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Competing Interests: Declaration of Competing Interest The authors have no competing interest to declare.

Background and Objective: In silico methods are gaining attention for predicting drug-induced Torsade de Pointes (TdP) in different stages of drug development. However, many computational models tended not to account for inter-individual response variability due to demographic covariates, such as sex, or physiologic covariates, such as renal function, which may be crucial when predicting TdP. This study aims to compare the effects of drugs in male and female populations with normal and impaired renal function using in silico methods., Methods: Pharmacokinetic models considering sex and renal function as covariates were implemented from data published in pharmacokinetic studies. Drug effects were simulated using an electrophysiologically calibrated population of cellular models of 300 males and 300 females. The population of models was built by modifying the endocardial action potential model published by O'Hara et al. (2011) according to the experimentally measured gene expression levels of 12 ion channels., Results: Fifteen pharmacokinetic models for CiPA drugs were implemented and validated in this study. Eight pharmacokinetic models included the effect of renal function and four the effect of sex. The mean difference in action potential duration (APD) between male and female populations was 24.9 ms (p<0.05). Our simulations indicated that women with impaired renal function were particularly susceptible to drug-induced arrhythmias, whereas healthy men were less prone to TdP. Differences between patient groups were more pronounced for high TdP-risk drugs. The proposed in silico tool also revealed that individuals with impaired renal function, electrophysiologically simulated with hyperkalemia (extracellular potassium concentration [K + ] o  = 7 mM) exhibited less pronounced APD prolongation than individuals with normal potassium levels. The pharmacokinetic/electrophysiological framework was used to determine the maximum safe dose of dofetilide in different patient groups. As a proof of concept, 3D simulations were also run for dofetilide obtaining QT prolongation in accordance with previously reported clinical values., Conclusions: This study presents a novel methodology that combines pharmacokinetic and electrophysiological models to incorporate the effects of sex and renal function into in silico drug simulations and highlights their impact on TdP-risk assessment. Furthermore, it may also help inform maximum dose regimens that ensure TdP-related safety in a specific sub-population of patients., Competing Interests: Declaration of Competing Interest Samuel Baroudi, Kévin Koloskoff, Mathieu Basset, Sylvain Benito, and Frederic Dayan work for ExactCure®. All the other authors declare no potential commercial or financial relationships., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Patients receiving cardiorenal-protective renin-angiotensin-aldosterone system inhibitors (RAASis) are at increased risk of developing hyperkalemia, which is associated with increased medical costs. The aim of this study was to evaluate the impact of adding sodium zirconium cyclosilicate (SZC) therapy on 3-month medical costs in patients who experienced hyperkalemia while receiving RAASi therapy., Methods: The retrospective OPTIMIZE II study used medical and pharmacy claims data from IQVIA PharMetrics ® Plus. Patients aged ≥ 18 years who received SZC (≥ 60 day supply over 3 months' follow-up) and continued RAASi between July 2019 and December 2021 (Continue RAASi + SZC cohort) were 1:1 exact and propensity score matched with patients who discontinued RAASi after hyperkalemia diagnosis and did not receive SZC (Discontinue RAASi + no SZC cohort). The primary outcome was hyperkalemia-related medical costs to payers over 3 months; all-cause medical and pharmacy costs were also analyzed., Results: In the Continue RAASi + SZC (n = 467) versus Discontinue RAASi + no SZC (n = 467) cohort, there were significant reductions in mean per-patient hyperkalemia-related medical costs (reduction of $2216.07; p = 0.01) and all-cause medical costs (reduction of $6102.43; p < 0.001); mean hyperkalemia-related inpatient medical costs and all-cause inpatient and emergency department medical costs were significantly reduced. The reduction in all-cause medical cost in the Continue RAASi + SZC cohort offset an increase in the mean per-patient all-cause pharmacy cost (increase of $3117.71; p < 0.001)., Conclusion: RAASi therapy has well-established cardiorenal benefits. In OPTIMIZE II, management of RAASi-induced hyperkalemia with SZC was associated with lower hyperkalemia-related and all-cause medical costs than RAASi discontinuation without SZC, demonstrating medical cost savings with maintaining RAASi therapy with SZC., (© 2023. The Author(s).)

Background Cardiac hypertrophy is associated with abnormal electrophysiology and increased arrhythmia risk. This study assessed whether candesartan cilexetil, an angiotensin II type 1 receptor blocker, could suppress arrhythmogenecity by attenuating cardiac electrical remodeling and calcium mishandling in rats with pressure-overload hypertrophy. Methods and Results Male Sprague-Dawley rats were randomly subjected to abdominal aorta banding or sham procedure and received either candesartan cilexetil (3.0 mg/kg per day) or vehicle by gavage for 5 weeks. Pressure overload was characterized by compensated left ventricular (LV) hypertrophy and fibrosis, increased LV pressure and its decay time, and prolonged corrected QT interval, all of which were attenuated by candesartan cilexetil treatment. Candesartan cilexetil-treated banded rat hearts displayed shorter QT intervals and lower vulnerability to atrial and ventricular tachyarrhythmias than vehicle-treated banded hearts. Candesartan cilexetil prevented banding-induced prolonged action potential duration and reduced the occurrence of triggered activity in LV papillary muscles. In addition, the prolonged time to 50% cell relengthening and calcium transient decay time were normalized in LV myocytes from candesartan cilexetil-treated banded rats, along with a normalization of decreased SERCA2a (sarco[endo]plasmic reticulum calcium-ATPase) expression in LV tissues. Furthermore, candesartan cilexetil normalized depressed transient outward potassium current densities and protein and mRNA levels of both voltage-gated potassium 4.2 and 4.3 channel subunits (Kv4.2 and Kv4.3) in banded rats. Conclusions Candesartan cilexetil protects the heart from pressure overload-induced adverse electrical remodeling by preserving potassium channel densities. In addition, calcium handling and its molecular regulation also improved after treatment. These beneficial effects may contribute to a lower susceptibility to arrhythmias in hearts from candesartan cilexetil-treated pressure-overloaded rats.

