Interactions of Subsymptomatic Doses of Sarin With Pyridostigmine - Neurochemical, Behavioral, and Physiological Effects

Abstract

This report describes the effects of treatment with low levels of the cholinesterase (ChE) inhibitors Sarin (0.5 LDSO s.c. 3 times weekly) and pyridostigmine bromide (PB, 80 mg/L in drinking water) alone or in combination for 3 weeks as compared with untreated controls. At 2, 4 and 16 weeks after exposure, we studied the brain regional levels of glucose utilization (rCGU), as well as electroencephalographic activity, heart rate and locomotor activity with a telemetry system, on an hourly basis throughout the day, during seven-day periods. Statistical parametric maps of cerebral cortex rCGU obtained were compared with similar maps of cortical cerebral blood flow (rCBF) obtained during the previous year. The slope relating rCBF to rCGU in cerebral cortex was enhanced by sarin and depressed by sarin + PB four weeks after treatment. The analysis of cardiovascular regulation indicated significant reduction of heart rate and enhanced heart rate variability during PB treatment that recovered partially one week after treatment. Sarin (4 weeks) and PB (4 and 16 weeks) also showed enhanced HR variability. Sarin induced enhanced heart rate variability at all times after treatment. In conclusion, the changes in rCBF/rCGU coupling observed 4 weeks after sarin are consistent with residual cholinesterase inhibition in vascular compartments. The changes in heart rate variability deserve further exploration.

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Document Details

Document Type
Technical Report
Publication Date
Mar 01, 2003
Accession Number
ADA412773

Entities

People

  • Donald J. Jenden
  • Oscar U. Scremin
  • Tsung-Ming Shih

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Biomedical Research
  • Brain
  • Cardiovascular Physiological Phenomena
  • Cardiovascular System
  • Cerebral Cortex
  • Chemical Synthesis
  • Chemical Warfare
  • Chemical Warfare Agents
  • Chemistry
  • Data Science
  • Laboratory Animals
  • Myocardial Ischemia
  • Nerve Agents
  • Nervous System
  • Neurosciences
  • Physiological Effects
  • Rodents

Fields of Study

  • Biology
  • Medicine

Readers

  • Cardiovascular Physiology
  • Neurotoxicology