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Plasma potassium concentration and cardiac repolarisation markers, Tpeak-Tend and Tpeak-Tend/QT, during and after exercise in healthy participants and in end-stage renal disease.
Tran, CT, Atanasovska, T, Graff, C, Melgaard, J, Kanters, JK, Smith, R, Petersen, AC, Kjeldsen, KP, McKenna, MJ
European journal of applied physiology. 2022;(3):691-702
Abstract
PURPOSE The cardiac T-wave peak-to-end interval (Tpe) is thought to reflect dispersion in ventricular repolarisation, with abnormalities in Tpe associated with increased risk of arrhythmia. Extracellular K+ modulates cardiac repolarisation, and since arterial plasma K+ concentration ([K+]) rapidly increases during and declines following exercise, we investigated the relationship between [K+] and Tpe with exercise. METHODS Serial ECGs (Tpe, Tpe/QT ratio) and [K+] were obtained from 8 healthy, normokalaemic volunteers and 22 patients with end-stage renal disease (ESRD), at rest, during, and after exhaustive exercise. RESULTS Post-exercise [K+] nadir was 3.1 ± 0.1, 5.0 ± 0.2 and 4.0 ± 0.1 mmol.L-1 (mean ± SEM) for healthy participants and ESRD patients before and after haemodialysis, respectively. In healthy participants, compared to pre-exercise, recovery-induced low [K+] was associated with a prolongation of Tpe (110 ± 8 vs. 87 ± 5 ms, respectively, p = 0.03) and an increase in Tpe/QT ratio (0.28 ± 0.01 vs. 0.23 ± 0.01, respectively, p = 0.01). Analyses of serial data revealed [K+] as a predictor of Tpe in healthy participants (β = -0.54 ±0.05, p < 0.0001), in ESRD patients (β = -0.75 ± 0.06, p < 0.0001) and for all data pooled (β = -0.61 ± 0.04, p < 0.0001). The [K+] was also a predictor of Tpe/QT ratio in healthy participants and ESRD patients. CONCLUSIONS Tpe and Tpe/QT ratio are predicted by [K+] during exercise. Low [K+] during recovery from exercise was associated with increased Tpe and Tpe/QT, indicating accentuated dispersion of ventricular repolarisation. The findings suggest that variations in [K+] with physical exertion may unmask electrophysiological vulnerabilities to arrhythmia.
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Epidemiology, prognosis and management of potassium disorders in Covid-19.
Noori, M, Nejadghaderi, SA, Sullman, MJM, Carson-Chahhoud, K, Kolahi, AA, Safiri, S
Reviews in medical virology. 2022;(1):e2262
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Abstract
Coronavirus disease (Covid-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently the largest health crisis facing most countries. Several factors have been linked with a poor prognosis for this disease, including demographic factors, pre-existing comorbidities and laboratory parameters such as white blood cell count, D-dimer, C-reactive protein, albumin, lactate dehydrogenase, creatinine and electrolytes. Electrolyte abnormalities particularly potassium disorders are common among Covid-19 patients. Based on our pooled analysis, hypokalemia and hyperkalemia occur in 24.3% and 4.15% of Covid-19 patients, respectively. Potassium level deviation from the normal range may increase the chances of unfavorable outcomes and even death. Therefore, this article reviewed the epidemiology of potassium disorders and explained how hypokalemia and hyperkalemia are capable of deteriorating cardiac outcomes and the prognosis of Covid-19 for infected patients. The article finishes by highlighting some important considerations in the management of hypokalemia and hyperkalemia in these patients.
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Computational modeling of mitochondrial K+- and H+-driven ATP synthesis.
