Effects of Acute Potassium Chloride Administration on Ventricular Dysrhythmias after Myocardial Infarction in a Rat Model of Ischemia/Reperfusion
Abstract
Background: Acute myocardial infarction is an important cause of morbidity. This study aimed to investigate the effects of the administration of potassium chloride (KCl) on reperfusion-induced injuries in a rat model of myocardial ischemia/reperfusion.
Methods: Thirty-six male Wistar rats, weighing 200 to 250 g, were randomly assigned to 3 experimental groups: control, K1 (10 µg/kg of KCl), and K2 (20 µg/kg of KCl). Twenty minutes before ischemia, a single dose of 10 and 20 µg/kg of KCl was intraperitoneally administered in the K1 and K2 groups, respectively. The coronary artery was occluded for 30 minutes (ischemia); thereafter, it was opened for 60 minutes (reperfusion) to measure hemodynamic parameters and ventricular arrhythmias. Blood sampling was performed after the reperfusion period to determine the serum levels of lactate dehydrogenase, troponin I, creatine kinase (CK)-MB, malondialdehyde, and pro-oxidant-antioxidant balance.
Results: Serological parameters significantly decreased in the potassium groups compared with the control group. In particular, the decline was more pronounced for the serum levels of lactate dehydrogenase (1180.25±69.48 vs 1556.67±77.02 U/L; P=0.011), troponin I (21.98±0.61 vs 28.76±1.65 ng/mL; P=0.020), and pro-oxidant-antioxidant balance (15.51±0.72 vs 20.63±1.42 HK; P=0.041) in the K2 group compared with the K1 group. Moreover, the administration of 20 µg/kg of KCl significantly decreased the incidence of ventricular tachycardias and fibrillations compared with the control group (P=0.002). Additionally, no considerable differences were observed between the control group and the groups with 10 µg/kg and 20 µg/kg of KCl regarding the number of ventricular ectopic beats.
Conclusion: The administration of KCl before ischemia could reduce ventricular arrhythmias and reperfusion-induced injuries by reducing oxidative stress.
1. Hausenloy DJ, Yellon DM. Myocardial ischemia-reperfusion injury: a neglected therapeutic target. J Clin Invest 2013;123:92-100.
2. Edalatyzadeh Z, Aghajani M, Imani A, Faghihi M, Sadeghniiat-Haghighi K, Askari S, Choopani S. Cardioprotective effects of acute sleep deprivation on ischemia/reperfusion injury. Auton Neurosci 2021;230:102761.
3. Kong SS, Liu JJ, Yu XJ, Lu Y, Zang WJ. Protection against ischemia-induced oxidative stress conferred by vagal stimulation in the rat heart: involvement of the AMPK-PKC pathway. Int J Mol Sci 2012;13:14311-14325.
4. Garcia-Dorado D, Rodríguez-Sinovas A, Ruiz-Meana M, Inserte J. Protection against myocardial ischemia-reperfusion injury in clinical practice. Rev Esp Cardiol (Engl Ed) 2014;67:394-404.
5. Runsiö M, Kallner A, Källner G, Rosenqvist M, Bergfeldt L. Myocardial injury after electrical therapy for cardiac arrhythmias assessed by troponin-T release. Am J Cardiol 1997;79:1241-1245.
6. Tazmini K, Frisk M, Lewalle A, Laasmaa M, Morotti S, Lipsett DB, Manfra O, Skogestad J, Aronsen JM, Sejersted OM, Sjaastad I, Edwards AG, Grandi E, Niederer SA, Øie E, Louch WE. Hypokalemia promotes arrhythmia by distinct mechanisms in atrial and ventricular myocytes. Circ Res 2020;126:889-906.
7. Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol. 2012;298:229-317.
8. Li N, Qin S, Xie L, Qin T, Yang Y, Fang W, Chen MH. Elevated serum potassium concentration alleviates cerebral ischemia-reperfusion injury via mitochondrial preservation. Cell Physiol Biochem 2018;48:1664-1674.
9. Zhang HF, Fan Q, Qian XX, Lopez BL, Christopher TA, Ma XL, Gao F. Role of insulin in the anti-apoptotic effect of glucose-insulin-potassium in rabbits with acute myocardial ischemia and reperfusion. Apoptosis 2004;9:777-783.
10. Weinstock L, Clark JH. Successful treatment of ventricular fibrillation with intracardiac potassium chloride. Am J Cardiol 1961;7:742-745.
11. Watanabe G, Yashiki N, Tomita S, Yamaguchi S. Potassium-induced cardiac resetting technique for persistent ventricular tachycardia and fibrillation after aortic declamping. Ann Thorac Surg 2011;91:619-620.
12. Turkoz R, Ozker E, Turkoz A. Secondary cross-clamping and blood cardioplegia for refractory ventricular fibrillation. Ann Thorac Surg 2011;92:403.
