Changes In Potassium Concentration Research Articles

Potassium-mediated bacterial chemotactic response.

Bacteria in biofilms secrete potassium ions to attract free swimming cells. However, the basis of chemotaxis to potassium remains poorly understood. Here, using a microfluidic device, we found that Escherichia coli can rapidly accumulate in regions of high potassium concentration on the order of millimoles. Using a bead assay, we measured the dynamic response of individual flagellar motors to stepwise changes in potassium concentration, finding that the response resulted from the chemotaxis signaling pathway. To characterize the chemotactic response to potassium, we measured the dose-response curve and adaptation kinetics via an Förster resonance energy transfer (FRET) assay, finding that the chemotaxis pathway exhibited a sensitive response and fast adaptation to potassium. We further found that the two major chemoreceptors Tar and Tsr respond differently to potassium. Tar receptors exhibit a biphasic response, whereas Tsr receptors respond to potassium as an attractant. These different responses were consistent with the responses of the two receptors to intracellular pH changes. The sensitive response and fast adaptation allow bacteria to sense and localize small changes in potassium concentration. The differential responses of Tar and Tsr receptors to potassium suggest that cells at different growth stages respond differently to potassium and may have different requirements for potassium.

Potassium-mediated bacterial chemotactic response

Bacteria in biofilms secrete potassium ions to attract free swimming cells. However, the basis of chemotaxis to potassium remains poorly understood. Here, using a microfluidic device, we found that Escherichia coli can rapidly accumulate in regions of high potassium concentration on the order of millimoles. Using a bead assay, we measured the dynamic response of individual flagellar motors to stepwise changes in potassium concentration, finding that the response resulted from the chemotaxis signaling pathway. To characterize the chemotactic response to potassium, we measured the dose–response curve and adaptation kinetics via an Förster resonance energy transfer (FRET) assay, finding that the chemotaxis pathway exhibited a sensitive response and fast adaptation to potassium. We further found that the two major chemoreceptors Tar and Tsr respond differently to potassium. Tar receptors exhibit a biphasic response, whereas Tsr receptors respond to potassium as an attractant. These different responses were consistent with the responses of the two receptors to intracellular pH changes. The sensitive response and fast adaptation allow bacteria to sense and localize small changes in potassium concentration. The differential responses of Tar and Tsr receptors to potassium suggest that cells at different growth stages respond differently to potassium and may have different requirements for potassium.

Activation of KCa channels downstream of TRPV4 amplify pulmonary edema formation

Study objective: In patients with acute respiratory failure (ARDS), mechanical ventilation is the only life-saving treatment. However, mechanical ventilation also can cause ventilator-induced lung injury (VILI) due to the excessive biomechanical forces acting on the distal lung and especially the microvascular endothelium, which in turn further exacerbate endothelial barrier failure thus initiating a vicious cycle leading to irreversible lung damage. The endothelial mechanosensitive transient receptor potential vanilloid 4 (TRPV4) is directly activated by mechanical force and leads to Ca2+ influx, which can activate Ca2+-activated K+ (KCa) channels, categorized into small (SK1-3), intermediate (IK1), and big (BK) KCa. We hypothesized that KCa channels acting downstream of TRPV4 may in turn amplify Ca2+ influx by increasing the electrochemical Ca2+ gradient and thus, promote stretch-induced barrier failure and aggravate lung injury in a positive feedback loop. Methods: Male C57Bl/6J wild-type mice were ventilated for 2 h with low or high tidal volumes in the presence or absence of the non-selective KCa antagonists apamin, charybdotoxin, or the selective IK1 antagonist TRAM34. In a second model, male wild-type mice were challenged with intratracheal HCl instillation (pH 1.5) and ventilated with a low tidal volume for 2h with or without TRAM34. Changes in endothelial Ca2+ concentration ([Ca2+]i) were monitored by real-time imaging of Fura-2 AM in isolated-perfused lungs in response to airway pressure elevation or in human pulmonary microvascular endothelial cells (HPMECs) in response to TRPV4 activation with or without inhibition of KCa channels. Analogously, changes in intracellular potassium concentration ([K+]i) and membrane potential ( Vm) were imaged in vitro. Results: In our established experimental lung injury models, pharmacological inhibition of KCa channels, in particular IK1 attenuated characteristic hallmarks of lung injury in response to high tidal volume ventilation or HCl instillation. Consistent with these findings, inhibition of IK1 channels in the ex vivo perfused lung reduced the sustained [Ca2+]i response to airway pressure elevation over time. In HPMECs, TRPV4-mediated Ca2+ influx induced a pronounced K+ efflux, which in turn caused membrane hyperpolarization. These effects could be prevented by different KCa inhibitors, with IK1 inhibition by TRAM34 showing the most pronounced protective effect. Antagonizing KCa channels as downstream mediators of TRPV4 also reduced endothelial [Ca2+]i transients in response to TRPV4 activation in vitro, indicating that KCa channels, and specifically IK1 serve as amplifiers by increasing the electrochemical gradient for TRPV4-mediated Ca2+ influx. Conclusion: KCa channels, specifically IK1 amplify TRPV4-mediated Ca2+ influx in lung endothelial cells and as such, establish a detrimental feedback that promotes barrier failure and drives the progression of VILI in overventilated lungs. WMK is supported by the German Research Foundation (DFG) (SFB-TR84: subprojects A02 & C09, SFB-1449 subproject B01, SFB 1470 subproject A04, KU1218/9-1, KU1218/11-1, and KU1218/12-1), the Berlin Institute of Health (BIH), the German Federal Ministry of Education and Research (BMBF) in the framework of the projects PROVID (01KI20160A) and SYMPATH (01ZX1906A), and the German Centre for Cardiovascular Research (DZHK). LM is supported by the German Centre for Cardiovascular Research (DZHK) (81X3100216). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Relationship between the behavior change model and salt intake in hypertensive patients: a single non-specialized hypertension clinic prospective observational study.

