Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to determine whether hamsters with elastase-induced emphysema (EMP) would demonstrate a reduction in exercise capacity compared to control (CON) hamsters and whether changes in activity levels, muscle function and structure could explain any changes in exercise capacity. Peak oxygen consumption and daily activity levels were measured on two occasions. Inspiratory capacity under deep anesthesia, in vitro measurements of muscle force and fatigability for the diaphragm (DIA) and extensor digitorum longus (EDL) and fiber proportions, muscle cross-sectional area and fiber specific SDH activity from the DIA, EDL and vastus lateralis (VLA) were obtained. Inspiratory capacity was 60% higher in the EMP compared to CON hamsters (p=0.0004). Activity levels and exercise capacity were not significantly different between EMP and CON hamsters. Muscle strength and fatigability, fiber proportions, muscle cross-sectional area and fiber specific SDH activity were similar between EMP and CON hamsters. In conclusion, in hamsters, elastase-induced emphysema did not reduce maximal exercise capacity.
 ...
PMID:Exercise capacity in hamsters with elastase-induced emphysema compared to normal controls. 2062 78

Patients with chronic obstructive pulmonary disease (COPD) usually develop skeletal muscle dysfunction, which represents a major comorbidity in these patients and is strongly associated with mortality and other poor outcomes. Although clinical data indicates that accelerated protein degradation and metabolic disruption are common associations of muscle dysfunction in COPD, there is very limited data on the mechanisms regulating the process, in part, due to the lack of research performed on a validated animal model of pulmonary emphysema. This model deficiency complicates the translational value of data generated with highly reductionist settings. Here, we use an established transgenic animal model of COPD based on inducible IL-13-driven pulmonary emphysema (IL-13TG) to interrogate the mechanisms of skeletal muscle dysfunction. Skeletal muscles from these emphysematous mice develop most features present in COPD patients, including atrophy, decreased oxygen consumption, and reduced force-generation capacity. Analysis of muscle proteome indicates downregulation of succinate dehydrogenase C (SDH-C), which correlates with reduced enzymatic activity, also consistent with previous clinical observations. Ontology terms identified with human data, such as ATP binding/bioenergetics are also downregulated in this animal's skeletal muscles. Moreover, chronic exercise can partially restore muscle mass, metabolic and force-generation capacity, and SDH activity in COPD mice. We conclude that this animal model of COPD/emphysema is an adequate platform to further investigate mechanisms of muscle dysfunction in this setting and demonstrates multiple approaches that can be used to address specific mechanisms regulating this process.NEW & NOTEWORTHY Skeletal muscle dysfunction is a relevant comorbidity in patients with chronic obstructive pulmonary disease (COPD). Mechanistic research in the area has so far been accomplished with models based on specific exposures to otherwise healthy animals, and no investigation using an established and validated animal model of COPD has been accomplished. We present an animal model of COPD that was previously shown to recapitulate pulmonary functional and histologic features present in patients with COPD, and demonstrates most of the features present in patients with pulmonary emphysema-associated muscle dysfunction, which we proposed as an adequate tool to develop mechanistic research in the area.
 ...
PMID:IL-13-driven pulmonary emphysema leads to skeletal muscle dysfunction attenuated by endurance exercise. 3177 58