Infusion Of Calcium Gluconate Research Articles

Direct in vivo comparison of calcium-regulated parathyroid hormone secretion in normal volunteers and patients with secondary hyperparathyroidism.

The regulation of PTH secretion by calcium is altered in patients with primary hyperparathyroidism. A similar disturbance may occur in secondary hyperparathyroidism, but direct in vivo comparisons of PTH secretion in normal subjects and those with secondary hyperparathyroidism have not been made. Thus, 13 patients with end-stage renal failure and secondary hyperparathyroidism and 20 healthy volunteers underwent dynamic tests of PTH secretion. Changes in ionized calcium were induced by 2-h iv infusions of calcium gluconate or sodium citrate on consecutive days, and the sigmoidal relationship between serum ionized calcium and PTH levels was examined. During sodium citrate infusions, serum ionized calcium levels decreased by 0.21 +/- 0.04 and 0.20 +/- 0.05 mmol/L, respectively (mean +/- SD), in normal volunteers and dialyzed patients (P = NS). Serum PTH levels rose from 27 +/- 7 to 107 +/- 33 pg/mL in controls and from 480 +/- 238 to 859 +/- 412 pg/mL in dialyzed subjects; thus, maximum PTH levels were 396% of preinfusion values in normal subjects, but only 79% greater than baseline values in dialyzed patients (P < 0.001). During the first 30 min of calcium infusions, the increase in serum ionized calcium did not differ between groups, but PTH levels fell more rapidly in normal volunteers; values were 24% of preinfusion levels in controls, but only 56% of the baseline in dialyzed patients (P < 0.01) after 30 min. Minimum PTH levels were attained after 50 min of calcium infusion in normal volunteers and after 70 min in dialyzed patients. The derived values for set-point were 1.21 +/- 0.04 and 1.24 +/- 0.06 mmol/L, respectively, in control and dialyzed subjects (P = NS). These results do not support the contention that the set-point for calcium-regulated PTH secretion is greater than normal in patients with secondary hyperparathyroidism due to end-stage renal disease.

Annular dystrophic calcinosis cutis in an infant

Dystrophic calcinosis curls occurs in the heels of newborns subjected to repeated heel sticks, l in infants who have received calcium gluconate infusions, 24 and in children who have undergone electroencephalography with calcium chloride-containing paste on abraded skin. 5 The usual appearance is of scattered yellow-white papules and nodules. Radiologic examination confirms the presence of amorphous calcification. We report annular dystrophic calcinosis cutis in an infant who had received both calcium chloride and sodium bicarbonate intravenously.

Role of prostaglandins in the renal response to calcium infusion

The effects of intrarenal infusions of calcium gluconate (10 and 100 micrograms Ca.kg-1.min-1) on renal hemodynamics and on renal excretory function were studied in anesthetized mongrel dogs. In one group, the two doses of calcium were infused for 30 min each (1 ml/min). In a second group, the same doses were administered 30 min after the start of an infusion of prostaglandin (PG) inhibitors (intrarenal indomethacin, 10 micrograms.kg-1.min-1, or intravenous bolus injection of meclofenamate, 5 mg/kg). No change with physiological significance was observed during the infusion of 10 micrograms Ca.kg-1.min-1. However, the infusion of 100 micrograms Ca.kg-1.min-1 induced increases (P less than 0.05) in glomerular filtration rate (50%), sodium excretion rate (180%), and fractional excretion of sodium (160%), with respect to control precalcium values. All these changes were prevented by the concurrent administration of PG synthesis inhibitors. Urinary PGE2 and 6-keto-PGF1 alpha increased 220 and 85%, respectively, during the infusion of 100 micrograms Ca.kg-1.min-1, but both decreased (P less than 0.05) below basal levels during the concurrent administration of PG synthesis inhibitors. The infusion of 100 micrograms Ca.kg-1.min-1 decreased (P less than 0.05) renal blood flow by 16% during the administration of PG synthesis inhibitors. These results suggest that PGs are mediating the increase in hemodynamic and excretory factors induced by the intrarenal infusion of 100 micrograms Ca.kg-1.min-1.