We investigated whether changes in salt reduction readiness are associated with changes in estimated daily salt intake and blood pressure (BP). We divided 86 hypertensive patients into groups with high and low readiness for salt-reducing behavior [an up (UP) and a down (DN) groups, respectively] based on the transtheoretical model (TTM) over a 12-month observation period. We then investigated the relationships between changes in the TTM stage and changes in daily salt intake and BP over 12 months. The patients in the UP group had significantly increased urine potassium concentrations (from 51.2 ± 23.3 mEq/L at baseline to 56.9 ± 25.5 mEq/L at 12 months; P = 0.048) and significantly decreased estimated 24-h urinary salt excretion (from 9.7 ± 2.9 g/day at baseline to 8.4 ± 2.8 g/day at 12 months; P = 0.045). In addition, they also had significantly lower changes in urine sodium concentration (-13.1 ± 46.1 vs. -6.6 ± 59.7 mEq/L; P = 0.048), significantly increased changes in urine potassium concentration (5.7 ± 20.1 vs. -4.8 ± 28.6 mEq/L; P = 0.030), and significantly decreased changes in estimated 24-h urinary salt excretion (-1.3 ± 2.6 vs. -0.1 ± 2.6 g/day; P = 0.045) compared with patients in the DN group. However, their home BP did not improve over 12 months. The hypertensive patients who increased their readiness or maintained a high readiness for salt reduction over 12 months showed a significant increase in daily potassium intake and significant decrease in daily salt intake.

Pharmacokinetics, pharmacodynamics and safety of 15mg-tolvaptan administered orally for 7 consecutive days to Chinese patients with child-Pugh B cirrhosis.

Background: Tolvaptan, a selective vasopressin V2-receptor antagonist, can elicit a diuretic effect without significant electrolyte loss. The aims were to evaluate multiple-dose pharmacokinetics, pharmacodynamics and safety of daily administration of 15mg tolvaptan in Chinese adult patients with confirmed Child-Pugh Class B cirrhosis accompanied by ascites. Methods: This was an open-label, single-center, single- and multiple-dose study. All patients received a daily 15mg dose of tolvaptan for 7 consecutive days. The plasma concentrations of tolvaptan and its two metabolites (DM-4103, DM-4107) were measured using high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). In addition, various pharmacokinetics parameters were calculated. The pharmacodynamic outcomes evaluated changes in serum sodium and potassium concentrations, daily urine volume, daily water consumption, fluid balance and body weight. Safety profiles, including the incidence of treatment-emergent adverse events (TEAEs), were carefully recorded. Results: Eleven patients with Child-Pugh B cirrhosis were eventually enrolled in the study. Plasma concentrations of tolvaptan and DM-4107 reached steady-states after 7 days of consecutive oral administration. No accumulation of tolvaptan or DM-4107 was found, but DM-4103 accumulated 18.2-fold after multiple-dosing. The daily urine volume and daily water consumption were statistically significantly increased after administration of tolvaptan from Day 1 to Day 7 (all p < 0.05), accompanied by an increased serum sodium concentration. Of 11 patients, 9 (81.8%) reported 20 TEAEs, with the majority being mild to moderate in severity. The most commonly occurring TEAEs were thirst (45.5%), pollakiuria (36.4%) and dry mouth (27.3%). Conclusion: Tolvaptan at a daily dose of 15mg had a diuretic effect but did not increase serum sodium excretion or lead to tolvaptan accumulation. It is therefore can be safely used for short-term treatment of Chinese adult patients with confirmed Child-Pugh B cirrhosis. Clinical Trial Registration: https://clinicaltrials.gov/search?term=NCT01359462, identifier NCT01359462.

Preparation of β-Cyclodextrin Functionalized Platform for Monitoring Changes in Potassium Content in Perspiration.

