Plasma Potassium Concentration Research Articles

Features of the exchange of electrolytes and nitrogenous metabolites under different options of uric acid exchange in healthy female rats

Background. We previously identified 4 variants-clusters of uricemia and uricosuria both in rats and in humans. It was shown that the clusters differ from each other in the constellation of immune, autonomic and endocrine parameters, which correlate with uricemia and uricosuria. The aim of this study was to identify the electrolytes and nitrogenous metabolites, the combination of which differentiates previously formed quantitative and qualitative variants of uric acid metabolism in rats. Materials and Methods. Experiment was performed on 60 healthy female Wistar rats 220-300 g. The plasma and urine levels of the uric acid, urea, creatinine, calcium, phosphates, chloride, magnesium, sodium and potassium (also in erythrocytes) as well as glucose (in plasma only) were determined. Results. 10 metabolic parameters characteristic of four variants of uric acid exchange were identified: the concentration of glucose, urea, phosphates, magnesium and potassium in plasma, and the latter in erythrocytes, as well as the excretion of creatinine, urea, phosphates and calcium with urine. The accuracy of discrimination of clusters based on the totality of this metabolic constellation together with uricemia is 95%. The cumulative determining influence of the parameters of uric acid exchange (due to the significant advantage of uricosuria over uricemia) on the constellation of metabolic parameters is 56%. Diuresis and excretion of phosphates and potassium are subject to the maximum positive determination from the side of uric acid; excretion of calcium, creatinine and urea are determined to a lesser extent; levels of creatinine, urea and potassium in the plasma are even less, and magnesiumuria is subject to the minimum determination. Conclusion. Uric acid is naturally associated with the state of electrolytes and nitrogenous metabolites exchange in healthy female rats.

Altered muscle membrane potential and redox status differentiates two subgroups of patients with chronic fatigue syndrome

BackgroundIn myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), altered membrane excitability often occurs in exercising muscles demonstrating muscle dysfunction regardless of any psychiatric disorder. Increased oxidative stress is also present in many ME/CFS patients and could affect the membrane excitability of resting muscles.MethodsSeventy-two patients were examined at rest, during an incremental cycling exercise and during a 10-min post-exercise recovery period. All patients had at least four criteria leading to a diagnosis of ME/CFS. To explore muscle membrane excitability, M-waves were recorded during exercise (rectus femoris (RF) muscle) and at rest (flexor digitorum longus (FDL) muscle). Two plasma markers of oxidative stress (thiobarbituric acid reactive substance (TBARS) and oxidation–reduction potential (ORP)) were measured. Plasma potassium (K+) concentration was also measured at rest and at the end of exercise to explore K+ outflow.ResultsThirty-nine patients had marked M-wave alterations in both the RF and FDL muscles during and after exercise while the resting values of plasma TBARS and ORP were increased and exercise-induced K+ outflow was decreased. In contrast, 33 other patients with a diagnosis of ME/CFS had no M-wave alterations and had lower baseline levels of TBARS and ORP. M-wave changes were inversely proportional to TBARS and ORP levels.ConclusionsResting muscles of ME/CFS patients have altered muscle membrane excitability. However, our data reveal heterogeneity in some major biomarkers in ME/CFS patients. Measurement of ORP may help to improve the diagnosis of ME/CFS.Trial registration Ethics Committee “Ouest II” of Angers (May 17, 2019) RCB ID: number 2019-A00611-56

Nutrients and Diabetes Mellitus: Potassium

Potassium (K) is an essential mineral that plays major roles in intracellular osmolality and acid-base balance. In addition, potassium affects endothelial and vascular smooth muscle functions and has been shown to decrease blood pressure. Recently, potassium intake and plasma potassium concentration have been reported to be related to insulin secretion and diabetes risk. Therefore, in this article, we review how potassium intake reduces blood pressure and affects insulin release. We also determine methods for safe consumption and dose of potassium. Keywords: Blood glucose; Blood pressure; Diabetes mellitus; Potassium

Effects of caffeine on neuromuscular function in a non-fatigued state and during fatiguing exercise.

