Short‐term central activation of descending sympathetic outflow does not restore alcohol‐induced hemodynamic instability during hemorrhagic shock

Abstract

Mean arterial blood pressure (MABP) at the time of admittance into the emergency department is one of the most critical determinants of outcome from traumatic injury. We have demonstrated that acute alcohol intoxication (AAI) suppresses MABP during hemorrhagic shock (HS) and blunts the pressor response to fluid resuscitation (FR). We hypothesized that attenuation of neuroendocrine and sympathetic nervous system (SNS) responses to HS aggravates hemodynamic instability in AAI animals. This study investigates whether outcome is improved by the acetylcholine precursor, choline. Chronically-catheterized, conscious male Sprague-Dawley rats received intragastric 30% alcohol [1.75 g/kg bolus pre & post 15-h infusion (250-300 mg/kg/h)] or isocaloric/isovolumic dextrose, followed by intracerebroventricular (ICV) choline (150μg) 15 min prior to fixed-volume (50%) HS and FR. AAI (174 ± 13 mg/dL) decreased basal MABP (−15%), accentuated hypotension (−20% at 15 min) and prevented restoration of MABP post-FR (all p<0.05). Choline increased basal MABP (+17%) without altering the initial drop in MABP or the response to FR (effects similar in AAI). Baseline plasma epinephrine (EPI), norepinephrine (NE), and arginine vasopressin (AVP) were not altered by AAI. Choline increased baseline EPI (198%), NE (76%) and AVP (145%), all of which were abolished in AAI. Choline did not alter post-HS levels of EPI, NE, or AVP. We conclude that ICV choline immediately and transiently stimulates SNS, but is insufficient in improving MABP response to HS in AAI. We speculate that combined choline and acetylcholinesterase inhibitors may improve hemodynamic instability in AAI-HS animals. Supported by DOD-W81XWH-06-1-0236 and NIAAA-5T32AA-007577-7.