Cortassa, S, Aon, MA, Juhaszova, M, Kobrinsky, E, Zorov, DB, Sollott, SJ
Journal of molecular and cellular cardiology. 2022;:9-18
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Abstract
ATP synthase (F1Fo) is a rotary molecular engine that harnesses energy from electrochemical-gradients across the inner mitochondrial membrane for ATP synthesis. Despite the accepted tenet that F1Fo transports exclusively H+, our laboratory has demonstrated that, in addition to H+, F1Fo ATP synthase transports a significant fraction of ΔΨm-driven charge as K+ to synthesize ATP. Herein, we utilize a computational modeling approach as a proof of principle of the feasibility of the core mechanism underlying the enhanced ATP synthesis, and to explore its bioenergetic consequences. A minimal model comprising the 'core' mechanism constituted by ATP synthase, driven by both proton (PMF) and potassium motive force (KMF), respiratory chain, adenine nucleotide translocator, Pi carrier, and K+/H+ exchanger (KHEmito) was able to simulate enhanced ATP synthesis and respiratory fluxes determined experimentally with isolated heart mitochondria. This capacity of F1Fo ATP synthase confers mitochondria with a significant energetic advantage compared to K+ transport through a channel not linked to oxidative phosphorylation (OxPhos). The K+-cycling mechanism requires a KHEmito that exchanges matrix K+ for intermembrane space H+, leaving PMF as the overall driving energy of OxPhos, in full agreement with the standard chemiosmotic mechanism. Experimental data of state 4➔3 energetic transitions, mimicking low to high energy demand, could be reproduced by an integrated computational model of mitochondrial function that incorporates the 'core' mechanism. Model simulations display similar behavior compared to the experimentally observed changes in ΔΨm, mitochondrial K+ uptake, matrix volume, respiration, and ATP synthesis during the energetic transitions at physiological pH and K+ concentration. The model also explores the role played by KHEmito in modulating the energetic performance of mitochondria. The results obtained support the available experimental evidence on ATP synthesis driven by K+ and H+ transport through the F1Fo ATP synthase.
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Potassium and phosphorus transport and signaling in plants.
Wang, Y, Chen, YF, Wu, WH
Journal of integrative plant biology. 2021;(1):34-52
Abstract
Nitrogen (N), potassium (K), and phosphorus (P) are essential macronutrients for plant growth and development, and their availability affects crop yield. Compared with N, the relatively low availability of K and P in soils limits crop production and thus threatens food security and agricultural sustainability. Improvement of plant nutrient utilization efficiency provides a potential route to overcome the effects of K and P deficiencies. Investigation of the molecular mechanisms underlying how plants sense, absorb, transport, and use K and P is an important prerequisite to improve crop nutrient utilization efficiency. In this review, we summarize current understanding of K and P transport and signaling in plants, mainly taking Arabidopsis thaliana and rice (Oryza sativa) as examples. We also discuss the mechanisms coordinating transport of N and K, as well as P and N.
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The role of potassium in atherosclerosis.
Sahranavard, T, Carbone, F, Montecucco, F, Xu, S, Al-Rasadi, K, Jamialahmadi, T, Sahebkar, A
European journal of clinical investigation. 2021;(3):e13454
Abstract
BACKGROUND Atherosclerosis (AS) is a chronic progressive inflammatory condition with a leading prevalence worldwide. Endothelial dysfunction leads to low-density lipoprotein trafficking into subendothelial space and the subsequent form of oxidized LDL (ox-LDL) within intimal layer, perpetuating the vicious cycle of endothelial dysfunction. K+ exerts beneficial effects in vascular wall by reducing LDL oxidization, vascular smooth muscle cells (VSMCs) proliferation, and free radical generation. K+ also modulates vascular tone through a regulatory effect on cell membrane potential. MATERIALS AND METHODS The most relevant papers on the association between 'potassium channels' and 'atherosclerosis' were selected among those deposited on PubMed from 1990 to 2020. RESULTS Here, we provide a short narrative review that elaborates on the role of K+ in atherosclerosis. This review also update the current knowledge about potential pharmacological agents targeting K+ channels with a special focus on pleiotropic activities of agents such as statins, sulfonylureas and dihydropyridines. CONCLUSION In this review, the mechanism of different K+ channels on vascular endothelium will be summarized, mainly focusing on their pathophysiological role in atherosclerosis and potential therapeutic application.
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Urinary Potassium and Kidney Function Decline in the Population-Observational Study.
