Impaired cardiac autophagy in patients developing postoperative atrial fibrillation

Lorena Garcia, Hugo E. Verdejo, Jovan Kuzmicic, Ricardo Zalaquett, Sergio Gonzalez, Sergio Lavandero, Ramon Corbalan

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

Objectives: Postoperative atrial fibrillation (POAF) is a common complication after on-pump heart surgery. Several histologic abnormalities, such as interstitial fibrosis and vacuolization, have been described in atrial samples from patients developing POAF. This ultrastructural remodeling has been associated with the establishment of a proarrhythmic substrate. We studied whether atrial autophagy is activated in patients who develop POAF. Methods: A total of 170 patients in sinus rhythm who had undergone elective coronary artery bypass grafting were included. Systemic inflammatory markers were measured at baseline and 72 hours after surgery. During the procedure, samples of the right atrial appendages were obtained for evaluation of remodeling by light and electron microscopy. Protein ubiquitination and autophagy-related LC3B processing were assessed by Western blot. Results: Of these patients, 22% developed POAF. The level of high-sensitivity C-reactive protein, fibrosis, inflammation, myxoid degeneration, and ubiquitin-aggregates in the atria did not differ between patients with and without POAF. Electron microphotographs of those with POAF showed a significant accumulation of autophagic vesicles and lipofuscin deposits. Total protein ubiquitination was similar in the patients with and without POAF, but LC3B processing was markedly reduced in those with POAF, suggesting a selective impairment in autophagic flow. Conclusions: This study provides novel evidence that ultrastructural atrial remodeling characterized by an impaired cardiac autophagy is present in patients developing POAF after coronary artery bypass surgery.

Original languageEnglish (US)
Pages (from-to)451-459.e1
JournalJournal of Thoracic and Cardiovascular Surgery
Volume143
Issue number2
DOIs
StatePublished - Feb 2012

Bibliographical note

Funding Information:
The study was supported by grants from FONDECYT 1070641 and 1100801 (to R.C.) and FONDAP grant 15010006 (to L.G. and S.L.). H. E. Verdejo and J. Kuzmicic hold PhD fellowships from CONICYT, Chile. S. Lavandero is on a sabbatical leave at the University of Texas Southwestern Medical Center, Dallas, Tex.

Keywords

  • AF
  • CABG
  • POAF
  • RAA
  • atrial fibrillation
  • coronary artery bypass grafting
  • postoperative atrial fibrillation
  • right atrial appendage

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