Vitamin D metabolism in chronic childhood hypoparathyroidism: Evidence for a direct regulatory effect of calcium

We noted the presence of elevated levels of circulating 1,25-dihydroxyvitamin D (83 pg/ml (200 pmol/L), with low total serum calcium concentration (6.5 mg/dl (1.88 mmol/L), in an untreated adolescent boy with hypoparathyroidism. Furthermore, an inverse relationship between total serum calcium and circulating 1,25-dihydroxyvitamin D levels was evident during treatment with 1,25-dihydroxyvitamin D3. We examined this relationship with a 33-hour intravenous infusion of calcium gluconate in the absence of exogenous 1,25-dihydroxyvitamin D3 therapy. The infusion was accompanied by a gradual increase of both total serum calcium and blood ionized calcium concentrations from hypocalcemic to normocalcemic ranges, and produced a 50% reduction in circulating 1,25-dihydroxyvitamin D values, with minimal changes in circulating phosphorus, magnesium, and 25-hydroxyvitamin D values. These results suggest that calcium-dependent, parathyroid hormone-independent regulation of 1,25-dihydroxyvitamin D production may exist in human beings.

Stimulation of renin release by intrarenal calcium infusion.

The effects of intrarenal infusions of calcium gluconate (10 and 100 micrograms Ca/kg/min) on renin secretion were studied in anesthetized mongrel dogs. In one group, the two doses of calcium were infused for 30 minutes each (1 ml/min). In a second group, the same doses were administered 30 minutes after the start of infusion of prostaglandin synthesis inhibitors (indomethacin 10 micrograms/kg/min intrarenal or injection of meclofenamate 5 mg/kg i.v. bolus). Mean arterial pressure, renal blood flow, and glomerular filtration rate remained unchanged during the infusion of calcium in both groups. The infusion of 10 micrograms Ca/kg/min increased renin secretion 77% and sodium excretion 123%. During the infusion of 100 micrograms Ca/kg/min, renin secretion was not different from precalcium values, whereas urinary 6-keto-PGF1 alpha, urine flow, sodium, potassium, and calcium excretion rates were increased (p less than 0.05). During the administration of prostaglandin synthesis inhibitors, the urinary 6-keto-PGF1 alpha levels were reduced, and the infusion of 10 micrograms Ca/kg/min failed to increase renin secretion, sodium excretion, or 6-keto-PGF1 alpha excretion rates. The infusion of 100 micrograms Ca/kg/min during prostaglandin synthesis inhibition did not modify urine flow or sodium excretion; however, potassium and calcium excretions increased. It is concluded that 1) the intrarenal infusion of small doses of calcium gluconate is capable of stimulating renin secretion through a prostaglandin-mediated mechanism, and 2) the stimulation of renin secretion as well as the increase in sodium excretion induced by calcium are independent of hemodynamic alterations.

Regulation of Calciotropic Hormonesin Vivoin the New Zealand White Rabbit*

Serum levels of ionized calcium, 25-hydroxyvitamin D (25OHD), and 1,25-dihydroxyvitamin D[1,25-(OH)2D], intact immunoreactive PTH and calcitonin were measured in the laboratory rabbit to evaluate the role of these calciotropic hormones in calcium homeostasis in this species. We confirm the finding of previous researchers that the resting serum ionized and total calcium concentrations are elevated in rabbits compared to those in other species (ionized calcium, 1.70 +/- 0.13 mmol/liter; total calcium, 3.23 +/- 0.25 mmol/liter). The serum calcium concentrations in animals maintained on a breeding farm or in the laboratory did not differ significantly despite nearly 3-fold higher levels of vitamin D in the feed at the farm, which were associated with 3- to 4-fold higher concentrations of 25OHD and 1,25-(OH)2D. Baseline intact PTH levels for the farm and laboratory populations also did not differ significantly and averaged 69.4 +/- 43.6 human pgeq/ml (laboratory animals, 52.1 +/- 28.4; breeding farm animals, 86.0 +/- 49.5 human pgeq/ml). Infusions of calcium gluconate or EDTA for 15 min into anesthetized animals in the laboratory induced dramatic reciprocal changes in the measured circulating levels of PTH. Calcium gluconate infusions (190-300 nmol/g BW) produced 50-85% increases in serum ionized calcium, which were accompanied by 74-91% decreases in PTH levels (from 68.8 +/- 29.2 at time zero to 10.1 +/- 3.1 human pgeq/ml at 15 min) as well as 7-fold increases in calcitonin levels. EDTA infusions (14-120 nmol/g BW) reduced serum ionized calcium by 9-49%, while PTH levels increased by 68-560% (from 61.4 +/- 32.3 at time zero to a maximum of 138 +/- 48.6 human pgeq/ml at 3 min). During the EDTA infusion, the PTH response was variable after 3 min despite further decreases in ionized Ca2+, indicating either exhaustion of PTH reserves or regulation of the secretory response by some parameter other than ionized calcium concentration per se. Thus, the rabbit appears to defend its serum ionized calcium concentration against hypo- and hypercalcemia by rapid changes in PTH secretion and calcitonin. Unlike other mammalian species, however, the changes in PTH occur at relatively high levels of calcium, suggesting that the parathyroid gland of the rabbit is reset to respond to changes in ionized Ca2+ within the physiological range in that species. The relative insensitivity of the rabbit parathyroid to extracellular calcium is analogous to that observed in primary hyperparathyroidism and may be a useful model to study the control of normal and abnormal PTH secretion.

