Article

Cardiomyocytic apoptosis limited by bradykinin via restoration of nitric oxide after cardioplegic arrest.

Department of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital, Keelung, Taiwan.
Journal of Surgical Research (Impact Factor: 2.02). 09/2010; 163(1):e1-9. DOI: 10.1016/j.jss.2010.04.005
Source: PubMed

ABSTRACT Our previous studies revealed that cardioplegia-induced cardiac arrest under cardiopulmonary bypass (CPB) decreased cardiomyocytic nitric oxide and increased apoptosis. We hypothesized that pretreatment with bradykinin (BK) would improve the profile of anti-apoptotic proteins and inhibit cardiomyocytic apoptosis.
New Zealand white rabbits received total CPB. Rabbits were weaned from CPB and reperfused for 4 h. Blood was sampled at various time points. Bradykinin and/or nitric oxide synthase (NOS) inhibitors or BK-receptor antagonists were infused systemically 30 min before beginning of CPB, and continued throughout the procedure. The ascending aorta was cross-clamped for 60 min while cold crystalloid cardioplegic solution was intermittently infused into the aortic root. The hearts were harvested and studied for evidence of apoptosis and ischemia/reperfusion induced inflammation-related cytokine production by cardiomyocytes.
Our results revealed that bradykinin supplementation during cardioplegia could prevent I/R-induced inflammatory and apoptotic effects, which could be reversed with a NOS inhibitor. BK antagonists and NOS inhibitors worsened the inflammatory and apoptotic responses of cardiomyocytes, which could be reversed with an exogenous NO donor.
Restoring the NO concentration after cardioplegia-induced cardiac arrest (CCA) under CPB with bradykinin could modulate (1) the nuclear translocation of NF-kappaB, (2) the plasma levels of inflammation-related cytokines, (3) the Bcl-2/Bax ratio, and (4) the occurrence of apoptosis. Exogenous bradykinin administration was associated with the myocardial apoptotic response by inhibition of NF-kappaB translocation, inflammatory cytokine production, Akt activation, and elevation of the Bcl-2/Bax ratio via a NO-mediated pathway.

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