What is the central question of the study? What are the effects of caffeine on neuromuscular function in a non-fatigued state and during fatiguing exercise? What is the main finding and its importance? In a non-fatigued state, caffeine decreased the duration of the silent period evoked by transcranial magnetic stimulation. Caffeine-induced reduction of inhibitory mechanisms in the central nervous system before exercise was associated with an increased performance. Individuals who benefit from caffeine ingestion may experience lower perception of effort during exercise and an accelerated recovery of M-wave amplitude postfatigue. This study elucidates the mechanisms of action of caffeine and demonstrates that inter-individual variability of its effects on neuromuscular function is a fruitful area for further work. Caffeine enhances exercise performance, but its mechanisms of action remain unclear. In this study, we investigated its effects on neuromuscular function in a non-fatigued state and during fatiguing exercise. Eighteen men participated in this randomized, double-blind, placebo-controlled crossover trial. Baseline measures included plantarflexion force, drop jump, squat jump, voluntary activation of triceps surae muscle, soleus muscle contractile properties, M-wave, α-motoneuron excitability (H-reflex), corticospinal excitability, short-interval intracortical inhibition, intracortical facilitation, silent period evoked by transcranial magnetic stimulation (SP) and plasma potassium and caffeine concentrations. Immediately after baseline testing, participants ingested caffeine (6mg·kg-1 ) or placebo. After a 1-h rest, baseline measures were repeated, followed by a fatiguing stretch-shortening cycle exercise (sets of 40 bilateral rebound jumps on a sledge apparatus) until task failure. Neuromuscular testing was carried out throughout the fatigue protocol and afterwards. Caffeine enhanced drop jump height (by 4.2%) and decreased the SP (by 12.6%) in a non-fatigued state. A caffeine-related decrease in SP and short-interval intracortical inhibition before the fatiguing activity was associated with an increased time to task failure. The participants who benefitted from an improved performance on the caffeine day reported a significantly lower sense of effort during exercise and had an accelerated postexercise recovery of M-wave amplitude. Caffeine modulates inhibitory mechanisms of the CNS, recovery of M-wave amplitude and perception of effort. This study lays the groundwork for future examinations of differences in caffeine-induced neuromuscular changes between those who are deemed to benefit from caffeine ingestion and those who are not.

Early detection of diabetic kidney disease by urinary proteomics and subsequent intervention with spironolactone to delay progression (PRIORITY): a prospective observational study and embedded randomised placebo-controlled trial

Microalbuminuria is an early sign of kidney disease in people with diabetes and indicates increased risk of cardiovascular disease. We tested whether a urinary proteomic risk classifier (CKD273) score was associated with development of microalbuminuria and whether progression to microalbuminuria could be prevented with the mineralocorticoid receptor antagonist spironolactone. In this multicentre, prospective, observational study with embedded randomised controlled trial (PRIORITY), we recruited people with type 2 diabetes, normal urinary albumin excretion, and preserved renal function from 15 specialist centres in ten European countries. All participants (observational cohort) were tested with the CKD273 classifier and classified as high risk (CKD273 classifier score >0·154) or low risk (≤0·154). Participants who were classified as high risk were entered into a randomised controlled trial and randomly assigned (1:1), by use of an interactive web-response system, to receive spironolactone 25 mg once daily or matched placebo (trial cohort). The primary endpoint was development of confirmed microalbuminuria in all individuals with available data (observational cohort). Secondary endpoints included reduction in incidence of microalbuminuria with spironolactone (trial cohort, intention-to-treat population) and association between CKD273 risk score and measures of impaired renal function based on estimated glomerular filtration rate (eGFR; observational cohort). Adverse events (particularly gynaecomastia and hyperkalaemia) and serious adverse events were recorded for the intention-to-treat population (trial cohort). This study is registered with the EU Clinical Trials Register (EudraCT 20120-004523-4) and ClinicalTrials.gov (NCT02040441) and is completed. Between March 25, 2014, and Sept 30, 2018, we enrolled and followed-up 1775 participants (observational cohort), 1559 (88%) of 1775 participants had a low-risk urinary proteomic pattern and 216 (12%) had a high-risk pattern, of whom 209 were included in the trial cohort and assigned to spironolactone (n=102) or placebo (n=107). The overall median follow-up time was 2·51 years (IQR 2·0-3·0). Progression to microalbuminuria was seen in 61 (28%) of 216 high-risk participants and 139 (9%) of 1559 low-risk participants (hazard ratio [HR] 2·48, 95% CI 1·80-3·42; p<0·0001, after adjustment for baseline variables of age, sex, HbA1c, systolic blood pressure, retinopathy, urine albumin-to-creatinine ratio [UACR], and eGFR). Development of impaired renal function (eGFR <60 mL/min per 1·73 m2) was seen in 48 (26%) of 184 high-risk participants and 119 (8%) of 1423 low-risk participants (HR 3·50; 95% CI 2·50-4·90, after adjustment for baseline variables). A 30% decrease in eGFR from baseline (post-hoc endpoint) was seen in 42 (19%) of 216 high-risk participants and 62 (4%) of 1559 low-risk participants (HR 5·15, 95% CI 3·41-7·76; p<0·0001, after adjustment for basline eGFR and UACR). In the intention-to-treat trial cohort, development of microalbuminuria was seen in 35 (33%) of 107 in the placebo group and 26 (25%) of 102 in the spironolactone group (HR 0·81, 95% CI 0·49-1·34; p=0·41). In the safety analysis (intention-to-treat trial cohort), events of plasma potassium concentrations of more than 5·5 mmol/L were seen in 13 (13%) of 102 participants in the spironolactone group and four (4%) of 107 participants in the placebo group, and gynaecomastia was seen in three (3%) participants in the spironolactone group and none in the placebo group. One patient died in the placebo group due to a cardiac event (considered possibly related to study drug) and one patient died in the spironolactone group due to cancer, deemed unrelated to study drug. In people with type 2 diabetes and normoalbuminuria, a high-risk score from the urinary proteomic classifier CKD273 was associated with an increased risk of progression to microalbuminuria over a median of 2·5 years, independent of clinical characteristics. However, spironolactone did not prevent progression to microalbuminuria in high-risk patients. European Union Seventh Framework Programme.

