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Ann Thorac Surg 2000;70:2107-2112
© 2000 The Society of Thoracic Surgeons

Original article: cardiovascular

Inhibition of RNA transcription modulates magnesium-supplemented potassium cardioplegia protection

Hitoshi Matsuda, MDa, Sidney Levitsky, MDa, James D. McCully, PhDa

a Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA

Accepted for publication May 1, 2000.

Address reprint requests to Dr McCully, Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, 77 Avenue Louis Pasteur, Room 140, Boston, MA 02115
e-mail: james_mccully{at}hms.harvard.edu

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 postischemic 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.




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