Inhibition of RNA transcription modulates magnesium-supplemented potassium cardioplegia protection.

Abstract

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. 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. 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). These results indicate that K/Mg cardioprotection in the aged myocardium was modulated by an RNA-dependent mechanism.