The Effect of Colchicine on St. Thomas II Cardioplegia on Ischemia-Reperfusion Injury: A Histomorphological Study in Rabbits
DOI:
https://doi.org/10.55606/klinik.v5i1.5677Keywords:
Cardioplegia Adjuvant, Colchicine, Ischemia-Reperfusion Injury, Myocardial Histomorphology, Myocardial ProtectionAbstract
The maternal mortality rate in South Sumatra Province was recorded at 128 cases in 2020 and increased Cardioplegia is an important method for protecting the heart from ischemia-reperfusion (I/R) injury. However, myocardial damage from reperfusion can't be completely prevented by standard cardioplegia solutions alone. The St. Thomas II cardioplegia solution, with a lower potassium concentration, has been shown to have a cardioprotective effect, while colchicine, as an anti-inflammatory agent, works by inhibiting NLRP3 inflammasome activation and neutrophil modulation. This experimental study used a randomized controlled trial (RCT) post-test-only design on 12 New Zealand white rabbits, which were randomly divided into two groups: a control group (St. Thomas II) and a treatment group (St. Thomas II + colchicine). The primary outcome was the degree of myocardial histomorphological damage at 200× magnification. The results showed that five out of six samples from the control group had severe damage (score 3), while five out of six samples from the treatment group had no damage (score 0). A Mann-Whitney test yielded a p-value of 0.0152, indicating a significant difference. The addition of colchicine to St. Thomas II was shown to significantly reduce myocardial histomorphological damage. These findings suggest that colchicine could be considered as a cardioplegia adjuvant to enhance myocardial protection during cardiac surgery.
References
Akodad, M., Sicard, P., Fauconnier, J., & Roubille, F. (2020). Colchicine and myocardial infarction: A review. Archives of Cardiovascular Diseases, 113(10), 652–659. https://doi.org/10.1016/j.acvd.2020.04.007
Bakhta, O., Blanchard, S., Guihot, A. L., Tamareille, S., Mirebeau-Prunier, D., Jeannin, P., Le Corvoisier, P., & Prunier, F. (2018). Cardioprotective role of colchicine against inflammatory injury in a rat model of acute myocardial infarction. Journal of Cardiovascular Pharmacology and Therapeutics, 23(5), 446–455. https://doi.org/10.1177/1074248418763611
Bar-El, Y., Adler, Z., Kophit, A., Kertzman, V., Sawaed, S., Ross, A., & Pifano, M. (1999). Myocardial protection in operations requiring more than 2 h of aortic cross-clamping. European Journal of Cardio-Thoracic Surgery, 15(3), 271–275. https://doi.org/10.1016/S1010-7940(99)00025-1
Beyersdorf, F. (2009). The use of controlled reperfusion strategies in cardiac surgery to minimize ischaemia/reperfusion damage. Cardiovascular Research, 83(2), 262–268. https://doi.org/10.1093/cvr/cvp110
Beyersdorf, F., Trummer, G., Benk, C., & Pooth, J. S. (2021). Application of cardiac surgery techniques to improve the results of cardiopulmonary resuscitation after cardiac arrest: Controlled automated reperfusion of the whole body. JTCVS Open, 8, 47–52. https://doi.org/10.1016/j.xjon.2021.10.006
Bolli, R., Becker, L., Gross, G., Mentzer, R., Balshaw, D., & Lathrop, D. A. (2004). Myocardial protection at a crossroads: The need for translation into clinical therapy. Circulation Research, 95(2), 125–134. https://doi.org/10.1161/01.RES.0000137171.97172.d7
Bonaventura, A., & Abbate, A. (2023). Colchicine for cardiovascular prevention: The dawn of a new era has finally come. European Heart Journal, 44(35), 3303–3304. https://doi.org/10.1093/eurheartj/ehad453
Catinella, F. P., Cunningham, J. N. J., Adams, P. X., Snively, S. L., Gross, R. I., & Spencer, F. C. (1982). Myocardial protection with cold blood potassium cardioplegia during prolonged aortic cross-clamping. The Annals of Thoracic Surgery, 33(3), 228–233. https://doi.org/10.1016/S0003-4975(10)61916-9
Deftereos, S., Giannopoulos, G., Panagopoulou, V., Bouras, G., Raisakis, K., Kossyvakis, C., Toli, K., Karageorgiou, S., Toutouzas, K., & Pyrgakis, V. (2014). Anti-inflammatory treatment with colchicine instable chronic heart failure. A prospective, randomized study. JACC. Heart Failure, 2(2), 131–137.
