Respiratory failure due to altered central drive during inspiratory loading in rabbits

Mechanisms of respiratory muscle dysfunction leading to respiratory failure during incremental inspiratory threshold loading were studied in unbound spontaneously breathing rabbits during light and deeper anesthesia. Low or high frequency contractile fatigue was not found at the point of respiratory failure in any of the animals. On the other hand, alterations in central drive to the diaphragm played a dominant role in the observed respiratory failure. In animals receiving light anesthesia the intensity of central drive increased with loading, but then fell as respiratory failure approached. In all animals the intensity of central drive at peak activation and at the point of respiratory failure was submaximal, in spite of the diaphragm's ability to generate additional forces. In addition, the time tension index of the diaphragm rose in response to increasing loads to a level reported to produce contractile fatigue, at which time the index peaked and then fell in spite of increasing load demands. The fall in the time tension index as respiratory failure approached was due primarily to a fall in inspiratory time and duty cycle. Ultimately, there was an abrupt cessation in central drive resulting in apnea. These findings suggest that alterations in central drive play a major role in respiratory muscle dysfunction and respiratory failure associated with inspiratory loading in unbound spontaneously breathing rabbits.