Cirillo, M, Bilancio, G, Cavallo, P, Palladino, R, Zulli, E, Villa, R, Veneziano, R, Laurenzi, M
Nutrients. 2021;(8)
Abstract
Background-Some data suggest favorable effects of a high potassium intake on kidney function. The present population-based study investigated cross-sectional and longitudinal relations of urinary potassium with kidney function. Methods-Study cohort included 2027 Gubbio Study examinees (56.9% women) with age ≥ 18 years at exam-1 and with complete data on selected variables at exam-1 (1983-1985), exam-2 (1989-1992), and exam-3 (2001-2007). Urinary potassium as urinary potassium/creatinine ratio was measured in daytime spot samples at exam-1 and in overnight timed collections at exam-2. Estimated glomerular filtration rate (eGFR) was measured at all exams. Covariates in analyses included demographics, anthropometry, blood pressure, drug treatments, diabetes, smoking, alcohol intake, and urinary markers of dietary sodium and protein. Results-In multivariable regression, urinary potassium/creatinine ratio cross-sectionally related to eGFR neither at exam-1 (standardized coefficient and 95%CI = 0.020 and -0.059/0.019) nor at exam-2 (0.024 and -0.013/0.056). Exam-1 urinary potassium/creatinine ratio related to eGFR change from exam-1 to exam-2 (0.051 and 0.018/0.084). Exam-2 urinary potassium/creatinine ratio related to eGFR change from exam-2 to exam-3 (0.048 and 0.005/0.091). Mean of urinary potassium/creatinine ratio at exam-1 and exam-2 related to eGFR change from exam-1 to exam-3 (0.056 and 0.027/0.087) and to incidence of eGFR < 60 mL/min per 1.73 m2 from exam-1 to exam-3 (odds ratio and 95%CI = 0.78 and 0.61/0.98). Conclusion-In the population, urinary potassium did not relate cross-sectionally to eGFR but related to eGFR decline over time. Data support the existence of favorable effects of potassium intake on ageing-associated decline in kidney function.
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Management of Hyperkalemia in Heart Failure.
Altay, H, Çavuşoğlu, Y, Çelik, A, Demir, Ş, Kılıçarslan, B, Nalbantgil, S, Temizhan, A, Tokgöz, B, Ural, D, Yeşilbursa, D, et al
Turk Kardiyoloji Dernegi arsivi : Turk Kardiyoloji Derneginin yayin organidir. 2021;(Supp1):1-32
Abstract
Hyperkalemia is a common electrolyte abnormality in heart failure (HF) that can cause potentially life-threatening cardiac arrhythmias and sudden cardiac death. HF patients with diabetes, chronic kidney disease and older age are at higher risk of hyperkalemia. Moreover, hyperkalemia is also often associated with the use of renin-angiotensin-aldosterone system inhibitors (RAASi) including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists and sacubitril-valsartan. In clinical practice, the occurrence of hyperkalemia is a major concern among the clinicians and often limits RAASi use and/or lead to dose reduction or discontinuation, thereby reducing their potential benefits for HF. Furthermore, recurrent hyperkalemia is frequent in the long-term and is associated with an increase in hyperkalemia-related hospitalizations. Therefore, management of hyperkalemia has a special importance in HF patients. However, treatment options in chronic management are currently limited. Dietary restriction of potassium is usually ineffective with variable adherence. Sodium polystyrene sulfonate is commonly used, but its effectiveness is uncertain and reported to be associated with intestinal toxicity. New therapeutic options such as potassium binders have been suggested as potentially beneficial agents in the management of hyperkalemia. This document discusses prevalence, predictors and management of hyperkalemia in HF, emphasizing the importance of careful patient selection for medical treatment, uptitration of the doses of RAASi, regular surveillance of potassium and treatment options of hyperkalemia.
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An evaluation of sodium zirconium cyclosilicate as a treatment option for hyperkalemia.
