Previous studies from our laboratory have identified a role for blunted central sympathetic activation in the acute alcohol intoxication (AAI)-induced impairment of the counterregulatory response to hemorrhagic shock (HS). Immediate fluid resuscitation (FR) with acetylcholinesterase-inhibitors restores the neuroendocrine and pressor responses to FR in AAI+HS. We hypothesized this intervention would remain beneficial following delay and that restoration of MABP during FR would attenuate organ damage. Male Sprague-Dawley rats received a primed constant alcohol infusion (2.5 g/kg + 0.3 g/kg/h for 15h) or isocaloric dextrose (DEX) prior to HS (40 mmHg for 60 min) and FR with lactated Ringer’s (LR) ± physostigmine (PHYS; 100 ug/kg) immediately or following a 60 min delay post-HS. Immediate LR elevated MABP in DEX+HS. AAI delayed the initial MABP recovery. Delayed LR did not further increase MABP in DEX- or AAI+HS. LR+PHYS increased MABP in DEX- and AAI+HS following immediate and delayed FR. No differences were noted in markers of organ dysfunction (ALT, AST, BUN, creatinine) following DEX+HS and this was unaltered by immediate or delayed LR+PHYS. AAI+HS increased ALT, which was attenuated by immediate LR+PHYS. In contrast, delayed LR+PHYS exacerbated tissue injury in AAI+HS, as reflected by increased ALT, AST, BUN, creatinine, and liver protein carbonylation over time-matched LR. In conclusion, PHYS enhanced blood pressure recovery independent of time of FR and presence of AAI. However, in AAI+HS, delayed LR+PHYS accentuated organ damage and dysfunction. These findings suggest that while enhancing the sympathetic response can improve hemodynamic recovery during AAI, it may compromise tissue perfusion and enhance tissue injury.
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