The cardiopulmonary effects of calcium infusion in infants with persistent pulmonary hypertension of the newborn.

Low blood ionized calcium levels have been reported previously in association with alkalosis in infants undergoing hyperventilation for persistent pulmonary hypertension. We investigated the effect of acute calcium infusions on the cardiopulmonary status of 10 hypocalcemic, hyperventilated infants with persistent pulmonary hypertension. Acid-base status, arterial partial pressure of oxygen, vital signs, and echocardiographically determined right and left systolic time interval ratios and left ventricular shortening fractions were obtained before and after rapid infusions of calcium gluconate or saline. At 5 and 15 min after calcium infusion, but not after saline infusion, there were significant decreases in both right and left ventricular systolic time interval ratios, and an increase in transcutaneous PO2 and PaO2 that coincided with peak levels of ionized calcium. These findings provide evidence that high levels of ionized calcium in newborns with persistent pulmonary hypertension transiently improve myocardial performance and oxygenation.

Characterization of the renal effects of an intravenous calcium gluconate infusion in normotensive volunteers.

The effects on renal function of an intravenous infusion of calcium gluconate at subpressor doses have been investigated in a group of seven normotensive male volunteers. In the absence of changes in blood pressure, the calcium gluconate induced a significant increase in renal plasma flow and the glomerular filtration rate (P less than 0.01) with a significant fall in the filtration fraction (P less than 0.01). Both diuresis and natriuresis increased significantly (P less than 0.01), plasma renin activity fell (P less than 0.01) and the urinary excretion of 6-keto prostaglandin F1 alpha (PGF1 alpha) and prostaglandin E2 (PGE2) increased (P less than 0.01). These results indicate that calcium infusion at subpressor doses has renal vasodilating, diuretic and natriuretic properties that appear to be facilitated by an increase in the renal production of vasodilatory and natriuretic prostaglandins.

Relationship between the concentration and rate of change of calcium and serum intact parathyroid hormone levels in normal humans.

We employed variable rates of infusion of EDTA or calcium gluconate to examine the relationships between the concentration and rate of change of serum total and plasma ionized calcium and serum immunoreactive intact PTH concentrations in normal subjects. Use of a sensitive immunoradiometric assay specific for PTH-(1-84) made it possible to determine the full range of PTH responses to perturbations in the extracellular calcium concentration. By progressively increasing the rate of administration of calcium gluconate or EDTA during rapid or slow infusions, linear rates of change in the serum calcium concentration were achieved in eight men. The slopes were 2-fold greater during the rapid infusions. Both the calcium infusions decreased serum PTH-(1-84) levels from a mean of 23.2 +/- 2.0 (+/- SE) to 6.4 +/- 1.0 and 5.6 +/- 1.0 ng/L for the rapid and slow infusions, respectively, with no obvious rate dependence. The rapid or slow EDTA infusions increased serum PTH levels to the same maximal extent (95.0 +/- 20.2 and 99.9 +/- 14.5 ng/L, respectively), also with no significant rate dependence. Thus, there was no effect of the rate of change of calcium on the PTH response, which was reflected in similar inverse sigmoidal relationships between PTH and serum total and plasma ionized calcium when the data for the slow and rapid infusions were pooled separately. Similar sigmoidal curves were found in normal women. These data suggest the feasibility of using calcium and EDTA infusions combined with an intact PTH assay to define the relationships between circulating levels of PTH-(1-84) and calcium in states of normal and deranged parathyroid physiology.

