Plasma Ionized Calcium Levels Research Articles

Negative calcium balance despite normal plasma ionized calcium concentrations during citrate anticoagulated continuous venovenous hemofiltration (CVVH) in ICU patients

BackgroundSupplementation of calcium during continuous venovenous hemofiltration (CVVH) with citrate anticoagulation is usually titrated using a target blood ionized calcium concentration. Plasma calcium concentrations may be normal despite substantial calcium loss, by mobilization of calcium from the skeleton. Aim of our study is to develop an equation to calculate CVVH calcium and to retrospectively calculate CVVH calcium balance in a cohort of ICU-patients.MethodsThis is a single-center retrospective observational cohort study. In a subcohort of patients, all calcium excretion measurements in patients treated with citrate CVVH were randomly divided into a development set (n = 324 in 42 patients) and a validation set (n = 441 in 42 different patients). Using mixed linear models, we developed an equation to calculate calcium excretion from routinely available parameters. We retrospectively calculated calcium balance in 788 patients treated with citrate CVVH between 2014 and 2021.ResultsCalcium excretion (mmol/24 h) was − 1.2877 + 0.646*[Ca]blood,total * ultrafiltrate (l/24 h) + 0.107*blood flow (ml/h). The mean error of the estimation was − 1.0 ± 6.7 mmol/24 h, the mean absolute error was 4.8 ± 4.8 mmol/24 h. Calculated calcium excretion was 105.8 ± 19.3 mmol/24 h. Mean daily CVVH calcium balance was − 12.0 ± 20.0 mmol/24 h. Mean cumulative calcium balance ranged from − 3687 to 448 mmol.ConclusionDuring citrate CVVH, calcium balance was negative in most patients, despite supplementation of calcium based on plasma ionized calcium levels. This may contribute to demineralization of the skeleton. We propose that calcium supplementation should be based on both plasma ionized calcium and a simple calculation of calcium excretion by CVVH.Graphical abstract

Preliminary Results of Adding Meglumine Sodium Succinate to the Treatment of Patients with Moderate to Severe Acute Pancreatitis

Objective: to develop criteria of inclusion/noninclusion of patients for further randomized clinical trial of meglumine sodium succinate in patients with acute pancreatitis based on analysis of individual outcomes.Material and methods. The efficacy of treatment of patients with moderate-to-severe and severe acute pancreatitis (n=100, 23–65 years old) with meglumine sodium succinate (intravenous drip infusions, 10 ml/kg daily, for 11 days) was assessed. Data were collected by 10 medical centers as a part of an observational program developed in accordance with the requirements of the Guidelines and Clinical Trial Committee of the AllRussia Public Organization «Federation of Anesthesiologists and Reanimatologists» (FAR) and approved by local ethical committees of the institutions. Treatment was prescribed in accordance with national and international standards. The patients were divided into two groups based on the outcome: group 1 (n=81) included patients who survived, while the patients of group 2 (n=19) died. We analyzed demographic characteristics of the groups, life and illness history, physical examination, routine laboratory and instrumental investigation data. The obtained results were statistically analyzed.Results. We identified several factors occurring during hospitalization and/or transfer to intensive care unit (ICU), which could be predictors of adverse outcome and had varying impact on the risk of death in patients treated with the study drug. High-risk factors included stupor, platelet count below 248.5×109/l, base excess (BE) less than -2.9 mmol/l, and urea above 11.85 mmol/l. Risk factors included body temperature below 37.1°C, plasma creatinine above 237 µmol/l, and glucose above 9.45 mmol/l. Mottled skin and plasma ionized calcium levels below 1.13 mmol/l were considered probable risk factors.Conclusion. Determined prognostically significant predictors of adverse outcome in patients with acute pancreatitis receiving Reamberin should be considered when selecting inclusion/exclusion criteria for the randomized controlled comparative clinical study of the efficacy of meglumine sodium succinate in patients with acute pancreatitis.

WNK4 limits distal calcium losses following acute furosemide treatment.

