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Published on: March 12, 2013
Transcriptomic analysis reveals atrial KCNE1 down-regulation following lung lobectomy
Paul M Heerdt1, Ritu Kant, Zhaoyang Hu
1Dept. of Anesthesiology, Weill Cornell Medical College, 1300 York Ave., New York, NY 10021, USA. pmheerd@med.cornell.edu
Journal of Molecular and Cellular Cardiology
|May 30, 2012
Summary
Postoperative atrial fibrillation (POAF) may be linked to KCNE1 gene down-regulation after lung surgery. This study found KCNE1 changes in pigs, suggesting a common mechanism for POAF and lone AF.
Area of Science:
- Cardiovascular Physiology
- Molecular Cardiology
- Surgical Research
Background:
- Lone atrial fibrillation (AF) is linked to KCNE1 gene variants.
- Postoperative AF (POAF) molecular bases are poorly understood.
- POAF often occurs after thoracic surgery.
Purpose of the Study:
- Investigate molecular and electrophysiological changes in the left atrium (LA) after lung lobectomy.
- Determine the relationship between these changes and the capacity to sustain AF.
- Identify potential molecular mechanisms underlying POAF.
Main Methods:
- Left upper lung lobectomy in swine model.
- Hemodynamic monitoring and electrophysiological assessment (LA ERP).
- Transcriptomic and protein analysis of LA tissue.
- Electrically-induced AF induction and sustainment.
Main Results:
- Post-lobectomy pigs showed increased pulmonary artery pressure and resistance.
- LA effective refractory period (ERP) trended lower in lobectomy pigs.
- All lobectomy pigs sustained electrically-induced AF, unlike controls.
- KCNE1 gene and protein expression were significantly down-regulated post-surgery.
- DSCR5 and Teneurin-2 were among up-regulated transcripts.
Conclusions:
- Lung lobectomy in swine leads to electrophysiological changes and increased AF susceptibility.
- KCNE1 down-regulation is a potential mechanistic link between POAF and lone AF.
- Further studies will investigate the functional roles of identified gene expression changes.
