Abstract
The role of endogenous nitric oxide (NO) in producing diaphragmatic fatigue was examined in 26 anaesthetized, mechanically ventilated dogs divided into four groups. In Group la (n=5), dogs without fatigue received only Ringer's lactate solution. In Group lb (n=5), dogs without fatigue were given IV L-arginine analog Nω-nitro-L-arginine methyl ester (L-NAME) 10 mg.kg-1 to inhibit NO synthase (NOS). Groups Ila and lib (n=8 of each) received the same doses of IV lactate and L-NAME as Groups la and lb effectively. Following administration of the IVsolution, diaphragmatic fatigue was induced by intermittent supramaximal bilateral electrophrenic stimulation at a frequency of 20 Hz applied for 30 min. Diaphragmatic contractility was assessed in each group by measuring transdiaphragmatic pressure (Pdi). No difference in Pdi was observed between Groups Ia and Ib. After the fatigue-producing period, in Group IIa, Pdi at low-frequency (20 Hz) stimulation decreased from the pre-fatigued values (P<0.05), whereas Pdi at high-frequency (100 Hz) stimulation did not change. In Group IIb, given L-NAME before producing fatigue, Pdi at both stimuli did not change. In conclusion, L-NAME inhibits the production of diaphragmatic fatigue. This finding suggests that endogenous NO plays an important role in producing diaphragmatic fatigue.