Diuretic-induced hypokalaemia is a common and potentially life-threatening adverse drug reaction in clinical practice. Previous studies revealed a prevalence of 7%-56% of hypokalaemia in patients taking thiazide diuretics. The clinical manifestations of hypokalaemia due to diuretics are non-specific, varying from asymptomatic to fatal arrhythmia. Diagnosis of hypokalaemia is based on the level of serum potassium. ECG is useful in identifying the more severe consequences. A high dosage of diuretics and concomitant use of other drugs that increase the risk of potassium depletion or cardiac arrhythmias can increase the risk of cardiovascular events and mortality. Thiazide-induced potassium depletion may cause dysglycaemia. The risk of thiazide-induced hypokalaemia is higher in women and in black people. Reducing diuretic dose and potassium supplementation are the most direct and effective therapies for hypokalaemia. Combining with a potassium-sparing diuretic or blocker of the renin-angiotensin system also reduces the risk of hypokalaemia. Lowering salt intake and increasing intake of vegetables and fruits help to reduce blood pressure as well as prevent hypokalaemia., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Calcineurin inhibitors are the cornerstone of immunosuppression following solid-organ transplant. However, hyperkalemia may occur by multiple mechanisms affecting potassium in the distal tubule. Hyperkalemia is commonly observed in renal transplant recipients, and it is dose-dependent. Here, we evaluated the impact of fludrocortisone in the management of calcineurin inhibitor-induced hyperkalemia after renal transplant., Materials and Methods: We evaluated newly transplanted patients who developed hyperkalemia or those with hyperkalemia who attended our outpatient renal transplant clinic (Hamed Al-Essa Organ Transplant Center, Kuwait). Clinical and laboratory parameters were collected before starting fludrocortisone (baseline values) and then at 1, 2, 4, and 8 weeks. Drug history was assessed, with any drugs that could induce hyperkalemia being discontinued (such as spironolactone); otherwise, essential drugs like prophylactic agents (sulfamethoxazole-trimethoprim) were maintained. Oral anti-hyperkalemic doses (bicarbonate, resonium calcium, fludrocortisone) were noted., Results: Our study included 29 patients; most were men (aged 45.8 ± 15 years). Body weight did not significantly change after introduction of fludrocortisone (79.53 ± 24.31, 79.82 ± 23.85, 80.62 ± 24.24, 77.03 ± 20.7, and 79.21 ± 27.93 kg at baseline and at postdose week 1, 2, 4, and 8, respectively). Systolic and diastolic blood pressure levels were also similar at baseline versus postdose. Steroid doses (prednisolone) were significantly reduced over 1 month (15.7 ± 12.4, 14.1 ± 10.19, 12.6 ± 8.7, 9.5 ± 5.2, and 9.5 ± 5.2 mg/ day). Serum potassium levels significantly improved (5.18 ± 0.58, 4.9 ± 0.49, 4.8 ± 0.54, 4.8 ± 0.65, and 4.4 ± 0.72 mmol/L). Serum creatinine levels significantly improved by postdose week 8 (129.28 ± 48.9, 130.92 ± 52.2, 127.66 ± 50.9, 121.42 ± 41.7, and 124.1 ± 51.27 μmol/L). Serum bicarbonate levels remained similar., Conclusions: Fludrocortisone was a safe and effective option in management of calcineurin inhibitor-induced hyperkalemia among renal transplant recipients.

Background: Hypokalemia and acute kidney injury (AKI) occur in patients administered liposomal amphotericin B (L-AMB), a wide-spectrum anti-fungicidal drug. However, the association between potassium supplementation and the occurrence of AKI in patients with hypokalemia who were administered L-AMB is not well understood., Methods: Using nationwide claims data and laboratory data, the occurrence of AKI during L-AMB treatment was retrospectively compared between patients with hypokalemia who were or were not supplemented with potassium and between those adequately or inadequately supplemented with potassium (serum potassium levels corrected to ≥3.5 mEq/L or remained < 3.5 mEq/L, respectively) before or after L-AMB treatment initiation., Results: We identified 118 patients who developed hypokalemia before L-AMB treatment initiation (43 received potassium supplementation [25 adequate and 18 inadequate supplementation] and 75 did not receive potassium supplementation), and 117 patients who developed hypokalemia after L-AMB initiation (79 received potassium supplementation [including 23 adequate and 15 inadequate supplementation] and 38 did not receive potassium supplementation). The occurrence of any stage of AKI was similar between patients with hypokalemia, regardless of potassium supplementation (i.e., before L-AMB treatment initiation [supplementation, 51%; non-supplementation, 45%; P = 0.570] or after L-AMB initiation [supplementation, 28%; non-supplementation, 32%; P = 0.671]). After adjusting for confounding factors, we found that the occurrence of any stage of AKI was not associated with potassium supplementation before L-AMB initiation (odds ratio [OR]: 1.291, 95% confidence interval [CI]: 0.584-2.852, P = 0.528) or after L-AMB initiation (OR: 0.954, 95% CI: 0.400-2.275, P = 0.915). The occurrence of any stage of AKI tended to decline in patients with hypokalemia who were adequately supplemented with potassium (44%) before, but not after, L-AMB initiation relative to that in patients inadequately supplemented with potassium (61%), however this result was not significant (P = 0.358)., Conclusion: Potassium supplementation was not associated with any stage of AKI in patients with hypokalemia who were administered L-AMB.

Background Hyperkalemia can be harmful, but the effect of correcting hyperkalemia is sparsely studied. We used nationwide data to examine hyperkalemia follow-up in patients with hypertension. Methods and Results We identified 7620 patients with hypertension, who had the first plasma potassium measurement ≥4.7 mmol/L (hyperkalemia) within 100 days of combination antihypertensive therapy initiation. A second potassium was measured 6 to 100 days after the episode of hyperkalemia. All-cause mortality within 90 days of the second potassium measurement was assessed using Cox regression. Mortality was examined for 8 predefined potassium intervals derived from the second measurement: 2.2 to 2.9 mmol/L (n=37), 3.0 to 3.4 mmol/L (n=184), 3.5 to 3.7 mmol/L (n=325), 3.8 to 4.0 mmol/L (n=791), 4.1 to 4.6 mmol/L (n=3533, reference), 4.7 to 5.0 mmol/L (n=1786), 5.1 to 5.5 mmol/L (n=720), and 5.6 to 7.8 mmol/L (n=244). Ninety-day mortality in the 8 strata was 37.8%, 21.2%, 14.5%, 9.6%, 6.3%, 6.2%, 10.0%, and 16.4%, respectively. The multivariable analysis showed that patients with concentrations >5.5 mmol/L after an episode of hyperkalemia had increased mortality risk compared with the reference (hazard ratio [HR], 2.27; 95% CI, 1.60-3.20; P <0.001). Potassium intervals 3.5 to 3.7 mmol/L and 3.8 to 4.0 mmol/L were also associated with increased risk of death (HR, 1.71; 95% CI, 1.23-2.37; P <0.001; HR, 1.36; 95% CI, 1.04-1.76; P <0.001, respectively) compared with the reference group. We observed a trend toward increased risk of death within the interval 5.1 to 5.5 mmol/L (HR, 1.29; 95% CI, 0.98-1.69). Potassium concentrations <4.1 mmol/L and >5.0 mmol/L were associated with increased risk of cardiovascular death. Conclusions Overcorrection of hyperkalemia to levels <4.1 mmol/L was frequent and associated with increased all-cause and cardiovascular mortality. Potassium concentrations >5.5 mmol/L were also associated with an increased all-cause and cardiovascular mortality.

Introduction: Acute aluminum phosphide poisoning is common in low- and middle-income countries, and is associated with very high case fatality. The addition of glucose-insulin-potassium (GIK) infusion to the standard supportive care has been proposed to improve outcomes. We aimed to assess the effectiveness of GIK infusion in acute aluminum phosphide toxicity. Methods: We performed a prospective open-label pilot study in a tertiary care hospital in north India in patients over 13 years of age with acute aluminum phosphide poisoning, to determine whether the treatment with GIK infusion improved outcomes. The primary outcome was in-hospital case fatality, and the secondary outcomes were the duration of hospital stay, the requirement of mechanical ventilation, and the change in hemodynamic and metabolic parameters. Results: A total of 60 patients were randomly assigned to groups that received either GIK infusion with supportive care or supportive care alone. Baseline parameters in both groups were comparable. Treatment with GIK infusion was associated with significantly lower in-hospital case fatality compared with supportive care alone (46.7% versus 73.3%; p -value 0.03). It was associated with a longer duration of hospital stay ( p -value < 0.01) and reduced requirement of mechanical ventilation ( p -value < 0.01). The treatment improved blood pressure (systolic, diastolic, and mean arterial pressure) and Glasgow coma scale score at various time intervals; however, pulse rate and metabolic acidosis (blood pH and bicarbonate levels) remained comparable in both the groups. Hyperglycemia was significantly higher in the GIK group but was easily managed. Conclusion: Treatment with GIK infusion may improve survival and hemodynamics in patients with acute aluminum phosphide poisoning.