The distal nephron is essential for calcium homeostasis. This is evidenced by disordered calcium transport following disrupted distal nephron function occurring in salt‐wasting tubulopathies or with diuretic use. A plethora of studies support a role for WNK4 in thick ascending limb (TAL) and distal convoluted tubule ion transport with most studies focusing on sodium transport. Little is known about the in vivo role of WNK4 in regulating calcium homeostsis. Here, we investigated the role of WNK4 in regulating distal nephron calcium transport using WNK4 knockout animals (WNK4−/−). As has been shown previously, we found that baseline urinary calcium levels are normal following WNK4 deletion. Following acute treatment with the loop diuretic, furosemide, which causes hypercalciuria through TAL inhibition, WNK4−/− animals demonstrated increased calcium wasting compared with wild‐type controls. WNK4−/− animals had decreased TRPV5 expression along DCT2 supporting a mechanistic role for this calcium channel in the increased calciuresis. As this supported the hypothesis that WNK4−/− animals have a tendency toward calcium wasting under stress, we tested the effects of a calcium‐deplete diet on urinary calcium excretion. Urinary calcium excretion and plasma ionized calcium levels were not different between control and knockout animals following consumption of a calcium‐deplete diet. Our data show that WNK4, via regulation of TRPV5, limits distal calcium losses following acute treatment with furosemide; however, WNK4 deletion does not affect the chronic renal response to dietary calcium depletion. Our data reveal an in vivo role for WNK4 in distal nephron calcium handling that is important for fine‐tuning calcium reabsorption.

Hemodialysis: Core Curriculum 2014

From the Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN. Received May 1, 2013. Accepted in revised form July 1, 2013. Originally published online November 21, 2013. Address correspondence to Thomas A. Golper, MD, S3303 Medical Center North, Vanderbilt University Medical Center, 21st Ave S, Nashville, TN 37232. E-mail: thomas.golper@vanderbilt. edu 2013 by the National Kidney Foundation, Inc. 0272-6386/$36.00 http://dx.doi.org/10.1053/j.ajkd.2013.07.028 PRINCIPLES OF DIALYSIS AND HOW MODALITIES DIFFER

Replacement of acetate with citrate in dialysis fluid: a randomized clinical trial of short term safety and fluid biocompatibility

BackgroundThe majority of bicarbonate based dialysis fluids are acidified with acetate. Citrate, a well known anticoagulant and antioxidant, has been suggested as a biocompatible alternative. The objective of this study was to evaluate short term safety and biocompatibility of a citrate containing acetate-free dialysis fluid.MethodsTwenty four (24) patients on maintenance dialysis three times per week, 13 on on-line hemodiafiltration (HDF) and 11 on hemodialysis (HD), were randomly assigned to start with either citrate dialysis fluid (1 mM citrate, 1.5 mM calcium) or control fluid (3 mM acetate, 1.5 mM calcium) in an open-labeled cross-over trial (6 + 6 weeks with 8 treatments wash-out in between). Twenty (20) patients, 11 on HDF and 9 on HD were included in the analyses. Main objective was short term safety assessed by acid–base status, plasma ionized calcium and parathyroid hormone (PTH). In addition, biocompatibility was assessed by markers of inflammation (pentraxin 3 (PTX-3), CRP, IL-6, TNF-α and IL-1β) and thrombogenicity (activated partial thromboplastin time (APTT) and visual clotting scores).ResultsNo differences dependent on randomization order or treatment mode (HD vs. HDF) were detected. Citrate in the dialysis fluid reduced the intra-dialytic shift in pH (+0.04 week 6 vs. +0.06 week 0, p = 0.046) and base excess (+3.9 mM week 6 vs. +5.6 mM week 0, p = 0.006) over the study period. Using the same calcium concentration (1.5 mM), citrate dialysis fluid resulted in lower post-dialysis plasma ionized calcium level (1.10 mM vs. 1.27 mM for control, p < 0.0001) and higher post-dialysis PTH level (28.8 pM vs. 14.7 pM for control, p < 0.0001) while pre-dialysis levels were unaffected. Citrate reduced intra-dialytic induction of PTX-3 (+1.1 ng/ml vs. +1.4 ng/ml for control, p = 0.04) but had no effect on other markers of inflammation or oxidative stress. Citrate reduced visual clotting in the arterial air chamber during HDF (1.0 vs. 1.8 for control, p = 0.03) and caused an intra-dialytic increase in APTT (+6.8 s, p = 0.003) without affecting post-dialysis values compared to control.ConclusionsDuring this small short term study citrate dialysis fluid was apparently safe to use in HD and on-line HDF treatments. Indications of reduced treatment-induced inflammation and thrombogenicity suggest citrate as a biocompatible alternative to acetate in dialysis fluid. However, the results need to be confirmed in long term studies.Trial registrationISRCTN: ISRCTN28536511

