EFFECTS OF NITRIC-OXIDE ON DIAPHRAGMATIC MUSCLE ENDURANCE AND STRENGTH IN PIGS

The aim of the study was to evaluate the effects of nitric oxide (NO) on diaphragmatic fatigue in fifteen anaesthetized, mechanically ventil ated pigs, divided into three groups. The animals were pre-treated wit h indomethacin (3 mg kg(-1), I.V.) to block the cyclo-oxygenase pathwa y. To group 1 pigs (n = 6) N-G-nitro-L-arginine methyl ester (L-NAME, 5 mg kg(-1) I.V.) was administered as a bolus to block endogenous NO p roduction, while group 2 pigs (n = 6) were infused with sodium nitropr usside (SNP, 0.023 mg kg(-1) min(-1), I.V.), a donor of NO. Group 3 pi gs (n = 3) were used as the controls. We evaluated diaphragmatic stren gth by measuring the transdiaphragmatic pressure (P-di) generated duri ng bilateral phrenic nerve stimulation at 10, 20, 30 and 50 Hz, 15 V, while the diaphragmatic endurance was assessed by a 30 s stimulation a t 10 Hz, 15 V. Diaphragmatic index was assessed as the ratio of peak f orce between single twitches performed before and after the 30 s stimu lation test. We also evaluated mean systemic (MAP) and pulmonary (MPAP ) arterial pressures, pulmonary wedge pressure (P-W), systemic (SVR) a nd pulmonary vascular resistances (PVR) and cardiac output (GO). L-NAM E increased MAP, MPAP, P-W, SVR and PVR, but decreased CO. SNP caused a decrease in MAP, MPAP, P-W and SVR, while PVR and CO did not change. The main finding of this study was that diaphragmatic strength was no t significantly weakened after L-NAME administration, except at 10 Hz, while it did not change after SNP infusion. However, both L-NAME and SNP caused significant decreases in diaphragmatic endurance capacity. The fatigue appearing after L-NAME is probably correlated with a decli ne in diaphragmatic blood flow, as evidenced by the increase in SVR an d the decrease in CO, and consequently in oxygen supply. In contrast, the decrease in endurance capacity after SNP infusion can be attribute d to a direct action of NO on skeletal muscle.