Background Laboratory studies demonstrate glucose-insulin-potassium (GIK) as a potent cardioprotective intervention, but clinical trials have yielded mixed results, likely because of varying formulas and timing of GIK treatment and different clinical settings. This study sought to evaluate the effects of modified GIK regimen given perioperatively with an insulin-glucose ratio of 1:3 in patients undergoing cardiopulmonary bypass surgery. Methods and Results In this prospective, randomized, double-blinded trial with 930 patients referred for cardiac surgery with cardiopulmonary bypass, GIK (200 g/L glucose, 66.7 U/L insulin, and 80 mmol/L KCl) or placebo treatment was administered intravenously at 1 mL/kg per hour 10 minutes before anesthesia and continuously for 12.5 hours. The primary outcome was the incidence of in-hospital major adverse cardiac events including all-cause death, low cardiac output syndrome, acute myocardial infarction, cardiac arrest with successful resuscitation, congestive heart failure, and arrhythmia. GIK therapy reduced the incidence of major adverse cardiac events and enhanced cardiac function recovery without increasing perioperative blood glucose compared with the control group. Mechanistically, this treatment resulted in increased glucose uptake and less lactate excretion calculated by the differences between arterial and coronary sinus, and increased phosphorylation of insulin receptor substrate-1 and protein kinase B in the hearts of GIK-treated patients. Systemic blood lactate was also reduced in GIK-treated patients during cardiopulmonary bypass surgery. Conclusions A modified GIK regimen administered perioperatively reduces the incidence of in-hospital major adverse cardiac events in patients undergoing cardiopulmonary bypass surgery. These benefits are likely a result of enhanced systemic tissue perfusion and improved myocardial metabolism via activation of insulin signaling by GIK. Clinical Trial Registration URL: clinicaltrials.gov. Identifier: NCT01516138.

Hyperkalemia is a frequent finding in patients with chronic kidney disease (CKD). This increase in serum potassium levels is associated with decreased renal ion excretion, as well as the use of medications to reduce the progression of CKD or to control associated diseases such as diabetes mellitus and heart failure. Hyperkalemia increases the risk of cardiac arrhythmia episodes and sudden death. Thus, the control of potassium elevation is essential for reducing the mortality rate in this population. Initially, the management of hyperkalemia includes orientation of low potassium diets and monitoring of patients' adherence to this procedure. It is also important to know the medications in use and the presence of comorbidities to guide dose reduction or even temporary withdrawal of any of the potassium retention-related drugs. And finally, the use of potassium binders is indicated in both acute episodes and chronic hyperkalemia.

Sugarcane cultivation requires correct fertilizer rates. However, when nutrients are not available, or there is over-fertilization, the yields are significantly reduced and the environmental burden increase. In this study, it is proposed a decision support system (DSS) for the correct NPK (nitrogen, phosphorus and potassium) fertilization. The DSS consists of two fuzzy models; the edaphic condition model (EDC-M) and the NPK fertilization model (NPK-M). The DSS using parameters from soil analysis and is based on the experience of two groups of experts to avoid the bias to the reality of a single group of professionals. The results of the DSS are compared with the results of soil analysis and those of the group of experts. One hundred and sixty tests were developed in the NPK-M. The N rate shows R 2 =0.981 for the DSS and R 2 =0.963 for soil analyzes. The P rate shows R 2 =0.9702 for the DSS and R 2 =0.9183 for the soil analyzes. The K rate shows R 2 =0.9691 for the DSS and R 2 =0.9663 for the soil analyzes. Environmental results indicate that the estimated rates with the DSS do reduce the environmental impact on the tests performed.

Hypokalemia prolongs the QRS and QT intervals, deteriorates intercellular coupling, and increases the risk for arrhythmia. Melatonin preserves gap junctions and shortens action potential as potential antiarrhythmic mechanisms, but its properties under hypokalemia remain unknown. We hypothesized that melatonin protects against low potassium-induced arrhythmias through the activation of its receptors, resulting in action potential shortening and connexin-43 preservation. After stabilization in Krebs-Henseleit solution (4.5 mEq/L K + ), isolated hearts from Wistar rats underwent perfusion with low-potassium (1 mEq/L) solution and melatonin (100 μmol/L), a melatonin receptor blocker (luzindole, 5 μmol/L), melatonin + luzindole or vehicle. The primary endpoint of the study was the prevention of ventricular fibrillation. Electrocardiography was used, and epicardial action potentials and heart function were measured and analyzed. The ventricular expression, dephosphorylation, and distribution of connexin-43 were examined. Melatonin reduced the incidence of low potassium-induced ventricular fibrillation from 100% to 59%, delayed the occurrence of ventricular fibrillation and induced a faster recovery of sinus rhythm during potassium restitution. Melatonin prevented QRS widening, action potential activation delay, and the prolongation of action potential duration at 50% of repolarization. Other ECG and action potential parameters, the left ventricular developed pressure, and nonsustained ventricular arrhythmias did not differ among groups. Melatonin prevented connexin-43 dephosphorylation and its abnormal topology (lateralization). Luzindole abrogated the protective effects of melatonin on electrophysiological properties and connexin-43 misdistribution. Our results indicate that melatonin receptor activation protects against low potassium-induced ventricular fibrillation, shortens action potential duration, preserves ventricular electrical activation, and prevents acute changes in connexin-43 distribution. All of these properties make melatonin a remarkable antifibrillatory agent., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: This experimental study compares myocardial function after prolonged arrest by St. Thomas' Hospital polarizing cardioplegic solution (esmolol, adenosine, Mg 2+ ) with depolarizing (hyperkalaemic) St. Thomas' Hospital No 2, both administered as cold oxygenated blood cardioplegia., Methods: Twenty anaesthetized pigs on tepid (34°C) cardiopulmonary bypass (CPB) were randomised to cardioplegic arrest for 120 min with antegrade, repeated, cold, oxygenated, polarizing (STH-POL) or depolarizing (STH-2) blood cardioplegia every 20 min. Cardiac function was evaluated at Baseline and 60, 150 and 240 min after weaning from CPB, using a pressure-conductance catheter and epicardial echocardiography. Regional tissue blood flow, cleaved caspase-3 activity and levels of malondialdehyde were evaluated in myocardial tissue samples., Results: Preload recruitable stroke work (PRSW) was increased after polarizing compared to depolarizing cardioplegia 150 min after declamping (73.0±3.2 vs. 64.3±2.4 mmHg, p=0.047). Myocardial tissue blood flow rate was high in both groups compared to the Baseline levels and decreased significantly in the STH-POL group only, from 60 min to 150 min after declamping (p<0.005). Blood flow was significantly reduced in the STH-POL compared to the STH-2 group 240 min after declamping (p<0.05). Left ventricular mechanical efficiency, the ratio between total pressure-volume area and blood flow rate, gradually decreased after STH-2 cardioplegia and was significantly reduced compared to STH-POL cardioplegia after 150 and 240 min (p<0.05 for both)., Conclusion: Myocardial protection for two hours of polarizing cardioplegic arrest with STH-POL in oxygenated blood is non-inferior compared to STH-2 blood cardioplegia. STH-POL cardioplegia alleviates the mismatch between myocardial function and perfusion after weaning from CPB.

