Histomorphometric Evaluation of Myocardial Tissue Zones in Patients With Persistent Hypokalaemia
DOI:
https://doi.org/10.36283/ziun-pjmd15-1/003Keywords:
Hypokalaemia, Myocardial remodeling, Histomorphometry, Fibrosis, Cardiac zones, Potassium ImbalanceAbstract
Background: Persistent hypokalaemia influences cardiac structure and function, but its zonal effect on myocardial remodeling is not definite. This study quantitatively examined myocardial tissue zones in chronic hypokalaemia, to build a schematic model of myocardial remodeling.
Methods: This a cross-sectional analytical study (March to September 2022) was carried out in Department of Histopathology including Sixty postmortem myocardial samples from patients with chronic hypokalemia (serum K+ <3.0 mmol/L) were examined. Tissue samples from the endocardial, mid-myocardial and epicardial areas were stained and histomorphometric parameters were determined. Zonal comparisons were done by the method of repeated measures analysis of variance, correlation was determined between serum levels of potassium by Pearson correlation (p < 0.05 is considered as significant).
Results: Zonal differences were found to be significant in myocyte diameter (F = 6.42, p = 0.002), nuclear density (F = 5.91, p = 0.004), interstitial fibrosis (F = 5.87, p = 0.004) and vascular density (F = 4.72, p = 0.011). The endocardial zone had the highest interstitial fibrosis (28.6 ± 6.2%), smallest diameter of myocytes (12.6 ± 2.1 um), lowest nuclear density (185 ± 22 nuclei/mm2) and vascular density (9.8 ± 2.1 vessels/mm2) compared to the mid-myocardial and epicardial zones. Lower serum potassium levels correlated with increased fibrosis (r = -0.52, p < 0.001), decreased myocyte diameter (r = +0.46, p = 0.003), decreased nuclear density (r = +0.39, p = 0.007) and decreased vascular density (r = +0.41, p = 0.005).
Conclusion: Chronic hypokalaemia results in zone-specific histomorphometric remodeling of myocardial tissue, which is mainly manifested as endocardial fibrosis, decreased vascularity, and depletion of nuclei.
References
1.Singh H. Mitochondrial ion channels in cardiac function. Am J Physiol Cell Physiol. 2021 Nov 1;321(5):C812-C825. doi: 10.1152/ajpcell.00246.2021.
2.Varró A, Tomek J, Nagy N, Virág L, Passini E, Rodriguez B, et al. Cardiac transmembrane ion channels and action potentials: cellular physiology and arrhythmogenic behavior. Physiol Rev. 2021 Jul 1;101(3):1083-1176. doi: 10.1152/physrev.00024.2019.
3.Kildegaard H, Brabrand M, Forberg JL, Platonov P, Lassen AT, Ekelund U. Prevalence and prognostic value of electrocardiographic abnormalities in hypokalemia: A multicenter cohort study. J Intern Med. 2024 Apr;295(4):544-556. doi: 10.1111/joim.13757.
4.Zhang X, Tian H, Xie C, Yang Y, Li P, Cheng J. The role and mechanism of vascular wall cell ion channels in vascular fibrosis remodeling. Channels (Austin). 2024 Dec;18(1):2418128. doi: 10.1080/19336950.2024.2418128.
5.Martinez-Navarro H, Zhou X, Rodriguez B. Mechanisms and Implications of Electrical Heterogeneity in Cardiac Function in Ischemic Heart Disease. Annu Rev Physiol. 2025 Feb;87(1):25-51. doi: 10.1146/annurev-physiol-042022-020541.
6.Severino P, D'Amato A, Prosperi S, Fanisio F, Birtolo LI, Costi B, et al. Myocardial Tissue Characterization in Heart Failure with Preserved Ejection Fraction: From Histopathology and Cardiac Magnetic Resonance Findings to Therapeutic Targets. Int J Mol Sci. 2021 Jul 17;22(14):7650. doi: 10.3390/ijms22147650.
7.Castro H, Raij L. Potassium in hypertension and cardiovascular disease. Semin Nephrol. 2013 May;33(3):277-89. doi: 10.1016/j.semnephrol.2013.04.008.
8.Amoni M, Vermoortele D, Ekhteraei-Tousi S, Doñate Puertas R, Gilbert G, Youness M, et al. Heterogeneity of Repolarization and Cell-Cell Variability of Cardiomyocyte Remodeling Within the Myocardial Infarction Border Zone Contribute to Arrhythmia Susceptibility. Circ Arrhythm Electrophysiol. 2023 May;16(5):e011677. doi: 10.1161/CIRCEP.122.011677.
