BACKGROUND: Myocardial contractile depression develops 4 to 24 h after major burn injury. We have reported previously that in a rat burn injury model (≈40% of total body surface area burn), mesenteric lymph duct ligation (LDL) prior to burn prevented myocardial dysfunction. However, the underlying cellular and molecular mechanisms are not well understood. MATERIALS AND METHODS: Left ventricular myocytes were isolated from sham burn (control), sham burn with LDL (sham + LDL), burn, and burn with LDL (burn + LDL) rats at 4 and 24 h after burn or sham burn. Electrophysiological techniques were used to study myocyte size, contractility and L-type Ca2+ channel current (ICa). Further studies examined changes in the messenger RNA expression levels of pore-forming subunit of the L-type Ca(2+) channel, α1C, and its auxiliary subunits, β1, β2, β3, and α2δ1, which modulate the abundance of the ICa in post-burn hearts. RESULTS: Depressed myocyte contractility (≈20%) developed during 4 to 24 h post-burn compared with control, sham + LDL, or burn + LDL groups, a pattern of changes consistent with whole heart studies. There was no significant alteration in myocyte size. The ICa density was significantly decreased (≈30%) at 24 h post-burn, whereas the messenger RNA expression levels of Ca(2+) channel gene were not significantly altered at 4 and 24 h after burn injury. CONCLUSIONS: These results suggest that the post-burn contractile phenotype in vivo was also present in isolated myocytes in vitro, but cellular remodeling was not a major factor. The results also suggest that changes in ICa regulation, but not from Ca(2+) channel gene modification, may be a key element involved in post-burn contractile depression and the beneficial effects of LDL.
BACKGROUND:Myocardial contractile depression develops 4 to 24 h after major burn injury. We have reported previously that in a ratburn injury model (≈40% of total body surface area burn), mesenteric lymph duct ligation (LDL) prior to burn prevented myocardial dysfunction. However, the underlying cellular and molecular mechanisms are not well understood. MATERIALS AND METHODS: Left ventricular myocytes were isolated from sham burn (control), sham burn with LDL (sham + LDL), burn, and burn with LDL (burn + LDL) rats at 4 and 24 h after burn or sham burn. Electrophysiological techniques were used to study myocyte size, contractility and L-type Ca2+ channel current (ICa). Further studies examined changes in the messenger RNA expression levels of pore-forming subunit of the L-type Ca(2+) channel, α1C, and its auxiliary subunits, β1, β2, β3, and α2δ1, which modulate the abundance of the ICa in post-burn hearts. RESULTS: Depressed myocyte contractility (≈20%) developed during 4 to 24 h post-burn compared with control, sham + LDL, or burn + LDL groups, a pattern of changes consistent with whole heart studies. There was no significant alteration in myocyte size. The ICa density was significantly decreased (≈30%) at 24 h post-burn, whereas the messenger RNA expression levels of Ca(2+) channel gene were not significantly altered at 4 and 24 h after burn injury. CONCLUSIONS: These results suggest that the post-burn contractile phenotype in vivo was also present in isolated myocytes in vitro, but cellular remodeling was not a major factor. The results also suggest that changes in ICa regulation, but not from Ca(2+) channel gene modification, may be a key element involved in post-burn contractile depression and the beneficial effects of LDL.
Authors: Junhui Sun; Eckard Picht; Kenneth S Ginsburg; Donald M Bers; Charles Steenbergen; Elizabeth Murphy Journal: Circ Res Date: 2006-01-05 Impact factor: 17.367
Authors: Emmanuel S Buys; Anje Cauwels; Michael J Raher; Jonathan J Passeri; Ion Hobai; Sharon M Cawley; Kristen M Rauwerdink; Helene Thibault; Patrick Y Sips; Robrecht Thoonen; Marielle Scherrer-Crosbie; Fumito Ichinose; Peter Brouckaert; Kenneth D Bloch Journal: Am J Physiol Heart Circ Physiol Date: 2009-06-05 Impact factor: 4.733