Diaphragm muscle fiber weakness in pulmonary hypertension.
SourceAmerican Journal of Respiratory and Critical Care Medicine, 183, 10, (2011), pp. 1411-1418
Article / Letter to editor
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American Journal of Respiratory and Critical Care Medicine
SubjectN4i 1: Pathogenesis and modulation of inflammation
RATIONALE: Recently it was suggested that patients with pulmonary hypertension (PH) suffer from inspiratory muscle dysfunction. However, the nature of inspiratory muscle weakness in PH remains unclear. OBJECTIVES: To assess whether alterations in contractile performance and in morphology of the diaphragm underlie inspiratory muscle weakness in PH. METHODS: PH was induced in Wistar rats by a single injection of monocrotaline (60 mg/kg). Diaphragm (PH n = 8; controls n = 7) and extensor digitorum longus (PH n = 5; controls n = 7) muscles were excised for determination of in vitro contractile properties and cross-sectional area (CSA) of the muscle fibers. In addition, important determinants of protein synthesis and degradation were determined. Finally, muscle fiber CSA was determined in diaphragm and quadriceps of patients with PH, and the contractile performance of single fibers of the diaphragm. MEASUREMENTS AND MAIN RESULTS: In rats with PH, twitch and maximal tetanic force generation of diaphragm strips were significantly lower, and the force-frequency relation was shifted to the right (i.e., impaired relative force generation) compared with control subjects. Diaphragm fiber CSA was significantly smaller in rats with PH compared with controls, and was associated with increased expression of E3-ligases MAFbx and MuRF-1. No significant differences in contractility and morphology of extensor digitorum longus muscle fibers were found between rats with PH and controls. In line with the rat data, studies on patients with PH revealed significantly reduced CSA and impaired contractility of diaphragm muscle fibers compared with control subjects, with no changes in quadriceps muscle. CONCLUSIONS: PH induces selective diaphragm muscle fiber weakness and atrophy.
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