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 em-physematous hamsters. However, ageing affects the regenerating capacity of muscles. We hypothesised that the diaphragm of aged emphysematous hamsters shows an increase of ultra-structural 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 electronmicro-scopical 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 mus-cle fibre damage (Z-line dislocation, disarray of myofibrils, misaligned sarcomeres, focal degeneration, focal necrosis and segmental necrosis) and more signs of sub-optimal regen-eration (fibre splitting and forking) and abortive regeneration. In conclusion, the diaphragm of aged emphysematous hamsters exhibits increased ultrastruc-tural abnormalities, which are likely to contribute to a reduced force generating capacity