Effects of calcium on renin and aldosterone

A series of experiments was undertaken to assess the effects of calcium administration, in vivo, on renin and aldosterone secretion. In the anesthetized dog, renin secretion was decreased by renal arterial infusions of calcium chloride and calcium gluconate; aldosterone excretion was not affected. In the sodium chloride-deprived rat, dietary calcium chloride loading decreased plasma renin activity, whereas calcium gluconate did not. Both calcium salts increased aldosterone production. In the non-filtering, denervated, papaverine-treated dog kidney, renin release was stimulated by renal arterial infusion of verapamil. In the rat, chronic oral verapamil administration decreased plasma aldosterone but had no effect on renin. In humans, chronic oral verapamil decreased aldosterone responsiveness to infusion of angiotensin II. Thus, in vivo renin release is inhibited by hypercalcemia and stimulated by blocking calcium transport; conversely, aldosterone production is stimulated by a high calcium intake and inhibited by blocking calcium transport. These effects of calcium on renin and aldosterone may have implications for understanding the putative relation between calcium and hypertension.

A Method for In Vivo Assessment of Calcium Slow Channel Blocking Drugs

A method is described, using the cardioaccelerator response in pithed rats, that distinguishes calcium entry blockers from other agents which have modes of action not involving direct blockade of calcium entry. Diltiazem (0.01-0.3 mg kg-1), verapamil (0.01-0.03 mg kg-1), nifedipine (0.1-1.0 mg kg-1), propranolol (0.003-0.3 mg kg-1), xylazine (0.01-1.0 mg kg-1), alinidine (0.03-1.0 mg kg-1), and, to a lesser extent, lignocaine (0.1-3.0 mg kg-1), reduced stimulation-evoked sustained cardioaccelerator responses in the pithed rat. BRL 34915 (0.3-10.0 mg kg-1) and nicorandil (1.0-10.0 mg kg-1) were without effect in this situation. Infusion of calcium gluconate (1.0 mg min-1) reversed the reduction of the cardioaccelerator responses by nifedipine (1.0 mg kg-1), verapamil (0.3 mg kg-1), and diltiazem (0.3 mg kg-1) but not to propranolol (0.1 mg kg-1), alinidine (0.5 mg kg-1), or xylazine (0.3 mg kg-1). Therefore, calcium gluconate is selective in reversing the effects of calcium slow channel blockers in this model, thereby making it a useful technique for distinguishing these drugs in vivo.

Can blood pressure reduction induced by slow calcium channel blockade (verapamil) be reversed by calcium infusion?

The pressor effects of a single infusion of calcium gluconate (1375 mg) were measured in 20 patients, aged 31-63 years, with mild and moderate essential hypertension, being on long-term treatment with the slow calcium channel blocker verapamil. The calcium load induced a significant (P less than 0.001) increase in mean serum ionized calcium (from 1.24 +/- 0.01 to 1.40 +/- 0.2 mmol/l). This did not alter mean blood pressure or mean heart rate, although the individual patients responded differently to the mild hypercalcaemia; a significant fall in blood pressure being observed in a few patients. These results demonstrate the unpredictable effects of an increase in extracellular calcium on vascular smooth muscle cells and suggest that an intravenous bolus of 1375 mg calcium gluconate is not effective in counteracting the hypotensive action of verapamil.

