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Loss of sarcolemmal dystrophin and dystroglycan may be a potential mechanism for myocardial dysfunction in severe sepsis
Critical Care volume 13, Article number: P14 (2009)
Myocardial function is severely compromised during sepsis. Several underlying mechanisms have been proposed to explain this fact. Evidence from our laboratory indicates that myocardial structural changes could be responsible for sepsis-induced myocardial dysfunction. Taking into account that the contractile machinery inside the myofibers must remain intimately connected with the membrane and extracellular matrix, association provided by the dystrophin–glycoprotein complex (DGC), the present study investigated the hypothesis that loss of dystrophin and associated glycoproteins could be involved in early increased sarcolemmal permeability in experimentally induced septic cardiomyopathy.
Methods and results
Male C57Bl/6 mice were subjected to sham operation, moderate septic injury or severe septic injury (SSI) induced by cecal ligation and puncture. SSI mice presented a large number of bacteria, high levels of TNFα and MIP-1α in both the peritoneal cavity and blood, marked hypotension, and a high mortality rate. Using immunofluorescence and western blot analysis, a downregulation of structural protein expression, dystrophin and β-dystroglycan in both severe and moderate injury could be seen in septic hearts. In contrast, the immunofluorescent analysis for laminin-α2 did not show a difference of expression in septic hearts as compared with sham-operated hearts. In addition, the evaluation of plasma membrane permeability by intracellular albumin staining provided evidence of severe injury of the sarcolemma in SSI hearts that presented accumulation of albumin in a large number of cardiomyocytes depleted of dystrophin.
Our data provide important insight regarding the alterations in the DGC resulting from severe septic injury. In this study, a significant decrease of dystrophin and β-dystroglycan results in loss of sarcolemmal permeability that may be partly responsible for sepsis-induced cardiac depression. These abnormal parameters emerge as therapeutic targets, and their modulation may provide beneficial effects on future cardiovascular outcomes and mortality in sepsis.
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Celes, M., Torres-Dueñas, D., Duarte, D. et al. Loss of sarcolemmal dystrophin and dystroglycan may be a potential mechanism for myocardial dysfunction in severe sepsis. Crit Care 13 (Suppl 3), P14 (2009). https://doi.org/10.1186/cc7816