Mmol Potassium Research Articles

Efficacy of Potassium Iodide and Glutathione for Correlation of Dentin Discoloration Caused by Silver Diamine Fluoride.

This study aimed to investigate and contrast the degree of dentin discoloration resulting from the application of silver diamine fluoride (SDF) alone, SDF in combination with potassium iodide (KI), and SDF in combination with glutathione. The aim was to assess the effectiveness of these combinations in reducing the aesthetic issues associated with SDF treatment in minimally invasive dentistry and preventive procedures. We conducted this in-vitro study on 136 permanent molar teeth. The teeth were randomly assigned to two main groups of total-etch and self-etch and four subgroups of control, SDF, SDF plus KI, and SDF with glutathione. The teeth underwent colorimetry before and 1 week after applying materials to compare the color change. We mounted the teeth in acrylic resin 1 mm below their cementoenamel junction. A low-speed diamond saw and 600-grit silicon carbide abrasive paper eliminated the occlusal enamel for 10 seconds under water coolant, exposing the dentin. The teeth were then immersed in a demineralizing solution (pH of 4.4, 50 mmol acetate, 2.2 mmol potassium dihydrogen phosphate, and 2.2 mmol calcium chloride) for 7 days at 37°C to induce dentin demineralization and simulate demineralized dentin artificially. The teeth were then gently polished with 600-grit silicon carbide abrasive paper to create a standard smear layer and eliminate the demineralized dentin layer. 136 teeth were evaluated in the total-etch (n = 68) and self-etch (n = 68) groups. Glutathione and KI significantly decreased the discoloration caused by SDF (P<0.05). No significant difference was noted in color change between SDF/glutathione and SDF plus KI groups (P > 0.05). In self-etch groups, glutathione yielded an ∆E=4.12, while KI yielded an ∆E=4.44, with no significant difference. The application of glutathione and KI can significantly decrease dentin discoloration caused by SDF.

Harmonising IV Oxycodone with Paediatric Perioperative Medications: A Compatibility Study Through Y-Type Connectors.

Co-administering multiple intravenous (IV) agents via Y-connectors is a common practice in hospitalised and fasting surgical patients. However, there is a lack of reliable data confirming the physical compatibility of some combinations including IV oxycodone, a drug that is gaining increasing popularity in the perioperative period. Concern regarding physical drug incompatibilities precludes concurrent coadministration with other common drugs through a single lumen. This can result in the cessation of infusions to allow the administration of other medications, resulting in exacerbation of acute pain. This study aims to evaluate the physical compatibility of IV oxycodone with some commonly co-administered drugs and IV fluids. Mixtures of oxycodone (1mg.mL-1) and the tested drugs and IV fluids were prepared in a ratio of 1:1. The mixtures were examined at 0 and 60 minutes from mixing and assessed using the European Conference Consensus Standards. This involved visual inspection (precipitation, turbidity, colour change, gas formation), spectrophotometry, and pH change. The tested drugs included ketamine, tramadol, clonidine, vancomycin, piperacillin/tazobactam, dexmedetomidine, cefotaxime, gentamicin, and paracetamol. In addition, the commonly used IV fluids tested included glucose 5% + sodium chloride 0.9% + 60 mmol potassium chloride, plasmalyte + dextrose 5%;plasmalyte + dextrose 5% + 55 mmol potassium chloride, plasmalyte + dextrose 5% + 55mmol potassium acetate, plasmalyte + dextrose 5% + 55mmol potassium dihydrogen phosphate, Hartmann's solution, Standard pediatric Total Parenteral Nutrition (TPN) 20/100 and TPN 25/150. IV oxycodone (1 mg.mL-1) showed no visual changes; no spectrophotometric absorption variability at 350, 410, or 550nm; and no pH changes of >0.5 at 0 or 60 minutes with any of the tested drugs or fluids in the concentrations tested. According to European Consensus Conference Standards, IV Oxycodone at 1 mg.mL-1 is physically compatible in a ratio of 1:1 v/v with all investigated drugs and fluids tested for at least 60 minutes.