Magnesium Supplementation Does Not Affect Blood Calcium Level in Treated Hypoparathyroid Patients

Magnesium is involved in the homeostasis of calcium metabolism, and magnesium deficiency may lead to clinically significant hypocalcemia. We have had two cases in our department in which treated hypoparathyroid patients with stable calcium levels developed hypercalcemia in conjunction with supplementary magnesium use. To our knowledge, there has been no prospective study looking at the effect of supplementary magnesium on calcium homeostasis in hypoparathyroid patients. The aim of this pilot study was to evaluate whether magnesium treatment affects plasma calcium levels in hypoparathyroid patients. We conducted a prospective, two-phase, uncontrolled treatment trial at a referral center of endocrine disorders. We enrolled treated (calcium + vitamin D analog) hypoparathyroid patients with normal plasma magnesium levels. Three weeks of treatment with oral magnesium (350 mg/d) were followed by 2 wk off treatment. We compared the plasma ionized calcium level after 3 wk of treatment to the pretreatment value. Plasma calcium, phosphate, magnesium, and creatinine levels were measured before treatment, after 3 wk on magnesium, and 2 wk after stopping magnesium treatment. Ten patients completed the trial. Supplementary treatment with magnesium for 3 wk did not change calcium levels in these patients. Magnesium supplementation induced a small but statistically significant increase in the plasma magnesium level, but levels of phosphate and creatinine remained stable. Magnesium supplementation did not influence plasma calcium levels in treated hypoparathyroid patients.

Recumbence syndrome around calving in cattle: A Study of Risk Factors of Milk Fever in Dairy units in Dar Es Salaam, Tanzania

A recumbency syndrome around calving in cattle was reported in Dar es salaam during the dry season and was thought to be associated with milk fever a disease common in high producing mature dairy cattle and is related to age, dry cow nutrition and general management. This study was conducted to establish the length of dry period of cows, determine the nutritive value of concentrate supplement fed to dry pregnant cows, levels of crude protein, calcium, phosphorus and magnesium and also to establish presence of other periparturient diseases in semi intensively kept dairy crosses cattle. The nutritive value was determined in 70 samples of concentrate supplement collected from purposively selected farms. Semi structured, pre tested questionnaires were used to get information on individual farms dry pregnant cows management including length of dry period of cows, feeding regime, supplement feeding also to establish presence of other periparturient diseases. Only 22.9% farmers dry cows around the recommended 60 days, 52 % dry cows between 60 – 90 days, about 21.4% of the farmers dry their cows more than 90 days, while 1.4% continue to milk their cows until the next calf is born. About 34% of the farmers reported to have experienced the problem of milk fever during the dry season. Daily intake of CP in concentrate supplement ranged from 110 – 245g, calcium 0 – 80 g, phosphorus 16 – 25.3 g and magnesium 5 – 10.2 g. Daily intake of nutrients from herbage was 3.7 g CP, 7.98 g Ca, 1.3 g P, and 0.6 g Mg. The daily recommended levels in dry cow ration are 150g, 20-40g, 5 g, and 10 g DM for crude protein, calcium, magnesium and phosphorus respectively. Periparturient diseases reported by farmers were mastitis 44%, retained placenta 43%, udder edema 20%, delayed estrus 24%, and repeated heat 24%. These findings indicated that dry period length and management of dry cows at close up period is variable among livestock farmers. Daily requirements of nutrients were within recommended limits. It is likely that the recumbency syndrome reported was due to hypocalcaemia but further studies should be conducted to assess plasma ionized calcium levels peripartum in Dar es salaam. Starvation ketosis in the dry season when herbage nutritive value is low may not be ruled out.

