Adenosine in cold blood cardioplegia--a placebo-controlled study

Abstract

OBJECTIVE Adenosine as an additive in blood cardioplegia is cardioprotective in animal studies, but its clinical role in myocardial protection remains controversial. The aim of this study was to investigate whether the addition of adenosine in continuous cold blood cardioplegia would enhance myocardial protection. METHODS In a prospective double-blind study comparing adenosine 400 μmol l(-1) to placebo in continuous cold blood cardioplegia, 80 patients undergoing isolated aortic valve replacement were randomized into four groups: antegrade cardioplegia with adenosine (n = 19), antegrade cardioplegia with placebo (n = 21), retrograde cardioplegia with adenosine (n = 21) and retrograde cardioplegia with placebo (n = 19). Myocardial arteriovenous differences in oxygen and lactate were measured before, during and after aortic occlusion. Myocardial concentrations of adenine nucleotides and lactate were determined from left ventricular biopsies obtained before aortic occlusion, after bolus cardioplegia, at 60 min of aortic occlusion and at 20 min after aortic occlusion. Plasma creatine kinase (CK-MB) and troponin T were measured at 1, 3, 6, 9, 12 and 24 h after aortic occlusion. Haemodynamic profiles were obtained before surgery and 1, 8 and 24 h after cardiopulmonary bypass. Repeated-measures analysis of variance was used for significance testing. RESULTS Adenosine had no effects on myocardial metabolism of oxygen, lactate and adenine nucleotides, postoperative enzyme release or haemodynamic performance. When compared with the antegrade groups, the retrograde groups showed higher myocardial oxygen uptake (17.3 ± 11.4 versus 2.5 ± 3.6 ml l(-1) at 60 min of aortic occlusion, P < 0.001) and lactate accumulation (43.1 ± 20.7 versus 36.3 ± 23.0 µmol g(-1) at 60 min of aortic occlusion, P = 0.052) in the myocardium during aortic occlusion, and lower postoperative left ventricular stroke work index (27.2 ± 8.4 versus 30.1 ± 7.9 g m m(-2), P = 0.034). CONCLUSIONS Adenosine 400 μmol l(-1) in cold blood cardioplegia showed no cardioprotective effects on the parameters studied. Myocardial ischaemia was more pronounced in patients receiving retrograde cardioplegia.

Figure 1:

Postoperative plasma concentrations of creatine kinase (CK-MB) and troponin T. Vertical bars denote ±standard error of the mean. P-values denote significance test of treatment allocation in repeated-measures ANOVA. (a) CK-MB. (b) Troponin T.

Figure 2:

Coronary arteriovenous (A-V) difference in oxygen and venoarterious (V-A) difference in lactate during and after aortic cross-clamp. Vertical bars denote ±standard error of the mean. P-values denote significance test of treatment allocation in repeated-measures ANOVA. (a) Oxygen. (b) Lactate.

Figure 3:

Concentration differences of adenine nucleotides and lactate in myocardial biopsies obtained after bolus cardioplegia (II), at 60 min of aortic occlusion (III) and at 20 min after release of aortic occlusion (IV). All values are subtracted from control biopsy before aortic occlusion (I). Vertical bars denote ±standard error of the mean. Post hoc significance test of time differences between biopsies are marked with an asterisk. ATP concentration: *P < 0.05 compared with biopsy II. **P < 0.01 compared with biopsy II. Total adenine nucleotide concentration: P < 0.01 compared with biopsy II. Lactate concentration: *P < 0.05 compared with biopsy I. **P < 0.01 compared with biopsy I.

Figure 4:

Differences between antegrade and retrograde cardioplegia. Vertical bars denote ±standard error of the mean. P-value denotes significance test of cardioplegia direction allocation in repeated-measures ANOVA. (a) Myocardial arteriovenous (A-V) differences in oxygen during aortic occlusion. (b) Concentration of lactate in myocardial biopsies obtained after bolus cardioplegia (II), at 60 min of aortic occlusion (III) and at 20 min after release of aortic occlusion (IV). All values are subtracted from control biopsy obtained before aortic occlusion (I). (c) LVSWI difference in the postoperative period. All time points subtracted from preoperative value.