Effect of Elastase-induced Emphysema on the Force-generating Ability of the Diaphragm

Abstract

A B S T R A C T The effect of emphysema on the ability of the diaphragm to generate force was examined in costal diaphragm muscle strips from 10 Golden hamsters killed 18 mo after intratracheal injection of pancreatic elastase in a dose producing hyperinflation (mean total lung capacity [TLC] = 163% of control) and generalized panacinar emphysema. 13 saline-injected normal animals served as controls. The time course of isometric tension and the effect of alterations in muscle fiber and sarcomere length on the isometric tension (T) generated in response to tetanizing electrical stimuli (length-tension [L-T] relationship) were examined. Elastase administration caused an increase in diaphragm muscle thickness and reduction in the length of costal diaphragm muscle fibers measured in situ. Emphysema significantly increased the maximum tetanic tension as a result of hypertrophy. Maximal tension corrected for increases in muscle cross-sectional area (T/cm2), however, was the same in emphysematous (E) and control (C) animals. Emphysema also shifted the muscle fiber L-T curve of the diaphragm but not of a control muscle, the soleus, toward shorter lengths. In contrast to the effects of E on the diaphragm muscle fiber L-T curve, the sarcomere L-T curve was the same in E and C. Since the length at which tension was maximal correlated closely with sarcomere number (r = 0.94; P < 0.001) reduction in the number of sarcomeres in series in muscles from emphysematous animals appeared to explain the shift in the muscle fiber L-T curve. We conclude that in elastase-induced emphysema adaptive changes both in diaphragm cross-sectional area and sarcomere number augment the force-generating ability of the diaphragm. We speculate that changes in sarcomere number compensate for alterations in muscle fiber length

Respiratory muscle fiber remodeling in chronic hyperinflation: dysfunction or adaptation?

“…1A. The two studies differed in that Farkas and Roussos (21) also described small reductions in average sarcomere length from ϳ2.6 to 2.5 m, whereas Supinski and Kelsen (85) saw no such changes (Fig. 1B).…”

“…1A, adapted from Ref. 85. As the muscle is stretched from a slackened state and then stimulated, there is a rise in maximum active force, over and above passive force, reaching a peak value.…”

“…In the early 1980s two research groups, one at MeakinsChristie Laboratories in Montreal (20,21) and the other at Case Western University in Cleveland (35,85), reported almost simultaneously that the diaphragms of hamsters exposed to elastase-induced emphysema for 6 -18 mo demonstrated a net diaphragm muscle shortening due to loss of sarcomeres in series. These changes shifted the L o of the diaphragm to a shorter length, thus preserving contractile force at hyperinflated lung volumes, as shown in Fig.…”

“…They observed that average sarcomere length was shorter in emphysema than in comparable controls and that the greater degree of hyperinflation or disease severity corresponded with shorter sarcomere lengths. This suggests that human diaphragm does not fully adapt to length changes like the hamster or rat diaphragm (72,85). However, muscle sarcomere length measurements from open-lung biopsy specimens are unlikely to be an accurate measure of in vivo sarcomere length, because the preload or lung volume at which the fiber is obtained is not controlled.…”

“…This would be in agreement with the study by that has shown shorter sarcomeres in the diaphragm of COPD patients. Thus the area remains unresolved.In most studies of rat or hamster elastase-induced emphysema, there is little or no biologically significant reduction in maximum specific force (Ͻ10% change) of muscle bundles or individual fibers (20,21,31,36,49,85), as summarized in Table 1. The largest exceptions to this are the work of Lewis et al.…”