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

Chi Hsiao Yeh*, Tzu Ping Chen, Yao Chang Wang, Yu Min Lin, Shu Wen Fang

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

13 Scopus citations

Abstract

Background: 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. Materials and Methods: 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. Results: 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. Conclusions: Restoring the NO concentration after cardioplegia-induced cardiac arrest (CCA) under CPB with bradykinin could modulate (1) the nuclear translocation of NF-κB, (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-κB translocation, inflammatory cytokine production, Akt activation, and elevation of the Bcl-2/Bax ratio via a NO-mediated pathway.

Original languageEnglish
Pages (from-to)e1-e9
JournalJournal of Surgical Research
Volume163
Issue number1
DOIs
StatePublished - 09 2010

Keywords

  • apoptosis
  • bradykinin
  • cardioplegia
  • ischemia
  • nitric oxide

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