Use of plasma ionized calcium levels and Ca2+ substitution response patterns as prognostic parameters for ileus and survival in colic horses

Summary Objective: Hypocalcaemia is a common finding in horses with enterocolitis and severe gastrointestinal disorders. The aims of this study were to investigate in colic horses !)the parameters related to hypocalcaemia, 2)the influence of hypocalcaemia on outcome and 3)the possible beneficial effect of Ca2+ substitution. Design: Randomized controlled trial. Setting: Intensive care unit. Patients: One hundred forty‐four horses that were admitted with an acute abdomen during a 1.5 year period were enrolled and daily evaluated for clinical criteria and whole blood ionized Ca levels. Colic horses with hypocalcaemia were randomly assigned to receive Ca2+. Interventions: Analysis of heparinised whole blood samples. Horses that were assigned to be treated received 400 mEq Ca2+ diluted in 10L of Ringer's lactate solution every 24 h until low reference range limits were obtained or until death. Measurements and main results: 88% of all colic patients showed blood ionized Ca levels below the reference range at the time of admission. Multivariable analysis revealed that the presence of reflux signs of endotoxaemia increased Packed Cell Volume (PCV) alkalinization of pH and the interaction PCV/pH all predispose colic horses to low ionized Ca2+ levels at the time of admission. The Odds for developing ileus during hospitalization are ± 11.94 times larger for horses in the “very low” calcaemia interval in comparison with normocalcaemic horses. The Odds for fatal outcome are respectively ± 9.82 and 8.33 times larger for horses in the “very low” and “low” calcaemia interval. Ca2+ substitution increased the probability of survival provided that Ca2+ levels could be normalized. The lack of an upward calcaemia response despite repetitive Ca2+ substitutions can be guarded as a poor ominous sign. Conclusions: Hypocalcaemia in colic horses is of prognostic relevance both with regard to survival as to the probability of development of ileus during hospitalization. This study shows the importance of routine measurement of ionized calcium levels in colic horses. Moreover correction of hypocalcaemia seems to improve clinical outcome.

Bone calcium changes during diabetic ketoacidosis: A comparison with lactic acidosis due to volume depletion

In this study, we aimed to compare bone calcium system changes from children with diabetic ketoacidosis or acute metabolic acidosis due to dehydration to find out the relative contribution of metabolic acidosis and diabetes-related factors on expected negative calcium balance. We studied a set of non-invasive parameters of bone remodeling in 16 children with diabetic ketoacidosis due to new onset type 1 diabetes and 25 children with acute metabolic acidosis due to dehydration complicating acute gastroenteritis before and after the correction of acidosis. The two groups of subjects were matched for age, sex, pubertal status, and degree of metabolic acidosis and dehydration. A group of 18 age and sex-matched healthy children served as the control group. Plasma ionized calcium levels were increased in both groups, significantly more so in diabetic ketoacidosis. While osteoblastic markers, osteocalcin and alkaline phosphatase, were depressed to a comparable degree in both groups, urinary calcium/creatinine ratio and hydroxyproline excretion were significantly greater in diabetic ketoacidosis. No significant changes in calcitrophic hormone (intact PTH, calcitonin, 25-hydroxy Vitamin D3) levels were observed. All study parameters except for serum phosphate levels behaved in parallel in both clinical conditions, and abnormalities disappeared with the correction of acidosis except for IGF-1, which remained low in diabetic subjects. In conclusion, our results suggest that, in diabetic ketoacidosis, the observed severe negative calcium balance occurred through diminished bone formation mediated by metabolic acidosis per se and increased bone mineral dissolution and bone resorption because of severe insulin deficiency and secondarily via metabolic acidosis. Observed changes appear to be independent of calcitrophic hormones.