Djordjević, A., Kotnik, P., Horvat, D., Knez, Ž., & Antonič, M. (2020). Pharmacodynamics of malondialdehyde as indirect oxidative stress marker after arrested-heart cardiopulmonary bypass surgery. Biomedicine & Pharmacotherapy, 132, 1–5. https://doi.org/10.1016/j.biopha.2020.110877
DWT, N., Leon De La Fuente, R., Gallo, P., Naesgaard, P., Dib Ashur, S., Michelsen, A. E., Omland, T., & Vethe, N. (2025). High admission levels of interleukin-1 receptor antagonist in acute myocardial infarction patients are associated with increased rates of all-cause mortality and cardiac death at five years follow-up. International Journal of Cardiology, 439, Article 133674. https://doi.org/10.1016/j.ijcard.2025.133674
Ferdinandy, P., Hausenloy, D. J., Heusch, G., Baxter, G. F., & Schulz, R. (2014). Interaction of risk factors, comorbidities, and comedications with ischemia/reperfusion injury and cardioprotection by preconditioning, postconditioning, and remote conditioning. Pharmacological Reviews, 66(4), 1142–1174. https://doi.org/10.1124/pr.113.008300
Fischesser, D. M., Bo, B., Benton, R. P., Su, H., Jahanpanah, N., & Haworth, K. J. (2021). Controlling reperfusion injury with controlled reperfusion: Historical perspectives and new paradigms. Journal of Cardiovascular Pharmacology and Therapeutics, 26(5), 504–523. https://doi.org/10.1177/10742484211046674
Frangogiannis, N. G. (2015). Pathophysiology of myocardial infarction. Comprehensive Physiology, 5(4), 1841–1875.
García-de-la-Asunción, J., Pastor, E., Perez-Griera, J., Belda, F. J., Moreno, T., García-del-Olmo, E., Boscá, L., & Sastre, J. (2013). Oxidative stress injury after on-pump cardiac surgery: Effects of aortic cross clamp time and type of surgery. Redox Report, 18(5), 193–199. https://doi.org/10.1179/1351000213Y.0000000060
Gavrieli, Y., Sherman, Y., & Ben-Sasson, S. A. (1992). Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. The Journal of Cell Biology, 119(3), 493–501. https://doi.org/10.1083/jcb.119.3.493
Hausenloy, D. J., & Yellon, D. M. (2013). Myocardial ischemia-reperfusion injury: A neglected therapeutic target. The Journal of Clinical Investigation, 123(1), 92–100. https://doi.org/10.1172/JCI62874
Hearse, D. J., Stewart, D. A., & Braimbridge, M. V. (1978). Myocardial protection during ischemic cardiac arrest. Possible deleterious effects of glucose and mannitol in coronary infusates. The Journal of Thoracic and Cardiovascular Surgery, 76(1), 16–23. https://doi.org/10.1016/S0022-5223(19)40927-6
Junqueira, L. C., Bignolas, G., & Brentani, R. R. (1979). Picrosirius staining plus polarization microscopy, a specific method for collagen detection in tissue sections. Histochemical Journal, 11(4), 447–455. https://link.springer.com/article/10.1007/bf01002772
Kumar, V., Abbas, A. K., & Aster, J. C. (2017). Robbins basic pathology (10th ed.). Elsevier - Health Sciences Division.
Leung, Y. Y., Yao Hui, L. L., & Kraus, V. B. (2015). Colchicine—Update on mechanisms of action and therapeutic uses. Seminars in Arthritis and Rheumatism, 45(3), 341–350. https://doi.org/10.1016/j.semarthrit.2015.06.013
Li, H., Yang, H., Qin, Z., Wang, Q., & Li, L. (2024). Colchicine ameliorates myocardial injury induced by coronary microembolization through suppressing pyroptosis via the AMPK/SIRT1/NLRP3 signaling pathway. BMC Cardiovascular Disorders, 24(1), Article 23.
Lilly, L. S. (2016). Pathophysiology of heart disease: A collaborative project of medical students and faculty (6th ed.). Lippincott Williams & Wilkins.
Lindsey, M. L., Bolli, R., Canty, J. M., Jr., Du, X. J., Frangogiannis, N. G., Frantz, S., Jones, S. P., Lefer, D. J., Mendiz, E. A., & Prunier, F. (2018). Guidelines for experimental models of myocardial ischemia and infarction. American Journal of Physiology. Heart and Circulatory Physiology, 314(4), H812–H838. https://doi.org/10.1152/ajpheart.00335.2017
Madabhushi, A., & Lee, G. (2016). Image analysis and machine learning in digital pathology: Challenges and opportunities. Medical Image Analysis, 33, 170–175. https://doi.org/10.1016/j.media.2016.06.037
Martin-Sanchez, F., Diamond, C., Zeitler, M., Gomez, A. I., Baroja-Mazo, A., Bagnall, J., Bovis, B., Clarke, A., place, M. L., & Latz, E. (2016). Inflammasome-dependent IL-1$beta$ release depends upon membrane permeabilisation. Cell Death and Differentiation, 23(7), 1219–1231.