Fluctuations in plasma potassium in patients on dialysis.

Plasma potassium concentration is maintained in a narrow range to avoid deleterious electrophysiologic consequences of both abnormally low and high levels. This is achieved by redundant physiologic mechanisms, with the kidneys playing a central role in maintaining both short-term plasma potassium stability and long-term total body potassium balance. In patients with end-stage renal disease, the lack of kidney function reduces the body's ability to maintain normal physiologic potassium balance. Routine thrice-weekly dialysis therapy achieves long-term total body potassium mass balance, but the intermittent nature of dialytic therapy can result in wide fluctuations in plasma potassium concentration and consequently contribute to an increased risk of arrhythmogenicity. Various dialytic and nondialytic interventions can reduce the magnitude of these fluctuations, but the impact of such interventions on clinical outcomes remains unclear.

A simple modification of dialysate potassium: its impact on plasma potassium concentrations and the electrocardiogram.

BackgroundSudden death is frequent in haemodialysis (HD) patients. Both hyperkalaemia and change of plasma potassium (K) concentrations induced by HD could explain this. The impact of increasing dialysate K by 1 mEq/L on plasma K concentrations and electrocardiogram (ECG) results before and after HD sessions was studied.MethodsPatients with pre-dialysis K >5.5 mEq/L were excluded. ECG and K measurements were obtained before and after the first session of the week for 2 weeks. Then, K in the dialysate was increased (from 1 or 3 to 2 or 4 mEq/L, respectively). Blood and ECG measurements were repeated after 2 weeks of this change.ResultsTwenty-seven prevalent HD patients were included. As expected, a significant decrease in K concentrations was observed after the dialysis session, but this decrease was significantly lower after the switch to an increased dialysate K. The pre-dialysis K concentrations were not different after changing, but post-dialysis K concentrations were higher after switching (P < 0.0001), with a lower incidence of post-dialysis hypokalaemia. Regarding ECG, before switching, the QT interval (QT) dispersion increased during the session, whereas no difference was observed after switching. One week after switching, post-dialysis QT dispersion [38 (34–42) ms] was lower than post-dialysis QT dispersion 2 weeks and 1 week before switching [42 (38–57) ms, P = 0.0004; and 40 (35–50) ms, P = 0.0002].ConclusionsA simple increase of 1 mEq/L of K in the dialysate is associated with a lower risk of hypokalaemia and a lower QT dispersion after the dialysis session. Further study is needed to determine if such a strategy is associated with a lower risk of sudden death.

Relationship between acute hypercarbia and hyperkalaemia during surgery.

BACKGROUNDThe relationship between hyperkalaemia and metabolic acidosis is well described in the critical care setting; however, the relationship between acute respiratory acidosis and plasma potassium concentration is less well understood. In a controlled model of increasing levels of hypercarbia, we tested the hypothesis of whether increasing levels of hypercarbia are associated with changes in plasma potassium concentrations.AIMTo determine whether increasing levels of hypercarbia are associated with changes in plasma potassium concentrations.METHODSWe performed a post-hoc study examining changes in serum potassium in 24 patients who received increased levels of hypercarbia during cardiac surgery. Arterial blood gases and plasma concentrations of potassium were measured at baseline, 3 min prior to, and then every 3 min for 15 min during the intervention of hypercarbia. The primary endpoint was the absolute change in serum K+ at 15 min compared to the baseline K+ value. The following secondary endpoints were evaluated: (1) The association between CO2 and serum K+ concentration; and (2) The correlation between plasma pH and serum K+ concentrations.RESULTSDuring the intervention, PaCO2 increased from 43.6 mmHg (95%CI: 40.1 to 47.1) at pre-intervention to 83.9 mmHg (95%CI: 78.0 to 89.8) at 15 min after intervention; P < 0.0001. The mean (SD) serum potassium increased from 4.16 (0.35) mmol/L at baseline to 4.28 (0.33) mmol/L at 15 min (effect size 0.09 mol/L; P = 0.22). There was no significant correlation between PaCO2 and potassium (Pearson’s coefficient 0.06; 95%CI: -0.09 to 0.21) or between pH and potassium (Pearson’s coefficient -0.07; 95%CI: -0.22 to 0.09).CONCLUSIONAcute hypercarbia and subsequent respiratory acidaemia were not associated with hyperkalaemia in patients undergoing major surgery.

