The identification of afterdepolarizations and their relationship to arrhythmias in vivo is not available. Experiments were undertaken to determine whether afterdepolarizations could be detected in monophasic action potentials (MAPs) recorded in vivo and whether they were related to arrhythmias in an intact canine preparation of the long QT syndrome. Isolated cardiac tissues from six dogs were studied to validate the technique. In simultaneous MAP and transmembrane recordings, afterdepolarizations induced with barium (early) or acetylstrophanthidin (delayed) were detected in MAPs when present in microelectrode recordings. MAPs were then recorded in situ in eight dogs with cesium chloride-induced long QT syndrome associated with ventricular arrhythmias. Afterdepolarizations were identified in each of the dogs and were similar to early afterdepolarizations identified in vitro; they occurred during phase 3 and were attenuated during overdrive pacing. The afterdepolarizations were closely related to arrhythmias: (1) afterdepolarizations always preceded ventricular arrhythmias, (2) the coupling intervals (CI) of the afterdepolarizations (AD) and the ventricular premature beats (VPB) were nearly identical (VPB CI = 1.06 AD CI -10.24; r2 = .87), (3) the take-off potentials of the ventricular premature beats were nearly identical to the amplitude of the afterdepolarizations (take-off potential = 0.98 afterdepolarization amplitude +0.46, r2 = .87), and (4) afterdepolarizations and ventricular arrhythmias resolved concurrently during overdrive pacing and with time. Thus, a new catheter technique has been validated and has been used to directly identify afterdepolarizations and triggered activity in vivo.

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We report a case of a 65-year-old man who developed an acute illness with fever, arthralgia and nephritic syndrome. Antinuclear antibodies were slightly positive and complement levels were low. Renal biopsy showed exudative diffuse proliferative endocapillary glomerulonephritis with diffuse immunoglobulin (IgG, IgA, IgM) and complement deposition (C3d, C4d, C1q) on immunofluorescence. The patient was first treated with corticosteroids and mycophenolate mofetil for suspected lupus with WHO class IV glomerulonephritis. The diagnosis was questioned and a diagnosis of parvovirus B19-associated nephritis was made based on elevation of serum IgM antibodies for parvovirus B19 and detection of parvovirus B19 DNA on renal biopsy. The immunosuppressive treatment was stopped and progressive spontaneous regression of clinical and laboratory abnormalities was observed. We conclude that human parvovirus B19 infection should be considered as a cause of lupus-like symptomatology and acute glomerulonephritis.

1 The pharmacokinetics, bioavailability and metabolism of nitrendipine were studied in six healthy volunteers (three females, three males) using [13C4]-nitrendipine as a biological internal standard. In the first study the drug was administered simultaneously by the i.v.[13C4] and p.o. (solution) routes and in a second study two oral preparations (13C4-solution and commercial tablet) were administered, also simultaneously. 2 The mean terminal elimination half-life was 8.3 ± 3.2 h (range 3.4 to 16 h) with no differences between the intravenous and oral route of administration. Total plasma clearance averaged 18.7 ± 0.6 ml min' kg-' and volume of distribution at steady state 5.4 + 2.4 1kg-. 3 Following oral administration of nitrendipine solution the percentage of dose absorbed was 88.4 ± 16.0% based on urinary excretion of metabolites. Despite its almost complete absorption, absolute bioavailability of the solution was only 22.6 ± 6.7% due to extensive presystemic elimination. The bioavailability of the commercial tablet relative to the solution was 82.2 ± 20.3%. 4 Both after i.v. and oral administration the drug was extensively metabolized with less than 0.5% of the dose excreted as unchanged drug in urine. Cleavage of the two ester functions in position 3 and 5, respectively, to carboxylic acids and further hydroxylation of the methyl groups in position 2 and 6 of the pyridine ring to the corresponding hydroxymethyl carboxylic acids constituted the major urinary metabolites accounting for 35.0 ± 16.5% (i.v.) and 32.8 ± 20.4% (p.o.), respectively, of the dose administered. 5 Binding of nitrendipine to plasma proteins was high with a fraction unbound of only 0.02 ± 0.012 (range 0.011 to 0.036).

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