Effects Of Hypocalcemia Research Articles

Effects of hypocalcaemia on blood flow to the ovaries of the sheep.

The objectives of the study were to use sheep as a model to determine whether a reduction in plasma calcium concentration similar to that observed during periods of postpartum subclinical hypocalcaemia in lactating dairy cattle might affect the blood flow to the ovaries. Different levels of hypocalcaemia were induced in each of six, non-pregnant sheep by the slow intravenous infusion of Na2-EDTA. Measurements of blood flow to the ovaries were made before and after the induction of hypocalcaemia, using 113Sn and 46Sc radiolabelled microspheres. As plasma ionized calcium was reduced, there was a significant decline in ovarian blood flow. Ovarian blood flow (percentage of resting) = 0.54 Ca++ (percentage of resting) + 58.4. This model was significant at P < 0.01, with R2 = 0.92. Accordingly, a reduction in plasma ionized calcium of 50% would yield a reduction in ovarian blood flow of 16%.

Effect of hypocalcemia on muscle in disorders of calcium metabolism

We reported on three hypocalcemic patients with various serum creatine kinase (CK) levels and Ca metabolic disorders. Two patients with moderate hypocalcemia had increased CK levels (hyper-CK-emia), which normalized during treatment for the hypocalcemia; a negative correlation between the Ca and CK levels was observed in both patients. The remaining patient with mild hypocalcemia had a normal CK level. We discuss the effect of hypocalcemia on muscle in our patients as well as previously reported patients. Muscle may respond to hypocalcemia in three stages, namely homeostatic, asymptomatic hyper-CK-emic and myopathic stages.

Effects of Preventing Periparturient Hypocalcemia in Cows by Parathyroid Hormone Administration on Hematology, Conglutinin, Immunoglobulin, and Shedding of Staphylococcus aureus in Milk

The effects of hypocalcemia at parturition on concentrations of serum immunoglobulin and conglutinin, number of bacteria shed into milk, and leukograms of dairy cows were investigated from –4 wk prepartum to 4 wk postpartum. Ten healthy multiparous Holstein cows were fed a high calcium diet to induce hypocalcemia at parturition. Five cows received intramuscular parathyroid hormone to prevent hypocalcemia at parturition. All cows experienced a leukopenia (attributable to an absolute and relative neutropenia) during the 1st wk after calving, decreased serum conglutinin activity during the first 3 wk postpartum, and decreased concentration of serum IgG1 during the 3 wk before calving. At parturition, a large increase in organisms was found in foremilk (1000 to 10,000 times more than prepartum values). Neither the hematological changes nor the decreased immunoglobulin concentration was influenced by hypocalcemia or the development of milk fever. This implies that the degree of hypocalcemia observed did not have a large or irreversible influence on bacterial infection, hematological, or humoral immunity changes in periparturient cows.

Somatosensory evoked potentials in rats with hypocalcemia.

The effects of hypocalcemia on somatosensory evoked potentials (SEPs) were studied in rats. The SEP in awake rats consisted of an unstable, large, negative wave (Nmax) preceded by a small positive one (P1). The P1 appeared to be a subcortical potential and Nmax appeared to represent the function of the cerebral cortex. With the decrease in calcium concentration caused by parathyroidectomy, as well as by administration of EDTA, an augmentation of amplitudes of the Nmax and a reduction in the SEP recovery functions were observed. The latency of P1 was hardly changed. The decrease in the SEP recovery functions possibly reflects a reduction in synaptic efficiency, and the increasing amplitude of the SEP probably reflects the cortical hyperexcitability caused by hypocalcemia.

Hemodialysis with calcium-free dialysate prevents myocardial creatine kinase depletion after brief coronary artery occlusion in dogs.

