Effectiveness of oximes 2-PAM and HI-6 in recovery of muscle function depressed by organophosphate agents in the rat hemidiaphragm: an in vitro study.
Phrenic nerve diaphragm muscles of young adult rats were used to study the ability of the oximes 2-PAM and HI-6 to recover muscle function depressed by organophosphate (OP) agents. The single twitch of diaphragm muscles which were exposed to soman (0.2 microM) recovered after washing with saline for 3 hr, but the muscles pretreated with sarin (0.4 microM), VX (0.2 microM), or tabun (0.4 microM) showed only partial recovery. In addition, after 3 hr washing, the muscles pretreated with soman as well as with tabun did not recover the tetanus sustaining ability (TSA), yet complete recovery was observed with muscles pretreated with sarin and VX. These results indicate that the OPs have different effects on muscle contractile properties and that VX- and sarin-pretreated muscles recover equally well after wash with physiological solution. The recovery of twitch tension of diaphragm muscles by 2-PAM and HI-6 was similar to that achieved by washing with saline for 3 hr for sarin- and soman-exposed muscles. The most remarkable differences were seen in the recovery of TSA. Both 2-PAM and HI-6 recovered the TSA of muscles that were pretreated with sarin and VX. Although 2-PAM recovered the TSA after tabun pretreatment, HI-6 had no discernible effect. On the other hand, HI-6 recovered the TSA of soman-pretreated muscles but 2-PAM did not. The effectiveness of muscle function recovery was not related to the oximes' ability to reactivate AChE, thus indicating that the recovery of muscle contractility may be attributed to a direct effect of these compounds on the muscle.
Reddy
V K
VK
Department of Pharmacology and Experimental Therapeutics, University of Maryland, School of Medicine, Baltimore 21201.
Deshpande
S S
SS
Cintra
W M
WM
Scoble
G T
GT
Albuquerque
E X
EX
D000818:Animals; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D003964:Diaphragm / Q000187:drug effects; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009943:Organophosphorus Compounds / Q000633:toxicity*; D010091:Oximes; D011220:Pralidoxime Compounds / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012132:Respiratory Muscles / Q000187:drug effects*
D002801:Cholinesterase Reactivators; D009943:Organophosphorus Compounds; D010091:Oximes; D011220:Pralidoxime Compounds; D011726:Pyridinium Compounds; C022870:asoxime chloride; C028797:pralidoxime