The monitoring of potassium ion (K+) levels in human sweat can provide valuable insights into electrolyte balance and muscle fatigue non-invasively. However, existing laboratory techniques for sweat testing are complex, while wearable sensors face limitations like drift, fouling and interference from ions such as Na+. This work develops printed electrodes using β-cyclodextrin functionalized reduced graphene oxide (β-CD-RGO) for selective K+ quantification in sweat. The β-CD prevents the aggregation of RGO sheets while also providing selective binding sites for K+ capture. Electrodes were fabricated by screen printing the β-CD-RGO ink onto conductive carbon substrates. Material characterization confirmed the successful functionalization of RGO with β-CD. Cyclic voltammetry (CV) showed enhanced electrochemical behavior for β-CD-RGO-printed electrodes compared with bare carbon and RGO. Sensor optimization resulted in a formulation with 30% β-CD-RGO loading. The printed electrodes were drop-casted with an ion-selective polyvinyl chloride (PVC) membrane. A linear range from 10 μM to 100 mM was obtained along with a sensitivity of 54.7 mV/decade. The sensor showed good reproducibility over 10 cycles in 10 mM KCl. Minimal interference from 100 mM Na+ and other common sweat constituents validated the sensor's selectivity. On-body trials were performed by mounting the printed electrodes on human subjects during exercise. The K+ levels measured in sweat were found to correlate well with serum analysis, demonstrating the sensor's ability for non-invasive electrolyte monitoring. Overall, the facile synthesis of stable β-CD-RGO inks enables the scalable fabrication of wearable sensors for sweat potassium detection.

Potassium Activates mTORC2-dependent SGK1 Phosphorylation to Stimulate Epithelial Sodium Channel: Role in Rapid Renal Responses to Dietary Potassium.

Rapid renal responses to ingested potassium are essential to prevent hyperkalemia and also play a central role in blood pressure regulation. Although local extracellular K + concentration in kidney tissue is increasingly recognized as an important regulator of K + secretion, the underlying mechanisms that are relevant in vivo remain controversial. To assess the role of the signaling kinase mTOR complex-2 (mTORC2), the authors compared the effects of K + administered by gavage in wild-type mice and knockout mice with kidney tubule-specific inactivation of mTORC2. They found that mTORC2 is rapidly activated to trigger K + secretion and maintain electrolyte homeostasis. Downstream targets of mTORC2 implicated in epithelial sodium channel regulation (SGK1 and Nedd4-2) were concomitantly phosphorylated in wild-type, but not knockout, mice. These findings offer insight into electrolyte physiologic and regulatory mechanisms. Increasing evidence implicates the signaling kinase mTOR complex-2 (mTORC2) in rapid renal responses to changes in plasma potassium concentration [K + ]. However, the underlying cellular and molecular mechanisms that are relevant in vivo for these responses remain controversial. We used Cre-Lox-mediated knockout of rapamycin-insensitive companion of TOR (Rictor) to inactivate mTORC2 in kidney tubule cells of mice. In a series of time-course experiments in wild-type and knockout mice, we assessed urinary and blood parameters and renal expression and activity of signaling molecules and transport proteins after a K + load by gavage. A K + load rapidly stimulated epithelial sodium channel (ENaC) processing, plasma membrane localization, and activity in wild-type, but not in knockout, mice. Downstream targets of mTORC2 implicated in ENaC regulation (SGK1 and Nedd4-2) were concomitantly phosphorylated in wild-type, but not knockout, mice. We observed differences in urine electrolytes within 60 minutes, and plasma [K + ] was greater in knockout mice within 3 hours of gavage. Renal outer medullary potassium (ROMK) channels were not acutely stimulated in wild-type or knockout mice, nor were phosphorylation of other mTORC2 substrates (PKC and Akt). The mTORC2-SGK1-Nedd4-2-ENaC signaling axis is a key mediator of rapid tubule cell responses to increased plasma [K + ] in vivo . The effects of K + on this signaling module are specific, in that other downstream mTORC2 targets, such as PKC and Akt, are not acutely affected, and ROMK and Large-conductance K + (BK) channels are not activated. These findings provide new insight into the signaling network and ion transport systems that underlie renal responses to K +in vivo .

Not so optimal: The evolution of mutual information in potassium voltage-gated channels.

Potassium voltage-gated (Kv) channels need to detect and respond to rapidly changing ionic concentrations in their environment. With an essential role in regulating electric signaling, they would be expected to be optimal sensors that evolved to predict the ionic concentrations. To explore these assumptions, we use statistical mechanics in conjunction with information theory to model how animal Kv channels respond to changes in potassium concentrations in their environment. By measuring mutual information in representative Kv channel types across a variety of environments, we find two things. First, under weak conditions, there is a gating charge that maximizes mutual information with the environment. Second, as Kv channels evolved, they have moved towards decreasing mutual information with the environment. This either suggests that Kv channels do not need to act as sensors of their environment or that Kv channels have other functionalities that interfere with their role as sensors of their environment.

