Changes in satellite cell mitotic activity during acute period of unilateral diaphragm denervation

The acute period of unilateral diaphragm denervation (DNV) is associated with increases in cell mitotic activity, protein synthesis, and muscle fiber hypertrophy. Our purpose was to determine whether acute unilateral diaphragm DNV is associated with changes in muscle isometric contractile properties, cross-sectional area of different muscle fiber types, mitotic activity of muscle fiber satellite cells, and muscle fiber ultrastructural properties indicative of injury. Adult male Fischer 344 rats underwent a right phrenicotomy, and DNV and intact (INT) hemidiaphragms were studied 72 h later. DNV hemidiaphragm displayed a significant decline in maximal isometric force (8.7 vs. 24.3 N/cm²) and a prolonged time to peak twitch force (47.8 vs. 37.5 ms) and time to half relaxation (72.3 vs. 44.3 ms) compared with INT contralateral hemidiaphragm (P < 0.05). DNV resulted in a significant increase in cross-sectional area of types I (33%), IIa (35%), and IIb (28%) fibers relative to INT hemidiaphragm (P < 0.05). Satellite cell mitotic activity (assessed by incorporation of bromodeoxyuridine) was ~5.5 times greater in DNV than in INT muscle (DNV 25.0 ± 3.8, INT 4.5 ± 1.4 labeled satellite cell nuclei/1,000 nuclei; P < 0.05). Ultrastructural examination of electron micrographs revealed alterations in Z-line and sarcomeric structure indicative of muscle injury. Cellular infiltration and segmental necrosis were also noted in some fibers. We conclude that acute unilateral diaphragm DNV results in muscle fiber injury that induces satellite cell activation. We also speculate that the specific force decrement associated with DNV is at least partially the result of muscle injury.