The inorganic NItrate and eXercise performance in Heart Failure (iNIX-HF) phase II clinical trial: Rationale and study design

BackgroundHeart failure (HF) is a debilitating and often fatal disease that affects millions of people worldwide. Diminished nitric oxide synthesis, signaling, and bioavailability are believed to contribute to poor skeletal muscle function and aerobic capacity. The aim of this clinical trial (iNIX-HF) is to determine the acute and longer-term effectiveness of inorganic nitrate supplementation on exercise performance in patients with HF with reduced ejection fraction (HFrEF). MethodsThis clinical trial is a double-blind, placebo-controlled, randomized, parallel-arm design study in which patients with HFrEF (n = 75) are randomized to receive 10 mmol potassium nitrate (KNO3) or a placebo capsule daily for 6 wk. Primary outcome measures are muscle power determined by isokinetic dynamometry and peak aerobic capacity (VO2peak) determined during an incremental treadmill exercise test. Endpoints include the acute effects of a single dose of KNO3 and longer-term effects of 6 wk of KNO3. The study is adequately powered to detect expected increases in these outcomes at P < 0.05 with 1-β>0.80. DiscussionThe iNIX-HF phase II clinical trial will evaluate the effectiveness of inorganic nitrate supplements as a new treatment to ameliorate poor exercise capacity in HFrEF. This study also will provide critical preliminary data for a future ‘pivotal’, phase III, multi-center trial of the effectiveness of nitrate supplements not only for improving exercise performance, but also for improving symptoms and decreasing other major cardiovascular endpoints. The potential public health impact of identifying a new, relatively inexpensive, safe, and effective treatment that improves overall exercise performance in patients with HFrEF is significant.

The effect of orally administered nitrate on renal function and blood pressure in a randomized, placebo-controlled, crossover study in healthy subjects

BackgroundSeveral studies have shown inorganic nitrate/nitrite to reduce blood pressure in both healthy subjects and hypertensive patients. An effect presumably caused through bioconversion to nitric oxide. However, studies on inorganic nitrate/nitrite have shown inconsistent results on renal functions such as GFR and sodium excretion. The current study investigated whether orally administered nitrate would decrease blood pressure and increase GFR and urinary sodium excretion. MethodsIn a randomized, placebo-controlled, double-blinded, crossover study, 18 healthy subjects received a daily dose of 24 mmol potassium nitrate and placebo (potassium chloride) during 4 days in a randomized order. Subjects also ingested a standardized diet and completed a 24-h urine collection. GFR was determined by the constant infusion technique and during GFR measurement, brachial blood pressure (BP) and central blood pressure (cBP), heart rate, and arterial stiffness were measured every half hour using the Mobil-O-Graph®. Blood samples was analyzed for nitrate, nitrite, cGMP, vasoactive hormones and electrolytes. Urine was analyzed for nitrate, nitrite, cGMP, electrolytes, ENaCγ, NCC, CrCl, CH2O and UO. ResultsNo differences in GFR, blood pressure or sodium excretion were found between the treatments with potassium nitrate and placebo. However, both nitrate and nitrite levels in plasma and urine were significantly increased by potassium nitrate intake and the 24-h urinary excretion of sodium and potassium were stable, showing adherence to the standardized diet and the study medication. ConclusionWe found no decrease in blood pressure or increase in GFR and sodium excretion of 24 mmol potassium nitrate capsules as compared to placebo after 4 days of treatment.Healthy subjects may be able to compensate the effects of nitrate supplementation during steady state conditions. Future research should focus on long-term studies on the difference in response between healthy subjects and patients with cardiac or renal disease.

