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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Unknown (R23)
Project #
1R23HL031431-01A1
Application #
3448601
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1985-01-01
Project End
1987-12-31
Budget Start
1985-01-01
Budget End
1985-12-31
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Montefiore Medical Center (Bronx, NY)
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10467
el-Sherif, N (1993) Electrophysiologic basis of ventricular late potentials. Prog Cardiovasc Dis 35:417-27
el-Sherif, N; Gough, W B; Restivo, M et al. (1990) Electrophysiological basis of ventricular late potentials. Pacing Clin Electrophysiol 13:2140-7
Aldrich, T K (1988) Respiratory muscle fatigue. Clin Chest Med 9:225-36
Aldrich, T K (1987) Transmission fatigue of the rabbit diaphragm. Respir Physiol 69:307-19
Aldrich, T K; Shander, A; Chaudhry, I et al. (1986) Fatigue of isolated rat diaphragm: role of impaired neuromuscular transmission. J Appl Physiol 61:1077-83
Aldrich, T K; Appel, D (1985) Diaphragm fatigue induced by inspiratory resistive loading in spontaneously breathing rabbits. J Appl Physiol 59:1527-32