H Matsuda1, S Levitsky, J D McCully. 1. Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA.
Abstract
BACKGROUND: Previously we reported that decreased postischemic functional recovery was associated with increased DNA fragmentation in the aged myocardium. Magnesium-supplemented potassium (K/Mg) cardioplegia ameliorated DNA fragmentation and enhanced post-ischemic functional recovery. We hypothesized that K/Mg cardioprotection might involve either an RNA- or a protein-dependent mechanism. METHODS: Aged rabbit hearts underwent Langendorff perfusion. Global ischemia hearts (GI) received 30 minutes of global ischemia and 60 minutes of reperfusion; K/Mg hearts received cardioplegia before global ischemia. To investigate the role of RNA and protein synthesis, K/Mg hearts were treated with alpha-amanitin or cycloheximide to inhibit RNA or protein synthesis. We also determined the quantity of DNA fragmentation and RNA/DNA ratio. RESULTS: Inhibition of RNA but not protein synthesis significantly decreased K/Mg cardioprotection and was associated with significantly decreased postischemic functional recovery (p < 0.05 versus K/Mg), increased DNA fragmentation, and decreased RNA/DNA ratio (p < 0.05 versus K/Mg). CONCLUSIONS: These results indicate that K/Mg cardioprotection in the aged myocardium was modulated by an RNA-dependent mechanism.
BACKGROUND: Previously we reported that decreased postischemic functional recovery was associated with increased DNA fragmentation in the aged myocardium. Magnesium-supplemented potassium (K/Mg) cardioplegia ameliorated DNA fragmentation and enhanced post-ischemic functional recovery. We hypothesized that K/Mg cardioprotection might involve either an RNA- or a protein-dependent mechanism. METHODS: Aged rabbit hearts underwent Langendorff perfusion. Global ischemia hearts (GI) received 30 minutes of global ischemia and 60 minutes of reperfusion; K/Mg hearts received cardioplegia before global ischemia. To investigate the role of RNA and protein synthesis, K/Mg hearts were treated with alpha-amanitin or cycloheximide to inhibit RNA or protein synthesis. We also determined the quantity of DNA fragmentation and RNA/DNA ratio. RESULTS: Inhibition of RNA but not protein synthesis significantly decreased K/Mg cardioprotection and was associated with significantly decreased postischemic functional recovery (p < 0.05 versus K/Mg), increased DNA fragmentation, and decreased RNA/DNA ratio (p < 0.05 versus K/Mg). CONCLUSIONS: These results indicate that K/Mg cardioprotection in the aged myocardium was modulated by an RNA-dependent mechanism.
Authors: James D McCully; Monoj K Bhasin; Christian Daly; Manuel C Guerrero; Simon Dillon; Towia A Liberman; Douglas B Cowan; John D Mably; Francis X McGowan; Sidney Levitsky Journal: Physiol Genomics Date: 2009-05-19 Impact factor: 3.107
Authors: Zoe E Plummer; Sarah Baos; Chris A Rogers; M-Saadeh Suleiman; Alan J Bryan; Gianni D Angelini; James Hillier; Richard Downes; Eamonn Nicholson; Barnaby C Reeves Journal: JMIR Res Protoc Date: 2014-07-08