13. Turkoz A, Toprak HI, Ersoy MO, Gulcan O, Turkoz R. Secondary cross-clamping and blood cardioplegia for refractory ventricular fibrillation after aortic cross-clamp removal. Tex Heart Inst J 2002;29:230-231.
14. Gadhinglajkar SV, Sreedhar R, Varma PK. Controlled aortic root perfusion: a novel method to treat refractory ventricular arrhythmias after aortic valve replacement. J Cardiothorac Vasc Anesth 2004;18:197-200.
15. Laursen M, Gregersen JL, Yatime L, Nissen P, Fedosova NU. Structures and characterization of digoxin- and bufalin-bound Na+,K+-ATPase compared with the ouabain-bound complex. Proc Natl Acad Sci U S A 2015;112:1755-1760.
16. Skogestad J, Aronsen JM. Hypokalemia-induced arrhythmias and heart failure: new insights and implications for therapy. Front Physiol 2018;9:1500.
17. Weiss JN, Qu Z, Shivkumar K. Electrophysiology of hypokalemia and hyperkalemia. Circ Arrhythm Electrophysiol 2017;10:e004667.
18. Carreira RS, Facundo HT, Kowaltowski AJ. Mitochondrial K+ transport and cardiac protection during ischemia/reperfusion. Braz J Med Biol Res 2005;38:345-352.
19. Aghajani M, Faghihi M, Imani A, Vaez Mahdavi MR, Shakoori A, Rastegar T, Parsa H, Mehrabi S, Moradi F, Kazemi Moghaddam E. Post-infarct sleep disruption and its relation to cardiac remodeling in a rat model of myocardial infarction. Chronobiol Int 2017;34:587-600.
20. Zhang X, Liang X, Lin X, Zhang S, Huang Z, Chen C, Guo Y, Xuan F, Xu X, Huang R. Mechanism of the protective effect of Yulangsan flavonoid on myocardial ischemia/reperfusion injury in rats. Cell Physiol Biochem 2014;34:1050-1062.
21. Vasatova M, Pudil R, Horacek JM, Buchler T. Current applications of cardiac troponin T for the diagnosis of myocardial damage. Adv Clin Chem 2013;61:33-65.
22. Pouru JP, Jaakkola S, Biancari F, Kiviniemi TO, Nuotio I, Airaksinen KEJ. Association of heart rate with troponin levels among patients with symptomatic atrial fibrillation. JAMA Netw Open 2020;3:e2016880.
23. Khow KS, Lau SY, Li JY, Yong TY. Asymptomatic elevation of creatine kinase in patients with hyponatremia. Ren Fail 2014;36:908-911.
24. Olt S, Yaylaci S, Tatli L, Gunduz Y, Garip T, Tamer A. Hypokalemia- induced myopathy and massive creatine kinase elevation as first manifestation of Conn's syndrome. Niger Med J 2013;54:283-284.
25. Zhang X, Zhang X, Xiong Y, Xu C, Liu X, Lin J, Mu G, Xu S, Liu W. Sarcolemmal ATP-sensitive potassium channel protects cardiac myocytes against lipopolysaccharide-induced apoptosis. Int J Mol Med 2016;38:758-766.
26. Walker DB. Serum chemical biomarkers of cardiac injury for nonclinical safety testing. Toxicol Pathol 2006;34:94-104.
27. Xia Z, Li H, Irwin MG. Myocardial ischaemia reperfusion injury: the challenge of translating ischaemic and anaesthetic protection from animal models to humans. Br J Anaesth 2016;117 Suppl 2:ii44-ii62.
28. Díaz-Araya G, Nettle D, Castro P, Miranda F, Greig D, Campos X, Chiong M, Nazzal C, Corbalán R, Lavandero S. Oxidative stress after reperfusion with primary coronary angioplasty: lack of effect of glucose-insulin-potassium infusion. Crit Care Med 2002;30:417-421.
29. Imani A, Faghihi M, Sadr SS, Keshavarz M, Niaraki SS. Noradrenaline reduces ischemia-induced arrhythmia in anesthetized rats: involvement of alpha1-adrenoceptors and mitochondrial K ATP channels. J Cardiovasc Electrophysiol 2008;19:309-315.
30. Demircan S, Yazici M, Diraman E, Demircan G, Kilicaslan F, Durna K, Acar Z, Eren Z. The effect of glucose-insulin-potassium treatment on myocardial oxidative stress in patients with acute coronary syndromes undergoing percutaneous coronary intervention. Coron Artery Dis 2008;19:99-104.
31. Oliveira RS, Alonso S, Campos FO, Rocha BM, Fernandes JF, Kuehne T, Dos Santos RW. Ectopic beats arise from micro-reentries near infarct regions in simulations of a patient-specific heart model. Sci Rep 2018;8:16392.