Development of a multivariate model with desirability-based optimization for simultaneous determination of five co-administrated drugs for the management of COVID-19 infection in their dosage forms via validated RP-HPLC method

More than 2.9 million people have died as a result of the global demographic impact of the coronavirus illness of 2019 (COVID-19). Numerous antiviral and anti-inflammatory medications have FDA approval to treat COVID-19 patients. For the simultaneous determination of COVID-19 utilized medications (Remdesivir, Moxifloxacin, Dexamethasone, Apixaban, and paracetamol) in their dosage forms, a sensitive technique has been developed and validated. The aforementioned medications were separated and quantified with the help of experimental design. The Box-Behnken design was used in the experiment to optimize the chromatographic method’s analytical parameters. It employed RP-HPLC with a UV detector. An INERTSIL ODS-3 C18 column (5 µm, 250 × 4.6 mm) with mobile phase composed of acetonitrile: 30 mmoL potassium dihydrogen phosphate buffer (pH = 7.5) (50:50, v/v), at room temperature was employed to separate the aforementioned drugs. Paracetamol was linear over the concentration range (1–50 µg/mL), Moxifloxacin (5–70 µg/mL), Apixaban (5–70 µg/mL), Dexamethasone (1–100 µg/mL), and Remdesivir (5–100 µg/mL). According to ICH guidelines, the new approach underwent thorough validation. Between the proposed method’s results and those from the reference or reported methods, there was no significant difference. The technique is simple to use in research of the cited medications in their dosage forms for quality control aspects.

DEVELOPMENT AND VALIDATION OF HPLC-UV METHOD FOR SIMULTANEOUS ANALYSIS OF ACRYLAMIDE AND GLYCIDAMIDE IN VOLUMETRIC ABSORPTIVE MICROSAMPLING

Objective: Acrylamide is a carcinogenic compound that can be found in commonly consumed foods and cigarette smoke. This compound is metabolized by cytochrome P450 in the human body to a more reactive metabolite, glycidamide. This study aimed to optimize and validate a sensitive HPLC-UV method for determining acrylamide and glycidamide simultaneously in the volumetric absorptive microsampling (VAMS) sample. Methods: Isoniazid as an internal standard was added to the VAMS sample containing acrylamide and glycidamide prior to protein precipitation. The analytes and internal standard were separated using reversed-phase chromatography with the C18 SunfireTMWaters® column (5 µm; 250 mm x 4.6 mm) and an ultraviolet detector. Results: The optimum chromatographic condition was eluted at a column temperature of 30 °C with a mobile phase of 6 mmol potassium dihydrogen phosphate pH 3.5–methanol (96:4 v/v) using a flow rate of 0.50 ml/min and was detected at 210 nm. The LLOQ was obtained at 1.0 µg/ml for both acrylamide and glycidamide. The calibration curve was linear over the concentration range of 1.0-100.0 µg/ml. Conclusion: The developed bioanalytical method was valid based on US FDA Guideline for Bioanalytical Method Validation 2018.

Effects of Short-Term Potassium Chloride Supplementation in Patients with CKD.

Observational studies suggest that adequate dietary potassium intake (90-120 mmol/day) may be renoprotective, but the effects of increasing dietary potassium and the risk of hyperkalemia are unknown. This is a prespecified analysis of the run-in phase of a clinical trial in which 191 patients (age 68±11 years, 74% males, 86% European ancestry, eGFR 31±9 ml/min per 1.73 m2, 83% renin-angiotensin system inhibitors, 38% diabetes) were treated with 40 mmol potassium chloride (KCl) per day for 2 weeks. KCl supplementation significantly increased urinary potassium excretion (72±24 to 107±29 mmol/day), plasma potassium (4.3±0.5 to 4.7±0.6 mmol/L), and plasma aldosterone (281 [198-431] to 351 [241-494] ng/L), but had no significant effect on urinary sodium excretion, plasma renin, BP, eGFR, or albuminuria. Furthermore, KCl supplementation increased plasma chloride (104±3 to 105±4 mmol/L) and reduced plasma bicarbonate (24.5±3.4 to 23.7±3.5 mmol/L) and urine pH (all P<0.001), but did not change urinary ammonium excretion. In total, 21 participants (11%) developed hyperkalemia (plasma potassium 5.9±0.4 mmol/L). They were older and had higher baseline plasma potassium. In patients with CKD stage G3b-4, increasing dietary potassium intake to recommended levels with potassium chloride supplementation raises plasma potassium by 0.4 mmol/L. This may result in hyperkalemia in older patients or those with higher baseline plasma potassium. Longer-term studies should address whether cardiorenal protection outweighs the risk of hyperkalemia.Clinical trial number: NCT03253172.

