Diaphragmatic failure during loaded breathing: role of neuromuscular transmission.

To determine whether central or peripheral mechanisms are responsible for diaphragmatic failure during loaded breathing, phrenic nerve activity (iENG), diaphragm muscle electromyogram (iEMG), and transdiaphragmatic pressure (Pdi) were measured in unanesthetized chronically instrumented sheep during inspiratory flow-resistive (IFR) loaded breathing. After placement of the IFR load, Pdi increased initially and remained relatively stable for 10-30 min [Pdi = 69.9 +/- 6.3 (SE) cmH2O, n = 6]; arterial PCO2 also increased from baseline (35.8 +/- 0.9 Torr) to 55.1 +/- 4.7 Torr. During IFR loading, iEMG and iENG also increased from baseline, but during the plateau phase of Pdi, iENG continued to increase at the same time while iEMG was stable, and the M wave, evoked by phrenic nerve stimulation, decreased during this period. After the plateau phase, Pdi decreased and arterial PCO2 increased, at which point the study was terminated (at 82.1 +/- 20.6 min). The observation that iENG increased while Pdi and iEMG were stable demonstrates a reduced efficiency of neuromuscular transmission and suggests that the neuromuscular junction is an important site of diaphragmatic failure in unanesthetized sheep during IFR loaded breathing.