An acute inflammatory response alters bone homeostasis, body composition, and the humoral immune response of broiler chickens

To quantify the effects of an acute phase response in broilers, chicks were injected with 1 mg/kg Escherichia coli lipopolysaccharide (LPS) at 15 and 23 d. Lipopolysaccharide injection increased feed/gain (P = 0.03), increased liver weight (P = 0.09), and decreased tibia calcium (P = 0.05) and breaking strength (P < 0.04) by d 28. In a second experiment, 3 d postinjection of chicks at d 31, LPS decreased BW (P < 0.01), breast weight (P = 0.08), and tibia breaking strength (P = 0.05), and increased liver weight (P < 0.01), mortality (P = 0.05), and titers to bronchitis and Mycoplasma gallisepticum that were induced by vaccination at hatch or by field exposure, respectively (P = 0.04). For experiment 3, chicks were challenged with LPS at 23d and 27d. Lipopolysaccharide-injected chicks had decreased BW (P = 0.06), feed consumption (P = 0.05), tibia weight (P< 0.01), and breaking strength (P < 0.01), and increased feed/gain (P < 0.01), liver weight (P < 0.01), and plasma ionized calcium level (P = 0.08). For experiment 4, chicks were injected with 0, 0.33, 0.66, 1.00, or 4.25 mg of LPS/kg of BW. There was an inverse relationship between LPS level and BW or bone breaking strength. Experiment 5 compared 4 broiler strains. Strain x LPS interactions were found for bone breaking strength (P = 0.01). Mortality before LPS challenge was inversely correlated to liver weight (r2 = 0.95, P = 0.02) and bone breaking strength (r2 = 0.99, P = 0.01) only after an LPS challenge.

Evaluation of plasma ionized magnesium levels in neonatal hyperbilirubinemia.

Plasma levels of ionized magnesium (IMg) measured by ion-selective electrode were investigated in neonatal hyperbilirubinemia by comparing the newborns with (> or =205 microM) and without (<205 microM) significant hyperbilirubinemia (groups of severe and moderate hyperbilirubinemia, respectively). Serum bilirubin, plasma IMg, and ionized calcium (ICa) levels were determined in 165 healthy term newborns with nonhemolytic indirect hyperbilirubinemia during the first 10 d of life. Mean serum bilirubin, plasma IMg, and ICa levels were 200.1 +/- 126.5 microM, 0.54 +/- 0.12 mM, and 1.15 +/- 0.12 mM, respectively, in 165 newborns whose mean postnatal age was 156.1 +/- 46.5 h, and there was a significant positive correlation between the mean serum bilirubin and plasma IMg levels (r = 0.535, p < 0.001). Serum bilirubin levels (304.4 +/- 83.8 microM versus 94.1 +/- 54.7 microM) and plasma IMg levels (0.6 +/- 0.12 mM versus 0.49 +/- 0.1 mM) were significantly higher and plasma ICa levels (1.13 +/- 0.12 mM versus 1.18 +/- 0.12 mM) were significantly lower in the group of severe hyperbilirubinemia (n = 83) when compared with the group with moderate hyperbilirubinemia (n = 82). Seventeen of the 83 cases of severe hyperbilirubinemia had IMg levels above the normal range (> or =0.69 mM), whereas none of the 82 cases of moderate hyperbilirubinemia had elevated IMg levels. Fifteen of the 17 with high IMg levels had bilirubin levels >290 microM. Results of the present study suggest that increase in plasma IMg may be due to extracellular movement of Mg, a principally intracellular ion, resulting from generalized cellular injury including neurons and erythrocytes. Considering neuroprotective functions and beneficial effects of Mg ion in improving neurologic outcome, we also may speculate the possibility of a neuroprotective role or a compensatory mechanism in IMg increase against emerging toxicity risk of increasing serum bilirubin levels.