Takkar, C, Nassar, T, Qunibi, W
Expert opinion on pharmacotherapy. 2021;(1):19-28
Abstract
INTRODUCTION Hyperkalemia, defined as serum potassium level > 5.0 mEq/l, is associated with serious cardiac dysrhythmias, sudden death and increased mortality risk. It is common in patients with chronic kidney disease (CKD), diabetes (DM) and heart failure (HF), particularly in those treated with the renin-angiotensin-aldosterone system (RAAS) inhibitors or potassium-sparing diuretics. Although these drugs have documented renal and cardiac protective benefits, frequent hyperkalemia associated with their use often dictates administration of suboptimal doses or their discontinuation altogether. Treatment for chronic hyperkalemia in these settings has been challenging; however, the recent introduction of two new potassium-binding resins has revolutionized our approach to treating hyperkalemia. AREAS COVERED We review key clinical data relating to the pharmacokinetics, efficacy and safety of sodium zirconium cyclosilicate (SZC) as a treatment option for hyperkalemia. EXPERT OPINION SZC and Patiromer are promising new agents for lowering serum potassium in hyperkalemic patients, including those with CKD, with and without DM or HF, facilitating the use of the RAAS inhibitors for renal and cardiac protection. Recent randomized clinical trials have shown that SZC effectively lowers serum potassium and maintains normokalemia in most hyperkalemic patients. Clinical trials showed that SZC lowers serum potassium within 1 h, although it is not approved for treating acute hyperkalemia. SZC was well tolerated and associated with minimal adverse effects.
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The association of acute hypercarbia and plasma potassium concentration during laparoscopic surgery: a retrospective observational study.
Weinberg, L, Lee, DK, Gan, C, Ianno, D, Ho, A, Fletcher, L, Banyasz, D, Tosif, S, Jones, D, Bellomo, R, et al
BMC surgery. 2021;(1):31
Abstract
BACKGROUND It is uncertain whether increases in PaCO2 during surgery lead to an increase in plasma potassium concentration and, if so, by how much. Hyperkalaemia may result in cardiac arrhythmias, muscle weakness or paralysis. The key objectives were to determine whether increases in PaCO2 during laparoscopic surgery induce increases in plasma potassium concentrations and, if so, to determine the magnitude of such changes. METHODS A retrospective observational study of adult patients undergoing laparoscopic abdominal surgery was perfomed. The independent association between increases in PaCO2 and changes in plasma potassium concentration was assessed by performing arterial blood gases within 15 min of induction of anaesthesia and within 15 min of completion of surgery. RESULTS 289 patients were studied (mean age of 63.2 years; 176 [60.9%] male, and mean body mass index of 29.3 kg/m2). At the completion of the surgery, PaCO2 had increased by 5.18 mmHg (95% CI 4.27 mmHg to 6.09 mmHg) compared to baseline values (P < 0.001) with an associated increase in potassium concentration of 0.25 mmol/L (95% CI 0.20 mmol/L to 0.31 mmol/L, P < 0.001). On multiple regression analysis, PaCO2 changes significantly predicted immediate changes in plasma potassium concentration and could account for 33.1% of the variance (r2 = 0.331, f(3,259) = 38.915, P < 0.001). For each 10 mmHg increment of PaCO2 the plasma potassium concentration increased by 0.18 mmol/L. CONCLUSION In patients receiving laparoscopic abdominal surgery, there is an increase in PaCO2 at the end of surgery, which is independently associated with an increase in plasma potassium concentration. However, this effect is small and is mostly influenced by intravenous fluid therapy (Plasma-Lyte 148 solution) and the presence of diabetes. Trial registration Retrospectively registered in the Australian New Zealand Clinical Trials Registry (Trial Number: ACTRN12619000716167).
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The Persistent Question of Potassium Channel Permeation Mechanisms.
Mironenko, A, Zachariae, U, de Groot, BL, Kopec, W
Journal of molecular biology. 2021;(17):167002
Abstract
Potassium channels play critical roles in many physiological processes, providing a selective permeation route for K+ ions in and out of a cell, by employing a carefully designed selectivity filter, evolutionarily conserved from viruses to mammals. The structure of the selectivity filter was determined at atomic resolution by x-ray crystallography, showing a tight coordination of desolvated K+ ions by the channel. However, the molecular mechanism of K+ ions permeation through potassium channels remains unclear, with structural, functional and computational studies often providing conflicting data and interpretations. In this review, we will present the proposed mechanisms, discuss their origins, and will critically assess them against all available data. General properties shared by all potassium channels are introduced first, followed by the introduction of two main mechanisms of ion permeation: soft and direct knock-on. Then, we will discuss critical computational and experimental studies that shaped the field. We will especially focus on molecular dynamics (MD) simulations, that provided mechanistic and energetic aspects of K+ permeation, but at the same time created long-standing controversies. Further challenges and possible solutions are presented as well.