Lack of effect of moderate hypercalcemia on gonadotropin responsiveness to GnRH

To investigate whether moderate exogenous hypercalcemia influences the release of gonadotropin from human gonadotrophs, 6 normal men were given 50 micrograms GnRH iv on two occasions. On one of these occasions GnRH was administered on an iv background infusion of calcium gluconate, on the other GnRH was injected on a background infusion of saline. The calcium infusion induced moderate hypercalcemia (2.7-2.9 mmol/l) during the GnRH stimulation, whereas normocalcemia prevailed (2.1-2.2 mmol/l) when saline was infused over an identical time period. Similar FSH and LH responses to GnRH were obtained during normo- and hypercalcemia. Moreover, serum testosterone (T) and estradiol (E2) remained unchanged by the hypercalcemia. These results imply that moderate exogenous hypercalcemia does not affect hormone release from pituitary gonadotrophs, and fails to affect peripheral cells involved in the production of T and E2.

Digital hydrofluoric acid burns: Treatment with intraarterial calcium infusion

Hydrofluoric acid (HF) produces a unique chemical burn due to tissue penetration by fluoride ion. Fluoride ion interferes with calcium activity in a variety of cell membranes and calcium-dependent processes, resulting in severe pain and deep tissue destruction. The currently accepted methods of treating HF burns include application of topical soaks or ointments with calcium or magnesium salts for minor burns and local injection of calcium gluconate for more severe burns. Digital burns also may require nail removal and direct injection into the nail bed. We present the cases of a series of patients with moderate to severe HF burns involving one or more fingers who were treated with selective intraarterial calcium infusion of dilute (1.66%) calcium salts. All patients had excellent relief of symptoms and marked improvement of the burn lesions following one to three four-hour infusions of calcium chloride or calcium gluconate. One patient required subsequent surgical intervention for grafting of a full-thickness burn, and one patient developed transient spasm at the site of percutaneous arterial line insertion. Intraarterial calcium infusion for the treatment of HF burns of the fingers provides many therapeutic advantages, including elimination of painful calcium injection directly into fingertips, avoidance of debilitating procedures such as fingernail removal, and assurance that all affected cells are receiving adequate amounts of calcium to replenish depleted stores and to complex with remaining free fluoride ion.

Role of the loop segment in the urinary concentrating defect of hypercalcemia

Hypercalcemia is associated with impaired urinary concentrating ability. To explore the mechanism(s) by which hypercalcemia impairs chloride transport in the loop of Henle, we carried out in vivo microperfusion of the loop segment in Sprague-Dawley rats rendered acutely hypercalcemic (12.1 +/- 0.1 mg/dliter) by calcium gluconate infusion. Control rats were infused with sodium gluconate and had normal plasma calcium (8.0 +/- 0.2 mg/dliter). Compared to control, fractional chloride reabsorption was decreased (61 +/- 4 to 50 +/- 3%; P less than 0.05) and early distal chloride increased 74 +/- 6 to 98 +/- 3 mEq/liter (P less than 0.001) in hypercalcemia. During hypercalcemia, infusion of verapamil failed to increase fractional chloride reabsorption (49 +/- 4%; P less than 0.05) or decrease early distal chloride (95 +/- 2; P less than 0.05) toward control values. Similarly, indomethacin did not improve fractional chloride reabsorption (48 +/- 4%; P less than 0.05) or distal chloride concentration (93 +/- 7; P less than 0.05). In control rats infused with Ringers HCO3, the addition of calcium 8.0 mEq/liter to the perfusate increased early distal calcium (9.22 to 3.11 mEq/liter) but was associated with no change in fractional chloride reabsorption (-6 +/- 6%) and a slight decrease in early distal chloride (-9 +/- 3 mEq/liter; P less than 0.05). These data are consistent with the hypothesis that an elevated plasma, not luminal calcium, concentration impairs chloride reabsorption in the loop segment, primarily the ADH-stimulated component. This may have an important role in the urinary concentrating defect of hypercalcemia.

Transplacental 45Ca and 32P flux in the guinea pig: effect of maternal hypercalcaemia and hypocalcaemia.

Transplacental 45Ca and 32P flux was measured across the in situ perfused guinea-pig placenta under conditions of acute maternal hypocalcaemia and hypercalcaemia. Maternal hypercalcaemia induced acutely by calcium gluconate infusion caused an increase in maternal-to-fetal 45Ca flux which was proportional to the increase in maternal plasma ionized calcium concentration. Acute maternal hypocalcaemia was induced by EGTA infusion and resulted in a decrease in maternal plasma ionized calcium concentration proportional to a corresponding decrease in transplacental 45Ca transfer. A bolus of calcium gluconate caused a transient decrease in 32P flux, whereas EGTA administration was without significant effect on transplacental 32P transfer. Calcium transport across the placenta is not saturated under conditions of maternal normocalcaemia and may be altered according to acute changes in maternal plasma calcium concentration. Thus, control of maternal-to-fetal calcium transfer does not appear to be at the placental level. This suggests that fetal calcium homeostasis may be regulated by the fetus itself.