Randomized crossover study comparing the phosphate-binding efficacy of calcium ketoglutarate versus calcium carbonate in patients on chronic hemodialysis

The objective of the study was to evaluate the phosphate-binding efficacy, side effects, and cost of therapy of calcium ketoglutarate granulate as compared with calcium carbonate tablets in patients on chronic hemodialysis. The study design used was a randomized, crossover open trial, and the main outcome measurements were plasma ionized calcium levels, plasma phosphate levels, plasma intact parathyroid hormone (PTH) levels, requirements for supplemental aluminum- aminoacetate therapy, patient tolerance, and cost of therapy. Nineteen patients on chronic hemodialysis were treated with a dialysate calcium concentration of 1.25 mmol/L and a fixed alfacalcidol dose for at least 2 months. All had previously tolerated therapy with calcium carbonate. Of the 19 patients included, 10 completed both treatment arms. After 12 weeks of therapy, the mean (+/-SEM) plasma ionized calcium level was significantly lower in the ketoglutarate arm compared with the calcium carbonate arm (4.8+/-0.1 mg/dL v 5.2+/-0.1 mg/dL; P = 0.004), whereas the mean plasma phosphate (4.5+/-0.3 mg/dL v 5.1+/-0.1 mg/dL) and PTH levels (266+/-125 pg/mL v 301+/-148 pg/mL) did not differ significantly between the two treatment arms. Supplemental aluminum-aminoacetate was not required during calcium ketoglutarate treatment, while two patients needed this supplement when treated with calcium carbonate. Five of 17 (29%) patients were withdrawn from calcium ketoglutarate therapy within 1 to 2 weeks due to intolerance (anorexia, vomiting, diarrhea, general uneasiness), whereas the remaining 12 patients did not experience any side effects at all. The five patients with calcium ketoglutarate intolerance all had pre-existing gastrointestinal symptoms; four of them had received treatment with cimetidine or omeprazol before inclusion into the study. Calculations based on median doses after 12 weeks showed that the cost of the therapy in Denmark was 10 times higher for calcium ketoglutarate compared with calcium carbonate (US$6.00/d v US$0.65/d). Calcium ketoglutarate may be an effective and safe alternative to treatment with aluminum-containing phosphate binders in patients on hemodialysis who are intolerant of calcium carbonate or acetate because of hypercalcemia. However, care must be exercised when dealing with patients with pre-existing gastrointestinal discomfort. Due to the high cost of the therapy, calcium ketoglutarate should be used only for selected patients. (Am J Kidney Dis 1998 Feb;31(2):257-62)

High-normal calcium (1.35 mmol/I) dialysate in patients on CAPD: efficient and safe long-term control of plasma calcium, phosphate, and parathyroid hormone

The aim of the present study was to examine the long-term efficacy and safety of treatment with a high-normal calcium dialysate with a calcium concentration of 1.35 mmol/l in patients on CAPD. This dialysate calcium concentration is close to the high-normal plasma ionized calcium level aimed at in dialysis patients in order to suppress the parathyroid hormone secretion. The end-points of the study were (1) plasma ionized calcium (iCa) and phosphate (P) levels, (2) plasma intact parathyroid hormone (PTH) levels, (3) doses of calcium carbonate and alfacalcidol, (4) requirements of Al-containing phosphate binders, and (5) bone mineral density (BMD). Thirty-seven non-selected patients on CAPD treatment were followed for an average of 10 months after switching from a dialysate Ca of 1.75 to 1.35 mmol/l. After 1 week, a significant decrease of mean iCa from 1.26 +/- 0.01 to 1.23 +/- 0.01 mmol/l (P < 0.05) and an increase of median PTH from 80 to 135 pg/ml (P < 0.01) were seen. From the 2nd week and onwards, however, basal levels of iCa and PTH were restored and remained stable. mean plasma iCa was kept within 1.23-1.31 mmol/l; mean plasma P below 1.65 mmol/l and median PTH within 52-135 pg/ml. Episodes of hypercalcaemia were few (1.2 cases of plasma iCa > 1.45 mmol/l per 100 treatment weeks), and the need for Al-containing P binders low with only five patients requring this treatment for isolated and four patients for repeated episodes of hyperphosphataemia or hypercalcaemia. After switching from a dialysate Ca of 1.75 to 1.35 mmol/l, the doses of calcium carbonate and alfacalcidol could be significantly increased. Furthermore, using the dialysate Ca of 1.35 mmol/l made it possible to induce a controlled increase of PTH levels to 80-100 pg/ml by a temporarily discontinuation of alfacalcidol and/or a reduction of calcium carbonate dosage in the patients where PTH had become suppressed to levels below the upper normal limit. The intention of the treatment was to maintain PTH levels within 1.5-2.5 times the upper normal limit for non-uraemic patients. Pre-study BMD of the vertebral bodies L2-L4 and of the femoral neck were normal and not significantly different from post-study measurements. The present study demonstrated that when using a high-normal dialysate Ca concentration of 1.35 mmol/l in non-selected patients on CAPD treatment, high-normal plasma iCa and near-normal plasma P levels could be readily achieved with a minimal risk of incidental hypercalcaemia despite use of calcium carbonate as the main P binder. As a consequence of the tight Ca and P regulation, minimal doses of alfacalcidol were required to keep PTH within acceptable limits. We recommend this dialysate Ca concentration as a first-choice therapy for the majority of patients starting on CAPD treatment.