Acute Effects of Inorganic Nitrate Intake on Brachial and Femoral Flow-Mediated Vasodilation, and on Carotid Artery Reactivity Responses: Results of a Randomized, Double-Blinded, Placebo-Controlled Cross-Over Study in Abdominally Obese Men.

Most trials on the effects of inorganic nitrate intake have focused on only one specific aspect of the endothelial cell response to a stimulus, thereby possibly missing other important effects. The aim of the present randomized, double-blinded, placebo-controlled cross-over study was therefore to investigate in eighteen healthy abdominally obese men (18–60 years, waist circumference ≥ 102 cm) acute effects of potassium nitrate on brachial and femoral flow-mediated vasodilation (FMD), and on carotid artery reactivity (CAR) to a cold pressure test. Participants received in random order a drink providing 10 mmol potassium nitrate (i.e., 625 mg of nitrate) or an iso-molar placebo drink with potassium chloride. Fasted and 4 h post-drink FMD and blood pressure measurements were performed. CAR responses were assessed at 4 h. Circulating nitrate plus nitrite concentration increased following nitrate intake (p = 0.003). Compared with placebo, potassium nitrate did not affect brachial (mean [95% confidence interval]: −0.2% [−2.5, 2.1], p = 0.86) and femoral FMD responses (−0.6% [−3.0; 1.7], p = 0.54). CAR responses were also not different (−0.8% [−2.5, 0.9], p = 0.32). Finally, changes in blood pressure and heart rate did not differ. No adverse events were observed. In conclusion, this trial did not provide evidence for effects of a single dose of inorganic nitrate on 4 h vascular endothelial function in abdominally obese men.

Characterization of Potassium-Induced Natriuresis in Hypertensive Postmenopausal Women During Both Low and High Sodium Intake.

Potassium-induced natriuresis may contribute to the beneficial effects of potassium on blood pressure but has not been well-characterized in human postmenopausal hypertension. We determined the time course and magnitude of potassium-induced natriuresis and kaliuresis compared with hydrochlorothiazide in 19 hypertensive Hispanic postmenopausal women. We also determined the modulating effects of sodium intake, sodium-sensitivity, and activity of the thiazide-sensitive NCC (sodium-chloride cotransporter). Sixteen-day inpatient confinement: 8 days low sodium followed by 8 days high sodium intake. During both periods, we determined sodium and potassium excretion following 35 mmol oral KCl versus 50 mg hydrochlorothiazide. We determined sodium-sensitivity as change in 24-hour systolic pressure from low to high sodium. We determined NCC activity by standard thiazide-sensitivity test. Steady-state sodium intake was the key determinant of potassium-induced natriuresis. During low sodium intake, sodium excretion was low and did not increase following 35 mmol KCl indicating continued sodium conservation. Conversely, during high sodium intake, sodium excretion increased sharply following 35 mmol KCl to ≈37% of that produced by hydrochlorothiazide. Under both low and high sodium intake, 35 mmol potassium was mostly excreted within 5 hours, accompanied by a sodium load reflecting the steady-state sodium intake, consistent with independent regulation of sodium/potassium excretion in the human distal nephron. Potassium-induced natriuresis was not greater in sodium-sensitive versus sodium-resistant hypertensives or hypertensives with higher versus lower basal NCC activity. We studied an acute KCl challenge. It remains to further characterize potassium-induced natriuresis during chronic potassium increase and when potassium is administered a complex potassium-containing meal.

