XWH - 06 - 1 - 0236 TITLE : Alcohol Intoxication Impact on Outcome from Traumatic Injury

on next page. Subject terms on next page. 29 [email protected] 3 APR 2006 2 APR 2011 Final 01-05-2011 14. ABSTRACT Acute alcohol intoxication (AAI) impairs the hemodynamic counteregulatory response to trauma and hemorrhagic shock (HS), blunts the pressor response to fluid resuscitation (FR), suppresses the HS·induced neuroendocrine response, impairs pro-inflammatory cytokine expression and increases mortality from infection during recovery. Studies conducted during this funding period examined a) whether the attenuated neuroendocrine response, particularly reduced sympathetic nervous system (SNS) activation, is the principal mechanism responsible for the hemodynamic instability seen in AAI+ HS and b) what the impact of AAI was on the integrity of host defense mechanisms during the immediate and delayed recovery from HS. We determined whether SNS activation can be restored by central (intracerebroventricular; ICV) neostigmine administration and whether this in turn is capable of improving the hemodynamic counteregulatory response to HS in AAI. Our results show that ICV neostigmine stimulates SNS activation and improves the recovery of blood pressure following hemorrhagic shock. Furthermore, our results indicate that this in part mediated by arginine vasopressin. Interestingly while the presser response to phenylephrine in vitro appears to be blunted by alcohol, the in vivo response to a presser with a different mechanism of action appears to be preserved. 15. SUBJECT TERMS Alcohol intoxication, hemorrhage, injury, blood pressure, immune function