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J Thorac Cardiovasc Surg 2002;124:1106-1112
© 2002 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology (CSP)

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

From the Departments of Cardiac Medicine and Medical Research, Mackay Memorial Hospital, Taipei Medical University,^a and the First Cardiovascular Division, Department of Internal Medicine, Chang Gung Memorial Hospital,^b Taipei, Taiwan, and the National Heart and Lung Institute, Imperial College, London, United Kingdom.^c

Supported by grants CCF-98-03 and 99-06 from the Cardiac Children Foundation, Republic of China, and MMH-8702 from the Medical Research Department of the Mackay Memorial Hospital, Taiwan. N.J.S acknowledges support from the European Commission (QLRT-1999-00516).

Received for publication Dec 26, 2001. Revisions requested Jan 15, 2002; revisions received March 22, 2002. Accepted for publication March 24, 2002. Address for reprints: Hung-I Yeh, MD, Mackay Memorial Hospital, Cardiac Medicine, 92, Section 2, Chung-San North Rd, Taipei, Taiwan 10449.

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.

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