Intra-arterial infusions in the treatment of hydrofluoric acid burns

Burns due to hydrofluoric acid are uncommon, but are severe injuries. The mode of action is discussed briefly and the routine management of these patients is outlined. The use of intra-arterial infusions of calcium gluconate is stressed, and case reports are given to support its use.

Platelet collection using the IBM 2997 cell separator.

Platelets were collected using the dual-channel module on the IBM 2997 Blood Fraction Separator. We carried out 320 procedures to harvest platelets for therapeutic purposes and yielded 5.1 +/- 1.5 X 10(11) platelets (mean +/- SD). Infusion into previously unsensitized recipients with hypomegakaryocytic thrombocytopenia achieved increments at 1 hr of 19 +/- 7.3 X 10(9)/liter/m2 (mean +/- SD) and at 24 hr of 15 +/- 6.3 X 10(9)/liter/m2. The only consistent donor reaction was mild hypocalcaemia, easily corrected by calcium gluconate infusion. Changes in donor packed-cell volume and white cell count were not statistically altered (p greater than 0.05) but donor platelet counts fell from 216 +/- 43.1 X 10(9)/liter to 162.5 +2- 41.7 X 10(9)/liter (mean +/- SD) (p less than 0.01). Additional plateletphereses were carried out in seven normal volunteers, using the same technique, in order that the function of the harvested platelets could be studied. Following radiochromium labelling and reinfusion into the same donors, normal in vivo recoveries were obtained at 10 min (59.4 +/- 3.4%; mean +/- SD) and platelet mean life span was also normal (218 +/- 12 hr; mean +/- SD). Furthermore, in vitro platelet factor III availability and aggregation patterns of the harvested platelets did not differ from control values and their ultrastructural appearance was normal.

Interaction of calcium and gastrin on gastric acid secretion in duodenal ulcer patients.

A dose response study of the effect on gastric acid secretion of synthetic human gastrin-17 in doses of 50,200, and 500 ng/kg/h was performed in eight healthy volunteers and in eight patients with duodenal ulcer. The study was repeated on a separate day during intravenous infusion of calcium gluconate (0.1 mmol Ca2+/kg/h). In healthy subjects the acid response to the combined infusion of synthetic human gastrin and calcium did not significantly exceed the response to synthetic human gastrin alone, in contrast with patients with duodenal ulcer in whom the combined infusion did significantly improve acid output compared with infusion of synthetic human gastrin alone. The dose of synthetic human gastrin required for half maximal acid response (D50) was reduced in both groups but significantly more in patients with duodenal ulcer. No difference in serum gastrin concentrations or in serum calcium concentrations were found. It is hypothesised that extracellular calcium plays a role in gastrin stimulated acid secretion in man and that patients with duodenal ulcer are more sensitive to this calcium dependent mechanism than non-duodenal ulcer subjects.

The cutaneous R-pulse interval

The time interval from the onset of the R wave of the ECG to the onset of the cutaneous capillary pulse wave, i.e., cutaneous R-pulse interval or RPIc, was evaluated in 21 full-term and 22 preterm infants as a measure of cardiovascular function. RPIc showed a significant linear relationship with birth weight (r = .58, p less than .001) and gestational age (r = .62, p less than .001) for healthy infants. At similar gestational ages, the sick infants showed a significant prolongation of RPIc when compared to their healthy counterparts (mean prolongation 18.5 msec, p less than .01). The infusion of calcium gluconate, an inotropic agent, consistently and significantly shortened the RPIc from its preinfusion value (p less than .01). In 7 infants, simultaneous measurement of intra-aortic R-pulse interval accompanied parallel changes in RPIc. These preliminary observations suggest that continuous monitoring of RPIc may provide a reliable noninvasive measure of neonatal cardiovascular function.