| Summary: | In experimental animal models, fatigue of the diaphragm has been implicated as the predominant determinant of hypercapnic ventilatory failure and ultimately as the cause of task failure of inspiratory muscles during inspiratory resistive breathing. The purpose of this study was to examine the effects of increased inspiratory resistive loads on diaphragm function in the anesthetized rabbit
model to test three hypotheses: first, that task failure results from a decrease in
neural activation; second, that task failure results from a decrease in
neuromuscular transmission to the diaphragm; and third, that the development
of hypoventilation and hypercapnia precede task failure. We assessed central
motor output and neuromuscular transmission to the diaphragm by continuous
monitoring of phrenic nerve activity and electromyogram activity of the costal
diaphragm during both sustainable and exhaustive inspiratory resistive loads. We
found a linear relationship between the severity of the target inspiratory airway
pressure achieved with resistive loading and the indices of motor output to the
diaphragm and activity of this muscle. Central motor output to the diaphragm
remained elevated throughout resistive loading even at task failure.
Neuromuscular transmission, as assessed by evoked compound potentials of the
diaphragm, remained intact throughout inspiratory resistive loading including at
task failure. The activity of the diaphragm remained elevated and coupled to
central motor output throughout resistive loading, including at task failure. Hence, task failure did not result from either a decrease in neural activation nor
from a decrease in neuromuscular transmission to the diaphragm. We found
that despite substantial increases in inspiratory effort, rabbits hypoventilated
during both sustainable and exhaustive loads. Therefore, hypercapnia typically
accompanied inspiratory resistive loading. Furthermore, we found that the
elevated levels of arterial P2c0 associated with prolonged loading alone,
suppressed central drive to the diaphragm through a time-dependent reduction
in breathing frequency. We observed task failure only during intense loading at
target pressure close to the maximum strength of the rabbit diaphragm. The
activity of the inspiratory muscles (parasternal intercostal and diaphragm)
remained elevated and coupled despite severe arterial hypoxemia and
hypercapnia during task failure. In contrast, a susbstantial decay in expiratory
muscle activity and in abdominal pressure swings preceded task failure. In
conclusion, neural activation and impulse propagation to the diaphragm were
maintained during inspiratory resistive loading even at task failure. Task failure
followed a loss in abdominal muscle assist to the diaphragm.
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