32. Bhar-Amato J, Davies W, Agarwal S. Ventricular arrhythmia after acute myocardial infarction: 'the perfect storm'. Arrhythm Electrophysiol Rev 2017;6:134-139.
33. Spannbauer A, Traxler D, Lukovic D, Zlabinger K, Winkler J, Gugerell A, Ferdinandy P, Hausenloy DJ, Pavo N, Emmert MY, Hoerstrup SP, Jakab A, Gyöngyösi M, Riesenhuber M. Effect of ischemic preconditioning and postconditioning on exosome-rich fraction microRNA levels, in relation with electrophysiological parameters and ventricular arrhythmia in experimental closed-chest reperfused myocardial infarction. Int J Mol Sci 2019;20:2140.
2. Edalatyzadeh Z, Aghajani M, Imani A, Faghihi M, Sadeghniiat-Haghighi K, Askari S, Choopani S. Cardioprotective effects of acute sleep deprivation on ischemia/reperfusion injury. Auton Neurosci 2021;230:102761.
3. Kong SS, Liu JJ, Yu XJ, Lu Y, Zang WJ. Protection against ischemia-induced oxidative stress conferred by vagal stimulation in the rat heart: involvement of the AMPK-PKC pathway. Int J Mol Sci 2012;13:14311-14325.
4. Garcia-Dorado D, Rodríguez-Sinovas A, Ruiz-Meana M, Inserte J. Protection against myocardial ischemia-reperfusion injury in clinical practice. Rev Esp Cardiol (Engl Ed) 2014;67:394-404.
5. Runsiö M, Kallner A, Källner G, Rosenqvist M, Bergfeldt L. Myocardial injury after electrical therapy for cardiac arrhythmias assessed by troponin-T release. Am J Cardiol 1997;79:1241-1245.
6. Tazmini K, Frisk M, Lewalle A, Laasmaa M, Morotti S, Lipsett DB, Manfra O, Skogestad J, Aronsen JM, Sejersted OM, Sjaastad I, Edwards AG, Grandi E, Niederer SA, Øie E, Louch WE. Hypokalemia promotes arrhythmia by distinct mechanisms in atrial and ventricular myocytes. Circ Res 2020;126:889-906.
7. Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol. 2012;298:229-317.
8. Li N, Qin S, Xie L, Qin T, Yang Y, Fang W, Chen MH. Elevated serum potassium concentration alleviates cerebral ischemia-reperfusion injury via mitochondrial preservation. Cell Physiol Biochem 2018;48:1664-1674.
9. Zhang HF, Fan Q, Qian XX, Lopez BL, Christopher TA, Ma XL, Gao F. Role of insulin in the anti-apoptotic effect of glucose-insulin-potassium in rabbits with acute myocardial ischemia and reperfusion. Apoptosis 2004;9:777-783.
10. Weinstock L, Clark JH. Successful treatment of ventricular fibrillation with intracardiac potassium chloride. Am J Cardiol 1961;7:742-745.
11. Watanabe G, Yashiki N, Tomita S, Yamaguchi S. Potassium-induced cardiac resetting technique for persistent ventricular tachycardia and fibrillation after aortic declamping. Ann Thorac Surg 2011;91:619-620.
12. Turkoz R, Ozker E, Turkoz A. Secondary cross-clamping and blood cardioplegia for refractory ventricular fibrillation. Ann Thorac Surg 2011;92:403.
13. Turkoz A, Toprak HI, Ersoy MO, Gulcan O, Turkoz R. Secondary cross-clamping and blood cardioplegia for refractory ventricular fibrillation after aortic cross-clamp removal. Tex Heart Inst J 2002;29:230-231.
14. Gadhinglajkar SV, Sreedhar R, Varma PK. Controlled aortic root perfusion: a novel method to treat refractory ventricular arrhythmias after aortic valve replacement. J Cardiothorac Vasc Anesth 2004;18:197-200.
15. Laursen M, Gregersen JL, Yatime L, Nissen P, Fedosova NU. Structures and characterization of digoxin- and bufalin-bound Na+,K+-ATPase compared with the ouabain-bound complex. Proc Natl Acad Sci U S A 2015;112:1755-1760.
16. Skogestad J, Aronsen JM. Hypokalemia-induced arrhythmias and heart failure: new insights and implications for therapy. Front Physiol 2018;9:1500.
17. Weiss JN, Qu Z, Shivkumar K. Electrophysiology of hypokalemia and hyperkalemia. Circ Arrhythm Electrophysiol 2017;10:e004667.
18. Carreira RS, Facundo HT, Kowaltowski AJ. Mitochondrial K+ transport and cardiac protection during ischemia/reperfusion. Braz J Med Biol Res 2005;38:345-352.