9.Hunter RW, Bailey MA. Hyperkalemia: pathophysiology, risk factors and consequences. Nephrol Dial Transplant. 2019 Dec 1;34(Suppl 3):iii2-iii11. doi: 10.1093/ndt/gfz206.
10.Kavelak HL. Electrolyte, acid-base, and medication management with renal replacement therapy. Nutr Clin Pract. 2022 Oct;37(5):1015-1022. doi: 10.1002/ncp.10880.
11.Bhardwaj R, Agrawal U, Vashist P, Manna S. Determination of sample size for various study designs in medical research: A practical primer. J Family Med Prim Care. 2024 Jul;13(7):2555-2561. doi: 10.4103/jfmpc.jfmpc_1675_23.
12.Husti Z, Varró A, Baczkó I. Arrhythmogenic Remodeling in the Failing Heart. Cells. 2021 Nov 17;10(11):3203. doi: 10.3390/cells10113203.
13.Pasut A, Lama E, Van Craenenbroeck AH, Kroon J, Carmeliet P. Endothelial cell metabolism in cardiovascular physiology and disease. Nat Rev Cardiol. 2025 May 9. doi: 10.1038/s41569-025-01162-x.
14.Grandi E, Sanguinetti MC, Bartos DC, Bers DM, Chen-Izu Y, Chiamvimonvat N, et al. Potassium channels in the heart: structure, function and regulation. J Physiol. 2017 Apr 1;595(7):2209-2228. doi: 10.1113/JP272864.
15.Xing C, Bao L, Li W, Fan H. Progress on role of ion channels of cardiac fibroblasts in fibrosis. Front Physiol. 2023 Mar 9;14:1138306. doi: 10.3389/fphys.2023.1138306.
16.Urso C, Brucculeri S, Caimi G. Acid-base and electrolyte abnormalities in heart failure: pathophysiology and implications. Heart Fail Rev. 2015 Jul;20(4):493-503. doi: 10.1007/s10741-015-9482-y.
17.Darby IA, Hewitson TD. Hypoxia in tissue repair and fibrosis. Cell Tissue Res. 2016 Sep;365(3):553-62. doi: 10.1007/s00441-016-2461-3.
18.Campbell DJ, Francis VCM, Young GR, Woodford NWF. Association of Coronary Microvascular Rarefaction and Myocardial Fibrosis With Coronary Artery Disease. J Am Heart Assoc. 2024 Nov 5;13(21):e037332. doi: 10.1161/JAHA.124.037332.
19.Falcão-Pires I, Ferreira AF, Trindade F, Bertrand L, Ciccarelli M, Visco V, et al. Mechanisms of myocardial reverse remodelling and its clinical significance: A scientific statement of the ESC Working Group on Myocardial Function. Eur J Heart Fail. 2024 Jul;26(7):1454-1479. doi: 10.1002/ejhf.3264.
20.Kothari M, Wanjari A, Shaikh SM, Tantia P, Waghmare BV, Parepalli A, et al. A Comprehensive Review on Understanding Magnesium Disorders: Pathophysiology, Clinical Manifestations, and Management Strategies. Cureus. 2024 Sep 1;16(9):e68385. doi: 10.7759/cureus.68385.
21.Fisch C. Relation of electrolyte disturbances to cardiac arrhythmias. Circulation. 1973 Feb;47(2):408-19. doi: 10.1161/01.cir.47.2.408.
22.Van den Eynde J, Verbrugge FH. Water and electrolyte homeostasis during decongestion in heart failure. Eur J Heart Fail. 2025 Jun 18. doi: 10.1002/ejhf.3727.
23.Travers JG, Tharp CA, Rubino M, McKinsey TA. Therapeutic targets for cardiac fibrosis: from old school to next-gen. J Clin Invest. 2022 Mar 1;132(5):e148554. doi: 10.1172/JCI148554.
24.Ivanova M, Pescia C, Trapani D, Venetis K, Frascarelli C, Mane E, et al. Early Breast Cancer Risk Assessment: Integrating Histopathology with Artificial Intelligence. Cancers (Basel). 2024 May 23;16(11):1981. doi: 10.3390/cancers16111981.
25.Di Cesare E, Carerj S, Palmisano A, Carerj ML, Catapano F, Vignale D, et al. Multimodality imaging in chronic heart failure. Radiol Med. 2021 Feb;126(2):231-242. doi: 10.1007/s11547-020-01245-4.
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