CONTRIBUTION OF DIRECT ACTIONS OF THE OXIME HI-6 IN REVERSING SOMAN-INDUCED MUSCLE WEAKNESS IN THE RAT DIAPHRAGM

The actions of the bispyridinium oxime HI-6 rbonyl)pyridino]-methoxy]m ethyl]-2-[(hydroxyimino) methyl]- pyridinium dichloride) were investig ated in vitro on rat phrenic nerve-hemidiaphragm preparations. Isometr ic twitch and tetanic tensions were elicited at 37 degrees C with supr amaximal nerve stimulation at frequencies of 20 and 50 Hz. To approxim ate normal respiration patterns, trials consisting of 30 successive 0. 55 s trains were alternated with 1.25 s rest periods. Under control co nditions, the above stimulation pattern generated tensions that were w ell maintained at both frequencies. In contrast, a marked depression o f muscle tension was observed in diaphragms removed from rats administ ered 339 mu g/kg soman (3 LD(50)) and tested in vitro. Addition of HI- 6, 4 h after soman exposure, led to a nearly complete recovery of musc le tension at 20 Hz. At 50 Hz, muscle tensions still declined especial ly when trains were elicited at 1.25 and 3 s intervals. The recovery b y HI-6 observed in this study appears to be mediated by mechanisms unr elated to acetylcholinesterase reactivation since no increase of enzym atic activity was detected and the effect was reversed by a brief wash out in oxime-free physiological solution. The results suggest that the direct action of HI-6 may play a role in restoring soman-induced diap hragmatic failure but this effect would be significant primarily under low use conditions.