19. Aghajani M, Faghihi M, Imani A, Vaez Mahdavi MR, Shakoori A, Rastegar T, Parsa H, Mehrabi S, Moradi F, Kazemi Moghaddam E. Post-infarct sleep disruption and its relation to cardiac remodeling in a rat model of myocardial infarction. Chronobiol Int 2017;34:587-600.
20. Zhang X, Liang X, Lin X, Zhang S, Huang Z, Chen C, Guo Y, Xuan F, Xu X, Huang R. Mechanism of the protective effect of Yulangsan flavonoid on myocardial ischemia/reperfusion injury in rats. Cell Physiol Biochem 2014;34:1050-1062.
21. Vasatova M, Pudil R, Horacek JM, Buchler T. Current applications of cardiac troponin T for the diagnosis of myocardial damage. Adv Clin Chem 2013;61:33-65.
22. Pouru JP, Jaakkola S, Biancari F, Kiviniemi TO, Nuotio I, Airaksinen KEJ. Association of heart rate with troponin levels among patients with symptomatic atrial fibrillation. JAMA Netw Open 2020;3:e2016880.
23. Khow KS, Lau SY, Li JY, Yong TY. Asymptomatic elevation of creatine kinase in patients with hyponatremia. Ren Fail 2014;36:908-911.
24. Olt S, Yaylaci S, Tatli L, Gunduz Y, Garip T, Tamer A. Hypokalemia- induced myopathy and massive creatine kinase elevation as first manifestation of Conn's syndrome. Niger Med J 2013;54:283-284.
25. Zhang X, Zhang X, Xiong Y, Xu C, Liu X, Lin J, Mu G, Xu S, Liu W. Sarcolemmal ATP-sensitive potassium channel protects cardiac myocytes against lipopolysaccharide-induced apoptosis. Int J Mol Med 2016;38:758-766.
26. Walker DB. Serum chemical biomarkers of cardiac injury for nonclinical safety testing. Toxicol Pathol 2006;34:94-104.
27. Xia Z, Li H, Irwin MG. Myocardial ischaemia reperfusion injury: the challenge of translating ischaemic and anaesthetic protection from animal models to humans. Br J Anaesth 2016;117 Suppl 2:ii44-ii62.
28. Díaz-Araya G, Nettle D, Castro P, Miranda F, Greig D, Campos X, Chiong M, Nazzal C, Corbalán R, Lavandero S. Oxidative stress after reperfusion with primary coronary angioplasty: lack of effect of glucose-insulin-potassium infusion. Crit Care Med 2002;30:417-421.
29. Imani A, Faghihi M, Sadr SS, Keshavarz M, Niaraki SS. Noradrenaline reduces ischemia-induced arrhythmia in anesthetized rats: involvement of alpha1-adrenoceptors and mitochondrial K ATP channels. J Cardiovasc Electrophysiol 2008;19:309-315.
30. Demircan S, Yazici M, Diraman E, Demircan G, Kilicaslan F, Durna K, Acar Z, Eren Z. The effect of glucose-insulin-potassium treatment on myocardial oxidative stress in patients with acute coronary syndromes undergoing percutaneous coronary intervention. Coron Artery Dis 2008;19:99-104.
31. Oliveira RS, Alonso S, Campos FO, Rocha BM, Fernandes JF, Kuehne T, Dos Santos RW. Ectopic beats arise from micro-reentries near infarct regions in simulations of a patient-specific heart model. Sci Rep 2018;8:16392.
32. Bhar-Amato J, Davies W, Agarwal S. Ventricular arrhythmia after acute myocardial infarction: 'the perfect storm'. Arrhythm Electrophysiol Rev 2017;6:134-139.
33. Spannbauer A, Traxler D, Lukovic D, Zlabinger K, Winkler J, Gugerell A, Ferdinandy P, Hausenloy DJ, Pavo N, Emmert MY, Hoerstrup SP, Jakab A, Gyöngyösi M, Riesenhuber M. Effect of ischemic preconditioning and postconditioning on exosome-rich fraction microRNA levels, in relation with electrophysiological parameters and ventricular arrhythmia in experimental closed-chest reperfused myocardial infarction. Int J Mol Sci 2019;20:2140.
| Files | ||
| Issue | Vol 17 No 1 (2022): J Teh Univ Heart Ctr | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/jthc.v17i1.9320 | |
| Keywords | ||
| Potassium chloride Ischemia Reperfusion injury Myocardial reperfusion injury Arrhythmias; cardiac Oxidative stress | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Madadi F, Aghajani M, Dabbagh A, Fani K, Sehati F, Imani A. Effects of Acute Potassium Chloride Administration on Ventricular Dysrhythmias after Myocardial Infarction in a Rat Model of Ischemia/Reperfusion. J Tehran Heart Cent. 2022;17(1):15-21.
