Temporal relationships of ventilatory failure, pump failure, and diaphragm fatigue.

The time course of ventilatory failure, pump failure, and diaphragm peripheral fatigue was determined during the application of external inspiratory resistive loads (IRL) in anesthetized rabbits. Pump failure is defined as the inability of the diaphragm to sustain the expected force under IRL. To assess contractile fatigue, transdiaphragmatic pressures (Pdi) generated by bilateral phrenic nerve stimulation at 75 Hz (Pdi-75) and 20 Hz (Pdi-20) were measured. The amplitude of evoked diaphragm electromyographic (EMG) signals was measured to assess neurotransmission failure. The rate of rise of spontaneous diaphragm EMG was used as an index of respiratory drive. Ventilation was evaluated together with arterial blood gases. During IRL the rate of rise of spontaneous diaphragm EMG increased, and there was a progressive hypercapnic acidosis and hypoxemia, indicating ventilatory failure. In contrast, Pdi-75 and Pdi-20 were stable until the time of respiratory arrest (apnea), when they decreased by 34 and 45%, respectively. The amplitude of evoked diaphragm EMG signals remained unchanged throughout the IRL and decreased only slightly at the time of apnea. We conclude that IRL induces progressive ventilatory failure long before any contractile fatigue of the diaphragm or pump failure occurs. This suggests that ventilatory failure is due to central fatigue, whereas pump failure (apnea) is attributable to multiple factors.