Modification of phenyl saligenin phosphate-induced delayed effects by calcium channel blockers: in vivo and in vitro electrophysiological assessment.

Effects of organophosphorus esters (OPs) inducing delayed neuropathy in the adult hen have traditionally been evaluated by assessment of morphology and function of nerve and muscle in the rear limbs of animals exposed. In this study, organophosphorus-induced delayed neuropathy (OPIDN), including neuromuscular function and histology, were studied in vivo using sciatic nerve, tibial nerve and gastrocnemius muscle in anesthetized hens that had been administered phenyl saligenin phosphate (PSP), 2.5 mg/kg by intramuscular injection. In addition, OPIDN was examined in vitro using the biventer cervicis nerve and muscle of the same adult hens. Both nerve-muscle preparations were used for construction of strength duration curves (SDC) on days 4-5, 7-8, and 15-16 after PSP; the biventer cervicis preparation was also used 21-22, 37 and 64 days after PSP administration. Histological examination was done at these same time periods. SDC revealed significant increases in excitability thresholds for preparations from hens receiving PSP only compared to preparations from control hens, or compared to preparations from hens treated with PSP and either nifedipine (1 mg/kg intramuscularly for 5 days), or verapamil (7 mg/kg intramuscularly for 4 days), with treatment beginning 24 hours before administration of PSP. Ataxia, which appeared 7-10 days after hens were given PSP, was less pronounced in hens given PSP plus either calcium channel blocker than in hens given PSP alone. Whether treatment was initiated before or after PSP, verapamil, a phenylalkylamine, reduced sensitivity of the biventer cervicis muscle to acetylcholine-induced stimulation. The dihydropyridine, nifedipine, was less effective at reducing muscle sensitivity to acetylcholine post-exposure than when used as a pretreatment. Lesions were extensive in the biventer cervicis nerve after PSP administration and modification by treatment with calcium channel blockers was evident.