The Role of Bradykinin and Angiotensin Converting Enzyme Inhibitors in Myocardial Protection: A Review of Randomized Control Trials
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Date
2018-07-31
0000-0001-7299-8533 Journal Title
Journal ISSN
Volume Title
Publisher
Brieflands
Abstract
Context: Bradykinin as a principal active agent of kallikrein-kinin can mediate the powerful cardioprotective mechanism. Both the bradykinin and angiotensin converting enzyme inhibitors (ACE-I) can stimulate this protective pathway through the B2 kinin receptors. We performed a systematic review to determine the effects of bradykinin on cardiac biomarkers and outcomes after surgery or coronary intervention. Evidence Acquisition: We searched the PubMed, Cochrane CENTRAL, and Scopus databases up to the end of August 2017. Only randomized controlled trials were included. Results: From a total of 1081 citations, 8 RCTs totaling 268 patients were included for review. Bradykinin could reduce the blood pressure and cause a slight increase in heart rate. But these changes were not significant in comparison to control groups. The major effect of bradykinin or ACE-I on cardiac biomarkers were related to creatine kinase-MB (CKMB). The ST-segment shift was much lower in patients treated with ACE-I as well as the ST-segment peak elevation. Conclusions: The remote ischemic preconditioning (RIPC) stimulus decreased expression of B1 and B2 kinin receptors and this suggested the role of kinins in cardioprotection. ST-segment shift could be reduced by administration of ACE-I before coronary interventions. In patients who were unresponsive to initial preconditioning ischemia, the infusion of intracoronary enalaprilat during the angioplasty could elicit adequate myocardial protection. The effect of bradykinin is dose dependent. Low doses of bradykinin prevent the increased leukocyte adhesion induced by ischemia reperfusion. High doses activate the bradykinin B2 receptors and lead to increase in leukocyte adhesion. The stimulation of kinin receptor pathway causes a reduction in infarct size, troponin T, peak CKMB levels, and edema of the myocardium. Considering the importance of bradykinin and ACE-I in cardiovascular interventions, further RCTs are required to determine the dosage and precise details of functional pathways of these agents.