P4481NI956/QGC006, a potent orally active, brain-penetrating aminopeptidase A inhibitor prodrug for treating hypertension

Abstract Background Brain renin-angiotensin system hyperactivity has been implicated in the development and maintenance of hypertension. We previously showed that aminopeptidase A (APA) generates in the brain, angiotensin III, which exerts a tonic stimulatory control over blood pressure in hypertensive rats. Thus, the central injection of the specific and selective APA inhibitor, EC33 ((3S)-3-amino-4-sulfanyl-butane-1-sulfonic acid), by blocking the formation of brain angiotensin III, normalizes blood pressure in experimental models of hypertension. Therefore, brain APA appears as a potential new therapeutic target for the treatment of hypertension. We then developed RB150/firibastat, a prodrug of EC33, able of inhibiting brain APA activity and decreasing blood pressure in hypertensive rats after oral administration. Purpose However, considering the high dose of orally active RB150/firibastat required to decrease BP in spontaneously hypertensive rats (SHR) (150 mg/kg) and deoxycorticosterone acetate-salt (DOCA-salt) (50 mg/kg) rats, the aim of our work was to develop new more potent APA inhibitor prodrugs with greater bioavailability for inhibiting brain APA activity. Methods We used a salt- and volume-dependent model of hypertension, the DOCA-salt rat. For in vivo assessments of brain APA activity, brains were collected 4 hours after the oral administration. A catheter was inserted into the right femoral artery to monitor mean arterial blood pressure in alert rats. We evaluated plasma arginine-vasopressin (AVP) levels by radioimmunoassay. Rats were individually housed in metabolic cages for urine and electrolyte output measurements. Results We report here the development of a new APA inhibitor prodrug, NI956/QGC006, obtained by the disulfide bridge-mediated dimerization of NI929 ((3S,4S)-3-amino-4-mercapto-6-phenyl-hexane-1-sulfonic acid). NI929 is 10 more efficient than EC33 at inhibiting recombinant mouse APA activity in vitro. Following oral administration at a dose of 4 mg/kg in conscious DOCA-salt rats, NI956/QGC006 normalized brain APA activity and induced a marked decrease in blood pressure of −44±13 mmHg four hours after treatment (p&lt;0.001), sustained over ten hours (−21±12 mmHg, p&lt;0.05). Moreover, NI956/QGC006 decreased plasma AVP levels, and increased diuresis and natriuresis, that may decrease blood pressure by reducing the size of the fluid compartment. Finally, NI956/QGC006 did not affect plasma sodium and potassium concentrations. Conclusions This study shows that NI956/QGC006 is a “best-in-class” central-acting APA inhibitor prodrug, belonging to the same drug class as RB150/firibastat, supporting the strategy of brain APA inhibition for hypertension treatment. Acknowledgement/Funding ANR (Agence Nationale de la Recherche) grant to Catherine Llorens-Cortes (LabCom CARDIOBAPAI) and Quantum Genomics financial support.

Potassium phosphate and potassium carbonate administration by feed or drinking water improved broiler performance, bone strength, digestive phosphatase activity and phosphorus digestibility under induced heat stress conditions.

Potassium phosphate (K2HPO4) and potassium carbonate (K2CO3) administration by feed or water were evaluated on broiler performance, bone strength, alkaline phosphatase activity (ALP), and phosphorus digestibility under heat stress and high chloride condition. Experimental groups include control; 15cc/kg K2HPO4; 30cc/kg K2HPO4; 15cc/l K2HPO4; and 3.7g/kg K2CO3. Body weight (BW), feed and water consumption, plasma potassium, phosphorus, and calcium concentration along with plasma and digestive ALP and intestinal digesta pH were measured during the trial. Tibia ash, calcium and phosphorus content, and breaking strength were measured on days 21 and 42 and phosphorus digestibility on day 36 of age. As a result of this, study feed and water consumption was increased by supplementation of the feed or water with K2HPO4 (P ≤ 0.001). K2HPO4 increased body weight at 42days of age (P ≤ 0.001). Tibia ash and phosphorus content was increased by K2HPO4 supplementation (P ≤ 0.004; P ≤ 0.003). K2CO3 did increased tibia ash but not changed tibia phosphorus content significantly. Tibia shear force, shear energy, extension, and length were improved by K2HPO4 administration at 42days of age (P ≤ 0.001). Administration of either feed or water with K2HPO4 increased plasma potassium, phosphorus, and calcium concentration at 21days of age, whereas K2CO3 reduced plasma potassium at 21days of age (P ≤ 0.05). Plasma ALP reduced by addition of 15cc K2HPO4 and K2CO3 to diets at 42days of age, whereas digestive ALP was increased by inclusion of K2HPO4 and not by K2CO3. Supplementation of either feed or water with K2HPO4 increased phosphorus digestibility, whereas K2CO3 reduced phosphorus digestibility (P ≤ 0.003). Jejunum and ileum pH was reduced by K2HPO4 or by K2CO3 at 21 and 42days of age (P ≤ 0.006; (P ≤ 0.05). Over all, results of current study revealed that K2HPO4 can be a suitable potassium salt choice instead of KCL in hot weather conditions especially when the water or diet contains high levels of chloride.

