Studies On The Relationship Between Diaphragmatic Fatigue And Myosin Heavy Chain Gene Expression

Chronic obstructive pulmonary disease (COPD) is a commonly encountered respiratory disease with high morbidity and mortality. As COPD progresses slowly, it can severely affect work ability and living conditions of the sufferings. COPD is also quite common in China like other countries in the world. According to the statistics in 1997, COPD accounts for approximately 3% of population above 15 year of age in our country. The mechanism of COPD is very complicated and factors including infection, genetics and environment etc may be involved. Recent clinical research also demonstrates that diaphragmatic fatigue probably plays an important role in COPD. However, the causality between COPD and diaphragmatic fatigue is still unclear till now especially the molecular mechanism of diaphragmatic fatigue in COPD patients. Diaphragm is the largest inspiratory muscle and makes up to 60~80% of resting ventilation by retraction. Although Roussos and Macklem put the conception of diaphragmatic fatigue forward in 1977, the mechanism is yet to be fully understood. Previous studies show more inspiratory work is done bydiaphragm in COPD patients because of airway obstruction increase. Hyperinflation increases the curvature of diaphragm. Structure derangement and retraction decrease may happen as a result of optimal conformation change. Meanwhile, COPD patients are complicated with such conditions as hypoxia and malnutrition to supply insufficient energy to the diaphragm. Thus, diaphragmatic fatigue may take place not able to sustain the pressure for normal alveolar ventilation and a vicious cycle is therefore formed. It was emphasized the correlation between nutrition, hypoxia and diaphragmatic fatigue but now clinical investigation shows some COPD patients with good nutrition and oxygen supply even manifests the symptom. So, these two factors are not the fundamental reasons of diaphragmatic fatigue. It was recently shown that the major change in COPD is chronic airflow limitation or chronic airflow obstruction instead of mere airway obstruction. Therefore, it is reasonable to infer that diaphragmatic fatigue is closely related with chronic airflow limitation. Like skeleton muscle, diaphragm retraction is regulated by multiple retraction proteins. Among them, myosin heavy chain (MHC) poses special physiological and pathological significance. MHC is the main determinant of all myosin ATPase activity and itself relates with the maximum retraction speed of muscle fibers. MHC is composed of three 'fast' isoforms and one 'slow' isoform (|3-MHC). The former exhibits highATPase activity which is low in the latter. In the research of past decade, given chronic and longstanding workload, the skeleton muscle MHC isoforms could change evidently. Fast isoform increases however low isoform decreases inferring that MHC isoform change may be the main reason of skeleton muscle retraction weakening caused by chronic burden increase. Nevertheless, there is still no clue about the MHC expression variation in diaphragmatic fatigue especially the change of composition in different MHC isoforms.In our study, expression change of MHC in COPD patients on protein and mRNA level is investigated. Moreover, combined with direct measuring diaphragm function and relevance analysis of pulmonary function, change in MHC isoforms expression proportion is observed to find relationship between MHC expression change and diaphragmatic fatigue. The theoretical significance of the research is exemplifying mechanism of diaphragmatic fatigue on molecular level. The application may contribute to making feasible therapeutical plans.Part IInfluence of oxygen or injection of aminophylline inhalation on Pdi of COPD patientsObjective Diaphragmatic fatigue is one of the reasons of progressing COPD but no effective measurement is available now. The research measured Pdi of COPD patients with continuous perfusion manometric tube and compare influence of oxygen or infection of aminophylline inhalation to ascertain the condition of diaphragmatic fatigue in COPD patients...