Remote Ischemic Preconditioning With the Use of Lower Limb Before Coronary Artery Bypass Surgery With Cardiopulmonary Bypass and Anesthesia With Propofol

Objective: to study potantial of remote ischemic preconditioning (RIP) as method of cardioprotection during coronary artery bypass surgery with cardiopulmonary bypass (CPB) and anesthesia with propofol.
Materials and methods. We included in this study 87 patients (7 were excluded) with ischemic heart disease, hospitalized in the clinic of aortic and cardiovascular surgery of the I. M. Sechenov First Moscow State Medical University clinical hospital № 1. All patients had indications for direct myocardial revascularization by coronary artery bypass surgery. One day before operation patients were randomly assigned to 2 groups depending on preparation scheme: main group of RIP and the control group. The frequency of complications during surgery and in the postoperative period was assessed. Troponin I level was measured before, and in 2 and 24 hours after surgery. The level of lactate in the venous blood was measured before and after surgery.
Results. Numbers of intraoperative and early postoperative complications in the main and control groups were similar. There were no differences between groups in troponin I and lactate levels after surgery.
Conclusions. Remote ischemic preconditioning has no effect on the outcome of coronary artery bypass surgery with cardiopulmonary bypass and anesthesia with propofol.

1. Brooks M. M., Alderman E. L., Bates E. et al. The final 10-year follow-up results from the BARI randomized trial. J Am Coll Cardiol 2007;49(15):1600–1606.

2. Møller C.H., Penninga L., Wetterslev J. et al. Off-pump versus onpump coronary artery bypass grafting for ischaemic heart disease. Cochrane Database Syst Rev 2012; (3):CD007224.

3. Meerson F.Z. Adaptive medicine: mechanisms and protective effects of adaptation. M.: Medicine 1993; 89–91. Russian (Меерсон Ф.З. Адаптационная медицина: механизмы и защит-ные эффекты адаптации. М.: Медицина 1993; 89–91).

4. Murry C.E., Jennings R.B., Reimer K.A. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 1986;74:1124–1136.

5. Przyklenk K., Bauer B., Ovize M. et al. Regional ischemic ‘preconditioning’ protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation 1993;87:893–899.

6. Birnbaum Y, Hale S.L., Kloner R.A. Ischemic preconditioning at a distance: reduction of myocardial infarct size by partial reduction of blood supply combined with rapid stimulation of the gastrocnemius muscle in the rabbit. Circulation 1997;96:1641–1646.

7. Kharbanda R.K., Mortensen U.M., White P.A. et al. Transient limb ischemia induces remote ischemic preconditioning in vivo. Circulation 2002;106:2881–2883.

8. Liu G.S., Thornton J., Van Winkle D.M. et al. Protection against infarction afforded by preconditioning is mediated by A1 adenosine receptors in rabbit heart. Circulation 1991;84(1):350–356.

9. Philipp S., Yang X.M., Cui L. et al. Postconditioning protects rabbit hearts through a protein kinase C-adenosine A2b receptor cascade. Cardiovasc Res 2006;70:308–314.

10. Yang X.M., Krieg T., Cui L. et al. NECA and bradykinin at reperfusion reduce infarction in rabbit hearts by signaling through PI3K, ERK, and NO. J Mol Cell Cardiol 2004;36:411–421.

11. Gedik N., Kottenberg E., Thielmann M. et al. Potential humoral mediators of remote ischemic preconditioning in patients undergoing surgical coronary revascularization. Sci Rep 2017;7(1):12660. DOI: 10.1038/s41598-017-12833-2.

12. Heusch G., Bøtker H.E., Przyklenk K. et al. Remote ischemic conditioning. J Am Coll Cardiol 2015;65(2):177–195. DOI: 10.1016/j.jacc.2014.10.031.

13. Argaud L., Gateau-Roesch O., Raisky O. et al. Postconditioning inhibits mitochondrial permeability transition. Circulation 2005;111(2):194–197.

14. Heusch G. Molecular basis of cardioprotection signal transduction in ischemic pre-, post-, and remote conditioning. Circulation Research 2015;116:674–699.