Time course of human skeletal muscle nitrate and nitrite concentration changes following dietary nitrate ingestion

Dietary nitrate (NO3−) ingestion can be beneficial for health and exercise performance. Recently, based on animal and limited human studies, a skeletal muscle NO3− reservoir has been suggested to be important in whole body nitric oxide (NO) homeostasis. The purpose of this study was to determine the time course of changes in human skeletal muscle NO3− concentration ([NO3−]) following the ingestion of dietary NO3−. Sixteen participants were allocated to either an experimental group (NIT: n = 11) which consumed a bolus of ∼1300 mg (12.8 mmol) potassium nitrate (KNO3), or a placebo group (PLA: n = 5) which consumed a bolus of potassium chloride (KCl). Biological samples (muscle (vastus lateralis), blood, saliva and urine) were collected shortly before NIT or PLA ingestion and at intervals over the course of the subsequent 24 h. At baseline, no differences were observed for muscle [NO3−] and [NO2−] between NIT and PLA (P > 0.05). In PLA, there were no changes in muscle [NO3−] or [NO2−] over time. In NIT, muscle [NO3−] was significantly elevated above baseline (54 ± 29 nmol/g) at 0.5 h, reached a peak at 3 h (181 ± 128 nmol/g), and was not different to baseline from 9 h onwards (P > 0.05). Muscle [NO2−] did not change significantly over time. Following ingestion of a bolus of dietary NO3−, skeletal muscle [NO3−] increases rapidly, reaches a peak at ∼3 h and subsequently declines towards baseline values. Following dietary NO3− ingestion, human m. vastus lateralis [NO3−] expressed a slightly delayed pharmacokinetic profile compared to plasma [NO3−].

Acute inorganic nitrate intake increases regional insulin action in the brain: Results of a double-blind, randomized, controlled cross-over trial with abdominally obese men

AimsImproving brain insulin sensitivity may be a promising approach in the prevention and treatment of metabolic and cognitive diseases. Our aim was to investigate acute effects of inorganic nitrate on regional cerebral blood flow (CBF) responses to intranasal insulin in abdominally obese men. MethodsEighteen apparently healthy men, aged 18–60 years and with a waist circumference ≥ 102 cm, participated in a randomized, double-blind, placebo-controlled cross-over trial. The study consisted of two test days separated by at least one week. Men received in random order a drink providing 10 mmol (i.e., 625 mg nitrate) potassium nitrate or an isomolar placebo drink with potassium chloride. Brain insulin action was assessed 120–150 min after the drinks by quantifying acute effects of nasal insulin on regional CBF using arterial spin labeling Magnetic Resonance Imaging. Glucose and insulin concentrations were measured at regular intervals, while blood pressure was determined fasted and at 240 min. ResultsInorganic nitrate intake increased regional insulin action in five brain clusters. The two largest clusters were located in the right temporal lobe (ΔCBF: 7.0 ± 3.8 mL/100 g/min, volume: 5296 mm3, P < 0.001; and ΔCBF: 6.5 ± 4.3 mL/100 g/min, volume: 3592 mm3, P < 0.001), while two other cortical clusters were part of the right frontal (ΔCBF: 9.0 ± 6.0 mL/100 g/min, volume: 1096 mm3, P = 0.007) and the left parietal lobe (ΔCBF: 6.1 ± 4.3 mL/100 g/min, volume: 1024 mm3, P = 0.012). One subcortical cluster was located in the striatum (ΔCBF: 5.9 ± 3.2 mL/100 g/min, volume: 1792 mm3, P < 0.001). No effects of nitrate were observed on CBF before administration. Following nitrate intake, circulating nitrate plus nitrite concentrations increased over time (P = 0.003), but insulin and glucose concentrations and blood pressure did not change. ConclusionAcute inorganic nitrate intake may improve regional brain insulin action in abdominally obese men. These regions are involved in the regulation of different metabolic and cognitive processes.The trial was registered on January 6th, 2021 at ClinicalTrials.gov as NCT04700241.

Removal of toxic cadmium using a binary site ion‐exchange material derived from waste printed circuit boards