Introduction: Options for the treatment of hyperkalemia in the pre-hospital setting are limited, particularly in the context of natural disaster or during combat operations. Contemporary interventions require extensive resources and technical expertise. Here we examined the potential for a simple, field deployable bridge-dialysis as a countermeasure for acute hyperkalemia induced by prolonged ischemia-reperfusion., Methods: Twenty female swine were randomized into two experimental groups undergoing a 2-hour bilateral hindlimb ischemia-reperfusion injury. Subsequent to injury, hemoperfusion was performed in the presence (Column) and absence (Sham Control) of a high-affinity potassium-binding column (CytoSorbents, Monmouth Junction, NJ, USA). Serial blood gas and chemistries were sampled. Primary endpoint was changed in serum potassium concentrations post-injury and filtration., Results: Serum potassium was significantly elevated following ischemia-reperfusion injury in both groups (149% (12) and 150% (22), p < 0.05 vs respective baseline values). There were no differences observed between groups in respect to physiologic parameters; mean arterial pressure, heart rate, systemic vascular resistance, cardiac output, or central venous oxygenation. Filtration resulted in a significant relative decrease in potassium compared with controls after the first hour as determined by repeated measures two-way ANOVA (p < 0.0001) which continued through end of the study. Significant thrombocytopenia was observed in animals undergoing filtration with a mean reduction in platelets measured at T = 480 minutes (168 × 103μL, p < 0.0001 vs baseline)., Conclusions: We demonstrate that serum potassium can be filtered via hemoperfusion utilizing a simple extracorporeal potassium-binding platform, though evolution of this technology will be required to achieve meaningful reduction of potassium in clinically significant hyperkalemia after trauma.

Background: Low cardiac output syndrome is a main cause of death after cardiac surgery. We sought to assess the impact of glucose-insulin-potassium (GIK) to enhance myocardial protection in moderate- to high-risk patients undergoing on-pump heart surgery., Methods: A randomized controlled trial was performed in adult patients (Bernstein-Parsonnet score >7) scheduled for elective aortic valve replacement and/or coronary artery bypass surgery. Patients were randomized to GIK (20 IU of insulin, 10 mEq of potassium chloride in 50 mL of glucose 40%) or saline infusion given over 60 minutes on anesthetic induction. The primary end point was postcardiotomy ventricular dysfunction (PCVD), defined as new/worsening left ventricular dysfunction requiring inotropic support (≥120 minutes). Secondary end points were the intraoperative changes in left ventricular function as assessed by transoesophageal echocardiography, postoperative troponin levels, cardiovascular and respiratory complications, and intensive care unit and hospital length of stay., Results: From 224 randomized patients, 222 were analyzed (112 and 110 in the placebo and GIK groups, respectively). GIK pretreatment was associated with a reduced occurrence of PCVD (risk ratio [RR], 0.41; 95% confidence interval [CI], 0.25-0.66). In GIK-treated patients, the left systolic ventricular function was better preserved after weaning from bypass, plasma troponin levels were lower on the first postoperative day (2.9 ng·mL(-) [interquartile range {IQR}, 1.5-6.6] vs 4.3 ng·mL(-) [IQR, 2.4-8.2]), and cardiovascular (RR, 0.69; 95% CI, 0.50-0.89) and respiratory complications (RR, 0.5; 95% CI, 0.38-0.74) were reduced, along with a shorter length of stay in intensive care unit (3 days [IQR, 2-4] vs 3.5 days [IQR, 2-7]) and in hospital (14 days [IQR, 11-18.5] vs 16 days [IQR, 12.5-23.5]), compared with placebo-treated patients., Conclusions: GIK pretreatment was shown to attenuate PCVD and to improve clinical outcome in moderate- to high-risk patients undergoing on-pump cardiac surgery.

Background/aims: Dietary potassium (K+) has beneficial effects on blood pressure and cardiovascular (CV) outcomes. Recently, several epidemiological studies have revealed an association between urinary K+ excretion (as proxy for dietary intake) and better renal outcomes in subjects with chronic kidney disease (CKD). To address causality, we designed the "K+ in CKD" study., Methods: The K+ in CKD study is a multicenter, randomized, double blind, placebo-controlled clinical trial aiming to include 399 patients with hypertension, CKD stage 3b or 4 (estimated glomerular filtration rate [eGFR] 15-44 mL/min/1.73 m2), and an average eGFR decline > 2 mL/min/1.73 m2/year. As safety measure, all included subjects will start with a 2-week open-label phase of 40 mmol potassium chloride daily. Patients who do not subsequently develop hyperkalemia (defined as serum K+ >5.5 mmol/L) will be randomized to receive potassium chloride, potassium citrate (both K+ 40 mmol/day), or placebo for 2 years. The primary end point is the difference in eGFR after 2 years of treatment. Secondary end points include other renal outcomes (> 30% decrease in eGFR, doubling of serum creatinine, end-stage renal disease, albuminuria), ambulatory blood pressure, CV events, all-cause mortality, and incidence of hyperkalemia. Several measurements will be performed to analyze the effects of potassium supplementation, including body composition monitoring, pulse wave velocity, plasma renin and aldosterone concentrations, urinary ammonium, and intracellular K+ concentrations., Conclusion: The K+ in CKD study will demonstrate if K+ sup-plementation has a renoprotective effect in progressive CKD, and whether alkali therapy has additional beneficial effects., (© 2018 S. Karger AG, Basel.)

Rice (Oryza sativa L.) is the primary staple food source for more than half of the world's population. In many developing countries, increased use of fertilizers is a response to increase demand for rice. In this study, we investigated the effects of three principal fertilizer components (nitrogen, phosphorus and potassium) on the development of potted rice plants and their effects on fitness traits of the brown planthopper (BPH) [Nilaparvata lugens (Stål) (Homoptera: Delphacidae)], which is a major pest of rice in Bangladesh and elsewhere. Compared to low fertilizer inputs, high fertilizer treatments induced plant growth but also favored BPH development. The BPH had higher survival, developed faster, and the intrinsic rate of natural increase (r m ) was higher on well-fertilized than under-fertilized plants. Among the fertilizer inputs, nitrogen had the strongest effect on the fitness traits of BPH. Furthermore, both the "Plant vigor hypothesis" and the "Plant stress hypothesis" were supported by the results, the former hypothesis more so than the latter. These hypotheses suggest that the most suitable/attractive hosts for insect herbivores are the most vigorous plants. Our findings emphasized that an exclusive focus on yield increases through only enhanced crop fertilization may have unforeseen, indirect, effects on crop susceptibility to pests, such as BPH.