Efficacy and mode of action of manidipine: A new calcium antagonist

Clinical studies were performed on patients with mild-to-moderate essential hypertension to elucidate the efficacy and mode of action of manidipine. Augmentation of diuresis and natriuresis during the short- and long-term phases of manidipine treatment was found in essential hypertensive patients. Manidipine partly inhibited sympathetic nerve activity and suppressed the mean arterial pressure response to infused norepinephrine. This drug also inhibited aldosterone secretion. Natriuresis and suppression of pressor responses may contribute to the depressor mechanisms of this drug. After manidipine administration, increases in both urinary calcium and uric acid were observed. Both parameters were positively correlated with urinary excretion of sodium, and the inhibition of tubular reabsorption may contribute to this mechanism. The increase in plasma parathyroid hormone may also be involved in the calciuresis produced by manidipine. Patients with lower plasma renin activity or lower plasma ionized calcium levels showed a greater reduction in blood pressure after manidipine administration. Thus the hypotensive action of manidipine was more pronounced in low renin essential hypertension.

Different Plasma Ionized Calcium Correlations with Blood Pressure in High and Low Renin Normotensive Adults in Utah

Plasma ionized calcium levels have been shown to be lower than normotensive control levels in hypertensive patients with low plasma renin activity and higher than control levels in hypertensive patients with high renin activity; they did not differ between high and low plasma renin activity groups of normotensive controls. To see if ionized calcium may have different relationships with blood pressure across renin categories in normotensive individuals, plasma ionized calcium was measured on 875 healthy individuals, ages 3 to 83, who had never been diagnosed as having hypertension. Blood pressures were measured in the sitting, standing, and supine positions, along with pressures measured during two stress maneuvers: isometric handgrip and a 50 degrees tilt from a supine position. There was no linear correlation of blood pressure with plasma ionized calcium in the entire sample of youths or adults. However, after dividing the adults into tertiles based on plasma renin activity, there were significant inverse correlations between ionized calcium and systolic and diastolic blood pressure in the low renin group (r = -0.16 to -0.25, P less than or equal to .05), while the systolic blood pressure correlations were significantly positive in the high renin group (r = 0.14 to 0.22, P less than or equal to .05). Adults with normal renin levels did not have any significant correlations of plasma ionized calcium with blood pressure. These confounding effects of renin were greater for systolic than for diastolic blood pressure. These correlations within renin tertiles occurred even though there were no differences in mean blood pressure, plasma ionized calcium, total plasma protein and plasma sodium across renin categories.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of age on egg production in the domestic hen

The effect of age on egg production was investigated in the domestic fowl. The rate of egg production was reduced with increasing age and the incidence of thin-shelled and cracked eggs was markedly increased. Older hens which remained in lay produced fewer but larger eggs than the younger birds. The ovaries of these two groups of hens were of similar appearance but the largest preovulatory follicle and the oviduct were significantly heavier in the older birds. No differences in the circulating levels of progesterone or estradiol were apprent between the young and old birds but the activity of the renal 25-hydroxycholecalciferol 1α-hydroxylase was found to be significantly reduced with age. Circulating levels of total and ionized calcium were very similar in the young and old laying birds, plasma ionized calcium levels being markedly depressed during egg shell calcification in both groups. The decreased rate of ovulation in the older birds and the increase with age in the size of the follicles ovulated is thought to be associated with a reduced rate of recruitment of follicles for rapid growth followed by a prolonged period of follicular growth and development. The poor calcification of egg shell in old birds would appear to be due to some dysfunction of the shell gland, possibly associated with reduced synthesis of 1,25-dihydroxycholecalciferol by the kidney. The maintenance of plasma ionized calcium concentrations does not appear to be of primary importance in this respect.

