Claus Hemmingsen

Ketamine in the treatment of bronchospasm during mechanical ventilation

The effect of ketamine on bronchospasm during mechanical ventilation was evaluated in a prospective, placebo-controlled, double-blind trial. Fourteen mechanically ventilated patients with bronchospasm were randomly allocated to either ketamine 1 mg/kg or saline placebo. In the ketamine-treated patients, PO2 increased from 10.5 (+/- 0.5) kPa to 16.4 (+/- 2.7) kPa (P < .05), whereas PO2 in the placebo-treated patients remained unchanged. The PCO2 was constant in the ketamine group, although it increased from 5.6 (+/- 0.9) kPa to 6.1 (+/- 0.9) kPa in the placebo group (P < .05). The pulmonary stethoscopic bronchospasm improved immediately after the administration of ketamine, whereas the thoracic compliance remained unchanged. In conclusion, the ketamine-treated patients showed an improvement by stethoscopic examination, in PO2 and in PCO2, suggesting that ketamine might be useful in the treatment of bronchospasm during mechanical ventilation. However, further studies are required to decide whether ketamine should be considered the drug of choice in patients with severe bronchospasm during ventilator treatment.

Bi-level positive airway pressure treatment of obstructive sleep apnoea syndrome

We evaluated the effect of non-invasive nocturnal ventilation with the bi-level positive airway pressure (BiPAP) ventilator in 12 overweight patients with verified obstructive sleep apnoea syndrome (OSAS) and nocturnal hypercapnia. All patients exhibited subsequently less overnight CO2 accumulation (p < 0.0001), the desaturation event frequency was reduced (p < 0.002), daytime O2 tension rose (p < 0.001), daytime CO2 tension was reduced (p < 0.01), and apnoeas were eliminated. All symptoms characterising the syndrome, when present at the beginning of the therapy, were eliminated during the treatment. Patient compliance was high. This study showed that OSAS patients with hypercapnia can be effectively treated by BiPAP ventilation during sleep.

Urinary Calcium Excretion and Renal Calbindin-D28k

The present investigation examined the possible influence of urinary calcium excretion on the concentration of renal calbindin-D28k. Thiazide diuretics stimulate calcium transport across the epithelial cells of the distal tubule, which express calbindin-D28k in high concentrations. Calbindin-D28k is assumed to facilitate transcellular Ca diffusion. Reduced urine calcium excretion and increased urine output were induced in Wistar rats by infusion of bendroflume-thiazide 1 mg/kg/day. The two control groups had infusions of either furosemide 20 mg/kg/day or vehicle, n = 8 in each group. Urinary Ca excretion was reduced to 10% in the thiazide group and increased by 50% in the furosemide group. Renal concentrations of calbindin-D28 showed no difference between vehicle, thiazide- and furosemide-treated rats. No differences in plasma concentrations of calcium, magnesium, phosphorus, urea, PTH, calcitonin and 1,25-(OH)2D were found between the groups. The present study describes that urine calcium excretion selectively can be manipulated without accompanying changes in renal calbindin-D28k concentrations. The data, therefore, suggest that urinary calcium excretion is not a significant determinator of cytosolic concentrations of renal calbindin-D28k.

Effect of Vitamin D Metabolites and Analogs on Renal and Intestinal Calbindin-D in the Rat