Intradialytic hypotensive episodes are deleterious for hemodialysis (HD) patients. Acetate-free biofiltration with profiled potassium (AFBK) dialysate concentration may improve their cardiovascular stability. The aim of the present crossover study was to compare intradialytic hemodynamic tolerance and biological parameters between online hemodiafiltration (olHDF) and AFBK. Ten frail HD patients (8 males) with a mean age of 66.71- ± 12.31 years were studied for three months on olHDF and AFBK. There was a significant reduction of the hypotensive episodes during the AFBK period compared to the olHDF period. Mean intradialytic systolic and diastolic blood pressures were significantly higher during the AFBK period. There was a significant postdialytic increase in serum sodium concentration with the AFBK compared to olHDF. The dry weight and ultrafiltration indices were significantly higher, and the Kt/V was significantly lower during the AFBK period. Serum albumin concentration significantly increased during the AFBK period. AFBK leads to a significantly improved intradialytic tolerance in hemodynamically instable HD patients.

Background: Gitelman syndrome (GS) is a rare autosomal recessive disease caused by loss-of-function mutations in the SLC12A3 gene, and is characterized by hypokalemia and metabolic alkalosis. In this study, we aimed to study the genotype, phenotype, and treatment in 42 GS patients, the largest sample size so far in mainland China., Method: We retrospectively studied the clinical data and genetic characteristics of 42 patients diagnosed with GS in Peking Union Medical College Hospital from 2012 to 2015. Therapeutic efficacy of spironolactone and potassium supplements was also studied retrospectively., Results: Eighty-one mutation alleles were found in 42 patients, and total of 52 distinctly different mutation alleles were identified, of which 15 were new mutation alleles. p.Asp486Asn was a hotspot in our series, with the allele frequency being 19.7 % (16/81), and was found in 13 patients (31.0 %). Treatment with spironolactone or potassium supplements alone significantly increased serum potassium concentration by 0.36 ± 0.37 and 0.45 ± 0.35 mmol/l, respectively (both P < 0.05), and combined therapy with spironolactone and potassium increased serum potassium concentration by 0.69 ± 0.64 mmol/l (P < 0.05)., Conclusions: 18.5 % (15/81) mutation sites identified in 42 Chinese GS patients are novel. p.Asp486Asn mutation is a hotspot, which is different from the reports from other countries. Spironolactone could moderately elevate serum potassium level, and spironolactone in combination with potassium supplements tended to be more effective.

Background and Aims: Increasing the intake of potassium has been shown to lower blood pressure, but whether it also affects heart rate (HR) is largely unknown. We therefore assessed the effect of potassium supplementation on HR in a meta-analysis of randomized controlled trials., Methods and Results: We searched PubMed (1966-October 2014) for randomized, placebo-controlled trials in healthy adults with a minimum duration of two weeks in which the effect of increased potassium intake on HR was assessed. In addition, reference lists from meta-analysis papers on potassium and blood pressure were hand-searched for publications. Two investigators independently extracted the data. We performed random effects meta-analyses, subgroup and meta-regression analyses for characteristics of the study (e.g. design, intervention duration, potassium dose and salt type, change in potassium excretion, sodium excretion during intervention) and study population (e.g. gender, age, hypertensive status, pre-study HR, pre-study potassium excretion). A total of 22 trials (1086 subjects), with a median potassium dose of 2.5 g/day (range: 0.9-4.7 g/day), and median intervention duration of 4 weeks (range: 2-24 weeks) were included. The meta-analysis showed no overall effect of increased potassium intake on HR (0.19 bpm, 95% CI: -0.44, 0.82). Stratified analyses yielded no significant effects of potassium intake on HR in subgroups, and there was no evidence for a dose-response relationship in meta-regression analyses., Conclusion: A chronic increase in potassium intake with supplemental doses of 2-3 g/day is unlikely to affect HR in apparently healthy adults., (Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Due to their composition, cheeses are suspected to induce an acid load to the body. To better understand this nutritional feature, the acid-forming potential of five cheeses from different cheese-making technologies and two milk was evaluated on the basis of their potential renal acid load (PRAL) index (considering protein, P, Cl, Na, K, Mg and Ca contents) and organic anions contents. PRAL index ranged from -0.8 mEq/100 g edible portion for fresh cheese to 25.3 mEq/100 g for hard cheese Cantal and 28 mEq/100 g for blue-veined cheese Fourme d'Ambert. PRAL values were greatly subjected to interbatch fluctuations. This work emphasized a great imbalance between acidifying elements of PRAL calculation (Cl, P and proteins elements) and alkalinizing ones (Na and Ca). Particularly, Cl followed by P elements had a strong impact on the PRAL value. Hard cheeses were rich in lactate, thus, might be less acidifying than suspected by their PRAL values only.

Dyskalemia is known to cause cardiac arrhythmias and cardiac arrest. In persons undergoing hemodialysis, potassium dialysate composition has been identified as a contributingfactor in addition to co-morbidities, medications, dietary potassium intake, and stage of kidney disease. Current evidence recommends a thorough evaluation of all factors affecting potassium balance, and lower potassium concentration should be used cautiously in patients who are likely to develop cardiac arrhythmias. Nephrology nurses play a key role inpatient assessment and edu- cation related to potassium balance.

Background: Dietary supplements, such as herbal or complementary nutritional products and micronutrients (vitamins and minerals), are commonly used in the United States, yet national data on adverse effects are limited., Methods: We used nationally representative surveillance data from 63 emergency departments obtained from 2004 through 2013 to describe visits to U.S. emergency departments because of adverse events related to dietary supplements., Results: On the basis of 3667 cases, we estimated that 23,005 (95% confidence interval [CI], 18,611 to 27,398) emergency department visits per year were attributed to adverse events related to dietary supplements. These visits resulted in an estimated 2154 hospitalizations (95% CI, 1342 to 2967) annually. Such visits frequently involved young adults between the ages of 20 and 34 years (28.0% of visits; 95% CI, 25.1 to 30.8) and unsupervised children (21.2% of visits; 95% CI, 18.4 to 24.0). After the exclusion of unsupervised ingestion of dietary supplements by children, 65.9% (95% CI, 63.2 to 68.5) of emergency department visits for single-supplement-related adverse events involved herbal or complementary nutritional products; 31.8% (95% CI, 29.2 to 34.3) involved micronutrients. Herbal or complementary nutritional products for weight loss (25.5%; 95% CI, 23.1 to 27.9) and increased energy (10.0%; 95% CI, 8.0 to 11.9) were commonly implicated. Weight-loss or energy products caused 71.8% (95% CI, 67.6 to 76.1) of supplement-related adverse events involving palpitations, chest pain, or tachycardia, and 58.0% (95% CI, 52.2 to 63.7) involved persons 20 to 34 years of age. Among adults 65 years of age or older, choking or pill-induced dysphagia or globus caused 37.6% (95% CI, 29.1 to 46.2) of all emergency department visits for supplement-related adverse events; micronutrients were implicated in 83.1% (95% CI, 73.3 to 92.9) of these visits., Conclusions: An estimated 23,000 emergency department visits in the United States every year are attributed to adverse events related to dietary supplements. Such visits commonly involve cardiovascular manifestations from weight-loss or energy products among young adults and swallowing problems, often associated with micronutrients, among older adults. (Funded by the Department of Health and Human Services.).

