Diaphragm adaptations following treatment for emphysema
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Cigarette smoking is the most important risk factor for the development of emphysema. With emphysema, the lungs become overinflated and this severely impairs the function of the diaphragm, the most important of the breathing muscles. During this disease progression, the diaphragm muscle adapts in an attempt to preserve its ability to sustain work capacity. In particular, the actual length of diaphragm muscle fibers become absolutely shorter. Lung volume reduction surgery (LVRS) is a new procedure for patients with severe emphysema who, despite the best medical therapy available and pulmonary rehabilitation programs, continue to have disabling shortness of breath and very poor quality of life. The procedure involves removing about a third of the most diseased portions of each lung. With the reduction in volume of the overinflated lungs, the shape and function of the diaphragm would be expected to be altered following this procedure. There are, however, no studies which characterize the functional, cellular, and biochemical adaptations occurring in the diaphragm muscle following this procedure. 
 
 
 
 
 
 Detailed examination of the diaphragm muscle structure and function is not feasible in patients undergoing this procedure, as it would be prohibitively invasive and unethical. We therefore elected to examine diaphragm per-formance following LVRS in a hamster model of emphysema. We believe that these studies are important because we hypothesize that in the immediate post-operative phase following LVRS, a variety of factors may act on the stretched but anatomically shortened diaphragm muscle, to temporarily injure it and thus impair its performance. We hypothesize, however, that in the long-term, partial or complete remodeling of the diaphragm to a more normal state will ensue. 
 
 
 
 
 
 Six months following the development of emphysema, a group of animals will be subjected to LVRS. The emphysemic animals subjected to LVRS will be compared to both a control group in which emphysema was not induced and an emphysema group. In both the control and emphysema only groups, sham surgery will be performed. Detailed studies on diaphragm structure and function will be performed two days following LVRS (the acute phase) and one at three months following LVRS (the chronic phase) in separate animals. A variety of sophisticated tests will be performed to assess the function of the diaphragm and its ability to generate force as well as indices of injury of the individual diaphragm muscle fibers. In addition, the long-term adaptations of the diaphragm during the chronic phase will be assessed using a variety of studies in a tissue bath to assess the function of the diaphragm as well as sophisticated tests to evaluate cellular, biochemical, and molecular adaptations. 
 
 
 
 
 
 This approach will allow us to test meaning-ful hypotheses with strong clinical implications that would not be possible in the human subject. Results from the acute phase may have important clinical implications for patients during the potentially vulnerable perioperative period. Likewise, data in the chronic phase will highlight the functional and cellular changes that occur in the diaphragm, which would have important inferences for the long-term rehabilitation of humans undergoing LVRS.