THE EFFECT OF SPIRONOLACTONE VERSUS TORSEMIDE ON BLOOD PRESSURE TARGETS IN RESISTANT HYPERTENSION PATIENTS

Objective: to evaluate effects on blood pressure (BP) control in two treatment options spironolactone (SPIR) versus torsemide (TOR) as an add-on therapy in resistant hypertensive (RAH) patients. Design and method: We studied 78 patients with true RAH confirmed by the office and ambulatory BP monitoring (ABPM). Patients were randomized into 2 groups through 12 weeks of once daily treatment with of SPIR (25–50 mg) or TOR (5–10 mg) in addition to their baseline triple-combination and then rotated with drugs. BP was measured in the office and by ABPM. Changes in laboratory tests were also studied. The predictive values of plasma aldosterone, active renin concentration (ARC) and aldosterone-renin ratio (ARR), serum potassium, 24-h urinary excretion sodium of determining the antihypertensive response were analyzed. Results: There were no significant differences on the reduction of average office BP and average nighttime BP by SPIR and TOR. SPIR reduced average systolic 24-h BP by 11.7 mmHg and average systolic daytime BP by 12.2 mmHg compared with a reduction of 8.9 mmHg (P < 0.05) and 9.1 mmHg (P < 0.05) with TOR, respectively. Overall, 36.8 % RAH patients achieved targets of clinical BP and 24-h ABPM levels on SPIR and 30.9 % on TOR. After 12 weeks of treatment mean plasma potassium concentrations increased from 4.3 to 4.7 mmol/L (P < 0.0001) on SPIR but did not significant change on TOR. Serum potassium (β = −0.441, P < 0.05), 24-h urinary excretion sodium (β = 0.432, P < 0.05) and ARR (β = 0.543, P < 0.03) were predictors of BP-lowering effect of SPIR and plasma aldosterone (β = −0.680, P < 0.001), ARC (β = 0.463, P < 0.03) were predictors of reduction BP for TOR in multivariate modeling. Conclusions: Greater antihypertensive effect of SPIR is related to aldosterone status, urinary sodium excretion and serum potassium level in resistant hypertension. TOR may be suited for RAH patients that have high ARC and in people with lower sodium intake or high serum potassium level.

A temperature shift on the migratory route similarly impairs hypo-osmoregulatory capacities in two strains of Atlantic salmon (Salmo salar L.) smolts

Anthropogenic use of water systems may cause temperature fluctuations between tributaries and large rivers for which physiological population related-effects on osmoregulatory capacity of Atlantic salmon are not well described. We simulated the downstream route in the case of the River Meuse basin to investigate the impact of a 5°C temperature shift during smoltification on hypo-osmoregulatory capacities of smolts. Three temperature regimes were tested: control temperature-treatment (T1) without temperature shift, early (T2) or late (T3) temperature shift-treatment. Moreover, fish were subjected to seawater challenge during and after the downstream migration peak time. Two allochtonous strains were used: Loire-Allier (LA) and Cong (CG). Without temperature shift (T1), significant differences between the strains were noticed in the peak date and maximum activity of gill Na+/K+ATPase as well as in plasma sodium and potassium concentrations. For early (T2) and late (T3) temperature shift-treatments, gill Na+/K+ATPase activity, plasma osmolality and ion concentrations were negatively influenced in both strains. After salinity challenge, the highest osmolality was measured in smolts subjected to the temperature shift. Predictably circulating levels of GH and IGF-1 changed over the smolting period but they did not explain the observed modifications in hypo-osmoregulatory abilities whatever the population. The results show a negative impact of a temperature shift on hypo-osmoregulatory capacities of smolts regardless of population differences in smoltification timing under conditions without temperature shift. The resilience of such physiological impact was sustained at least for 1week, comforting the role of high temperature in influencing the rate of changes occurring during smoltification. Therefore, favouring the downstream migration to help smolts reach the sea faster may mitigate the impact of a rapid temperature increase.