A 52-year old man developed hyperkalaemia on the 11th postoperative day following an extensive open retroperitoneal liposarcoma resection that included splenectomy. Despite thorough investigations, no aetiology for the hyperkalaemia was identified and standard empirical treatment was ineffective. On reconsideration, in view of the patient's concurrent thrombocytosis, a pseudofactual or artefactual hyperkalaemia was suspected. This was confirmed by contemporaneous testing of serum and plasma potassium levels, with the latter value lying within the normal range. Treatment for hyperkalaemia was discontinued, thus averting an iatrogenic and potentially dangerous hypokalaemia. This case highlights pseudohyperkalaemia as an often-neglected cause of elevated serum potassium levels and discusses its association with thrombocytosis following splenectomy., (2015 BMJ Publishing Group Ltd.)

Objective: Urinary excretion of angiotensinogen [urine angiotensinogen (UAGT)] has been proposed as a biomarker of intrarenal renin-angiotensin system activity. We investigated the association between UAGT and salt-sensitivity and potassium-sensitivity of blood pressure (BP) among Genetic Epidemiology Network of Salt Sensitivity study participants., Methods: The intervention consisted of a 7-day low-sodium diet (51.3  mmol sodium/day), 7-day high-sodium diet (307.8  mmol sodium/day), and 7-day high-sodium diet with potassium supplementation (307.8  mmol sodium/day and 60  mmol potassium/day). Twenty-four-hour UAGT was estimated at baseline and at the end of each intervention for 100 randomly selected participants., Results: Median UAGT (μg/24  h) and UAGT-to-creatinine ratio (UAGT/Cr, μg/g) were significantly reduced during the low-sodium and potassium-supplementation interventions and increased during the high-sodium intervention (both P = 0.01). Baseline log-transformed UAGT and UAGT/Cr ratio were significantly positively associated with BP at baseline and at the end of each intervention. For example, one standard deviation higher log-UAGT/Cr ratio (1.2  μg/g) was associated with a 5.0-mmHg (95% confidence interval 2.3-7.8) higher SBP at the end of the high-sodium intervention, after adjusting for multiple covariates (P = 0.003). In addition, one standard deviation higher log-UAGT/Cr ratio was associated with a 1.6-mmHg increase in age-adjusted and sex-adjusted SBP from the low-sodium intervention to the high-sodium intervention (95% confidence interval 0.1-3.1, P = 0.04). This association was no longer statistically significant after multivariable adjustment., Conclusion: These data indicate that elevated UAGT are associated with BP sodium sensitivity. Augmentation of intrarenal renin-angiotensin system activity may play an important role in developing salt-sensitive hypertension.

Background: Ambient particulate matter (PM) exposure is associated with children's respiratory health. Little is known about the importance of different PM constituents. We investigated the effects of PM constituents on asthma, allergy, and lung function until the age of 11-12 years., Methods: For 3,702 participants of a prospective birth cohort study, questionnaire-reported asthma and hay fever and measurements of allergic sensitization and lung function were linked with annual average concentrations of copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc in particles with diameters of less than 2.5 and 10 μm (PM2.5 and PM10) at birth addresses and current addresses from land-use regression models. Exposure-health relations were analyzed by multiple (repeated measures) logistic and linear regressions., Results: Asthma incidence and prevalence of asthma symptoms and rhinitis were positively associated with zinc in PM10 at the birth address (odds ratio [95% confidence interval] per interquartile range increase in exposure 1.13 [1.02, 1.25], 1.08 [1.00, 1.17], and 1.16 [1.04, 1.30], respectively). Moreover, asthma symptoms were positively associated with copper in PM10 at the current address (1.06 [1.00, 1.12]). Allergic sensitization was positively associated with copper and iron in PM10 at the birth address (relative risk [95% confidence interval] 1.07 [1.01, 1.14] and 1.10 [1.03, 1.18]) and current address. Forced expiratory volume in 1 second was negatively associated with copper and iron in PM2.5 (change [95% confidence interval] -2.1% [-1.1, -0.1%] and -1.0% [-2.0, -0.0%]) and FEF75-50 with copper in PM10 at the current address (-2.3% [-4.3, -0.3%])., Conclusion: PM constituents, in particular iron, copper, and zinc, reflecting poorly regulated non-tailpipe road traffic emissions, may increase the risk of asthma and allergy in schoolchildren.

Objective: To determine whether maternal exposure to particulate matter (PM₂.₅) speciation chemicals during pregnancy is associated with the risk of preeclampsia., Methods: We allocated average daily exposure values for 36 ambient particulate matter speciation chemicals to mothers during their first trimester and their entire pregnancy. The main outcome of interest was preeclampsia occurrence. Adjusted odd ratios and 95% confidence intervals were computed., Results: The odds for preeclampsia were increased per interquartile range increase in pollutants for exposure to elemental carbon during the first trimester of pregnancy (odds ratio = 1.08; confidence interval = 1.01 to 1.16) and during the entire pregnancy period (odds ratio = 1.05; confidence interval = 1.01 to 1.11). The most substantial risk for preeclampsia was observed for PM2.5 aluminum exposure during the entire pregnancy, resulting in 10% increased risk (odds ratio = 1.10; confidence interval = 1.03 to 1.18) per interquartile range increase in aluminum., Conclusions: Maternal exposure to PM2.5, aluminum, and elemental carbon during pregnancy increases the risk of preeclampsia.

Background: Glucose-insulin-potassium (GIK) has been advocated in the setting of acute coronary syndrome (ACS) to reduce ischemia-related arrhythmias and myocardial injury. We conducted a meta-analysis of randomized controlled trials (RCTs) to assess whether the use of GIK infusions >3 or <3 hours after the onset of symptoms reduce mortality or cardiac arrest., Methods: Electronic databases (Medline, EMBASE, and Cochrane Central Register of Controlled Trials) and references of retrieved articles were searched for RCTs evaluating the effect of GIK infusions, <3 hours or >3 hours after the onset of symptoms, on mortality and/or cardiac arrest. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for each outcome., Results: Nine trials were identified and eligible for review. The summary OR for in-hospital mortality was 1.01 (95% CI 0.94 to 1.09), based on 2,542 deaths among 27,294 patients. The subgroup analysis according to the study enrollment time (within 3 hours [OR, 0.77, 95% CI 0.50-1.16], vs. >3 hours [OR, 0.90; 95% CI, 0.67-1.21]) did not reveal any difference in mortality., Conclusions: Administration of GIK in ACS patients does not significantly reduce mortality whether or not GIK administration >3 or <3 hours after the onset of symptoms.

