Inhibition of RNA transcription modulates magnesium-supplemented potassium cardioplegia protection.
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.
Matsuda
H
H
Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA.
Levitsky
S
S
McCully
J D
JD
D000818:Animals; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D004261:DNA Replication / Q000187:drug effects; D006324:Heart Arrest, Induced; D008278:Magnesium Sulfate / Q000494:pharmacology*; D009206:Myocardium / Q000473:pathology; D011189:Potassium Chloride / Q000494:pharmacology*; D012313:RNA / Q000187:drug effects* / Q000235:genetics; D011817:Rabbits; D014158:Transcription, Genetic / Q000187:drug effects* / Q000235:genetics
D002314:Cardioplegic Solutions; D012313:RNA; D011189:Potassium Chloride; D008278:Magnesium Sulfate