Physiological effects of diaphragm muscle denervation and disuse

G. C. Sieck

Research output: Contribution to journalReview articlepeer-review

75 Scopus citations


From our studies, it is clear that diaphragm muscle neuromotor control is responsive to alterations in innervation and activation. These adaptations to altered use appear to be most pronounced among fast-twitch motor units composed of type II muscle fibers. Because the plasticity involves diminished contractile strength and a slowing of shortening velocity, it might be considered maladaptive with respect to diaphragm functional demands; however, because ventilatory behaviors of the diaphragm most likely require the recruitment of only type S motor units (type I muscle fibers) that appear to be less adaptive, the functional decrements following disuse may involve only nonventilatory behaviors that require the recruitment of fast-twitch (type II muscle fibers) motor units. In other words, in many circumstances, diaphragm muscle adaptations may reduce the functional reserve capacity of the muscle without affecting normal ventilatory performance. The extent to which these observations can be applied to humans remains speculative. Certainly, the animal models approximate the human condition in that ventilatory require- ments of the diaphragm are comparable across mammalian species. It is known that type II fibers comprise approximately 60% of the human diaphragm. Therefore, type II muscle fibers in humans may also be particularly vulnerable to adaptive changes associated with diaphragm disuse. With regard to the functional decrements that might ensue in humans, we have estimated that the forces generated by the human diaphragm during tidal breathing are approximately 10% of maximum. Therefore, as in other species, ventilatory forces generated by the diaphragm in humans most likely do not require the recruitment of fast-twitch (type II) motor units. Normal ventilatory behaviors may therefore be spared from maladaptive changes in diaphragm performance. With the imposition of mechanical loads to breathing associated with certain chronic pulmonary diseases, however, it might be expected that the recruitment of fast-twitch motor traits would be required on a more continuous basis. Such diseases are normally progressive and incremental, therefore allowing sufficient time for adaptation. One adaptation that might be expected would be an overall improvement in the fatigue resistance of fast-twitch motor units. This adaptation could be accomplished by altering the metabolic enzyme activities of type II muscle fibers, by affecting the expression of contractile proteins, or both. Improvement of muscle fiber fatigue resistance is usually at the expense of fiber size, contractile strength, or both. Therefore, although disease-related adaptations of type II muscle fibers may improve fatigue resistance and maintain ventilatory performance, they would also involve reductions in contractile strength of the diaphragm that could impair important nonventilatory behaviors of the diaphragm such as coughing, sneezing, and defecation. Moreover, if such adaptations reduced the functional reserve capacity of the diaphragm, they could also limit ventilatory performance under certain conditions of increased mechanical or metabolic loads. In addition to disease conditions, adaptive changes of the diaphragm may be particularly important for patients placed on mechanical ventilators. Our studies suggest that, in response to inactivity, significant reductions in diaphragm strength and shortening velocity can occur as early as 1 to 3 days afterward, becoming more pronounced with time. Such adaptations might underlie the inability to wean some patients from mechanical ventilation. Certainly, maladaptation of dia- phragm neuromotor control should be considered as part of the cause of several pathologic conditions.

Original languageEnglish (US)
Pages (from-to)641-659
Number of pages19
JournalClinics in Chest Medicine
Issue number4
StatePublished - 1994

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine


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