Background: This study aimed to determine the safety and efficacy of intraoperative intensive glycaemic treatment with modified glucose-insulin-potassium solution by hyperinsulinemic normoglycaemic clamp in cardiopulmonary bypass surgery patients. We hypothesised that the treatment would reduce infection rates in this group of patients., Methods: A prospective, randomised, double-blind trial was conducted in cardiopulmonary bypass surgery patients. A total of 199 adult patients (out of a planned 400) were randomly allocated to intensive or conventional treatment with target glucose levels of 4.4-8.3 mmol/l and < 13.8 mmol/l, respectively. The primary outcomes were clinical infection and cytokine levels, including interleukin (IL)-6 and IL-10. The secondary outcomes were morbidity and mortality., Results: The study was terminated early because of safety concerns (hypoglycaemia). The clinical post-operative infection rate was 17% in the intensive group and 13% in the conventional group (P = 0.53). The proportion of patients with hypoglycaemia was significantly higher in the intensive group (23%) compared with the conventional group (3%) (P < 0.001). Morbidity and mortality rates were similar for both groups. Anaesthetic duration > 2 h (vs. ≤ 2 h), pre-operative IL-6 level > 15 pg/ml (vs. ≤ 15 pg/ml) and post-operative IL-6 level 56-110 pg/ml (vs. ≤ 55 pg/ml) were independent predictors for post-operative infection., Conclusions: Intraoperative intensive glycaemic treatment significantly increased the risk of hypoglycaemia, but its effect on post-operative infection by clinical assessment could not be determined. Anaesthetic duration, pre-operative and post-operative IL-6 levels can independently predict post-operative infection., (© 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Introduction: Tight blood glucose control has become a therapeutical goal for anesthetic management for patients scheduled for cardiac surgery, especially if they are diabetic patients., Aim: This study was created to confirm the benefits of intraoperative GIK solution usage during coronary bypass operation of diabetic patients., Methods: Patients with type 1 and 2 diabetes mellitus (DM) referred for coronary artery bypass grafting (CABG) were randomized to receive GIK solution (GIK--study group) in the first 24 hours intraoperatively or to receive official Clinical protocol without GIK solution (non GIK - control group). The primary clinical outcome was the cardiac index (CI) since it represents the most sensitive measure of cardiac work in the immediate postoperative period, and the secondary clinical outcomes were the glycemic control, insulin consumption, duration of mechanical ventilation (MV), potassium level and atrial fibrillation (AF) appearance., Results: One hundred diabetic patients, divided into two groups, were included in the study. The cardiac index did not show a significant difference, although the study group had CI with only minor variations than those of the controlled group, hence the reason we considered the study group as the more stable. The atrial fibrillation showed a difference between two groups, with 14 (28%) patients with postoperative AF in the control group compared with 3 (6%) patients with postoperative AF in the study group. As potassium values were stable in study group, we concluded that it can be one of the reasons for less postoperative AF in this group. The duration of MV showed a significant difference (0,003) between the two groups as well. In the study group the average MV time was 534,38 minutes, compared with the control group with 749,20 minutes. The average value of glucose was 11.1 mmol/l in the control group vs. 9.8 mmol/l in the study group. The study group had less insulin consumption in order to maintain target glycemia (p = 0.001). In the non GIK group average insulin consumption was 44 IJ per patient vs. 28.5 IJ in the GIK group., Conclusion: Intraoperative GIK solution given to diabetic patients with CABG operation provides more stable CI, shorter time of MV, more stable values of potassium which provides normal rhythm and less AF onset, less insulin to maintain target glycemia. All the above mentioned provides more stable intraoperative hemodynamic and better recovery of diabetic

Introduction: Serum concentrations of potassium (K) and calcium (Ca) influence ionic currents and play an important role in the duration of ventricular action potential. Further, the influence of alkalosis in reducing ionized calcium has been well known for a long time. The aim of this study was to assess the effects of different dialysate electrolytes and bicarbonate concentrations on changes of QTc interval in patients on chronic hemodialysis., Methods: The study hemodialysis sessions were performed in 22 patients, with different electrolyte and bicarbonate concentrations in dialysate. Tested dialysate concentrations were K of 2 and 3 mmol/L; Ca 1.25, 1.5 and 1.75 mmol/L; and bicarbonate 30 and 34 mmol/L. An electrocardiogram (ECG) was recorded 1 hour before, at the end and every hour for 4 hours after each study dialysis session. QTc interval was measured from the beginning of the QRS complex to the end of a T wave on a 12-lead ECG. Blood was collected and K, total Ca, ionic Ca and pH evaluated., Results: At the end of the study hemodialysis session with dialysate containing low K (2 mmol/L), low Ca (1.25 mmol/L) and high bicarbonate concentration (34 mmol), mean QTc interval was significantly prolonged compared with that recorded with dialysate containing high K (3 mmol/L), high Ca (1.75 mmol/L) and bicarbonate (30 mmol) (40 ± 10 milliseconds vs. 2 ± 2 milliseconds; p<0.01). Dialysate with low concentration of low Ca, K and high concentration of bicarbonate was an independent predictor of QTc; the combination of low Ca and K and high bicarbonate strongly increased the risk of prolonged QTc interval., Conclusion: The present pilot study shows that changes in QTc interval during hemodialysis depend on both electrolyte and bicarbonate concentrations in dialysate.

Background: A daily single capsule (polycap) of 3 blood pressure (BP) lowering drugs (hydrochlorthiazide, 12.5 mg; atenolol, 50 mg; ramipril, 5 mg) at low doses, simvastatin (20 mg), and aspirin (100 mg) has been demonstrated to be well tolerated and to reduce BP and low-density lipoprotein cholesterol. We examined the incremental effects of 2 (full dose) plus K(+) supplementation versus single polycap (low dose) on risk factors and tolerability., Methods and Results: After a run-in period, 518 individuals with previous vascular disease or diabetes mellitus from 27 centers in India were randomly assigned to a single-dose polycap or to 2 capsules of the polycap plus K(+) supplementation for 8 weeks. The effects on BP, heart rate (HR), serum lipids, serum and urinary K(+), and tolerability were assessed using an intention-to-treat analysis. The full-dose polycap (plus K(+) supplementation) reduced BP by a further 2.8 mm Hg systolic and 1.7 mm Hg diastolic, compared with that observed with the low-dose polycap (P=0.003; P=0.001), but there were no differences in HR (0.1 bpm). The differences in total and low-density lipoprotein cholesterol between the full-dose and low-dose polycap was 7.2 mg/dL (P=0.014) and 6.6 mg/dL (P=0.006), respectively, but there were no differences in high-density lipoprotein cholesterol or triglycerides. The rates of discontinuation of the study drug after randomization were similar in the 2 groups (6.9% low dose versus 7.8% full dose)., Conclusions: The full-dose polycap (plus K(+) supplementation) reduces BP and low-density lipoprotein cholesterol to a greater extent compared with the low dose, with similar tolerability. Therefore, the full-dose polycap should potentially lead to larger benefits. Clinical Trial Registration- URL: http://www.ctri.nic.in. Unique identifier: CTRI/2010/091/000054.

In the ischemic myocardium, extracellular potassium ([K(+)](o)) increases to ≥20 mmol/l. To determine how lethal arrhythmias occur during ischemia, we investigated whether the increased spatial pattern of [K(+)](o), i.e., a regional or a global increase, affects the incidence of arrhythmias. Force, sarcomere length, membrane potential, and nonuniform intracellular Ca(2+) ([Ca(2+)](i)) were measured in rat ventricular trabeculae. A "regional" or "global" increase in [K(+)](o) was produced by exposing a restricted region of muscle to a jet of 30 mmol/l KCl or by superfusing trabeculae with a solution containing 30 mmol/l KCl, respectively. The increase in [Ca(2+)](i) (Ca(CW)) during Ca(2+) waves was measured (24°C, 3.0 mmol/l [Ca(2+)](o)). A regional increase in [K(+)](o) caused nonuniform [Ca(2+)](i) and contraction. In the presence of isoproterenol, the regional increase in [K(+)](o) induced sustained arrhythmias in 10 of 14 trabeculae, whereas the global increase did not induce such arrhythmias. During sustained arrhythmias, Ca(2+) surged within the jet-exposed region. In the absence of isoproterenol, the regional increase in [K(+)](o) increased Ca(CW), whereas the global increase decreased it. This increase in Ca(CW) with the regional increase in [K(+)](o) was not suppressed by 100 μmol/l streptomycin, whereas it was suppressed by 1) a combination of 10 μmol/l cilnidipine and 3 μmol/l SEA0400; 2) 20 mmol/l 2,3-butanedione monoxime; and 3) 10 μmol/l blebbistatin. A regional but not a global increase in [K(+)](o) induces sustained arrhythmias, probably due to nonuniform excitation-contraction coupling. The same mechanism may underlie arrhythmias during ischemia.

