Multidisciplinary Cardiovascular Annals

Published by: Kowsar

The Role of Bradykinin and Angiotensin Converting Enzyme Inhibitors in Myocardial Protection: A Review of Randomized Control Trials

Shervin Ziabakhsh Tabary 1 and Alireza Sanei Motlagh 2 , *
Authors Information
1 Professor of Cardiac Surgery, Cardiovascular Research Center, Mazandaran Heart Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
2 Department of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
Article information
  • Multidisciplinary Cardiovascular Annals: July 2018, 9 (2); e68994
  • Published Online: September 25, 2018
  • Article Type: Review Article
  • Received: March 30, 2018
  • Revised: July 23, 2018
  • Accepted: August 6, 2018
  • DOI: 10.5812/mca.68994

To Cite: Ziabakhsh Tabary S, Sanei Motlagh A. The Role of Bradykinin and Angiotensin Converting Enzyme Inhibitors in Myocardial Protection: A Review of Randomized Control Trials, Multidiscip Cardio Annal. 2018 ; 9(2):e68994. doi: 10.5812/mca.68994.

Copyright © 2018, Multidisciplinary Cardiovascular Annals. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
1. Context
2. Evidence Acquisition
3. Results
4. Conclusions
  • 1. Hausenloy DJ, Candilio L, Evans R, Ariti C, Jenkins DP, Kolvekar S, et al. Remote ischemic preconditioning and outcomes of cardiac surgery. N Engl J Med. 2015;373(15):1408-17. doi: 10.1056/NEJMoa1413534. [PubMed: 26436207].
  • 2. Sharma R, Randhawa PK, Singh N, Jaggi AS. Bradykinin in ischemic conditioning-induced tissue protection: Evidences and possible mechanisms. Eur J Pharmacol. 2015;768:58-70. doi: 10.1016/j.ejphar.2015.10.029. [PubMed: 26499976].
  • 3. Jancso G, Jaberansari M, Gasz B, Szanto Z, Cserepes B, Roth E. Bradykinin and angiotensin-converting enzyme inhibition in cardioprotection. Exp Clin Cardiol. 2004;9(1):21-5. [PubMed: 19641692]. [PubMed Central: PMC2716258].
  • 4. Pedersen CM, Schmidt MR, Barnes G, Botker HE, Kharbanda RK, Newby DE, et al. Bradykinin does not mediate remote ischaemic preconditioning or ischaemia-reperfusion injury in vivo in man. Heart. 2011;97(22):1857-61. doi: 10.1136/heartjnl-2011-300323. [PubMed: 21873443].
  • 5. Walsh SR, Tang T, Sadat U, Dutka DP, Gaunt ME. Cardioprotection by remote ischaemic preconditioning. Br J Anaesth. 2007;99(5):611-6. doi: 10.1093/bja/aem273. [PubMed: 17905751].
  • 6. Morris P, Knechtle S. Immunology of Graft Rejection. Kidney transplantation: principles and practice. 7th ed. Philadelphia: Elsevier; 2014.
  • 7. Boldt J, Rothe G, Schindler E, Doll C, Gorlach G, Hempelmann G. Can clonidine, enoximone, and enalaprilat help to protect the myocardium against ischaemia in cardiac surgery? Heart. 1996;76(3):207-13. [PubMed: 8868976]. [PubMed Central: PMC484507].
  • 8. Leesar MA, Stoddard MF, Manchikalapudi S, Bolli R. Bradykinin-induced preconditioning in patients undergoing coronary angioplasty. J Am Coll Cardiol. 1999;34(3):639-50. [PubMed: 10483942].
  • 9. Walter T, Helber U, Bail D, Heller W, Hoffmeister HM. Influence of ACE inhibition on myocardial damage, the Kallikrein-Kinin system and hemostasis during cardiopulmonary bypass surgery. Thorac Cardiovasc Surg. 2002;50(3):150-4. doi: 10.1055/s-2002-32409. [PubMed: 12077687].
  • 10. Wei M, Wang X, Kuukasjarvi P, Laurikka J, Rinne T, Honkonen EL, et al. Bradykinin preconditioning in coronary artery bypass grafting. Ann Thorac Surg. 2004;78(2):492-7. doi: 10.1016/j.athoracsur.2003.11.039. [PubMed: 15276504].
  • 11. Leesar MA, Jneid H, Tang XL, Bolli R. Pretreatment with intracoronary enalaprilat protects human myocardium during percutaneous coronary angioplasty. J Am Coll Cardiol. 2007;49(15):1607-10. doi: 10.1016/j.jacc.2007.01.060. [PubMed: 17433950].
  • 12. Ungi I, Palinkas A, Nemes A, Ungi T, Thury A, Sepp R, et al. Myocardial protection with enalaprilat in patients unresponsive to ischemic preconditioning during percutaneous coronary intervention. Can J Physiol Pharmacol. 2008;86(12):827-34. doi: 10.1139/Y08-096. [PubMed: 19088803].
  • 13. Wang X, Wei M, Kuukasjarvi P, Laurikka J, Rinne T, Moilanen E, et al. The anti-inflammatory effect of bradykinin preconditioning in coronary artery bypass grafting (bradykinin and preconditioning). Scand Cardiovasc J. 2009;43(1):72-9. doi: 10.1080/14017430802180449. [PubMed: 18609065].