To evaluate the effect of hypocalcemia on myocardial creatine kinase (CK) depletion after brief coronary artery occlusion and reperfusion, dogs were rendered hypocalcemic via systemic hemodialysis for eighty minutes in the absence of Ca. Control animals were hemodialysed in the presence of Ca. The left anterior descending coronary artery was then occluded for six minutes and reperfusion for eighty minutes occurred at low flow of dialysate. A 50% decrease in serum Ca of the hypocalcemic animals during the eighty minutes of hemodialysis resulted in a significant (about 35%) decrease of myocardial Ca. Comparison of the myocardial creatine kinase activity following reperfusion showed preservation of the enzyme in the ischemic areas of the hypocalcemic animals, whereas the CK activities of the ischemic areas of the normocalcemic animals were much lower (p less than 0.005). During the reperfusion period serum Ca of the hypocalcemic group increased to 75% of that of the normocalcemic group while myocardial Ca of both ischemic and nonischemic areas reequilibrated to normocalcemic values. Hemodynamic parameters during the various phases of the experiment were not altered significantly. It is concluded that transient decrease of myocardial Ca produced by hypocalcemia prior to occlusion leads to protection against myocardial damage after brief coronary ligation.

Effects of hypocalcaemia on abomasal motility

Abomasal mechanical and myoelectric activity were measured in two adult Holstein cows. Hypocalcaemia was induced using a constant infusion of disodium EDTA and serum total and diffusible calcium concentrations were measured. Abomasal motility remained normal in the face of declining calcium concentrations until a threshold value was reached (1.2 +/- 0.2 mmol litre-1) below which all mechanical and electrical activity was absent. A similar threshold effect was observed when calcium concentrations were allowed to rise. These data do not support hypocalcaemia as being a clinically important cause of abomasal atony.

Intracerebral bilateral symmetrical calcification demonstrated in a patient with pseudohypoparathyroidism

Bilateral Symmetrical Calcifications (B.S.C.) in cerebro represent calcium deposits usually found in the basal ganglia and/or dentate nucleus. They can be the result of diverse disorders, but can also present themselves without any underlying disease. Most often they are asymptomatic, but if the calcifications are extensive, extrapyramidal and cerebellar signs may arise. The following case concerns a patient with pseudohypoparathyroidism. Besides the usual signs and symptoms found in this disease, the patient also showed extensive B.S.C. The etiology and clinical symptoms of B.S.C. will be discussed. Furthermore, attention will be given to the syndrome of the pseudohypoparathyroidism and the effects of hypocalcemia.

Somatosensory evoked potentials in patients with hypocalcaemia after parathyroidectomy.

The effects of hypocalcaemia on somatosensory evoked potentials (SEPs) were studied in five patients after parathyroidectomy. Despite normal latencies the mean value of amplitudes of the SEPs in hypocalcaemic patients was greater than that in normocalcaemic subjects. Recovery functions of the SEPs showed a significant decrease in hypocalcaemic patients at interstimulus intervals of about 10 ms compared with those in normocalcaemic patients and in normal volunteers. Recovery functions appear to be a valid indicator of synaptic efficacy, especially for evaluation of the reduction in conduction efficacy of the central nervous system in hypocalcaemia.

Hypocalcemia-associated modulation of renal response to acute volume expansion in rats.

The present study used free-flow micropuncture and whole-kidney clearance studies to determine the renal response to normocalcemic vs. hypocalcemic acute volume expansion (AVE) in anesthetized Munich-Wistar rats. Animals received AVE with Ringer bicarbonate to 10% body weight; half of these animals were supplemented with calcium to maintain normocalcemia (VE + Ca2+) and half were allowed to become hypocalcemic (VE). Filtered load of chloride and total CO2 (TCO2) to the superficial proximal tubule and delivered load to the superficial loop segment were not different between groups. Superficial proximal tubule absolute Cl reabsorption was not different, but superficial loop segment absolute Cl reabsorption was less in the VE + Ca2+ animals (2,221 +/- 106 vs. 2,651 +/- 125 pmol/min, P less than 0.05) and whole-kidney fractional chloride excretion was greater (10.5 +/- 1.6 vs. 4.3 +/- 0.5%, P less than 0.05). When indomethacin (I) was administered to hypocalcemic (VE + I) and normocalcemic (VE + Ca2+ + I) AVE animals, both groups of animals had tubular and whole-kidney chloride reabsorption similar to VE animals. TCO2 reabsorption was not influenced by Ca2+ or I. The data indicate that normocalcemic vs. hypocalcemic AVE results in reduced superficial loop segment chloride reabsorption and greater whole-kidney fractional chloride excretion in the absence but not in the presence of prostaglandin inhibition. The data are compatible with an effect of hypocalcemia during AVE to limit superficial loop segment and whole-kidney chloride excretion by inhibiting renal prostaglandin synthesis.

