DEMONSTRATION OF CIRCULATING 1,24,25-TRIHYDROXYVITAMIN D3 IN MAN BY RADIOIMMUNOASSAY

1,24,25-trihydroxyvitamin D3 has been detected in human serum using a sensitive radioimmunoassay. Tritiated 1,24,25-trihydroxyvitamin D3 was synthesized biologically and used as tracer to monitor the recovery of endogenous metabolite during isolation from serum. Circulating 1,24,25(OH)3D3 in normal subjects ranged from 9.3 to 18.5 pmol/l but was not detectable (less than 2.3 pmol/l) in serum from nephrectomized subjects. The trihydroxymetabolite was elevated in three out of four vitamin D deficient subjects who were being treated with vitamin D3.     

RADIOIMMUNOASSAY OF 1,25-DIHYDROXY VITAMIN D2: STUDIES ON THE METABOLISM OF VITAMIN D2 IN MAN

A sensitive radioimmunoassay for 1,25-dihydroxy vitamin D₂ was developed using a sheep antiserum which preferentially reacts with 1-hydroxylated forms of vitamin D. An improved isolation procedure was also developed using acetonitrile for the initial extraction of serum followed by chromatography on cartridges of C₁₈ silica and high pressure liquid chromatography eluted with a ternary solvent system to separate 1,25-dihydroxy vitamin D₂ and 1,25-dihydroxy vitamin D_3. 25-hydroxy vitamin D₂ and 25-hydroxy vitamin D₃ were separated by further reverse phase high pressure liquid chromatography prior to competitive protein binding assay. The limits of detection were 4.3 pmol/l (2.0 pg/ml) for the 1,25-dihydroxy metabolites and 1.25 nmol/l (0.5 ng/ml) for both 25-hydroxy vitamin D₂ and 25-hydroxy vitamin D₃. 25-hydroxy vitamin D₂ ranged from 2.0 to 11.3 nmol/l (0.8–4.5 ng/ml) with a mean of 4.75 nmol/l (1.9 ng/ml) in thirteen healthy British adults and this accounted for 9.0% of the mean total 25-hydroxy vitamin D. 1,25-dihydroxy vitamin D₂ was detected in the sera of only one of these subjects whereas 1,25-dihydroxy vitamin D₃ was present in all ranging from 48 to 163 pmol/l (20–65 pg/ml) with a mean of 100 pmol/l (42 pg/ml). Both 1,25-dihydroxy vitamin D₂ and 1,25-dihydroxy vitamin D₃ were detected in the sera of hypoparathyroid patients treated with vitamin D₂ but the relationship between 25-hydroxy vitamin D and 1,25-dihydroxy vitamin D was complex. For example, when an excess of 25-hydroxy vitamin D₂ was present the serum concentration of 1,25-dihydroxy vitamin D₃ was disproportionately high. Conversely, in patients who had previously been treated with vitamin D₂ but were receiving only vitamin D₃ at the time of study, the major 25-hydroxy metabolite was in the vitamin D₃ form and there was a disproportionately high amount of 1,25-dihydroxy vitamin D_2. Total 1,25-dihydroxy vitamin D ranged from 110 to 400 pmol/l (45–165 pg/ml) and was above the upper limit of normal for 1,25-dihydroxy vitamin D₃ in half of these hypoparathyroid patients treated with pharmacological doses of vitamin D.     

The Modified Anterior Line: An Alternative Linear Lesion in Perimitral Flutter

Modified Anterior Line for Perimitral Flutter. Introduction: Ablation of left atrial flutter (LAF) is often limited by the need for technically demanding linear lesions. We evaluated the safety and efficacy of a new modified anterior line (MAL), connecting the anterior/anterolateral mitral annulus with the left superior pulmonary vein for ablation of perimitral flutter. Methods and Results: MAL was performed in 65 patients (15 females, age 63.6 ± 9.8 years) with perimitral flutter using 3D mapping systems (70.8% Carto, 29.2% NavX). Perimitral flutter was either the presenting arrhythmia (73.8%) or an intermediate organized rhythm during atrial fibrillation ablation. Follow‐up included repetitive 7‐day Holter with 93.8% of patients off antiarrhythmics. MAL was acutely effective in 63/65 patients (96.9%). Termination to sinus rhythm occurred in 36 of 65 patients (55.4%), and in 27 of 65 patients (41.5%) there was a change to another LAF type. Bidirectional block across the MAL was achieved in 56 of 65 patients (86.1%). After 6 months of follow‐up, 20 of 41 patients (48.8%) had a LAF recurrence, with 6 patients undergoing a reablation. In all redo patients the MAL was still complete and LAF mechanism was different to the initially targeted. No major complication occurred during the ablation procedures or in the postablation period. Conclusion: The MAL is a safe and effective linear lesion for the treatment of perimitral LAF. Its value compared to more established linear lesions as the mitral isthmus line has to be evaluated in larger studies. (J Cardiovasc Electrophysiol, Vol. 21, pp. 665‐670, June 2010)