Chronic airflow limitation (CAL) increases the work of breathing, but diminishes the ability of the inspiratory muscles to sustain the increased ventilatory load. Hyperinflation of the lung shortens the inspiratory muscles, placing them at a mechanical disadvantage. Hypoxemia, hypercapnia and undernutrition further compromise inspiratory muscle contractility and endurance. Electromyographic (EMG) studies have shown that inspiratory muscle fatigue is responsible for exercise limitation and respiratory failure in CAL. At present there is no simple way to diagnose diaphragmatic fatigue. In limb skeletal muscle a uniform time constant of relaxation exists which becomes prolonged as the muscle fatigues.
Our first aim i s to study fatigue-induced delay of relaxation of the inspiratory muscles as a clinical test for diaphragmatic fatigue. This phenomenon, which coincides with EMG signs of fatigue, can be quantified from the decay in transdiaphragmatic pressure following a brief inspiratory effort against a closed airway. Preliminary data suggest that a similar rise and fall of pressure can be measured at the mouth and has a simular time constant to transdiaphragmatic pressure. Another indirect estimation of inspiratory muscle relaxation can be made from changes in abdominal displacement as measured with a respitrace.
Our second aim i s to investigate using the hamster diaphragm, the role of the exitation-contraction coupling mechanisms in delayed relaxation. Initially we will study the effect of increased sarcolemmal membrane resistance on relaxation rate. We also expect to find that fatigue-induced delay in diaphragmatic relaxation is associated with fatigue consequent to high rather than low stimulation rates.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL001183-04
Application #
3081714
Study Section
(SRC)
Project Start
1983-07-01
Project End
1988-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Virginia
Department
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904