Effect of hypocalcaemia on blood flow distribution in sheep

Cardiac output, the proportion of blood passing through arteriovenous shunts and blood flow distribution to various organs were measured and compared in five normocalcaemic and five hypocalcaemic sheep using radioactive microspheres. Hypocalcaemia was induced by infusing sodium EDTA solution intravenously for two hours. There was evidence that microspheres were leached from liver, muscle, adrenal and thyroid tissues during the induction of hypocalcaemia. Hypocalcaemia reduced blood flow rates by more than 58 per cent in all tissues examined except kidney (48 per cent), heart (53 per cent), lung (10 per cent) and bladder (47 per cent) and reduced cardiac output from 3.70 +/- 0.19 (mean +/- SE) litres min-1 to 2.39 +/- 0.14 litres min-1. Approximately 2.2 per cent of cardiac output passed through arteriovenous shunts. This percentage was unaffected by hypocalcaemia.

Effect of Hypocalcemia on Cardiac Function in Very-Low-Birth-Weight Preterm Neonates: Studies of Blood Ionized Calcium, Echocardiography, and Cardiac Effect of Intravenous Calcium Therapy

Traditionally, in infants, a serum calcium value less than 7.0 mg/dL is considered to impair cardiac function. In very-low-birth-weight infants, we studied the hypotheses that decline in serum calcium to 6.0 mg/dL (1) would not impair cardiac function and (2) ionized calcium would remain greater than 3.0 mg/dL. We also evaluated the effect of calcium infusion on cardiac function. We studied 15 normokalemic and normonatremic infants whose birth weights were 822 to 1,450 g and were less than 32 weeks' gestation. When serum calcium declined to less than 6.0 mg/dL, 18 mg/kg of calcium as 5% calcium gluconate was infused for 10 minutes. Serum total calcium concentration, blood ionized calcium concentration, ECG, and M-mode echocardiogram were obtained on entry into the study, when the infants were hypocalcemic, immediately after treatment with calcium, and eight hours after treatment. Ionized calcium values were calculated based on serum total calcium and serum protein, and corrected calcium values were calculated based on serum total calcium, serum albumin, and blood pH. In all infants, serum calcium value declined to less than 7.0 and in eight infants to less than 6.0 mg/dL. Assessment of heart rate, systolic blood pressure, ejection fraction, left ventricular systolic time interval, right ventricular systolic time interval, fiber shortening index, and left ventricular mean velocity of circumferential fiber shortening showed no significant alteration from baseline during hypocalcemia or in association with intravenous slow bolus infusion of 18 mg/kg of calcium.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of hypocalcemia on isoproterenol induced cardiotoxicity in dogs.