MRI of Potassium and Sodium Enables Comprehensive Analysis of Ion Perturbations in Skeletal Muscle Tissue After Eccentric Exercise.

The aims were to investigate if potassium ( 39 K) magnetic resonance imaging (MRI) can be used to analyze changes in the apparent tissue potassium concentration (aTPC) in calf muscle tissue after eccentric exercise and in delayed-onset muscle soreness, and to compare these to corresponding changes in the apparent tissue sodium concentration (aTSC) measured with sodium ( 23 Na) MRI. Fourteen healthy subjects (7 female, 7 male; 25.0 ± 2.8 years) underwent 39 K and 23 Na MRI at a 7 T MR system, as well as 1 H MRI at a 3 T MR system. Magnetic resonance imaging data and blood samples were collected at baseline (t0), directly after performing eccentric exercise (t1) and 48 hours after exercise (t2). Self-reported muscle soreness was evaluated using a 10-cm visual analog scale for pain (0, no pain; 10, worst pain) at t0, t1, and t2. Quantification of aTPC/aTSC was performed after correcting the measured 39 K/ 23 Na signal intensities for partial volume and relaxation effects using 5 external reference phantoms. Edema volume and 1 H T 2 relaxation times were determined based on the 1 H MRI data. Participants were divided according to their increase in creatine kinase (CK) level into high (CK t2 ≥ 10·CK t0 ) and low CK (CK t2 < 10·CK t0 ) subjects. Blood serum CK and edema volume were significantly increased 48 hours after exercise compared with baseline ( P < 0.001). Six participants showed a high increase in blood serum CK level at t2 relative to baseline, whereas 8 participants had only a low to moderate increase in blood serum CK. All participants reported increased muscle soreness both at rest and when climbing stairs at t1 (0.4 ± 0.7; 1.4 ± 1.2) and t2 (1.6 ± 1.4; 4.8 ± 1.9) compared with baseline (0 ± 0; 0 ± 0). Moreover, aTSC was increased at t1 in exercised muscles of all participants (increase by 57% ± 24% in high CK, 73% ± 33% in low CK subjects). Forty-eight hours after training, subjects with high increase in blood serum CK still showed highly increased aTSC (increase by 79% ± 57% compared with t0). In contrast, aTPC at t2 was elevated in exercised muscles of low CK subjects (increase by 19% ± 11% compared with t0), in which aTSC had returned to baseline or below. Overall, aTSC and aTPC showed inverse evolution, with changes in aTSC being approximately twice as high as in aTPC. Our results showed that 39 K MRI is able to detect changes in muscular potassium concentrations caused by eccentric exercise. In combination with 23 Na MRI, this enables a more holistic analysis of tissue ion concentration changes.

Common electrocardiogram manifestations in electrolyte imbalance

Abnormalities in serum electrolyte levels and impaired electrolyte homeostasis may aberrate cardiac conduction by altering cardiac ion current kinetics. Oftentimes, the bedside electrocardiogram (ECG) can render expeditious insight and prompt emergency therapy while laboratory investigations of fluid, acid-base and electrolyte imbalances are underway for establishing a definitive diagnosis. The most frequent electrolyte aberrations affecting the ECG include disturbances of potassium, calcium, and magnesium concentrations. Electrolyte dyshomeostasis impacts the depolarization and repolarization phases of action potential in cardiomyocytes by modifying potentials across their cell membranes. Further, individual electrolyte disturbances often have wide-ranging consequences due to their effect on one another. Serum potassium concentration changes can cause considerable repercussions on myocyte conduction and potentially resulting in ECG changes. The ECG changes in hypokalemia mimic those of myocardial ischemia. With severe hypokalemia, the telltale ECG change is the development of U waves. In hyperkalemia, the primary ECG manifestation is T wave tenting, that is seen as a symmetrical narrowing or peaking but with oftentimes a wide deflection and high amplitude. With very severe hyperkalemia, a slurring “sine-wave” appearance may be observed on the ECG due to significant prolongation and widening of QRS complex and subsequent fusion with the T wave. Hyper-and hypo-calcemia mainly change the action potential span (phase 2), which causes either shrinking (in hypercalcemia) or extension (in hypocalcemia) of the QT interval. The effect on the QT interval is mainly the result of an alteration of the ST-segment time span. Both situations can impact T wave structure. No classic ECG presentation is observed in hypo-or hyper-states of magnesium. Bedside electrocardiography serves as an important aid in forming diagnoses and managing patients presenting with electrolytic dyshomeostasis.

Comparison of the efficacy between Del Nido cardioplegia and HTK cardioplegia in Stanford type A aortic dissection patients undergoing open-heart surgery.

