Mechanical ventilation-induced oxidative stress in the diaphragm

ZERGEROĞLU A. M., McKenzie M., Shanely R., Van Gammeren D., DeRuisseau K., Powers S.

JOURNAL OF APPLIED PHYSIOLOGY, vol.95, no.3, pp.1116-1124, 2003 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 95 Issue: 3
  • Publication Date: 2003
  • Doi Number: 10.1152/japplphysiol.00824.2002
  • Journal Name: JOURNAL OF APPLIED PHYSIOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1116-1124
  • Keywords: respiratory muscles, muscle atrophy, free radicals, protein oxidation, weaning from mechanical ventilation, muscle injury, VIVO-ISCHEMIA-REPERFUSION, SKELETAL-MUSCLE, CONTRACTILE PROPERTIES, RESPIRATORY MUSCLES, PROTEINS, RAT, MITOCHONDRIAL, EXERCISE, FAILURE, DAMAGE
  • Ankara University Affiliated: No

Abstract

Prolonged mechanical ventilation (MV) results in oxidative damage in the diaphragm; however, it is unclear whether this MV-induced oxidative injury occurs rapidly or develops slowly over time. Furthermore, it is unknown whether both soluble ( cytosolic) and insoluble ( myofibrillar) proteins are equally susceptible to oxidation during MV. These experiments tested two hypotheses: 1) MV-induced oxidative injury in the diaphragm occurs within the first 6 h after the initiation of MV; and 2) MV is associated with oxidative modification of both soluble and insoluble proteins. Adult Sprague-Dawley rats were randomly divided into one of seven experimental groups: 1) control (n = 8); 2) 3-h MV (n = 8); 3) 6-h MV (n = 6); 4) 18-h MV (n = 8); 5) 3-h anesthesia-spontaneous breathing (n = 8); 6) 6-h anesthesia-spontaneous breathing (n = 6); and 7) 18-h anesthesia-spontaneous breathing (n = 8). Markers of oxidative injury in the diaphragm included the measurement of reactive ( protein) carbonyl derivatives (RCD) and total lipid hydroperoxides. Three hours of MV did not result in oxidative injury in the diaphragm. In contrast, both 6 and 18 h of MV promoted oxidative injury in the diaphragm, as indicated by increases in both protein RCD and lipid hydroperoxides. Electrophoretic separation of soluble and insoluble proteins indicated that the MV-induced accumulation of RCD was limited to insoluble proteins with molecular masses of similar to 200, 120, 80, and 40 kDa. We conclude that MV results in a rapid onset of oxidative injury in the diaphragm and that insoluble proteins are primary targets of MV-induced protein oxidation.