The effect of serum calcium on the myocardial damages produced by isoproterenol was studied in the dog. Hemodialysis for 80 min in the absence of calcium was used to alter serum calcium concentration in seven experimental animals. The same number of animals were dialysed in the presence of calcium and were used as controls. After hemodialysis all animals were infused with isoproterenol 2.0 micrograms/kg/min for 4 hours. The myocardial damage was assessed by comparing serial measurements of the serum cardiac enzyme activities CK and CK-MB and the electrocardiographic findings of the two groups, before, during and after isoproterenol infusion. Serum calcium decreased significantly after dialysis only in the experimental group (1.15 vs 2.19 mmol X L-1). Total CK activities of the experimental group during and after isoproterenol infusion were 2 to 3 times lower than in the controls (190-360 vs 410-1370 IU X L-1). Changes of the CK-MB isoenzyme activities were more profound, these were detectable and measured only in 4 of the experimental animals and in much lower activities than in the controls (25-61 vs 45-445 IU X L-1). A positive correlation was found (r = 0.673, p less than 0.05) between the highest value of CK-MB of both groups and the serum calcium concentration after hemodialysis. In accordance to the differences of the biochemical estimates the effect of serum calcium on the cardiotoxic effect of isoproterenol has been further emphasized by the electrocardiographic findings. Thus arrhythmias, negative T-waves and significant ST segment depression were observed only in one experimental animal. In contrast these electrocardiographic disturbances were common and marked findings in all but one of the control animals. In both groups these electrocardiographic findings were reversed one to three hours after the termination of the isoproterenol infusion. Myocardial calcium at the end of the experiment was lower in the experimentals compared to the controls (0.23 vs 0.30 mmol X kg-1 wet weight). On the contrary magnesium concentration increased respectively. It is concluded that low serum calcium has a protective effect against the cardiotoxic action of isoproterenol. This protective action may be relevant to the decreased calcium and increased magnesium of the heart of the animals hemodialysed in the absence of calcium.

Parathyroid function and magnesium depletion in the rat.

Hypocalcemia is characteristically observed in magnesium deficiency in a number of animal species. Previous studies demonstrated impaired release of PTH in magnesium-depleted hypocalcemic humans. However, an enigma remains in that, unlike in other animals, hypercalcemia, rather than hypocalcemia, accompanies magnesium deficiency in the rat. Because intact parathyroids are necessary for the development of this hypercalcemia, it has been postulated that magnesium depletion stimulates, rather than impairs, PTH secretion in the rat. In an effort to more directly evaluate this thesis, sequential measurements of circulating immunoreactive PTH (iPTH) were made over a 30-day period in rats maintained on a magnesium-deficient diet and in match-fed controls. In the control rats, serum calcium, magnesium, and iPTH remained relatively constant throughout the study. By contrast, during the first 4 days of a low magnesium diet, serum magnesium decreased to 1.0 mg/dl, serum calcium increased moderately, while serum iPTH increased to a mean level that was twice that in controls. After 5 days, when serum magnesium progressively fell to levels less than 0.6 mg/dl and serum calcium continued to rise, serum iPTH fell to levels significantly lower than the control value. In a second set of experiments, the effect of hypocalcemia on circulating iPTH in magnesium deficiency was evaluated. Circulating iPTH was greatly increased and not significantly different in magnesium-deficient and magnesium-replete animals who were rendered chronically hypocalcemic by diets deficient in either calcium or vitamin D. The results of this study indicate that: 1) in the rat, an increase in PTH secretion occurs early in the genesis of magnesium deficiency in the presence of a modest increase in serum calcium; however, the subsequent further increase in serum calcium counteracts the stimulatory effect of hypomagnesemia on PTH secretion; 2) unlike the human parathyroid gland, the rat parathyroid gland responds appropriately to both hypo- and hypercalcemia in magnesium deficiency; and 3) the hypercalcemia that occurs in the magnesium-deficient rat is not due to increased PTH secretion and must be accounted for by another mechanism.

Attenuation by hypocalcemia of pulsatile growth hormone secretion in conscious male rats.

