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Ann Thorac Surg 2005;80:2229-2234
© 2005 The Society of Thoracic Surgeons

Original article: Cardiovascular

Cardiomyocyte Apoptosis After Antegrade and Retrograde Cardioplegia

Tommi Vähäsilta, MD a , d , * , Antti Saraste, MD, PhD e , Ville Kytö, MD, PhD e , Markus Malmberg, MB a , d , Jan Kiss, MB a , d , Erkki Kentala, MD, PhD b , Markku Kallajoki, MD, PhD c , Timo Savunen, MD, PhD a , d

a Department of Cardiothoracic Surgery, Turku University Central Hospital, Turku, Finland
b Department of Anaesthesiology and Intensive Care, Turku University Central Hospital, Turku, Finland
c Department of Pathology, Turku University Central Hospital, Turku, Finland
d Research Centre of Applied and Preventive Cardiovascular Medicine, Turku University, Turku, Finland
e Department of Anatomy, Turku University, Turku, Finland

Accepted for publication May 17, 2005.

* Address correspondence to Dr Vähäsilta, Turku University Central Hospital, FIN-20520, Turku, Finland (Email: tommi.vahasilta{at}tyks.fi).

BACKGROUND: Retrograde cardioplegia alone is often used in aortic valve and aortic root surgery. Due to the differences in venous anatomy between the right and the left side of the heart, retrograde cardioplegia is associated with incomplete protection of the right side. Since some apoptotic cardiomyocyte death is inevitable during an open heart surgery, we compared the extent of cardiomyocyte apoptosis in the left and right ventricles after antegrade and retrograde cardioplegia in a pig ischemia-reperfusion model.

METHODS: Pigs (n = 16, mean weight 30 kg) were openly assigned into the groups of antegrade and retrograde cardioplegia. After aortic cross-clamping, 500 mL of cold crystalloid (modified St Thomas) cardioplegia was administered into the ascending aorta or the coronary sinus. Aortic cross-clamp time was 30 minutes. Cardiomyocyte apoptosis was measured using the terminal transferase mediated ddUTP nick end-labeling (TUNEL) assay and immunohistochemical (IHC) staining for active caspase-3 in myocardial biopsies obtained before ischemia and after 90 minutes of reperfusion.

RESULTS: Apoptotic cardiomyocytes were significantly increased after ischemia-reperfusion as shown by both the TUNEL assay and caspase-3 activation. In the right ventricle, retrograde cardioplegia was associated with a 3.4-fold higher amount (TUNEL assay) of apoptotic cardiomyocytes as compared with antegrade cardioplegia (0.107% vs 0.032%, p < 0.05). A similar difference was also found in the left ventricle, although at a lower level (0.027% vs 0.012%, p < 0.05).

CONCLUSIONS: Increased apoptotic death of cardiomyocytes after retrograde cardioplegia as compared with the antegrade procedure implicates that retrograde cardioplegia alone provides inferior cardioprotection against irreversible ischemia-reperfusion injury both in the right and the left ventricle.




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