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Delayed resuscitation with physostigmine increases end organ damage in intoxicated rats
Author(s) -
Sulzer Jesse,
Molina Patricia
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.788.5
Subject(s) - medicine , physostigmine , resuscitation , anesthesia , blood pressure , organ dysfunction , bolus (digestion) , shock (circulatory) , mean arterial pressure , acetylcholine , heart rate , sepsis
Acute alcohol intoxication (AAI) increases injury risk and complicates the clinical course of trauma victims. We have shown that AAI impairs hemorrhagic shock (HS)‐induced neuroendocrine activation and restoration of mean arterial blood pressure (MABP) during fluid resuscitation (FR) with Ringer's lactate. These outcomes are improved with central cholinesterase inhibition with physostigmine (PHYS). We examined whether delayed FR+PHYS alters the intervention's effectiveness and safety. Conscious and chronically catheterized male Sprague Dawley rats received alcohol (2.5 g/kg bolus+ 0.3 g/kg/h × 15 h) infusion or isovolemic dextrose (DEX) prior to HS (40 mmHg × 60 min) followed by immediate or delayed (60 min) FR +/− PHYS (100 ug/kg). Immediate FR improved MABP in DEX‐HS animals. This response was delayed by AAI. Delayed FR did not improve MABP in DEX‐ or AAI‐HS animals. Immediate and delayed FR+PHYS effectively increased MABP in DEX‐ and AAI‐HS animals. No differences were noted in markers of organ dysfunction (ALT, AST, BUN, creatinine) in DEX‐HS with respect to time of FR+PHYS. However, delayed FR+PHYS of AAI‐HS animals exacerbated the rise in all markers of organ dysfunction compared to time‐matched FR‐vehicle treated animals. These findings suggest that AAI increases susceptibility to tissue injury in response to FR+PHYS following prolonged hypotension. DOD‐PR‐054196, BoR‐110350057A, NIAAA‐7577.