Pathophysiology of Anticholinesterase Agents
Abstract
We complete the description of the acute, delayed, and long-term effects on rat neuromuscular junction (NMJ) ultrastructure and physiology following single acute injections of very low to near lethal doses of physostigmine, a reversible anticholinesterase (anti-ChE) compound. We also complete the descriptions of the immediate and long term effects of subacute exposures at doses which produce sustained blood ChE inhibitions of 40% (+ or - 10%) and 80% (+ or - 10%) for up to 14 days and of the reversibility of effects during recovery for 3-28 days following termination of subacute exposure. In additional correlative experiments using guinea pigs as alternative models to rats, sub-lethal but acute high doses of physostigmine produced equally severe and apparently identical pathological alterations in endplate ultrastructure at similar blood ChE inhibition levels. We conclude that the rat and guinea pig are essentially equivalent as models for characterizing the ultrastructural alterations of neuromusuclar junctions caused by acute high doses of physostigimine. Finally, we present additional physiological and ultrastructural data showing that the threshold for producing neuromuscular pathology is lowered (i.e., toxic alterations of the endplates are increased) by sustained neuromuscular activity. These data may be of value in evaluating and comparing anti-ChE medications and dosages used for protection against the irreversible anti-ChE agents. (AW)
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 21, 1987
- Accession Number
- ADA202893
Entities
People
- John E. Rash
- Julie K. Elmund
Organizations
- Colorado State University