Alteration of gap junctions and connexins in the right atrial appendage during cardiopulmonary bypass

J Thorac Cardiovasc Surg. 2002 Dec;124(6):1106-12. doi: 10.1067/mtc.2002.124993.

Abstract

Objectives: We investigated the influence of cardiopulmonary bypass on cardiomyocyte gap junctions and connexins.

Methods: Samples were collected at intervals during operation from the right atrial appendage in 21 patients (mean [+/- SD] age 55 +/- 21 years). Immunodetection of connexins was conducted by Western blotting and confocal microscopy with parallel electron microscopic examination of gap junctions.

Results: Downregulation of connexin 43 during the course of operation occurred in more than half of the patients. The mean densitometric value of connexin 43 decreased by 23%, with samples from patients with coronary artery disease showing a greater reduction than seen in those from patients with other diseases (31% +/- 22% vs 10% +/- 24%, P =.04). Such alterations were confirmed by confocal microscopy, which also demonstrated reduced connexin 45 immunolabeling in most patients. Electron microscopy revealed a reduction in the dimensions of cell membrane-located gap junctions and more frequent intracytoplasmic gap junctional membrane in samples from later time points (P =.04).

Conclusions: Downregulation of connexins accompanied by a reduction in gap junctions is common in the cardiomyocytes of the right atrial appendage during cardiopulmonary bypass. The association of a marked reduction in connexin 43 with coronary artery disease may imply inadequate intraoperative cardiac protection in patients with this disease.

MeSH terms

  • Atrial Appendage / metabolism*
  • Blotting, Western
  • Cardiopulmonary Bypass*
  • Connexin 43 / metabolism
  • Connexins / metabolism*
  • Down-Regulation
  • Female
  • Gap Junction alpha-5 Protein
  • Gap Junctions / metabolism*
  • Humans
  • Male
  • Microscopy, Confocal
  • Microscopy, Electron
  • Middle Aged

Substances

  • Connexin 43
  • Connexins