EFFECT OF AIRWAY OBSTRUCTION ON DIAPHRAGMATIC FUNCTION

Although the excessive work of breathing is the major cause of shortness of
breath and exercise intolerance in patients with chronic obstructive
pulmonary disease (COPD), fatigue of the respiratory muscles, particularly
of the diaphragm, may also contribute. Since therapy directed at relieving
obstruction is frequently unsuccessful, measures to prevent or reverse
diaphragmatic fatigue might allow such patients to tolerate their excessive
workloads. A better understanding of the pathophysiology of diaphragmatic
fatigue is therefore required. This proposal would contribute to our
knowledge of diaphragmatic fatigue by exploring its onset and recovery in
spontaneously breathing animals exposed to excessive respiratory loads. Rabbits will be studied because their diaphragmatic fiber composition is
relatively similar to human diaphragms. The respiratory loading will be
supplied by an inspiratory threshold resistor, which is adjustable for
precise quantitation of degree of respiratory effort required. Mean rabbit
diaphragmatic endurance, the pattern of development of fatigue and of
respiratory acidosis, and biochemical features of fatigued diaphragm muscle
will be determined. Subsequent experiments will address the influences of
anesthesia, hypoxemia, and the continuing presence of respiratory loading
during recovery on the pattern of onset and/or recovery from fatigue.
Finally, investigations of the influence of high or low diaphragmatic
levels of pH or lactate concentration on the onset and recovery from
fatigue will be carried out.