RESPIRATORY-FAILURE DUE TO ALTERED CENTRAL DRIVE DURING INSPIRATORY LOADING IN RABBITS

Mechanisms of respiratory muscle dysfunction leading to respiratory fa ilure during incremental inspiratory threshold loading were studied in unbound spontaneously breathing rabbits during light and deeper anest hesia. 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 anesth esia the intensity of central drive increased with loading, but then f ell as respiratory failure approached. In all animals the intensity of central drive at peak activation and at the point of respiratory fail ure was submaximal, in spite of the diaphragm's ability to generate ad ditional forces. In addition, the time tension index of the diaphragm rose in response to increasing loads to a level reported to produce co ntractile fatigue, at which time the index peaked and then fell in spi te of increasing load demands. The fall in the time tension index as r espiratory failure approached was due primarily to a fall in inspirato ry time and duty cycle. Ultimately, there was an abrupt cessation in c entral drive resulting in apnea. These findings suggest that alteratio ns in central drive play a major role in respiratory muscle dysfunctio n and respiratory failure associated with inspiratory loading in unbou nd spontaneously breathing rabbits.