McCarty, K. S., Jr., Miller, L. S., Cox, E. B., Konrath, J., & McCarty, K. S., Sr. (1985). Estrogen receptor analyses. Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies. Archives of Pathology & Laboratory Medicine, 109(8), 716–721.
Minamino, T. (2012). Cardioprotection from ischemia/reperfusion injury: Basic and translational research. Circulation Journal, 76(5), 1074–1082. https://doi.org/10.1253/circj.CJ-12-0132
Nidorf, S. M., Fiolet, A. T. L., Mosterd, A., Eikelboom, J. W., Schut, A., Opstal, T. S. J., The, S. H. K., Feenstra, J., Marais, G. F., & De Smet, B. J. G. L. (2020). Colchicine in patients with chronic coronary disease. The New England Journal of Medicine, 383(19), 1838–1847. https://doi.org/10.1056/NEJMoa2021372
Oberman, R., Shumway, K. R., & Bhardwaj, A. (2023). Physiology, cardiac. StatPearls. Retrieved May 17, 2025, from https://www.ncbi.nlm.nih.gov/books/NBK526089/
Perrelli, M. G., Pagliaro, P., & Penna, C. (2011). Ischemia/reperfusion injury and cardioprotective mechanisms: Role of mitochondria and reactive oxygen species. World Journal of Cardiology, 3(6), 186–200. https://doi.org/10.4330/wjc.v3.i6.186
Reichlin, T., Hochholzer, W., Bassetti, S., Steuer, S., Stelzig, C., Hartwiger, S., Biedert, S., Schaub, N., Buergler, D., & Freidank, H. (2009). Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. The New England Journal of Medicine, 361(9), 858–867. https://doi.org/10.1056/NEJMoa0900428
Reimer, K. A., & Jennings, R. B. (1979). The changing anatomic reference base of evolving myocardial infarction. Underestimation of myocardial collateral blood flow and overestimation of experimental anatomic infarct size due to tissue edema, hemorrhage and acute inflammation. Circulation, 60(4), 866–876. https://doi.org/10.1161/01.CIR.60.4.866
Robertson, S., Martínez, G. J., Payet, C. A., Barraclough, J. Y., Celermajer, D. S., Bursill, C., & Patel, S. (2016). Colchicine therapy in acute coronary syndrome patients acts on caspase-1 to suppress NLRP3 inflammasome monocyte activation. Clinical Science, 130(15), 1237–1246. https://doi.org/10.1042/CS20160090
Sun, X., Duan, J., Gong, C., Feng, Y., Hu, J., Gu, R., Zhang, M., Hou, J., Zhang, F., & Li, G. (2022). Colchicine ameliorates dilated cardiomyopathy via SIRT2-mediated suppression of NLRP3 inflammasome activation. Journal of the American Heart Association, 11(11), Article e025266. https://doi.org/10.1161/JAHA.122.025266
Tardif, J. C., Kouz, S., Waters, D. D., Bertrand, O. F., Diaz, R., Maggioni, A. P., Schunck, R. J., Pericard, S., Koenig, W., & Pinto, F. J. (2019). Efficacy and safety of low-dose colchicine after myocardial infarction. The New England Journal of Medicine, 381(26), 2497–2505. https://doi.org/10.1056/NEJMoa1912388
Terkeltaub, R. A. (2009). Colchicine update: 2008. Seminars in Arthritis and Rheumatism, 38(6), 411–419. https://doi.org/10.1016/j.semarthrit.2008.08.006
Toldo, S., & Abbate, A. (2018). The NLRP3 inflammasome in acute myocardial infarction. Nature Reviews. Cardiology, 15(4), 203–214.
Toldo, S., Mauro, A. G., Cutter, Z., & Abbate, A. (2018). Inflammasome, pyroptosis, and cytokines in myocardial ischemia-reperfusion injury. American Journal of Physiology. Heart and Circulatory Physiology, 315(6), H1553–H1568. https://doi.org/10.1152/ajpheart.00158.2018
Wardoyo, S., Djer, M. M., & Busro, P. W. (2025). Evaluation of myocardial injury from use of aortic cross-clamp and cardiopulmonary bypass duration in patients undergoing tetralogy of Fallot corrective surgery. Paediatrica Indonesiana, 65(3), 147–155. https://doi.org/10.14238/pi65.2.2025.147-55
Yang, X., Cohen, M. V., & Downey, J. M. (2010). Mechanism of cardioprotection by early ischemic preconditioning. Cardiovascular Drugs and Therapy, 24(3), 225–234.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Jurnal Ilmiah Kedokteran dan Kesehatan
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
