Effects of neostigmine and salbutamol on diaphragmatic fatigue

We studied the effects of neostigmine and salbutamol on the force generated by the fatigued diaphragm in anesthetized dogs. Mechanically ventilated animals were prepared with an open thorax. A thin-walled latex balloon was positioned beneath the diaphragm to measure transdiaphragmatic pressure (Pdi) and a rigid cast was fixed around the abdomen to limit changes in diaphragmatic length and geometry during contractions. Pdi was the index of force generated by the diaphragm. We measured Pdi during supramaximal phrenic stimulation at different frequencies and during spontaneous inspiratory efforts. The diaphragm was fatigued by repeated phrenic stimulation. Fatigue significantly reduced Pdi at all frequencies of stimulation and during spontaneous contractions (P less than 0.05). The reduction in Pdi was associated with a decrease in peak twitch tension (PTT) to 50% of control (P less than 0.05). Infusion of neostigmine restored PTT to values equivalent with or greater than control (P less than 0.05) and improved Pdi at low stimulation frequencies (P less than 0.05) and during spontaneous inspiratory efforts (P less than 0.05). Infusion of salbutamol had no effect on PTT, but did significantly shortened twitch half relaxation time (P less than 0.05). Salbutamol also had no effect on Pdi during stimulated and spontaneous contractions. We conclude that neostigmine improves force generated by the fatigued diaphragm by increasing twitch amplitude while salbutamol did not have a positive inotropic effect.