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Initial results of a clinical study: adenosine enhanced cardioprotection and its effect on cardiomyocytes apoptosis during coronary artery bypass grafting

^a Heart Center, Division of Cardiothoracic Surgery, Tampere University Hospital, Tampere, Finland
^b Heart Center, Division of Cardiothoracic Surgery, Affiliated 1st Hospital, Alexandria University, Faculty of Medicine, Egypt
^c Department of Forensic Medicine, University of Turku, Finland

Received 24 August 2007; received in revised form 18 December 2007; accepted 19 December 2007.

^_* Corresponding author. Address: Division of Cardiothoracic Surgery, Heart Center, Pirkanmaa Hospital District, PO Box 2000, Fin-33521 Tampere, Finland. Tel.: +358 3 31166378; fax: +358 3 31165756. (Email: matti.tarkka{at}pshp.fi).

Objective: Apoptosis has been considered as one of the mechanisms of cardiomyocyte loss during open heart surgery. Adenosine is cardioprotective against ischemia-reperfusion injury in experimental models. The aim of this study was to find out whether the administration of single dose adenosine added to blood cardioplegia is effective in decreasing the apoptosis process. Methods: In a double-blinded randomized control intervention study, 40 patients were enrolled for elective coronary artery bypass grafting. In the adenosine group (n = 20) patients received 250 µg/kg adenosine in the aortic root after cross-clamping followed by cold blood cardioplegia. In the control group (n = 20) patients had only antegrade cardioplegia. Left ventricular tissue samples (from apex) were taken before and after the bypass. The apoptotic cells were identified by dUTP nick-end labeling (TUNEL) using an apoptosis detection kit. The number of TUNEL-positive cardiomyocytes was expressed as percentage of the total number of cardiomyocytes in histological tissue sections. Results: The groups were closely identical in demographic data, cross-clamp time, cardiopulmonary bypass time and weaning time. The postoperative cardiac index and other hemodynamic parameters, including the patterns of CK-MB, did not show statistically significant differences. In the tissue samples there were an equal number of patients who developed apoptosis after the cross-clamp. Although the frequency of apoptosis in the control group was two times higher than in the adenosine group, this was statistically not significant. Conclusions: Adenosine enhanced blood cardioplegia could not prevent myocardial apoptosis completely. However, it seems to be that adenosine might influence the frequency of apoptosis and this needs to be considered in future investigations.

Key Words: Adenosine • Apoptosis • Cardioplegic solution • Cardiopulmonary bypass • Myocardial protection

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