AbstractBACKGROUNDAdsorption has been widely applied in wastewater treatment for heavy metal removal. Due to the high cost of adsorbent materials, various types of materials including agricultural, industrial wastes and naturally abundant materials have emerged as low‐cost adsorbents in recent years. However, enhancement processes need to be developed to improve the adsorption capability of the raw materials. It is still a challenge to find an economic material with high adsorption capacity. This paper demonstrates a strategy to activate a recycled waste material using a simple activating process, while significantly improving the adsorption capacity of cadmium from wastewater.RESULTSThe raw material feedstock is the non‐metallic aluminosilicate material obtained from the recycling of waste printed circuit boards (PCBs). By a simple thermal alkali activation process using potassium hydroxide as activation agent, the product material shows a strong capability of cadmium removal from effluent containing a high adsorption capacity of 2.12 mmol g−1. Initial metal concentration, dosage and pH effect on the adsorption isotherm and kinetics have been investigated. The experimental results include full characterization tests on this waste PCB‐derived adsorbent, and the in situ measurement of cadmium, calcium and potassium ions, since all are involved in the exchange sorption mechanism.CONCLUSIONBy combining kinetic modelling analysis and X‐ray photoelectron spectroscopy, the novel adsorption mechanism has been explained and quantified as a dual ion‐exchange mechanism with the millimoles of cadmium exchanged mass balancing with the millimoles of calcium and 0.5 mmol potassium going into solution. © 2021 Society of Chemical Industry (SCI).

Electrolyte disorders are ERAS-associated in patients undergoing hepato-pancreato-biliary surgery.

Emerging evidences have raised concerns about electrolyte disorders caused by restrictive fluid management in the enhanced recovery after surgery (ERAS) protocol. This study aims to investigate the morbidity and treatment of electrolyte disorders associated with ERAS in patients undergoing hepato-pancreato-biliary (HPB) surgery. Clinical data from 157 patients under the ERAS program and 166 patients under the traditional (Non-ERAS) program after HPB surgery were retrospectively analyzed. Risk factors and predictive factors of postoperative electrolyte disorders were analyzed by logistic regression analysis and receiver operator characteristic (ROC) curve analysis, respectively. The average of intravenous fluid, sodium, chloride, and potassium supplementation after surgery were significantly lower in the ERAS group. Hypokalemia was the most common type of electrolyte disorders in the ERAS group, whose incidence was substantially increased compared to that in the Non-ERAS group [28.77% vs. 8.97%, p < 0.001, on postoperative (POD) 5]. Logistic regression analysis identified the ERAS program and age as independent risk factors of hypokalemia. ROC curve analysis identified serum potassium levels below 3.76mmol/L on POD 3 (area under curve 0.731, sensitivity 58.54%, specificity 82.69%) as a predictive factor for postoperative hypokalemia in ERAS patients. Oral supplementation at an average of 35.41mmol potassium per day was effective in restoring the ERAS-associated hypokalemia. ERAS procedures were particularly associated with a lower supplementation of potassium and a higher incidence of hypokalemia in patients after HPB surgery. Oral potassium supplementation could be an adopted ERAS program for the elderly undergoing HPB surgery.

Suicide attempt using potassium tablets for congenital chloride diarrhea: A case report

BACKGROUNDCongenital chloride diarrhea (CCD) is a rare inherited disorder of intestinal electrolyte transport that results in a large wastage of electrolytes and water. Advances in substitution therapy using sodium chloride (NaCl) and potassium chloride (KCl) have dramatically improved survival for patients with CCD. Slow-release KCl is widely prescribed as a potassium supplement; however, it has also occasionally been used in suicide attempts, as potassium poisoning can generate life-threatening hyperkalemia.CASE SUMMARYA 26-year-old female presented to the emergency department (ED) with self-poisoning, having taken 30 tablets of slow-release KCl (total: 240 mmol potassium) following an auditory hallucination. The patient had been undergoing substitution therapy with NaCl and KCl for CCD and been followed up in the pediatric department. One month prior, she developed insomnia and anxiety and had consulted a psychiatrist. At the ED, although her general condition was good, she appeared agitated. Her serum potassium level was 7.0 mmol/L, indicating hyperkalemia, and electrocardiographic changes showed tenting of the T-waves. She responded to the administration of calcium gluconate, sodium bicarbonate, and insulin with glucose, and the serum potassium level improved. Finally, she was diagnosed with schizophrenia.CONCLUSIONIn CCD management, physicians should pay careful attention to patients’ extraintestinal issues, including psychological disorders that may emerge in adulthood.

Clinical implementation of a novel myocardial protection pathway in coronary artery bypass surgery with minimal extracorporeal circulation.

