Cardiomyocyte apoptosis after antegrade and retrograde cardioplegia during aortic valve surgery

Abstract

Background: Retrograde delivery is associated with inadequate perfusion of cardioplegia to all regions of the heart, but the effects on cardiomyocyte death and functional outcome remain unknown. We compared antegrade and retrograde cardioplegia in a randomized clinical trial to see whether it has effect on cardiomyocyte apoptosis and left ventricular function.

Methods: Patients underwent elective aortic valve replacement surgery due to aortic valve stenosis. They were randomly allocated to receive antegrade (n = 10) or retrograde (n = 10) cardioplegia. Apoptotic cardiomyocytes (terminal transferase-mediated dUTP nick end labeling, caspase activation) and RNA levels of apoptosis-regulating proteins were studied in transmyocardial biopsies obtained before and after the operation. Magnetic resonance imaging and transesophageal echocardiography were performed, and cardiac enzymes were measured.

Results: Clinical outcome and cardiac enzyme release were comparable between the groups. Cardiomyocyte apoptosis was significantly increased (terminal transferase-mediated dUTP nick end labeling) in the left ventricle after the operation in the retrograde, but not in the antegrade group (respectively, 0.00% [0.039%] versus 0.092% [0.205%], p = 0.01; and 0.00% [0.00%] versus 0.023% [0.054%], p = 0.14). Expression of apoptosis-regulating proteins BAX, BAD, and BCL-2 were comparable between groups. By transesophageal echocardiography, the systolic mitral annulus movement was decreased immediately after the operation in the retrograde group. By magnetic resonance imaging, the left ventricle mass index was reduced preoperatively to 9 months postoperatively in the antegrade group.

Conclusions: In contrast to antegrade cardioplegia, retrograde cardioplegia is associated with increased cardiomyocyte apoptosis, impaired immediate postoperative systolic function, and lack of long-term favorable left ventricle remodeling after aortic valve replacement, suggesting inadequate myocardial protection.