15. Cheung M.M., Kharbanda R.K., Konstantinov I.E. et al. Randomized controlled trial of the effects of remote ischemic preconditioning on children undergoing cardiac surgery: first clinical application in humans. J Am Coll Cardiol 2006;47(11):2277–82.

16. Pierce B., Bole I., Patel V. et al. Clinical outcomes of remote ischemic preconditioning prior to cardiac surgery: a meta-analysis of randomized controlled trials. J Am Heart Assoc 2017;6(2). pii: e004666. DOI: 10.1161/JAHA.116.004666.

17. Deferrari G., Bonanni A., Bruschi M. et al. Remote ischaemic preconditioning for renal and cardiac protection in adult patients undergoing cardiac surgery with cardiopulmonary bypass: systematic review and meta-analysis of randomized controlled trials. Nephrol Dial Transplant 2017; DOI: 10.1093/ndt/gfx210.

18. Xie J., Zhang X., Xu J. et al. Effect of remote ischemic preconditioning on outcomes in adult cardiac surgery: a systematic review and meta-analysis of randomized controlled studies. Anesth Analg 2017; DOI: 10.1213/ANE.0000000000002674.

19. Randhawa P.K., Jaggi A.S. Unraveling the role of adenosine in remote ischemic preconditioning-induced cardioprotection. Life Sci 2016;15(155):140–146.

20. Thielmann M., Kottenberg E., Kleinbongard P. et al. Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised, double-blind, controlled trial. Lancet 2013;17:382 (9892):597–604. DOI: 10.1016/S0140-6736(13)61450-6.

21. Kottenberg E., Thielmann M., Bergmann L. et al. Protection by remote ischemic preconditioning during coronary artery bypass graft surgery with isoflurane but not propofol – a clinical trial. Acta Anaesthesiol Scand 2012;56:30–38.

22. Jones W.K., Fan G.C., Liao S. et al. Peripheral nociception associated with surgical incision elicits remote nonischemic cardioprotection via neurogenic activation of protein kinase C signaling. Circulation 2009;120:1–9.

23. Shirakawa M., Imura H., Nitta T. Propofol protects the immature rabbit heart against ischemia and reperfusion injury: impact on functional recovery and histopathological changes. Biomed Res Int 2014;2014:601250.

24. Kloner R.A., Jennings R.B. Consequences of brief ischemia: stunning, preconditioning, and their clinical implications: part 1. Circulation 2001;104(24):2981–9.

25. Lucchinetti E., Bestmann L., Feng J. et al. Remote ischemic preconditioning applied during isoflurane inhalation provides no benefit to the myocardium of patients undergoing on-pump coronary artery bypass graft surgery: lack of synergy or evidence of antagonism in cardioprotection? Anesthesiology 2012;116(2):296–310. DOI: 10.1097/ALN.0b013e318242349a.

26. D’Ascenzo F., Moretti C., Omedè P. et al. Cardiac remote ischaemic preconditioning reduces periprocedural myocardial infarction for patients undergoing percutaneous coronary interventions: a meta-analysis of randomised clinical trials. EuroIntervention 2014;9(12):1463-1471. DOI: 10.4244/EIJV9I12A244.

27. Wu Q., Gui P., Wu J. et al. Effect of limb ischemic preconditioning on myocardial injury in patients undergoing mitral valve replacement surgery. A randomized controlled trial. Circ J 2011;75:1885–1889.

28. Karami A., Khosravi M.B., Shafa M. et al. Cardioprotective Effect of Extended Remote Ischemic Preconditioning in Patients Coronary Artery Bypass Grafting Undergoing: A Randomized Clinical Trial. Iran J Med Sci 2016;41(4):265–274.

29. Sharma V., Cunniffe B., Verma A.P. et al. Characterization of acute ischemia-related physiological responses associated with remoteischemic preconditioning: a randomized controlled, crossover human study. Physiol Rep 2014;2(11)pii: e12200. DOI: 10.14814/phy2.12200.