The effect of hypocalcemia following parathyroidectomy (PTX) on growth hormone (GH) secretion was investigated in unrestrained, unanesthetized male rats bearing chronically implanted indwelling cannulae. During a 6-hour period, starting at about 10 a.m., control rats with a serum calcium (Ca) value of 8.11 +/- 0.38 mg/dl (mean +/- SEM) 2 weeks after sham-operation showed secretory bursts of GH similar to those observed in conscious intact rats. Under hypocalcemia of 4.88 +/- 0.32 mg/dl 2 weeks after PTX, GH secretory episodes were completely suppressed throughout the study. Plasma prolactin (PRL) levels were also decreased in PTX rats as compared with those of sham-operated rats. Daily food intake and body weight gain as well as serum T4 levels in PTX rats were not different from those of sham-operated and intact rats. Pituitary GH content of PTX rats was significantly lower than that of sham-operated and control rats. Pulsatile GH secretion was partially restored in PTX rats by raising serum Ca to 8.43 +/- 0.27 mg/dl through feeding with high Ca diet containing 7% Ca. Immediately after intravenous injection of antisomatostatin sheep serum, pulsatile GH surges recovered in PTX rats despite hypocalcemia of 4.48 +/- 0.74 mg/dl. The mean plasma 6-hour GH levels were significantly higher than those of normal sheep-serum-treated PTX rats (p less than 0.001). These findings suggest that the episodic release of GH is suppressed in hypocalcemic rats after PTX, at least partially via circulating endogenous somatostatin.

Effect of Hypocalcemia on Divalent Cation-Activated ATPase and Ca&lt;sup&gt;2+&lt;/sup&gt; Uptake in Microsomes of Rat Kidney Cortex

Effects of hypocalcemia on Ca&lt;sup&gt;2+&lt;/sup&gt; metabolism of microsomes from rat kidney cortex were studied. Microsomal activities of Ca&lt;sup&gt;2+&lt;/sup&gt;-ATPase, Mg&lt;sup&gt;2+&lt;/sup&gt;-ATPase and (Na&lt;sup&gt;+&lt;/sup&gt;+K&lt;sup&gt;+&lt;/sup&gt;)-ATPase increased 30–33 days after Ca&lt;sup&gt;2+&lt;/sup&gt; restriction or low Ca&lt;sup&gt;2+&lt;/sup&gt;· vitamin D depletion, but alkaline phosphatase activity decreased. Calcium repletion in diet and injection of lα-hydroxycholecalciferol or 1,25-dihydroxycholecalciferol were partially successful in returning Ca&lt;sup&gt;2+&lt;/sup&gt;-ATPase and Mg&lt;sup&gt;2+&lt;/sup&gt;-ATPase activity, but not (Na&lt;sup&gt;+&lt;/sup&gt;+K&lt;sup&gt;+&lt;/sup&gt;)-ATPase and alkaline phosphatase activity, to normal. Correlations between serum Ca&lt;sup&gt;2+&lt;/sup&gt; level and both ATPase activities were significant. ATP-dependent Ca&lt;sup&gt;2+&lt;/sup&gt; uptake of microsomes was not affected by hypocalcemia and vitamin D metabolites.

Effects of Hypocalcemia and Theophylline on Glucose Tolerance and Insulin Release in Human Beings

A study was carried out to investigate the role of serum calcium in the regulation of insulin secretion and glucose tolerance in response to an oral glucose load on human subjects in hypocalcemie and normocalcemic states. The subjects for this study comprised three groups. Group 1 consisted of 15 patients with hypoparathy-roidism. They were subjected to an oral glucose load, and blood samples were taken at 0, 30, 60, 90, 120, 150, and 180 minutes to determine the blood glucose and serum insulin levels. These patients were treated with vitamin D2; after normocalcemic states were achieved the same study was repeated. This group of patients showed an abnormal glucose tolerance test and a markedly reduced insulin release during their hypocalcemie state; these abnormalities returned to normal after treatment. Group 2 consisted of six patients with hypoparathyroidism and one patient with vitamin-D-resistant rickets. These patients were subjected to an oral glucose load and a theophylline infusion (1 gm. in three hours) when they were hypocalcemie. The theophylline infusion increased the insulin release to the level of control subjects' in spite of hypocalcemia. Ten healthy volunteers served as a control group (group 3). Our results indicate that serum calcium has an important role in glucose utilization by insulin release. This is the first experiment to be performed on human beings and shows that theophylline has a stimulatory effect on insulin secretion in the presence of hypocalcemia.

