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U.S. Department of Energy
Office of Scientific and Technical Information

Sensitive and specific in-situ myoneural junction model to study the pharmacological mechanisms of agents and toxins

Technical Report ·
OSTI ID:7300626

Many biological warfare agents simultaneously intoxicate vital central and peripheral organ systems leading to death of the exposed victim from multiple unexplainable causes. The lethal effect of exposure to biological toxins is most often associated with (but not exclusively limited to) neuromuscular paralysis which contributes to death due to respiratory cessation. The systemic administration of the toxin often involves many different systems simultaneously leading to a confusing evaluation of the effect of the toxin and an erroneous assessment of the effectiveness of pretreatments or antidotes. In order to correct for these ambiguous results an in-situ animal model has been modified to more accurately characterize the toxic effect of biological agents on a physiologically functioning gastrocnemius muscle preparation. In the improved animal model both sciatic nerves of phenobarbital anesthetized rabbits are isolated for electrical stimulation of the corresponding gastrocnemius muscles. Toxin and drug solutions are administered directly to the gastrocnemius muscle mass of the experimental leg by intraarterial injections to the femoral artery through a catheterized arterial branch of the femoral artery. The administration of minute quantities of drug or toxin solutions directly to the gastrocnemius muscle mass without contaminating the whole animal (systemic circulation or the central nervous system) assures a normal circulation and no interference from other physiological systems.

Research Organization:
Walter Reed Army Inst. of Research, Washington, DC (United States). Div. of Experimental Therapeutics
OSTI ID:
7300626
Report Number(s):
AD-P-008884/9/XAB
Country of Publication:
United States
Language:
English