NI956/QGC006, a Potent Orally Active, Brain-Penetrating Aminopeptidase A Inhibitor for Treating Hypertension.

Brain renin-angiotensin system hyperactivity has been implicated in the development and maintenance of hypertension. We have shown that aminopeptidase A is involved in the formation of brain angiotensin III, which exerts tonic stimulatory control over blood pressure in hypertensive deoxycorticosterone acetate-salt rats and spontaneously hypertensive rats. We have also shown that injection of the specific and selective aminopeptidase A inhibitor, (3S)-3-amino-4-sulfanyl-butane-1-sulfonic acid (EC33), by central route or its prodrug, RB150/firibastat, by oral route inhibited brain aminopeptidase A activity and blocked the formation of brain angiotensin III, normalizing blood pressure in hypertensive rats. These findings identified brain aminopeptidase A as a potential new therapeutic target for hypertension. We report here the development of a new aminopeptidase A inhibitor prodrug, NI956/QGC006, obtained by the disulfide bridge-mediated dimerization of NI929. NI929 is 10× more efficient than EC33 at inhibiting recombinant mouse aminopeptidase A activity in vitro. After oral administration at a dose of 4 mg/kg in conscious deoxycorticosterone acetate-salt rats, NI956/QGC006 normalized brain aminopeptidase A activity and induced a marked decrease in blood pressure of -44±13 mm Hg 4 hours after treatment ( P<0.001), sustained over 10 hours (-21±12 mm Hg; P<0.05). Moreover, NI956/QGC006 decreased plasma arginine-vasopressin levels, and increased diuresis and natriuresis, that may participate to the blood pressure decrease. Finally, NI956/QGC006 did not affect plasma sodium and potassium concentrations. This study shows that NI956/QGC006 is a best-in-class central-acting aminopeptidase A inhibitor prodrug. Our results support the development of hypertension treatments targeting brain aminopeptidase A.

Clinical Implications

Clinical Implications

The state of renin-aldosterone system in patients with resistant arterial hypertension

Purpose. The understanding of pathophysiology and clinical characteristics of resistant hypertension (RH) remains elusive. The aim of this work was to study the relationships between clinical course of RH and levels of renin and aldosterone (AS). Materials and methods. A total of 47 patients with true RH were included in the study. The control group included 50 patients with controlled arterial hypertension (CAH). All patients underwent general clinical examination, calculation of body mass index (BMI), office blood pressure measurement, determination of plasma potassium, AS and active renin concentrations (ARC), assessment of plasma aldosterone-to-renin ratio, urinary albumin excretion, albumin-creatinine ratio (ACR), uric acid, serum creatinine, calculation of glomerular filtration rate (GFR) by Cockcroft–Gault formula, echocardiography. Results. AS and ARC levels were significantly higher (AS 145.21 ± 11.90 ng/ml and 122.04 ± 8.60 ng/ml, P < 0.001; ARC 18.21 ± 3.50 ng/ml and 14.40 ± 2.20 ng/ml, P < 0.05) in patients with RH compared to those with CAH, respectively. At the same time, among patients with RH, only 38 % had a normal ARC; increased ARC was in 27 % and reduced ARC was in 35 % of patients. Among patients with CAH, 78 % had a normal ARC; increased ARC was in 7 % and reduced ARC was in 15 % of patients. In patients with CAH, there was negative correlation between AS and ARC levels (r = -0.38, P < 0.05), at the same time in patients with RH, no correlation was found between AS and ARC levels. However, in patients with RH, there were negative correlations between AS, ARC and GFR (r = -0.36, P < 0.05; r = -0.32, P < 0.05, respectively); positive – ARC and left ventricular mass index (r = 0.43, P < 0.05); AS and ACR (r = 0.76, Р < 0.01); AS and left ventricular end-diastolic volume (r = 0.38, P < 0.05). Moreover, significant correlations were found between ARC and BMI (r = 0.59, P < 0.001), AS and BMI (r = 0.42, P < 0.05). Conclusions. The results indicate that in patients with RH, higher renin and AS levels are mediated by overweight as well as renin and AS have a different influence on target organs in RH. Furthermore, stimulation of AS production occurs regardless of the renin-angiotensin system and angiotensin II effects. The group of patients with RH is not homogeneous according to renin concentration and “low-renin” and “high-renin” hypertension are more frequently registered among them. It seems that pathophysiologic mechanisms are different in each case and need to be identified for the selection of antihypertensive agents to treat patients successfully.