Effect of Hypocalcemia on Hormonal Responses to Thyrotropin-Releasing Hormone

The effects of chronic hypocalcemia on pituitary and thyroidal responses to TRH were studied in six euthyroid and three mildly hypothyroid subjects with surgical hypoparathyroidism orpseudohypoparathyroidism. In the euthyroid patients, increments in serum TSH, T3, and T4 were equal under hypocalcemic or nonnocalcemic conditions;however, a slightly but significantly lower basal serum T3 during hypocalcemia in conjunction with unaltered basalserum T4 and reverse T3 levels suggests that hypocalcemia may alter peripheral metabolism of T4 and/or T3. Hypothyroid subjects showed more variable responses to hypocalcemia; after restoration of normocalcemia, two patients demonstrated greater serum T3 increments following TRH and lowerTSH levels, suggesting an impairment of thyroidal secretion by hypocalcemia, while the third showed no effect of hypocalcemia on TSH, T3, or T4 responses to TRH. Hypocalcemia had no effect on prolactin responses to TRH in the combined group of euthyroid andhypothyroid patients. Since on...

Lack of effect of hypocalcemia on renal phosphate handling.

A possible effect of decreased plasma ionized calcium concentration on renal phosphate handling was investigated in dogs with control of parathyroid hormone. Intrarenal artery infusion of either EDTA or sodium citrate decreased ionized calcium concentration 25 per cent in renal vein blood but had no significant effect on fractional phosphate excretion. Similarly, intravenous infusion of chelators had no significant effect on fractional phosphate excretion. It is concluded that acute decreases in ionized calcium have no significant effect on the renal handling of phosphate.

Effect of hypocalcaemia on glucose tolerance, insulin release and free fatty acid levels in human subjects

Summary Eight patients with hypocalcaemia who presented with frank or latent tetany due to parathyroid insufficiency or nutritional osteomalacia were studied. Their serum calcium ranged from 6·85 to 7·7 mg/100 ml (mean 7·33±0·36 mg/100 ml). In six of them, serum calcium after treatment varied from 8·4 to 9·2 mg/100 ml. In ten healthy normal subjects the serum calcium levels were 9·0-10·2 mg/100 ml (9·50±0·47 mg/100 ml). The blood glucose levels during a 3 hr oral GTT were significantly elevated during hypocalcaemia and returned to normal levels after treatment. Serum insulin levels were low at 60 and 120 min after the administration of glucose in hypocalcaemia but returned to normal once the serum calcium levels were above 8·4 mg/100 ml. The FFA levels were high during the low calcium state and reached normal levels after treatment. The above studies suggest that an optimal level of serum calcium is essential for glucose-induced insulin release.

The effect of hypocalcaemia on the secretion of calcitonin.

SUMMARY Hypocalcaemia was produced by i.v. infusion of EDTA into pigs from which the thyroid venous effluent could be quantitatively collected. Calcitonin in the effluent was measured by radioimmunoassay. Reduction of plasma calcium concentration rapidly suppressed the secretion of calcitonin. In contrast, as plasma calcium was raised slowly from hypocalcaemic levels by infusion of CaCl2, calcitonin secretion quickly returned and increased rapidly. The secretion rate observed when the plasma calcium concentration had been raised from hypocalcaemia to the initial normocalcaemic level was 3½–10 times greater than that observed during the normocalcaemia which pertained at the start of each experiment. A previous period of hypocalcaemia also produced an exaggerated response to a subsequent hypercalcaemic stimulus. It is suggested that the preconditioned response of calcitonin secretion increases the efficiency of the role of calcitonin in calcium homeostasis.