Acute Stanford type A aortic dissection is an extremely dangerous and life-threatening cardiovascular disease, usually treated with extracorporeal circulation heart surgery. Histidine-tryptophan-ketoglutarate (HTK) cardioplegia is a protective intracellular myocardial fluid that has been used extensively in different types of extracorporeal circulation surgeries. Del Nido cardioplegia is an extracellular myocardial protection fluid, which was first used in pediatric heart surgery and has been gradually used in a variety of pediatric and adult heart procedures. This study aims to compare the myocardial protection effect between Del Nido and HTK in patients undergoing extracorporeal circulation heart surgery for acute Stanford type A dissection and its impact on patients' prognosis by analyzing selected parameters and clinical manifestations at different time points. Clinical data were collected from 431 patients with acute Stanford type A dissection who were diagnosed and underwent surgery between January 1, 2018 and December 31, 2020 at Xiangya Hospital, Central South University. After excluding some of the data based on exclusion criteria, patients were divided into a HTK group and a Del Nido (DN) group based on type of intraoperative cardioplegia. Propensity score-matching was performed subsequently using the the R statistical software to determine the DN group ( n =40) and HTK group ( n =41). The matching factors were age, sex, hypertension, cardiopulmonary bypass time, and aortic occlusion time. Perioperative data, postoperative complications, blood gas data, and myocardial injury data were collected from the patients, and SPSS 26.0 was used to analyze the data of each group. The DN group had a higher rate of spontaneous cardioversion (41.5% vs 15.0%, P =0.005) and a lower postoperative hospital stay [10.0(8.0,14.0) d vs 13.0(11.0,19.0) d, P <0.05] compared to the HTK group. In terms of changes in blood gas analysis, immediate sodium and potassium concentrations were significantly higher in the DN group than that in the HTK group (both P <0.05). There was no significant difference in myocardial injury indexes between the two groups at different time points (all P >0.05). In terms of postoperative complications, the cardiac complications in DN group were much lower than those in the HTK Group (0 vs 12.5%, P =0.026). Del Nido cardioplegia has similar myocardial protective effects as HTK cardioplegia used in Stanford type A aortic dissection, with a higher rate of cardiac recurrence and fewer cardiac complications. Del Nido cardioplegia should play an important role in future application for acute Stanford type A aortic dissection, but our findings need to be further validated in a large sample of prospective clinical studies.

Weighted Time Warping Improves T-Wave Morphology Markers Clinical Significance.

T-wave (TW) morphology indices based on time-warping ( dw) have shown significant cardiovascular risk stratification value. However, errors in the location of TW boundaries may impact their prognostic power. Our aim was to test the hypothesis that a weighted time-warping function (WF) would reduce the sensitivity of dw to these errors and improve their clinical significance. The WFs were proportional to (i) the reference TW ( T), and (ii) the absolute value of its derivative ( D). The index dw was recalculated using these WFs, and its performance was compared to the unweighted control case ( C) in four different scenarios: 1) robustness against simulated TW boundaries location errors; 2) ability to retain physiological information in an electrophysiological cardiac model; 3) ability to monitor blood potassium concentration changes ( ∆[K+]) in 29 hemodialysis (HD) patients; 4) and the sudden cardiac death (SCD) risk stratification value of the TW morphology restitution (TMR) index, derived from dw, in 651 chronic heart failure (CHF) patients. The WFs led to a reduced sensitivity ( R) of dw to TW boundary location errors as compared to C (median R=0.19 and 0.22 and 0.35 for T, D and C, respectively). They also preserved the physiological relationship between dw and repolarization dispersion changes at ventricular level. No improvements in ∆[K+] tracking were observed for the HD patients (Pearson's median correlation [ r] between ∆[K+] and dw was 0.86 ≤ r ≤ 0.90 for T, D and C). In CHF patients, the SCD risk stratification value of TMR was improved by applying T (hazard ratio, HAR, of 2.80), followed by D (HAR=2.32) and C (HAR=2.23). The proposed WFs, with T showing the best performance, increased the robustness of time-warping based markers against TW location errors preserving their physiological information content and boosting their SCD risk stratification value. Results from this work support the use of T when deriving dw for future clinical applications.

Potassium Concentrations in Transgender Women Using Spironolactone: A Retrospective Chart Review

ObjectiveTo assess the incidence of hyperkalemia in transgender women using spironolactone. MethodsThis was a retrospective chart review of transgender women who received gender-affirming hormone therapy that included spironolactone between January 2000 and September 2018. Forty-four participants who had paired potassium concentrations documented and were on spironolactone were included and analyzed. Study outcomes included the incidence of hyperkalemia (serum potassium concentrations > 5.0 mmol/L), the relationship between the duration of treatment and degree of hyperkalemia, and difference between serum potassium concentrations at the beginning of spironolactone treatment versus last serum potassium concentrations. ResultsThe median age of the participants was 36.5 years. The cohort was predominantly non-Hispanic White (32/44). No serum potassium concentration was >5.5 mmol/L, and all participants had serum creatinine level of <2 mg/dL. Median duration of treatment was 25 months (range 2-92 months) and 140 potassium measurements were available. The mean potassium concentration (3.87 mmol/L) before the initiation of spironolactone was lower than the mean potassium concentration (4.03 mmol/L) while on spironolactone (mean difference, 0.16 mmol/L, P = .013). The regression β, that is, the average change in potassium concentration per 1 additional month of treatment duration, was −.001 (95% CI [−.004, .001]; P = .255) signifying no relation between treatment duration and spironolactone use. ConclusionNo participant had laboratory evidence of significant hyperkalemia (K > 5.5 mmol/L) after initiation of spironolactone. Frequent measurement of potassium concentrations might be unnecessary in transgender women taking spironolactone in patients with serum creatinine levels of <2 mg/dL.

