Cardiomyocyte apoptosis and duration of aortic clamping in pig model of open heart surgery.
OBJECTIVE
Apoptotic cardiomyocyte death is induced during open heart surgery, but its determinants are poorly understood. Prolonged aortic clamping time is associated with adverse clinical outcomes. The purpose of this study was to determine whether occurrence of cardiomyocyte apoptosis is related to the duration of aortic clamping in experimental pig model of cardiac surgery with cardiopulmonary bypass.


METHODS
The pigs (mean weight 29 +/- 1 kg) were randomly divided to undergo cardioplegic arrest for 60 (n = 4) or 90 (n = 4) min followed by reperfusion period of 120 min. Control group (n = 5) was connected to cardiopulmonary bypass for 120 min without cardioplegic arrest. Cardiomyocyte apoptosis was detected (TUNEL assay and immunohistochemical staining of active caspase-3) in left ventricular tissue samples obtained before ischemia and after the ischemia-reperfusion period.


RESULTS
Apoptotic cardiomyocytes were found in all samples obtained after cardioplegic arrest and cardiopulmonary bypass alone with the TUNEL assay. The amount of apoptosis after the 120 min of cardiopulmonary bypass alone in the control group was 0.006 +/- 0.001%. Compared with this, cardiomyocyte apoptosis was increased after cardioplegic arrest. After 60 min of aortic cross-clamp the amount of apoptosis was 0.019 +/- 0.004% (p = 0.031). After 90 min of aortic cross-clamp the amount was 0.042 +/- 0.005% (p < 0.001) being significantly higher than after 60 min (p = 0.001). Aortic cross-clamp of 90 min also resulted in a detectable increase in caspase-3 activation when compared with controls.


CONCLUSIONS
The occurrence of cardiomyocyte apoptosis increases with prolonged aortic clamping time during open heart surgery.
Malmberg
Markus
M
Research Centre of Applied and Preventive Cardiovascular Medicine, Turku University, FIN-20520 Turku, Finland. markus.malmberg@utu.fi
Vähäsilta
Tommi
T
Saraste
Antti
A
Kytö
Ville
V
Kiss
Jan
J
Kentala
Erkki
E
Kallajoki
Markku
M
Savunen
Timo
T
D000818:Animals; D001011:Aorta / Q000503:physiopathology*; D017209:Apoptosis / Q000502:physiology*; D001794:Blood Pressure / Q000502:physiology; D002315:Cardiopulmonary Bypass / Q000379:methods*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003250:Constriction; D006324:Heart Arrest, Induced / Q000379:methods; D006339:Heart Rate / Q000502:physiology; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling; D023421:Models, Animal; D032383:Myocytes, Cardiac / Q000502:physiology*; D013552:Swine; D013997:Time Factors
D053148:Caspase 3; D020169:Caspases