Cardioprotective effect of remote ischemic conditioning during ischemia of different duration in an experiment

The cardioprotective efficacy of remote ischemic preconditioning (RIPerC), remote ischemic postconditioning (RIPostC 10′), as well as their combinations, was studied under conditions of myocardial ischemia of varying durations. Myocardial ischemia/reperfusion was induced by 30-minute occlusion of the left coronary artery, followed by a 120-minute reperfusion period, or by a 45-minute occlusion of the left coronary artery, followed by a 120-minute reperfusion period. All remote ischemic conditioning protocols presented in this study demonstrated a pronounced cardioprotective effect under conditions of both 30-minute and 45-minute ischemia followed by 120 minutes of reperfusion. It was shown that the combined application of RIPerC and RIPostC 10′ under conditions of 30- and 45-minute ischemia followed by 120-minute reperfusion provides a cardioprotective effect comparable to that of each algorithm applied separately. Thirty-minute ischemia appears  to be more preferable for the development of new effective cardioprotective strategies.

1. Ministry of Health: 60% of deaths in January–March are due to cardiovascular diseases. BELTA. Available at: https://belta.by/society/view/minzdrav-60-smertej-za-janvar-mart-obuslovleny-serdechno-sosudistymi-zabole-vanijami-386749-2020 (accessed 08.01.2025) (in Russian).

2. Kuzmin A. I., Gourine A. V., Molosh A. I., Lakomkin V. L., Vassort G. Effects of preconditioning on myocardial interstitial levels of ATP and its catabolites during regional ischemia and reperfusion in the rat. Basic Research in Cardiology, 2000, vol. 95, no. 2, pp. 127–136. https://doi.org/10.1007/s003950050174

3. Heusch G. Myocardial ischemia/reperfusion: Translational pathophysiology of ischemic heart disease. Med, 2024, vol. 5, no. 1, pp. 10–31. https://doi.org/10.1016/j.medj.2023.12.007

4. Tissier R., Ghaleh B., Cohen M. V., Downey J. M., Berdeaux A. Myocardial protection with mild hypothermia. Cardiovascular Research, 2012, vol. 94, no. 2, pp. 217–225. https://doi.org/10.1093/cvr/cvr315

5. Heusch G. Vagal cardioprotection in reperfused acute myocardial infarction. JACC: Cardiovascular Interventions, 2017, vol. 10, no. 15, pp. 1521–1522. https://doi.org/10.1016/j.jcin.2017.05.063

6. Przyklenk K., Bauer B., Ovize M., Kloner R. A., Whittaker P. Regional ischemic “preconditioning” protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation, 1993, vol. 87, no. 3, pp. 893–899. https://doi.org/10.1161/01.cir.87.3.893

7. Murry C. E., Jennings R. B., Reimer K. A. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation, 1986, vol. 74, no. 5, pp. 1124–1136. https://doi.org/10.1161/01.CIR.74.5.1124

8. García-Ruiz J. M., Fernández-Jiménez R., García-Alvarez A., Pizarro G., Galán-Arriola C., FernándezFriera L.[et al.]. Impact of the timing of metoprolol administration during STEMI on infarct size and ventricular function. Journal of the American College of Cardiology, 2016, vol. 67, no. 18, pp. 2093–2104. https://doi.org/10.1016/j.jacc.2016.02.050

9. Giustino G., Dangas G. D. Ischemia-reperfusion injury and ischemic post-conditioning in acute myocardial infarction: Lost in transition. Catheterization and Cardiovascular Interventions, 2017, vol. 90, no. 7, pp. 1068–1069. https://doi.org/10.1002/ccd.27436

10. Crimi G., Pica S., Raineri C., Bramucci E., De Ferrari G. M., Klersy C. [et al.]. Remote ischemic postconditioning of the lower limb during primary percutaneous coronary intervention safely reduces enzymatic infarct size in anterior myocardial infarction: a randomized controlled trial. JACC: Cardiovascular Interventions, 2013, vol. 6, no. 10, pp. 1055–1063. https://doi.org/10.1016/j.jcin.2013.05.011

11. Basalay M., Barsukevich V., Mastitskaya S., Mrochek A., Pernow J., Sjöquist P.‐O., Ackland G. L., Gourine A. V., Gourine A. Remote ischaemic pre- and delayed postconditioning – similar degree of cardioprotection but distinct mechanisms. Experimental Physiology, 2012, vol. 97, no. 8, pp. 908–917. https://doi.org/10.1113/expphysiol.2012.064923

12. Heusch G., Bøtker H. E., Przyklenk K., Redington A., Yellon D. Remote ischemic conditioning. Journal of the American College of Cardiology, 2015, vol. 65, no. 2, pp. 177–195. https://doi.org/10.1016/j.jacc.2014.10.031

13. Prasad A., Gössl M., Hoyt J., Lennon R. J., Polk L., Simari R., Holmes D. R., Rihal Ch. S., Lerman A. Remote ischemic preconditioning immediately before percutaneous coronary intervention does not impact myocardial necrosis, inflammatory response, and circulating endothelial progenitor cell counts: a single center randomized sham controlled trial. Catheterization and Cardiovascular Interventions, 2013, vol. 81, no. 6, pp. 930–936. https://doi.org/10.1002/ccd.24443

14. Davies W. R., Brown A. J., Watson W., McCormick L. M., West N. E. J., Dutka D. P., Hoole St. P. Remote ischemic preconditioning improves outcome at 6 years after elective percutaneous coronary intervention: the CRISP stent trial longterm follow-up. Circulation: Cardiovascular Interventions, 2013, vol. 6, no. 3, pp. 246–251. https://doi.org/10.1161/CIRCINTERVENTIONS.112.000184

15. Hausenloy D. J., Kharbanda R. K., Møller U. K., Ramlall M., Aarøe J., Butler R. [et al.]. Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial. Lancet, 2019, vol. 394, no. 10207, pp. 1415–1424. https://doi.org/10.1016/S0140-6736(19)32039-2

16. Eitel I., Stiermaier T., Rommel K. P., Fuernau G., Sandri M., Mangner N. [et al.]. Cardioprotection by combined intrahospital remote ischaemic perconditioning and postconditioning in ST-elevation myocardial infarction: the randomized LIPSIA CONDITIONING trial. European Heart Journal, 2015, vol. 36, no. 44, pp. 3049–3057. https://doi.org/10.1093/eurheartj/ehv463

17. Koreneva E. A., Denisevich T. L., Mrochek A. G., Stel’mashok V. I. Combined protocol of remote ischemic conditioning as a cardioprotection method in patients with ST-elevation myocardial infarction. Sibirskii zhurnal klinicheskoi i eksperimental’noi meditsiny [Siberian journal of clinical and experimental medicine], 2021, vol. 36, no. 2, pp. 76–83 (in Russian).

18. Barsukevich V., Basalay M., Sanchez J., Mrochek A., Whittle J., Ackland G. L., Gourine A. V., Gourine A. Distinct cardioprotective mechanisms of immediate, early and delayed ischaemic postconditioning. Basic Research in Cardiology, 2015, vol. 110, no. 1, art. 452. https://doi.org/10.1007/s00395-014-0452-7