High-dose radiation exposure of cold-stored whole blood does not affect hemostatic function.

Whole blood (WB) transfusion is routinely used to resuscitate severely injured military trauma patients. Blood can be stored refrigerated while still maintaining reasonable function but is susceptible to environmental influences, including radiation exposure. Immune-compromised patients are transfused with irradiated blood to inactivate donor lymphocyte function (25 Gy per Association for the Advancement of Blood and Biotherapies [AARB] standard 5.7.3.2). However, there is limited information on function of WB exposed to high radiation doses. This study aimed to determine if stored irradiated WB still retains function. This will be important if the stored blood supply is exposed to radiation in a combat situation or mass casualty incident when the need for blood will be high. Whole blood collected from healthy donors was irradiated at 0, 25, or 75 Gy and stored at 4°C. Blood cell count, blood gas chemistry, thromboelastometry, platelet aggregation, and reactive oxygen species were measured before irradiation and at 1, 7, and 14 days of storage. Irradiated WB was compared with nonirradiated WB controls. Irradiated WB stored for up to 14 days was not significantly different than nonirradiated WB in most of the parameters measured. Stored blood showed expected changes associated with functional decline at longer storage times, but irradiation did not hasten the decline. There was a significant change in potassium and sodium ion concentrations after irradiation, but the functional relevance is not clear. High-dose irradiation had little effect on stored WB. Although there were changes in plasma sodium and potassium levels, there was little to no effect on hemostasis and blood cell viability. This suggests that stored blood subjected to a radiation event generating at least a dose of 75 Gy is still suitable for transfusion, which could be particularly important in the event of a mass casualty event where a large amount of blood is needed.

Вплив удобрення та вапнування на баланс і вміст форм калію в дерново-підзолистому ґрунті

Goal. To determine the effect of plant by-products and mineral fertilizers in combination with different doses of dolomite flour on the balance and content of different forms of potassium in soddy podzolic cohesive-sandy soil. Methods. Field (the study of the effect of fertilization and liming on the change in potassium content in the soil), laboratory (the determination of the content of potassium forms in the soil), calculation (the assessment of potassium balance), statistical (the variance analysis of the reliability of research results). Results. The research during 2 rotations of a 4-field crop rotation established that liming 1.9–5.6 tons of dolomite flour with the subsequent annual entering into the soil of an average of 5 tons of by-products of crops in combination with the application of mineral fertilizers at a dose of N112P87K105 per 1 ha of the crop rotation area created the positive balance of potassium in the soil at its intensity of 167–206%. A rapid increase in the content of mobile potassium in the soil in these variants was observed only during the first 4 years of research, in subsequent years it varied within the reached level. Fertilization and liming had a positive effect on the content of all forms of potassium available to plants: water-soluble, exchangeable, and non-exchangeable. During 8 years of research, their content increased by 57.1–121, 40.5–59.5, and 7.8–12.3%, respectively. Conclusions. The use against the background of liming and fertilization of by-products of crop rotation makes it possible to return to the soil 74.0–76.3% of the economic removal of potassium and, in combination with the application of 105 kg/ha of potassium with mineral fertilizers for 1 ha of crop rotation, to create a positive balance of the element at the level of 82.8–88.1 kg/ha. The content of mobile forms of potassium in the soil layer of 0–20 cm in the first 4 years of research in the variants with fertilizer increased from 53–57 to 89–102 mg/kg of soil, in the following 4 years it almost did not increase with certain variations over the years. Under the influence of the studied components of the fertilizer system in crop rotation, the content of all forms of potassium in the soil — water-soluble, exchangeable, and non-exchangeable — increased. Compared to the control, application of N112P87K105 per 1 ha of crop rotation area contributed to an increase in their content by 21.4 and 16.2%, respectively, for a combination of 3.8 t of CaMg(CO3)2 and N112P87K105 — by 57.1–121, 40.5–59.5, and 7.8–12.3%, respectively. However, increasing the dose of dolomite flour from 3.6 to 5.8 t/ha in the crop rotation fertilizer system did not significantly increase the content of non-exchangeable potassium in the 0–20 cm layer of soddy podzolic soil.

