Central neostigmine administration reverses alcohol‐ and hemorrhage‐induced hypotension
Abstract
The hemodynamic and neuroendocrine counteregulation to hemorrhage (HEM) is severely compromised during acute alcohol intoxication (AAI). We hypothesized that restoration of the neuroendocrine response would improve hemodynamic counter‐regulation in AAI + HEM. Previous studies showed that intracerebroventricular (ICV) choline (acetylcholine precursor) administration produced a transient activation of sympathetic nervous system outflow insufficient to improve MABP following AAI + HEM. We determined whether enhancing acetylcholine availability by ICV neostigmine (acetylcholinesterase inhibitor) would improve MABP following AAI and HEM. The dose response to ICV neostigmine (0.1–3 μg) was established in chronically‐catheterized, conscious male Sprague‐Dawley rats (225–250g) and 1 μg was selected based on its ability to produce an immediate (10 min) and sustained (2 h) increase (20%; P=0.07) in MABP. ICV neostigmine reversed the 12% (P=0.001) drop in MABP caused by alcohol (2.5 g/kg, 30% v/v) administration within 30 min, completely reversed the hypotension produced by 40% total blood loss, and improved 7‐day survival (100% vs. 25%) from HEM. These results demonstrate that ICV neostigmine reverses hemorrhage‐ and alcohol‐induced hypotension and produces a more sustained elevation in MABP. Therefore, we speculate that ICV neostigmine will improve compensatory responses to HEM during AAI. Supported by DOD PR‐054196 and NIAAA‐AA7577.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 01, 2008
- Source ID
- 10.1096/fasebj.22.1_supplement.1227.9
Entities
People
- Keisa W. Mathis
- Patricia E. Molina
Organizations
- Louisiana State University
- United States Department of Defense