title: Diaphragm injury and myofibrillar structure induced by resistive loading.
abstract: The purpose of this study was to determine whether ventilatory failure is associated with muscle fiber damage and myofibrillar protein alterations. Ventilatory failure was induced by tightening a polyvinyl band around the trachea of hamsters (TB; n = 14) for 6 days, which resulted in severe respiratory acidosis (PCO2: 97.9 +/- 29.6 vs. 51.6 +/- 19.6 Torr; pH: 7.16 vs. 7.35), hypoxemia (PO2: 42.8 +/- 16.8 vs. 65.9 +/- 25.8 Torr), and increased pulmonary resistance (1.89 +/- 1.61 vs. 0.29 +/- 0.27 cmH2O.ml-1 x min; P < 0.05). The point-counting technique of hematoxylin- and eosin-stained cross sections showed a higher area fraction of abnormal muscle and inflammatory cells in the costal [0.133 +/- (SE) 0.33 vs. 0.040 +/- 0.010] and crural regions (0.069 +/- 0.020 vs. 0.012 +/- 0.003) of the diaphragm in TB hamsters than in control hamsters. Electron micrographs revealed sarcomeric disruption and Z band streaming in the diaphragm of TB hamsters. Myofibrillar changes of the diaphragm associated with ventilatory failure were quantitative (i.e., a lower yield of purified myofibrils) but not qualitative (similar sodium dodecyl sulfate-polyacrylamide gel electrophoresis protein profiles); however, sulfhydryl group reactivities were reduced (P < 0.05). Proteolysis of purified myofibrils from the diaphragm digested with calpain showed faster degradation rates for tropomyosin and alpha-actinin but not for all proteins for the TB animals. Ventilatory failure induced by resistive loading was associated with diaphragm injury; some of this injury was linked to changes in myofibrillar complexes, specifically their susceptibility to calpain-mediated degradation.
authors.affiliation: School of Rehabilitation Sciences, University of British Columbia Pulmonary Research Laboratory, Vancouver, Canada.
authors.forename: W D
authors.initials: WD
authors.lastname: Reid
authors.forename: J
authors.initials: J
authors.lastname: Huang
authors.forename: S
authors.initials: S
authors.lastname: Bryson
authors.forename: D C
authors.initials: DC
authors.lastname: Walker
authors.forename: A N
authors.initials: AN
authors.lastname: Belcastro
mesh_terms: D000185:Actinin / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001784:Blood Gas Analysis; D002154:Calpain / Q000378:metabolism; D006224:Cricetinae; D003964:Diaphragm / Q000293:injuries* / Q000473:pathology; D004591:Electrophoresis, Polyacrylamide Gel; D006868:Hydrolysis; D008647:Mesocricetus; D008854:Microscopy, Electron; D009124:Muscle Proteins / Q000302:isolation & purification; D009210:Myofibrils / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D005082:Physical Exertion / Q000502:physiology*; D012518:Sarcomeres / Q000648:ultrastructure; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014132:Trachea / Q000503:physiopathology; D014335:Tropomyosin / Q000378:metabolism
chemical_list: D009124:Muscle Proteins; D013438:Sulfhydryl Compounds; D014335:Tropomyosin; D000185:Actinin; D002154:Calpain