Lethal ventricular arrhythmia can be prevented by adjusting the dialysate potassium concentration and the use of anti-arrhythmic agents: a case report and literature review

BackgroundHypokalemia is common in patients with malnutrition undergoing hemodialysis and is often involved in the development of lethal arrhythmia. Moreover, hemodialysis therapy decreases the serum potassium concentration due to potassium removal to the dialysate. However, it is difficult to adjust the dialysate potassium concentration owing to the use of the central dialysate delivery system in Japan. Here, we have presented a case undergoing hemodialysis with dialysate potassium concentration adjustment to prevent ventricular arrhythmia.Case presentationA 56-year-old man with Emery-Dreifuss muscular dystrophy and chronic heart failure was admitted to our hospital and needed subsequent hemodialysis therapy due to renal dysfunction. During hemodialysis, the cardiac resynchronization therapy defibrillator was activated to the treatment of his lethal ventricular arrhythmia. Decreases in serum potassium concentration after hemodialysis and changes in serum potassium concentration during HD were considered the causes of lethal ventricular arrythmia. Therefore, along with using anti-arrhythmic agents, the dialysate potassium concentration was increased from 2.0 to 3.5 mEq/L to minimize changes in the serum potassium concentration during hemodialysis. Post-dialysis hypokalemia disappeared and these changes during hemodialysis were minimized, and no lethal ventricular arrhythmia occurred thereafter.ConclusionsIn this case, we prevented lethal arrhythmia by maintaining the serum potassium concentration by increasing the dialysate potassium concentration, in addition to the use of anti-arrhythmic agents. In the acute phase of patients with frequent lethal arrhythmia undergoing hemodialysis, an increase in dialysate potassium concentration may be an effective method for preventing arrhythmogenic complications.

MO364: Population Pharmacodynamic Dose-Response Analysis of Serum Potassium Following Dosing With Sodium Zirconium Cyclosilicate

Abstract BACKGROUND AND AIMS Sodium zirconium cyclosilicate (SZC, LOKELMA®) is an orally administered suspension for treating hyperkalemia that permits selective, monovalent cation exchange and has a high exchange capacity for potassium cations in the gut leading to a net reduction in systemic potassium. The goals of the analysis were to describe the population pharmacodynamic response of serum potassium concentration (S-K) in hyperkalemic subjects treated with SZC; specifically, the longitudinal dose response of SZC for S-K in correction (0–48 h) and maintenance (&amp;gt;48 h) phases of treatment, and the differences in S-K response among populations identified by their intrinsic and extrinsic factors. METHOD A population pharmacodynamic model was developed using serum potassium, dose timing/amount, and patient demographic and medical history data pooled from 7 phase 2 and 3 clinical studies consisting of 2369 subjects with hyperkalemia (screening S K &amp;gt;5 mmol/L) with a total of 25 764 S-K observations. A virtual pharmacokinetic-pharmacodynamic model (K-PD) model was used to mimic a drug exposure without any measurements (none were available, drug was not absorbed). S-K over time was described by an indirect response model where potassium enters/leaves a compartment corresponding to serum potassium measurements. The impact of SZC exposure was modeled as an inhibition of the potassium production rate, consistent with the SZC mechanism of action to bind potassium and lower its absorption and appearance in circulation. RESULTS Diagnostics indicated good agreement between the observed data and the model, for mean S-K and change from baseline, and overall qualified the model as appropriate for predicting S-K changes following SZC dosing. The sigmoid exposure response on Kin was characterized by a high value for the EC50 (32.8 g) and a hill coefficient of 1.36. Not surprisingly, within the range of doses studied (0–15 g), the dose response appeared nearly linear. The placebo adjusted S-K change from baseline for QD maintenance treatment was 0.37 (95% CI –0.42 to –0.32) for 5 g, –0.75 (95% CI –0.82 to –0.65) for 10 g, and –1.06 (95% CI –1.17 to –0.89) for 15 g. Greater treatment response was associated with high S-K at baseline, more advanced age, lower body weight and lower eGFR. Furthermore, greater treatment response was also predicted for Black or African American and Asian patients, compared with Caucasian individuals, but they remained unworthy of dose adjustment. Lastly, dose-response simulations show no clinically meaningful difference between maintenance regimens of 5 g QOD and 2.5 g QD in the studied patient groups. CONCLUSION The population K-PD model of SZC adequately described the changes in serum potassium concentration during correction and maintenance phase dosing in the seven clinical studies. Greater treatment response was associated with high S-K at baseline, more advanced age, lower body weight, lower eGFR, Black or African American race and Asian race; however, the impact of each covariate was modest. The overall results of this analysis support the conclusion that no dose adjustment is needed for SZC based on any of the tested covariates.

