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Acetylcholinesterase inhibitor improves survival from hemorrhage in rodents
Author(s) -
Mathis Keisa W.,
Molina Patricia E.
Publication year - 2009
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.23.1_supplement.794.8
Subject(s) - physostigmine , atropine , acetylcholinesterase inhibitor , muscarinic acetylcholine receptor , mecamylamine , endocrinology , medicine , cholinergic , cholinesterase , antagonist , mean arterial pressure , norepinephrine , pyridostigmine , acetylcholine , anesthesia , blood pressure , heart rate , acetylcholinesterase , chemistry , receptor , dopamine , biochemistry , myasthenia gravis , enzyme
Decreased tissue perfusion leading to end organ injury remains a cause of high mortality in hemorrhagic shock (HS) victims. We have demonstrated that intracerebroventricular (ICV) administration of neostigmine, an acetylcholinesterase inhibitor, reverses hypotension following 50% blood loss. We hypothesized that systemic administration of the anti‐cholinesterase physostigmine would act via central cholinergic receptors, enhance sympathetic outflow and improve the pressor response to HS. Intravenous (IV) physostigmine (100µg/kg) increased plasma epinephrine (358%) and norepinephrine (105%), mean arterial pressure (MAP; 12%; p=0.003) and heart rate (21%; p=0.003) within 5 min in conscious male Sprague‐Dawley rats (225‐275g). Mecamylamine (nicotinic antagonist; 50µg, ICV), but not atropine sulfate (muscarinic antagonist; 10µg, ICV), diminished the pressor response to physostigmine. HS (40% blood loss) decreased MAP (50%) resulting in 36% mortality 4d post‐HS. Physostigmine enhanced the HS‐induced rise in plasma epinephrine (159%), reversed hypotension, and improved survival (100% at 4d). These results suggest that physostigmine increases central acetylcholine availability which activates central nicotinic receptors, increases SNS outflow, and in turn improves MAP recovery and survival post‐HS. DOD‐PR‐054196, BoR‐110350057A, NIAAA‐7577, APS Porter Physiology Development Award.