights reserved.