Plasma parathyroid hormone during acute volume expansion in the rat

Various studies have suggested the possibility that volume expansion may increase parathyroid hormone (PTH) secretion. PTH appears to have renal effects consistent with the actions of a natriuretic and diuretic and the possibility exists that PTH may play a physiological role in volume homeostasis. The present studies were designed to examine whether PTH levels in plasma from rats was influenced by acute volume expansion and whether such effects were independent of alterations in plasma ionized calcium concentration. Volume expansion with calcium-free bicarbonate Ringers (10% of body weight, IV) led to a drop in plasma ionized calcium from 1.08 to 0.92 mMol/1 (p < 0.01) while plasma PTH concentration was increased from 67.2 to 114.2 pMol/1. Volume expansion with bicarbonate Ringers solution (also 10% of body wt, IV) which contained 1.8 mM CaCl 2 was not associated with any significant change in either plasma ionized calcium or plasma PTH concentration. However, measurements of blood packed cell volume (PCV) revealed that infusion resulted in a drop in PCV from 49.7 to 41.1% (p < 0.01). This represents a dilution of plasma of approximately 42%. The absence of any drop in plasma PTH during isocalcemic volume expansion suggests an underlying stimulus to PTH secretion during volume expansion independent of plasma ionized calcium levels.

Respiratory alkalosis and reduced plasmatic concentration of ionized calcium in rats treated with 1,25 dihydroxycholecalciferol.

The daily administration of supraphysiological doses of 1,25 dihydroxycholecalciferol (0.1-2.5 micrograms/d/100 g body weight) to rats, produced respiratory alkalosis. With the doses of 0.1-0.2 micrograms/d/100 g and feeding a diet with 0.7% of calcium, calcemias did not exceed 2.75 mM, and significantly reduced plasma ionized calcium levels were measured. The latter phenomenon was found associated with increased urinary excretion of cAMP, soft tissue calcium content, and polyuria with hypostenuria, all known effects of parathyroid hormone. These effects were absent in thyroparathyroidectomized rats treated in the same fashion. Present results suggest that the stimulus of low levels of plasma ionized calcium overcomes the probably inhibitory effect of the steroid on parathyroid hormone secretion.

Determinants of reperfusion cardiac electrical activity after cold cardioplegic arrest during coronary bypass surgery

In a prospective study of 99 patients with coronary artery disease, reperfusion of the heart after a period of ischemia (protected by contemporary techniques of myocardial preservation) resulted in spontaneous resumption of cardiac electrical activity in 53%, spontaneous defibrillation in 10%, reperfusion ventricular fibrillation (VF) in 32% and indeterminate rhythm in 5%. In hearts spontaneously developing rhythms excluding VF (as opposed to hearts requiring direct-current shock), factors significantly associated were a higher plasma potassium concentration (5.2 vs 4.8 mEq/liter), shorter reperfusion time (1 vs 4 minutes), higher plasma magnesium concentration (1.36 vs 1.25 mg/dl) and a lower myocardial temperature (27 vs 32°C). The duration of ischemia, arterial blood gas levels, plasma catecholamine levels, plasma ionized calcium levels, volume of cardioplegia and mean arterial pressure did not relate to occurrence of spontaneous episodes. However, VF developed in 39 of 52 patients (75%) with spontaneous resumption of electrical activity. This event was associated with lower myocardial temperature. Thus, direct-current shocks were ultimately required in 77 of the 99 patients (78%). Although certain thermal, biochemical and hemodynamic variables facilitate spontaneous resumption of cardiac rhythm, the development of VF may negate the potential benefit of this event in the prevention of myocardial damage from directcurrent defibrillation.

Renal handling of calcium in fasting subjects: Relation to ketosis and plasma ionized calcium level

Renal handling of calcium in fasting subjects: Relation to ketosis and plasma ionized calcium level