The aim of this study was to report the clinical implementation of the joint use of the Myocardial Protection System (MPS®) and the minimal extracorporeal circulation system (MiECC), in conjunction with an institutionally refined dose/volume-dependent microplegia in coronary artery bypass grafting (CABG). Patients with isolated CABG surgery were included. The final protocol to achieve cardioplegic arrest consisted of warm blood cardioplegia with 20 mmol potassium (K), 1.6 g magnesium (Mg) and 40 mg lidocaine per liter (L) blood. We prospectively collected intra- and postoperative data to monitor and validate this novel approach. Eighty patients were operated accordingly. Mean (SD) aortic clamping time and extracorporeal perfusion time were 67.5 (22.6) and 101.1 (31.9) minutes, respectively. Failure to induce cardiac arrest was seen in six patients at the early stage of refinement of the formula. Median (IQR) high -sensitivity cardiac troponin T (hs-cTnT) on the first postoperative day (POD) and peak hs-cTnT were 262.5 ng/L (194.3-405.8) and 265.5 ng/L (194.3-405.8), respectively. Median (IQR) creatine kinase-myocardial type (CK-MB) on POD 1 and peak CK-MB were 14.2 µg/L (10.5-22.7) and 14.2 µg/L (10.7-23.2), respectively. Median (IQR) creatine kinase (CK) on POD 1 and peak CK were 517.5 U/L (389.3-849.8) and 597.5 U/L (455.0-943.0), respectively. No patient died during hospitalization. The combination of this cardioplegic formula with MPS® and MiECC in CABG was safe and feasible. With the final chemical makeup, cardiac arrest was reliably achieved. Remarkably low postoperative cardiac markers indicate shielded cardiac protection during surgery.

Opposite acute potassium and sodium shifts during transplantation of hypothermic machine perfused donor livers.

Liver transplantation is frequently associated with hyperkalemia, especially after graft reperfusion. Dual hypothermic oxygenated machine perfusion (DHOPE) reduces ischemia/reperfusion injury and improves graft function, compared to conventional static cold storage (SCS). We examined the effect of DHOPE on ex situ and in vivo shifts of potassium and sodium. Potassium and sodium shifts were derived from balance measurements in a preclinical study of livers that underwent DHOPE (n = 6) or SCS alone (n = 9), followed by ex situ normothermic reperfusion. Similar measurements were performed in a clinical study of DHOPE‐preserved livers (n = 10) and control livers that were transplanted after SCS only (n = 9). During DHOPE, preclinical and clinical livers released a mean of 17 ± 2 and 34 ± 6 mmol potassium and took up 25 ± 9 and 24 ± 14 mmol sodium, respectively. After subsequent normothermic reperfusion, DHOPE‐preserved livers took up a mean of 19 ± 3 mmol potassium, while controls released 8 ± 5 mmol potassium. During liver transplantation, blood potassium levels decreased upon reperfusion of DHOPE‐preserved livers while levels increased after reperfusion of SCS‐preserved liver, delta potassium levels were ‐0.77 ± 0.20 vs. +0.64 ± 0.37 mmol/L, respectively (P = .002). While hyperkalemia is generally anticipated during transplantation of SCS‐preserved livers, reperfusion of hypothermic machine perfused livers can lead to decreased blood potassium or even hypokalemia in the recipient.

Rationale and Design of a Randomized Placebo-Controlled Clinical Trial Assessing the Renoprotective Effects of Potassium Supplementation in Chronic Kidney Disease

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⁺ sup­plementation has a renoprotective effect in progressive CKD, and whether alkali therapy has additional beneficial effects.