  • 14. Saxena P, Aggarwal S, Misso NL, Passage J, Newman MA, Thompson PJ, et al. Remote ischaemic preconditioning down-regulates kinin receptor expression in neutrophils of patients undergoing heart surgery. Interact Cardiovasc Thorac Surg. 2013;17(4):653-8. doi: 10.1093/icvts/ivt279. [PubMed: 23814135]. [PubMed Central: PMC3781800].
  • 15. Wall TM, Sheehy R, Hartman JC. Role of bradykinin in myocardial preconditioning. J Pharmacol Exp Ther. 1994;270(2):681-9. [PubMed: 8071859].
  • 16. Brew EC, Mitchell MB, Rehring TF, Gamboni-Robertson F, McIntyre RC Jr, Harken AH, et al. Role of bradykinin in cardiac functional protection after global ischemia-reperfusion in rat heart. Am J Physiol. 1995;269(4 Pt 2):H1370-8. doi: 10.1152/ajpheart.1995.269.4.H1370. [PubMed: 7485570].
  • 17. Schulz R, Post H, Vahlhaus C, Heusch G. Ischemic preconditioning in pigs: a graded phenomenon: Its relation to adenosine and bradykinin. Circulation. 1998;98(10):1022-9. [PubMed: 9737523].
  • 18. Pan HL, Chen SR, Scicli GM, Carretero OA. Cardiac interstitial bradykinin release during ischemia is enhanced by ischemic preconditioning. Am J Physiol Heart Circ Physiol. 2000;279(1):H116-21. doi: 10.1152/ajpheart.2000.279.1.H116. [PubMed: 10899048].
  • 19. Miki T, Miura T, Ura N, Ogawa T, Suzuki K, Shimamoto K, et al. Captopril potentiates the myocardial infarct size-limiting effect of ischemic preconditioning through bradykinin B2 receptor activation. J Am Coll Cardiol. 1996;28(6):1616-22. [PubMed: 8917279].
  • 20. Sato M, Engelman RM, Otani H, Maulik N, Rousou JA, Flack JE 3rd, et al. Myocardial protection by preconditioning of heart with losartan, an angiotensin II type 1-receptor blocker: Implication of bradykinin-dependent and bradykinin-independent mechanisms. Circulation. 2000;102(19 Suppl 3):III346-51. [PubMed: 11082412].
  • 21. Schriefer JA, Broudy EP, Hassen AH. Inhibitors of bradykinin-inactivating enzymes decrease myocardial ischemia/reperfusion injury following 3 and 7 days of reperfusion. J Pharmacol Exp Ther. 2001;298(3):970-5. [PubMed: 11504792].
  • 22. Pierce B, Bole I, Patel V, Brown DL. Clinical outcomes of remote ischemic preconditioning prior to cardiac surgery: A meta-analysis of randomized controlled trials. J Am Heart Assoc. 2017;6(2). doi: 10.1161/JAHA.116.004666. [PubMed: 28219918]. [PubMed Central: PMC5523764].
  • 23. Sun Y. Myocardial repair/remodelling following infarction: Roles of local factors. Cardiovasc Res. 2009;81(3):482-90. doi: 10.1093/cvr/cvn333. [PubMed: 19050008]. [PubMed Central: PMC2639132].
  • 24. Penna C, Mancardi D, Rastaldo R, Losano G, Pagliaro P. Intermittent activation of bradykinin B2 receptors and mitochondrial KATP channels trigger cardiac postconditioning through redox signaling. Cardiovasc Res. 2007;75(1):168-77. doi: 10.1016/j.cardiores.2007.03.001. [PubMed: 17400201].
  • 25. Shigematsu S, Ishida S, Gute DC, Korthuis RJ. Concentration-dependent effects of bradykinin on leukocyte recruitment and venular hemodynamics in rat mesentery. Am J Physiol. 1999;277(1 Pt 2):H152-60. [PubMed: 10409193].
  • 26. Saxena P, Shaw OM, Misso NL, Naran A, Shehatha J, Newman MA, et al. Remote ischemic preconditioning stimulus decreases the expression of kinin receptors in human neutrophils. J Surg Res. 2011;171(1):311-6. doi: 10.1016/j.jss.2009.11.011. [PubMed: 20189583].
  • 27. Liuba P, Batra S, Pesonen E, Werner O. Bradykinin preconditions postischemic arterial endothelial function in humans. J Card Surg. 2005;20(5):420-4. doi: 10.1111/j.1540-8191.2005.2004120.x. [PubMed: 16153271].
  • 28. White SK, Frohlich GM, Sado DM, Maestrini V, Fontana M, Treibel TA, et al. Remote ischemic conditioning reduces myocardial infarct size and edema in patients with ST-segment elevation myocardial infarction. JACC Cardiovasc Interv. 2015;8(1 Pt B):178-88. doi: 10.1016/j.jcin.2014.05.015. [PubMed: 25240548].
  • 29. Prunier F, Angoulvant D, Saint Etienne C, Vermes E, Gilard M, Piot C, et al. The RIPOST-MI study, assessing remote ischemic perconditioning alone or in combination with local ischemic postconditioning in ST-segment elevation myocardial infarction. Basic Res Cardiol. 2014;109(2):400. doi: 10.1007/s00395-013-0400-y. [PubMed: 24407359].
  • 30. Sloth AD, Schmidt MR, Munk K, Kharbanda RK, Redington AN, Schmidt M, et al. Improved long-term clinical outcomes in patients with ST-elevation myocardial infarction undergoing remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention. Eur Heart J. 2014;35(3):168-75. doi: 10.1093/eurheartj/eht369. [PubMed: 24031025].

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