Abstract. The effects on renal and intestinal calbindin-D of vitamin D3 metabolites and synthetic 20-epi-vitamin D3 analogs with different calcemic actions were examined in Wistar rats. The compounds were administered intraperitoneally once daily for 5 days. The dosages of the metabolites were 1,25-(OH)2D3 0.01, 0.05, 0.1, and 0.4 μg/kg × d, 24,25-(OH)2D3 0.1, 1 and 10 μg/kg × d, and 25-(OH)D3 10 and 400 μg/kg × d. The dosage of the synthetic analogs were MC903 0.1, 10, and 100 μg/kg × d, EB1213 0.1 and 10 μg/kg × d, KH1060 0.1 and 0.4 μg/kg × d, and GS1725 0.01 and 0.1 μg/kg × d. Two control groups had either vehicle alone or no treatment. N= 8 in each group. 1,25-(OH)2D3 increased renal and intestinal calbindin-D levels, induced hypercalcemia, and suppressed plasma PTH and magnesium concentrations. 24,25-(OH)2D3 increased intestinal calbindin-D9k and plasma calcium, but had no effect on renal calbindin-D28k, plasma PTH, and magnesium. The dosage of 24,25-(OH)2D3 that was required to increase plasma calcium was larger than the dosage required to increase intestinal calbindin-D9k. 25-(OH)D3 did not change the calcium metabolic parameters. MC903, a low calcemic analog with a relative high affinity for the vitamin D receptor and a short half-life, increased renal calbindin-D28k without increasing ionized calcium or intestinal calbindin-D9k. EB1213, an analog with a reduced calcemic action and short half-life, increased renal calbindin-D28k and ionized calcium without increasing intestinal calbindin-D9k. The effect of the high calcemic vitamin D analogs KH1060 and GS1725 on calbindin-D was directly related to their calcemic activity. In conclusion, these results demonstrate that 24,25-(OH)2D3 increases intestinal calbindin-D9k, but has no effect on renal calbindin-D28k, that low calcemic analogs may increase renal calbindin-D28k without increasing intestinal calbindin-D9k, and that the effect of high calcemic analogs on calbindin-D is directly related to their calcemic activity.

Regulation of renal calbindin-D28K: The role of calcitonin

Infusion of calcitonin lowers circulating calcium, but in the distal tubule of the kidney, pharmacological doses of calcitonin increase the active calcium reabsorption. Calbindin-D28k plays a significant role in the calcium reabsorption in the distal convoluted tubule of the kidney. The effect of calcitonin on renal calbindin-D28k in relation to calcium metabolic changes was therefore examined. In study 1, thyroparathyroidectomy followed by autotransplantation of the parathyroid glands (TX) was compared with a sham operation in rats. TX reduced plasma calcitonin from 54±2 to 9±1 pg/ml (P<0.001), whereas ionized calcium and parathyroid hormone were returned to the control value after an initial decrease, indicating a successful implantation of the parathyroid glands. No changes were seen in calbindin-D or plasma 1,25(OH)2D. In study 2, subcutaneous infusion of salmon calcitonin 2.5 U/kg/hour via osmotic pumps was compared with infusion of vehicle in rats. Ionized calcium was reduced from 1.37±0.01 to 1.33±0.02 mmol/liter (P<0.05), whereas no changes were seen in renal or intestinal calbindin-D or in plasma 1,25(OH)2D. After TX, only calcitonin decreased whereas the other calcium metabolic parameters showed no change. This indicates that in rats, selective elimination of calcitonin does not influence other parameters of the calcium metabolism and that the effect of calcitonin on calcium transport in the distal tubule is not mediated via an increase in renal calbindin-D28k.

Calcium metabolic changes and calbindin-D in experimental hypertension.

Objective To examine renal and intestinal calbindin-D in relation to calcium metabolic changes in three different models of experimental hypertension. Design: Spontaneously hypertensive rats (SHR), hypertension-prone Dahl salt-sensitive (Dahl-S) rats and the Goldblatt two-kidney, one clip rat model of renovascular hypertension were examined. Results Both prehypertensive and hypertensive SHR had significantly lower concentrations of both renal calbindin-D28k and intestinal calbindin-D9k than Wistar control rats. This was accompanied by hypocalcaemia, hypomagnesaemia and increased plasma 1,25(OH)2 vitamin D levels. Induction of hypertension in Dahl-S rats reduced intestinal calbindin-D9k and increased plasma levels of 1,25(OH)2 vitamin D, while renal calbindin-D28k levels, plasma calcium levels and plasma magnesium levels were unchanged. Renovascular hypertension was associated with a significant increase in the intestinal calbindin-D9k, plasma 1,25(OH)2 vitamin D, parathyroid hormone and magnesium levels, while renal calbindin-D28k, plasma calcium and phosphorus levels were unaffected. Conclusions These three models of experimental hypertension have clearly demonstrated three separate patterns in the regulation of renal and intestinal calbindin-D, which relate to different alterations of factors involved in calcium and magnesium metabolism. In all three models hypertension was accompanied by a significant increase in plasma concentrations of 1,25(OH)2 vitamin D. Only rats with renovascular hypertension showed increased intestinal calbindin-D9k levels, whereas reduced concentrations were found in the SHR and in the hypertensive Dahl-S rats. This indicates the existence of a resistance at the cellular level to 1,25(OH)2 vitamin D affecting the expression of calbindin-D in both SHR and Dahl-S rats.