Proteinuria in relation to age-dependent changes in the plasma and urine concentrations of some electrolytes and hematological indices in Wistar rats

The study was carried out to determine the influence of proteinuria on plasma and urine concentrations of electrolytes and hematological indices in Wistar rats of different age groups.Eighty Wistar rats of both sexes were used for this study. Groups 1 and 2 each consisted of 8 one month old male and female rats; 3 and 4 had 8 three month old rats; 5 and 6 had 8 six month old rats; 7 and 8 had 8 nine month old rats; 9 and 10 had 8 twelve month old rats.The plasma sodium, potassium and calcium concentrations of 3 month old rats were significantly lower when compared with 1, 6, 9 and 12 months of age. Similarly, rats aged 3 months had significantly lower urine concentrations of sodium, potassium and calcium than rats of other age groups. A strong correlation was observed between the urine protein and urine sodium of the female rats at ages 3, 9 and 12 months but it was only significant at age 12 months (p = 0.105 and p = 0.021, respectively). Also, the female rats aged 3 and 12 months had a strong correlation between their urine protein and urine calcium (p = 0.002 and p = 0.131, respectively).The red blood cells, lymphocyte and monocyte counts of the rats increased gradually and peaked at age 9 months with a subsequent decline at 12 months of age.It was concluded that the influence of proteinuria on electrolytes was least observed in the rats aged 3 months, since they had reduced and consistent plasma and urine concentrations of electrolytes measured when compared with other age groups. This implies that long-term renal studies involving the use of rats must be carefully interpreted because of the changes in plasma and urine concentrations of electrolytes as the rats age.

Hematology and plasma chemistry reference intervals for wild population of Alburnus chalcoides (Guldenstadt, 1772): Influence of sex, habitat and seasonal variation

The study was aimed to establish reference interval for some blood biochemical (sodium, potassium, calcium, and magnesium) and hematological (total count of white blood cells, neutrophils, lymphocytes, monocytes, and eosinophils) indices in both sexes of Alburnus chalcoides in response to its habitats with different physiochemical conditions and to seasonal variation. Fish samples were collected from its seasonal habitats, including river, estuary, and Caspian Sea. The mean concentration of sodium, potassium, calcium, and magnesium in plasma of fish were 134.69±13.61 (mmol/l), 3.26±0.83 (mmol/l), 11.65±1.82 (mg/dl) and 2.13±1.12 (mmol/l), respectively. These electrolytes demonstrated significant differences between the male and female as well as between the fish collected from different habitats. Total WBCs count was 6045.35±960.25 (per mm 3 ) and the mean percentage of neutrophils, lymphocytes, monocytes and eosinophils were 26.55±3.37%, 67.74±3.72%, 3.04±0.70% and 0.98±0.04%, respectively. WBCs generally showed considerable differences between male and female. Furthermore, a higher percentage of monocytes, neutrophils and eosinophils were observed in the fish collected from river and estuary during spring and summer. The study demonstrated that differences in sex, habitat and seasonal variation cause variation in hematology and plasma chemistry reference intervals for wild population of A. chalcoides when migrating between its natural habitats.

Storage related haematological and biochemical changes in Plasmodium falciparum infected and sickle cell trait donor blood

BackgroundIn sub-Saharan Africa where sickle cell trait (SCT) and malaria is prevalent, significant proportions of blood donors may be affected by one or more of these abnormalities. The haemato-biochemical properties of SCT and asymptomatic malaria in donor blood have not been evaluated. This study evaluated the haemato-biochemical impact of SCT and asymptomatic malaria infections in citrate-phosphate-dextrose-adenine (CPDA-1) stored donor blood units.MethodsFifty-milliliters of sterile CPDA-1 anti-coagulated blood were drained into the sample pouch attached to the main blood bag. Ten units each of sickle cell/malaria negative, sickle cell and malaria positive blood were analyzed. Baseline and weekly haematological profiling and week 1, 3 and 5 concentrations of plasma haemoglobin, % haemolysis, sodium, potassium and chloride and lactate dehydrogenase (LDH) were assayed. Differences between baseline and weekly data were determined using one-way analysis of variance (ANOVA) and Kruskal-Wallis test, whereas differences between baseline parameters and week 1–3 data pairs were determined using paired t-test. P-value < 0.05 was considered statistically significant.ResultsStorage of SCT and malaria infected blood affected all haematological cell lines. In the SCT donors, red blood cells (RBC) (4.75 × 1012/L ± 1.43baseline to 3.49 × 1012/L ± 1.09week-5), haemoglobin (14.45 g/dl ± 1.63baseline to 11.43 g/dl ± 1.69week-5) and haematocrit (39.96% ± 3.18baseline to 33.22% ± 4.12week-5) were reduced. In the asymptomatic malaria group, reductions were observed in RBC (5.00 × 1012/L ± 0.75baseline to 3.72 × 1012/L ± 0.71week-5), haemoglobin (14.73 g/dl ± 1.67baseline to 11.53 g/dl ± 1.62week-5), haematocrit (42.72% ± 5.16baseline to 33.38% ± 5.80week-5), mean cell haemoglobin concentration (35.48 g/dl ± 1.84baseline to 35.01 g/dl ± 0.64week-5) and red cell distribution width coefficient of variation (14.81% ± 1.54baseline to 16.26% ± 1.37week-5). Biochemically, whereas plasma LDH levels significantly increased in asymptomatic malaria blood donors (319% increase at week 5 compared to baseline), SCT blood donors had the most significant increase in plasma potassium levels at week 5 (382% increase). Sodium ions significantly reduced in SCT/malaria negative and sickle cell trait blood at an average rate of 0.21 mmol/L per day. Moreover, elevations in lymphocytes-to-eosinophils and lymphocytes-to-neutrophils ratios were associated with SCT and malaria positive blood whilst elevation lymphocytes-to-basophils ratio was exclusive to malaria positive blood.ConclusionSevere storage lesions were significant in SCT or malaria positive donor blood units. Proper clinical evaluation must be done in prospective blood donors to ensure deferral of such donors.