Increase in venous [K+] During Hyperbaric Exposure Independent of Changes in pH or O2 Concentration

IntroductionPlasma potassium regulation is important for function of numerous cells in the body. Changes in potassium levels during exposure to an increased O2 concentration is thought to be the result of the changes in pH and increasing reactive oxygen species. However, the effects of hyperbaria on plasma potassium concentration are not well understood.MethodsEight subjects were exposed to 1.3 atmospheres absolute (ATA) of hyperbaric air for 90 minutes, 10‐times (M‐F) over 12‐days. Another eight subjects were exposed to 100% oxygen at 1 ATA over the same interval. Four venous blood draws were taken. On day 1 the first draw was taken immediately preceding treatment and the second was taken immediately following treatment. The third draw was taken prior to the 10th treatment and the 4th draw was taken 72 hours post final treatment. We analyzed samples on a blood gas analyzer and performed statistical analysis using a paired Wilcoxon signed‐rank test.ResultsThe concentration group saw strong trend towards an increase in the potassium concentration from 4.09 ± 0.12 (mmol/L) to 4.28 ± 0.28 (mmol/L) (p = 0.065). In the hyperbaric group we see a significant increase in potassium concentration from 4.19 ± 0.26 (mmol/L) to 4.55 ± 0.27 (mmol/L) (p = 0.0068). In the concentration group we also see a significant increase in pH concentration from 7.37 ± 0.03 to 7.39 ± 0.01 (p= 0.021). A similar significant increase is not seen in the hyperbaric group.SummaryThese finding suggest that changes in potassium concentration in response to hyperbaria are not the result of oxygen concentration nor pH. Possible explanations include increased nitrogen levels due to hyperbaric air, increased CO2 concentration in hyperbaric chamber or changes in the activity of Na+,K+ ATPase pumps at the cellular level which may be a homeostatic response to combat pulmonary edema

Short-term Effects of Losartan on Cardiovascular Risk and Allograft Injury Biomarkers in Kidney Transplant Recipients

There is a controversy over the renoprotective and cardioprotective effects of renin-angiotensin-aldosterone system blockade in kidney transplant recipients (KTRs). The aim of the study was to evaluate the short-term effects of losartan on allograft injury, cardiovascular risk biomarkers and safety of the treatment in KTRs. An interim analysis of a prospective, open, multicenter, controlled clinical trial CELART (Cardiovascular Effects of Losartan After Renal Transplantation) was performed. KTRs were allocated to losartan (L) 50 to 100 mg or standard hypotensive treatment (ST) group to reach target blood pressure (BP) <140/90 mm Hg. The short-term effects of the therapy were evaluated after 6 months: estimated glomerular filtration rate (eGFR), albuminuria, the intrarenal fibrosis biomarkers: urine excretion of transforming growth factor β-1 (TGFβ-1) and procollagen type III amino terminal propeptide (PIIINP), cardiac biomarker: serum concentration of N-terminal-pro-B-type natriuretic peptide (NT-proBNP), 24-hour ambulatory BP measurement, and hemoglobin and potassium concentrations. At baseline the groups did not differ with respect to age, primary nephropathy, comorbidity, immunosuppressive therapy, albuminuria, and graft function. A total of 61 (L group) and 73 (ST group) patients reached the target BP and completed protocol at 6 months. After 6 months of therapy there were no significant differences in changes of eGFR, albuminuria, hemoglobin and potassium concentrations, urine excretion of PIIINP, and TGFβ-1 between groups. There was a trend in the L group to decrease the concentration of serum NT-proBNP. Losartan shows minimal adverse effects and no influence on graft function and biomarkers of graft fibrosis. It may have a positive effect on cardiovascular risk in KTRs. Further interim analyses of the CELART study will be conducted.

Evaluation of the Relationship Between Changes in Potassium Concentration and Arrhythmia During Coronary Artery Bypass Grafting Surgery.

BackgroundCoronary artery bypass grafting (CABG) surgery is a treatment option for coronary artery diseases. Cardiac arrhythmias during CABG surgery can lead to serious complications. Potassium ion concentration is a factor involved in such arrhythmias. ObjectivesThis study aimed to investigate the relationship between potassium concentration and cardiac arrhythmias in CABG surgery.MethodsThis descriptive cross-sectional study was performed on 60 patients with the American Society of Anesthesiologists class I, II, and III undergoing CABG surgery at Golestan Hospital, Ahvaz, Iran. All patients underwent general anesthesia, and ventilator control was achieved by mechanical ventilation. The on-pump method was used for CABG. Potassium levels were measured at several time points during surgery. All cardiac arrhythmias were recorded. Mean arterial pressure (MAP), serum level of potassium, blood sugar, blood urea nitrogen (BUN), creatinine, calcium, magnesium, hemoglobin (Hb), and sodium were also recorded.Results The mean age of the patients was 60.87 ± 7.35 years, and 45% of the subjects were female. Moreover, there was no statistically significant difference between the patients. There was a significant relationship between the changes in MAP, potassium, blood sugar, BUN, creatinine, calcium, and magnesium with the incidence of cardiac arrhythmias (P < 0.05). However, no significant relationship was noted between Hb and sodium levels with the incidence of cardiac arrhythmias (P < 0.05).ConclusionsThe changes in potassium levels increase the risk of cardiac arrhythmias and their complications.