Ultrastructural Changes in the Diaphragm of Aged Emphysema-tous Hamsters

In emphysematous hamsters the diaphragm is continuously exposed to an increased workload. Previous lightmicroscopical observations showed only minor changes in relatively young emphysematous hamsters. However, ageing affects the regenerating capacity of muscles. We hypothesised that the diaphragm of aged emphysematous hamsters shows an increase of ultrastructural alterations in comparison to age-matched normal hamsters. This could contribute to a reduced force-generating capacity, which occurs in emphysematous hamsters. After intratracheally instillation of elastase or saline the animals were sacrificed at the age of 15-16 months for in vitro measurements of isometric contractile properties of the diaphragm. The hamsters were perfused in situ with glutaraldehyde for electronmicroscopical investigations. In emphysematous hamsters, twitch and tetanic forces were reduced by ~28% and ~14%, respectively (P<0.001). Compared to control hamsters the diaphragm showed distinct muscle fibre damage (Z-line dislocation, disarray of myofibrils, misaligned sarcomeres, focal degeneration, focal necrosis and segmental necrosis) and more signs of sub-optimal regeneration (fibre splitting and forking) and abortive regeneration. In conclusion, the diaphragm of aged emphysematous hamsters exhibits increased ultrastructural abnormalities, which are likely to contribute to a reduced force generating capacity.

[1]  N. Hopkinson,et al.  Skeletal muscle dysfunction in chronic obstructive pulmonary disease. A statement of the American Thoracic Society and European Respiratory Society. , 2009, American journal of respiratory and critical care medicine.

[2]  M. Decramer,et al.  Effects of lung volume reduction surgery in hamsters with elastase-induced emphysema , 2002, European Respiratory Journal.

[3]  L. Heunks,et al.  The effect of hypoxia on shortening contractions in rat diaphragm muscle. , 2001, Acta physiologica Scandinavica.

[4]  J. Gea,et al.  Injury of the human diaphragm associated with exertion and chronic obstructive pulmonary disease. , 2001, American journal of respiratory and critical care medicine.

[5]  F. Maltais,et al.  Peripheral muscle wasting in chronic obstructive pulmonary disease. Clinical relevance and mechanisms. , 2001, American journal of respiratory and critical care medicine.

[6]  W. Reid,et al.  Free radical scavengers and diaphragm injury following inspiratory resistive loading. , 2001, American journal of respiratory and critical care medicine.

[7]  W. Reid,et al.  Diaphragm injury in individuals with airflow obstruction. , 2001, American journal of respiratory and critical care medicine.

[8]  W. Reid,et al.  Time course of diaphragm injury and calpain activity during resistive loading. , 2000, American journal of respiratory and critical care medicine.

[9]  A. Bast,et al.  Effects of emphysema and training on glutathione oxidation in the hamster diaphragm. , 2000, Journal of applied physiology.

[10]  T. Best,et al.  Muscle injury and repair. , 2000, Physical medicine and rehabilitation clinics of North America.

[11]  W. Reid,et al.  Chronic resistive loading induces diaphragm injury and ventilatory failure in the hamster. , 1999, Respiration physiology.

[12]  J. Fransen,et al.  Effects of anabolic steroids on diaphragm impairment induced by methylprednisolone in emphysematous hamsters. , 1999, The European respiratory journal.

[13]  M. Grounds.  Age‐associated Changes in the Response of Skeletal Muscle Cells to Exercise and Regeneration a , 1998, Annals of the New York Academy of Sciences.

[14]  F. Maltais,et al.  Peripheral muscle weakness in patients with chronic obstructive pulmonary disease. , 1998, American journal of respiratory and critical care medicine.

[15]  H. Folgering,et al.  Long-term effects of clenbuterol on diaphragm morphology and contractile properties in emphysematous hamsters. , 1998, Journal of applied physiology.

[16]  A. Grassino,et al.  Diaphragm muscle fiber injury after inspiratory resistive breathing. , 1997, American journal of respiratory and critical care medicine.

[17]  M. Decramer,et al.  Muscle weakness is related to utilization of health care resources in COPD patients. , 1997, The European respiratory journal.

[18]  S. Brooks,et al.  The magnitude of the initial injury induced by stretches of maximally activated muscle fibres of mice and rats increases in old age. , 1996, The Journal of physiology.

[19]  N. Jones,et al.  Muscle strength, symptom intensity, and exercise capacity in patients with cardiorespiratory disorders. , 1995, American journal of respiratory and critical care medicine.

[20]  J. Faulkner,et al.  Muscle atrophy and weakness with aging: contraction-induced injury as an underlying mechanism. , 1995, The journals of gerontology. Series A, Biological sciences and medical sciences.

[21]  J. Watchko,et al.  Age-related differences in diaphragm muscle injury after lengthening activations. , 1994, Journal of applied physiology.

[22]  G. Sieck,et al.  Interactive effects of emphysema and malnutrition on diaphragm structure and function. , 1994, Journal of applied physiology.

[23]  J A Faulkner,et al.  Skeletal muscle weakness in old age: underlying mechanisms. , 1994, Medicine and science in sports and exercise.

[24]  R L Lieber,et al.  Myosin and actin filament lengths in diaphragms from emphysematous hamsters. , 1994, Journal of applied physiology.

[25]  J. Duarte,et al.  Endothelium-derived oxidative stress may contribute to exercise-induced muscle damage. , 1993, International journal of sports medicine.

[26]  G. Sieck,et al.  Adaptations of the diaphragm in emphysema. , 1992, Journal of applied physiology.

[27]  J. Faulkner,et al.  Contraction-induced injury: recovery of skeletal muscles in young and old mice. , 1990, The American journal of physiology.

[28]  M. Sadeh.  Effects of aging on skeletal muscle regeneration , 1988, Journal of the Neurological Sciences.

[29]  Marinos C. Dalakas,et al.  Muscle biopsy — a practical approach , 1986, The Ulster Medical Journal.

[30]  E. Schultz,et al.  Effects of skeletal muscle regeneration on the proliferation potential of satellite cells , 1985, Mechanisms of Ageing and Development.

[31]  S. Kelsen,et al.  Effect of elastase-induced emphysema on the force-generating ability of the diaphragm. , 1982, The Journal of clinical investigation.

[32]  C. Roussos,et al.  Adaptability of the hamster diaphragm to exercise and/or emphysema. , 1982, Journal of applied physiology: respiratory, environmental and exercise physiology.

[33]  W. Reid,et al.  Diaphragm injury and myofibrillar structure induced by resistive loading. , 1994, Journal of applied physiology.

[34]  G. Criner,et al.  The comparative effects of elastase-induced emphysema on costal and crural diaphragm and parasternal intercostal muscle contractility. , 1994, American journal of respiratory and critical care medicine.

[35]  S. Kelsen,et al.  Functional adaptation of diaphragm to chronic hyperinflation in emphysematous hamsters. , 1986, Journal of applied physiology.