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.