Radionuclide content of food and water in high mountainous regions of Georgia - Adjara (Keda, Shuakhevi, Khulo) has been studied, internal and total irradiation doses for the population have been defined and preventive measures for its reduction have been proposed. Internal irradiation dose for the population caused by K-40 was identified as 0,63 mSv/y, total irradiation dose - 1,73 mSv/y, that slightly exceeds acceptable levels, due to this it seems desirable to provide some measures with aim to reduce the radiation dose of the population and conduct further observation of the radiation situation. Measures intended to reduce irradiation doses includes: provision of population with less radioactive water sources, the regulation of medical radiation procedures (mostly - X-ray diagnostic procedures), the rational use of fertilizers with 40K content, construction of buildings on the territories with the lowest values of gamma radiation and radon release from soil, use of materials with low content of natural radionuclides for building construction, provision of premises with effective ventilation and radiation monitoring of buildings at any stages of construction, reconstruction or repair.

Hyperglycemia during admission for acute myocardial infarction (MI) is common and associated with poor outcomes. Prior studies employed two distinct approaches to improve outcomes in patients with acute MI--one focused on glucose control, and the other on provision of glucose, insulin, and potassium. However, despite multiple largescale studies, the benefits of glucose lowering in the setting of acute MI remain unclear. This article reviews data from observational studies and clinical trials and synthesizes this information into practical recommendations based on available evidence.

Background: External biphasic electrical cardioversion (CV) is a standard treatment option for patients suffering from acute symptoms of atrial fibrillation (AF). Nevertheless, CV is not always successful, and thus strategies to increase the success rate are desirable., Objective: The purpose of this study was to evaluate the effect of intravenously administered K/Mg solution on the biphasic CV energy threshold and success rate to restore sinus rhythm (SR) in patients with AF., Methods: The study consisted of 170 patients with persistent AF. The patients were randomly assigned to undergo biphasic CV either with (n = 84) or without (n = 86) pretreatment with K/Mg solution. An energy step-up protocol of 75, 100, and 150 W (J) was used., Results: Biphasic CV of AF was effective in 81 (96.4%) patients in the pretreatment and 74 (86.0%) patients in the control group (P = 0.005). The effective energy level required to achieve SR was significantly lower in the pretreated group (140.8 ± 26.9 J vs 182.5 ± 52.2 J, P = 0.02). No K/Mg-solution-associated side effects such as hypotension or bradycardia were observed., Conclusion: Administration of K/Mg solution positively influences the success rate of CV in patients with persistent AF. Furthermore, significantly less energy is required to successfully restore SR and therefore K/Mg pretreatment may facilitate SR restoration in patients undergoing CV for AF., (© 2011 Wiley Periodicals, Inc.)

Potassium chloride and other potassium compounds are used by the general public as salt substitutes, muscle-building supplements, and panacea. Severe hyperkalemia from oral potassium is extremely rare if kidney function is normal because of potassium adaptation. The oral potassium dose has to be large enough to overcome the normal renal excretory mechanisms to cause severe hyperkalemia. This occurs most commonly in patients with renal impairment or those who take potassium-sparing diuretics, angiotensin receptor blockers, or angiotensin-converting enzyme inhibitors. We present two unique cases of near-fatal hyperkalemia from nutritional supplements containing potassium. The first case was due to salt-substitute intake, whereas the second case was from a muscle-building supplement. Both patients suffered cardiac arrest, but were successfully resuscitated and survived. The acuity of intake and excessive quantity overwhelmed the kidneys' ability for adaptation. Potassium toxicity affects multiple organ systems and manifests in characteristic, acute cardiovascular changes with electrocardiographic abnormalities. Neuromuscular manifestations include general muscular weakness and ascending paralysis may occur, whereas gastrointestinal symptoms manifest as nausea, vomiting, paralytic ileus, and local mucosal necrosis that may lead to perforation. Once an urgent situation has been handled with intravenous push of a 10% calcium salt, short-term measures should be started with agents that cause a transcellular shift of potassium, namely, insulin with glucose, β2-agonist, and NaHCO(3). Patients are unaware of these potentially serious adverse effects, and there are inadequate consumer warnings. Clinicians should be vigilant in monitoring potassium intake from over-the-counter supplements., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The transcription factor E2F1 is upregulated when cerebellar granular neurons (CGNs) undergo apoptosis under potassium deprivation. In this study, we examined the effects of E2F1 upregulation on the survival and death of CGNs isolated from C57 mice and Sprague-Dawley (SD) rats. Plasmid- and adenovirus-mediated expression of E2F1 dose-dependently induced apoptosis in mouse CGNs but unexpectedly failed to induce apoptosis in rat CGNs. Caspase 3, a marker for neuronal apoptosis, was significantly activated by ectopic E2F1 expression in mouse CGNs but not in rat CGNs. Furthermore, overexpression of E2F1 significantly promoted apoptotic progression in mouse CGNs following potassium deprivation but attenuated apoptosis in rat CGNs, whereas E2F1 lacking DNA binding ability (E2F1-M132) lost its pro-apoptotic role in mouse CGNs and anti-apoptotic role in rat CGNs. Together, our results demonstrated that upregulation of E2F1 by potassium deprivation promotes apoptosis in C57 mouse CGNs but antagonizes apoptosis in SD rat CGNs, suggesting opposing roles for E2F1 in regulating CGN fate., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Case Description: 12 European shorthair cats (6 males and 6 females; age range, 2 months to 3 years) from 1 household were evaluated for clinical signs of recurrent and progressive muscle spasticity. Genetic relationships among the cats were suspected but were not known., Clinical Findings: Physical examination of all cats revealed a thin to mildly emaciated body condition and signs of suppurative rhinitis. Results of neurologic evaluations revealed no abnormalities in any cats at rest, but exercise- and stress-induced episodes of muscle spasticity were observed. Results of hematologic (7/12 cats) and CSF (4) analysis, diagnostic imaging (including radiography [7] and magnetic resonance imaging [4]), electromyography (4), motor nerve conduction tests (4), screening for metabolic storage diseases (4), provocation tests via exercise in a cold (4°C [39.2°F]) environment (7), and gross pathological and histologic examination (5) revealed no abnormalities that could potentially explain the clinical signs. However, consumption of a potassium-enriched diet resulted in severe aggravation of clinical signs in 7 of 7 cats, leading to a diagnosis of potassium-aggravated muscle stiffness., Treatment and Outcome: 5 cats were euthanized after initial examination because of poor physical condition and severe clinical signs. Spasticity in the 7 remaining cats was improved during a 6-week follow-up period as they reduced their own activity. Further investigation and treatment were declined., Clinical Relevance: Channelopathies are rarely recognized diseases in domestic animals. In addition to conventional diagnostic evaluation methods, provocation tests in a clinical environment can be used in the assessment of channelopathies.