A prediction model for primary aldosteronism when the salt loading test is inconclusive.

ObjectiveTo develop a prediction model to confirm or exclude primary aldosteronism (PA) in patients with an inconclusive salt loading test (SLT).ContextDiagnosis in patients with a suspicion of PA can be confirmed using an SLT. In case of inconclusive test results the decision about how to manage the patient is usually based on contextual clinical data.DesignWe included a retrospective cohort of 276 patients in the final analysis.MethodsAll patients underwent an SLT between 2005 and 2016 in our university medical center. The SLT was inconclusive (post-infusion aldosterone levels 140–280 pmol/L) in 115 patients. An expert panel then used contextual clinical data to diagnose PA in 45 of them. Together with 101 patients with a positive SLT this resulted in a total of 146 patients with PA. A total of 11 variables were used in a multivariable logistic regression analysis. We assessed internal validity by bootstrapping techniques.ResultsThe following variables were independently associated with PA: more intense potassium supplementation, lower plasma potassium concentration, lower plasma renin concentration before SLT and higher plasma aldosterone concentration after SLT. The resulting prediction model had a sensitivity of 84.4% and a specificity of 94.3% in patients with an inconclusive SLT. The positive and negative predictive values were 90.5 and 90.4%, respectively.ConclusionsWe developed a prediction model for the diagnosis of PA in patients with an inconclusive SLT that results in a diagnosis that was in high agreement with that of an expert panel.

Neuromuscular blockade of atracurium in permissive hypercapnic versus normocapnic swine undergoing laparoscopy.

Neuromuscular blocking agents (NMBAs) are commonly used in experimental laparoscopy in swine undergoing carbon dioxide pneumoperitoneum. Hypercapnia may be present and may prolong NMBAs’ pharmacologic activity. The aim of this study is to evaluate the effect of permissive hypercapnia on the neuromuscular blockade of atracurium in swine. Six Large White swine weighing 30.5 ± 1.6 kg were sedated with intramuscular ketamine and medetomidine, after which anaesthesia was induced with propofol and maintained with sevoflurane. Atracurium 0.4 mg/kg was administered intravenously and the neuromuscular block monitored by acceleromyography during normocapnic and hypercapnic conditions (PaCO2 range 35–45 mmHg and 60–70 mmHg, respectively). Onset time and time to reach a train of four ratio (TOFR) of 0.7 and 0.9 were recorded. Cardiorespiratory parameters, electrolytes and acid-base status were measured under both conditions. Onset time was similar between the two conditions. Time to reach a TOFR of 0.7 and 0.9 (duration of the neuromuscular block) was longer in hypercapnic compared to normocapnic animals being 1325 ± 300 vs 855 ±111 (p = 0.002) and 1823 ± 434 vs 1218 ± 210 seconds (p = 0.005), respectively. Three hypercapnic swine had a TOF count of 2 and 1 instead of a count of 4 with fade. Permissive hypercapnia was associated with a decrease in pH from 7.444 ± 0.039 to 7.257 ± 0.025 (p < 0.001). No differences were observed for heart rate, end-tidal concentration of sevoflurane, body temperature and arterial haemoglobin saturation. Nonetheless, hypercapnic swine had a statistically significant increase in mean arterial pressure (p = 0.020) and plasma potassium concentration (p = 0.003). The values of PaCO2 achieved during hypercapnia were well tolerated in swine undergoing CO2 pneumoperitoneum for laparoscopy. Permissive hypercapnia increased the duration of the atracurium effect and caused an increase in the intensity of the neuromuscular block in few swine.