Apoptosis during CABG surgery with the use of cardiopulmonary bypass is prominent in ventricular but not in atrial myocardium

Abstract

Objectives. We aimed to compare the rate of apoptosis after cardiopulmonary bypass (CPB) and cardioplegic arrest during coronary artery bypass grafting (CABG) surgery between atrial and ventricular tissue.Methods. During CABG surgery with CPB and cardioplegic arrest, sequential biopsies were taken from the right atrial appendage and left ventricular anterior wall before CPB and after aortic cross clamp release. Change in number of apoptotic cells and biochemical markers of myocardial ischaemia and renal dysfunction were assessed.Results. CPB was associated with a transient small, but significant increase in CK (1091+/-374%), CK-MB (128+/-38%), troponin-T (102+/-13%) and NT-proBNP (1308+/-372%) levels (all: p<0.05). A higher number of apoptotic cells as assessed by caspase-3 staining was found in the ventricular biopsies taken after aortic cross clamp release compared with the biopsies taken before CPB (5.3+/-0.6 vs. 14.0+/-1.5 cells/microscopic field, p<0.01). The number of apoptotic cells in the atrial appendage was not altered during CPB. Correlation between the duration of aortic cross clamp time and the change in caspase-3 positive cells in the left ventricular wall was of borderline significance (r of 0.58, p=0.08). Similar results were obtained from TUNEL staining for apoptosis.Conclusion. CABG surgery with CPB and cardioplegic arrest is associated with an elevated rate of apoptosis in ventricular but not in atrial myocardial tissue. Ventricular tissue may be more sensitive to detect changes than atrial tissue, and may be more useful to investigate the protective effects of therapeutic intervention. (Neth Heart J 2010;18:236-42.).

Keywords: Apoptosis; Coronary Artery Bypass; Heart Arrest; Heart Atria; Heart vetricules; Reperfusion Injury.

Figure 1

Study design. The figure shows the study design as described in the text.

Figure 2

Number of apoptotic cells during cardiopulmonary bypass. (A) Number of caspase-3+ and TUNEL+ cells in the atria. (B) Number of caspase-3+ and TUNEL+ cells in the ventricles. (C and D) Immunohistological examples of caspase-3+ staining in atria (C) and ventricles (D). (E) Percentage change in caspase-3+ and TUNEL+ cells during cardiopulmonary bypass in atria and ventricles. (F) Linear regression of aortic cross clamp time and change in caspase-3+ cells in the ventricles. Base=baseline: atrial biopsy taken after opening chest, pre=biopsies taken during placement of the venous cannula (for atrial biopsy) and just after going on cardiopulmonary bypass (for ventricular biopsy), post=biopsies taken 10 minutes after aortic cross clamp release. * p<0.05, ** p<0.01.

Figure 3

Time course of markers of myocardial ischaemia and renal function. (A) Time course of creatinine kinase-myoglobin (CK-MB) pre- and post-surgery. (B) Time course of troponin-T pre- and post-surgery. (C) Time course of creatinine kinase (CK) pre- and post-surgery. (D) Development of NT-pro-BNP pre- and post-surgery. E) Time course of creatinine pre- and post-surgery. (F) Time course of eGFR (estimated glomerular filtration rate) pre- and post-surgery. Screen=values during screening, pre=values directly before surgery, post=values during closing Chest. * p<0.05 vs. screening values.