STABILITY INDICATING RP-HPLC METHOD DEVELOPMENT AND VALIDATION FOR THE SIMULTANEOUS DETERMINATION OF VILDAGLIPTIN AND METFORMIN IN PHARMACEUTICAL DOSAGE FORM

Objective: The present study was aimed to develop a rapid, accurate, linear, sensitive and validate stability-indicating high performance liquid chromatographic [RP-HPLC] method for determination of vildagliptin and metformin in pharmaceutical dosage form.Methods: The chromatographic separation was performed on kromasil-C18 column [4.5 x 250 mm; 5 µm] using a mobile phase consisting of 0.05 mmol potassium dihydrogen phosphate buffer: acetonitrile [80:20 v/v], [pH adjusted to 3.5 using orthophosphoric acid]. The flow rate is 0.9 ml/min and the detection was carried out at 263 nm.Results: The chromatographic condition, the peak retention time of metformin and vildagliptin were found to be 2.215 min and 2.600 min respectively. Stress testing was performed in accordance with an international conference on harmonization [ICH] Q1A R2 guidelines. The method was validated as per ICH Q2 R1 guidelines. The calibration curve was found to be linear in the concentration range of 5-17.5 µg/ml and 50-175 µg/ml for vildagliptin and metformin. The limit of detection and quantification was found to be 0.0182 µg/ml and 0.0553 µg/ml for vildagliptin and 0.4451 µg/ml and 1.3490 µg/ml for metformin respectively.Conclusion: A new sensitive, simple and stability indicating reverse-phase high-performance liquid chromatography [RP-HPLC] method has been developed and validated for the determination of vildagliptin and metformin. The proposed method can be used for routine determination of vildagliptin and metformin.

Postoperative fluid retention after heart surgery is accompanied by a strongly positive sodium balance and a negative potassium balance.

The conventional model on the distribution of electrolyte infusions states that water will distribute proportionally over both the intracellular (ICV) and extracellular (ECV) volumes, while potassium homes to the ICV and sodium to the ECV. Therefore, total body potassium is the most accurate measure of ICV and thus potassium balances can be used to quantify changes in ICV. In cardiothoracic patients admitted to the ICU we performed complementary balance studies to measure changes in ICV and ECV. In 39 patients, fluid, sodium, potassium, and electrolyte‐free water (EFW) balances were determined to detect changes in ICV and ECV. Cumulatively over 4 days, these patients received a mean ± SE infusion of 14.0 ± 0.6 L containing 1465 ± 79 mmol sodium, 196 ± 11 mmol potassium and 2.1 ± 0.1 L EFW. This resulted in strongly positive fluid (4.0 ± 0.6 L) and sodium (814 ± 75 mmol) balances but in negative potassium (−101 ± 14 mmol) and EFW (−1.1 ± 0.2 L) balances. We subsequently compared potassium balances (528 patients) and fluid balances (117 patients) between patients who were assigned to either a 4.0 or 4.5 mmol/L blood potassium target. Although fluid balances were similar in both groups, the additionally administered potassium (76 ± 23 mmol) in the higher target group was fully excreted by the kidneys (70 ± 23 mmol). These findings indicate that even in the context of rapid and profound volume expansion neither water nor potassium moves into the ICV.

Evidence for a gastrointestinal–renal kaliuretic signaling axis in humans

A gastrointestinal-renal kaliuretic signaling axis has been proposed to regulate potassium excretion in response to acute potassium ingestion independent of the extracellular potassium concentration and aldosterone. Here we studied this presumed axis in 32 individuals in our clinical pharmacology unit while on a 20 mmol sodium and 60 mmol potassium diet. The serum potassium concentration, potassium excretion, aldosterone, and insulin were measured following either a 35 mmol oral potassium load, a potassium- and sodium-deficient complex meal, or a potassium-deficient complex meal plus 35 mmol potassium. This design allowed determination of the component effects on potassium handling of the meal and potassium load separately. The meal plus potassium test was repeated following aldosterone blockade with eplerenone to specifically evaluate the role of aldosterone. In response to the potassium-deficient meal plus 35 mmol potassium, the serum potassium did not increase but the hourly mean potassium excretion increased sharply. This kaliuresis persisted following aldosterone blockade with eplerenone, further suggesting independence from aldosterone. Thus, a gastrointestinal-renal kaliuretic signaling axis exists in humans mediating potassium excretion independent of changes in the serum potassium concentration and aldosterone. The implication of this mechanism is yet to be determined but may account for a significant component of potassium excretion following a complex potassium-rich meal.