Initial Clinical Experience with a New Dual Sensor SSIR Pacemaker Controlled by Body Activity and Minute Ventilation

Fourteen patients were implanted with a single chamber dual sensor pacemaker (Legend Plus®) that measures minute ventilation (VE) via variations in impedance between a bipolar lead and the pacemaker case, and activity via a piezoelectric crystal bonded to the pacemaker case. Chronotropic incompetent patients were exercised an a treadmill and a bicycle in dual sensor mode. Activity only indicated pacing rate was measured using a strap-on pacemaker. Both implanted and strap on pacemakers were adjusted to yield a steady-state pacing rate of 100 beats/min during hall walk. Pacing rate, VE, and oxygen uptake (VO₂) were measured continuously. Linear curve fit analysis slopes for plots of VE versus pacing rate during exercise (1.33-1.49) compared favorably to values reported in normals. Peak pacing rates achieved for treadmill and bicycle testing for dual sensor mode were higher than activity mode alone. Slopes of heart rate to VE or VO₂ were not significantly different (P < 0.05) for dual sensor mode in contrast to activity alone. In conclusion, the Legend Plus dual sensor rate adaptive pacing therapy delivered pacing rates more proportional to VE and VO₂ under different types of exercise than rates indicated by a strap-on pacemaker in activity mode.     

Iodogen-catalyzed iodination of transferrin

Transferrin (human, rabbit) labels at low efficiency (1%-10%) with ¹²⁵I when reaction of 0.5–0.7 ng of I^- (8–10μCi) with 20μg of the protein is catalyzed by iodogen in a constant volume of 0.1 ml. Microiodination by this technique was therefore analyzed with regard to the relative proportions of the reactants, oxidant requirement, and timing. In vials giving a reaction volume-to-active surface ratio of 0.88, efficiency was independent of the amount of iodogen in the range from 1 μg to 15 μg, and prolongation of the reaction beyond 1 min failed to improve yields. In contrast, the amount of I^- present was decisive. Butanol/NH₄OH chromatograms of iodination reactions carried out with 0.6 ng or 20 ng of I^- showed 3–4 radioactivity peaks, the relative proportions of which markedly depended on the amount of I^- present originally. A link was established between labeling efficiency and chromatographic profile of the I^- derivatives formed during oxidation. Dual-label experiments in rats showed that transferrin (20μg) can be labeled using iodogen (1–5μg, 1 min) to behave indistinguishably from its IC1-labeled counterpart. However, prolonged exposure to more oxidant progressively damaged the protein. The damage was independent of substituting I and it manifested itself in increased protein binding to the anion exchange resin, Dowex 1-X8. Over 99.5% of the labeled residues in iodotransferrin were mono- and diiodotyrosines (MIT, DIT). DIT content of the protein increased linearly with the number of I atoms substituted. At comparable levels of substitution, more label was present as MIT after using iodogen than after using ICl. Electrophoretic data are presented regarding homogeneity of the label as obtained after iodinating transferrin by different methods and to varying extents.     

Central Nervous System Toxicity of Manganese: I. Inhibition of Spontaneous Motor Activity in Rats after Intrathecal Administration of Manganese Chloride

The intrathecal administration of MnCl₂ to young male rats causeddoparnine depletion in the caudate-putamen and a decrease inspontaneous motor activity. Our experiments demonstrate thatin the young rat: (a) the lateral choroid plexus protects thecerebrospinal fluid (CSF) from high concentrations of Mn inthe blood by sequestering and thus preventing large amountsof this metal ion from entering the CSF. As blood Mn levelsrise, the lateral choroid plexus may become overwhelmed andleak an increasing amount of Mn into the CSF. (b) The lateralchoroid plexus does not remove Mn²⁺ from the CSF. (c) The injectionof MnCl² into the CSF of rats caused a rapid decrease in spontaneousmotor activity which is dose-dependent and reversible underthe present experimental conditions. Entrathecal Mn resultsin a substantial decrease in striatal dopamine but not homovanillicacid or 3,4-dihydroxyphenylacetic acid (DOPAC) concentrationsand is associated with an increase in the Mn concentration ofthe substantia nigra and caudate-putamen.     

Clinical cardiac electrophysiologic evaluation of the positive inotropic agent, DPI 201-106

DPI 201–106 is a new positive inotropic agent. The cardiacelectrophysiology of 16 patients was studied before and duringDPI 201–106 administration (loading dose of intravenousDPI 201–106, 1·8 mg kg^–1 h^–1 administeredover 10 min, followed by a maintenance dose of 0·2 mgkg^–1 h^–1). DPI 201–106 had no effect on thesinus node. The AH interval during fixed-rate atrial pacingbecame prolonged during DPI 201–106 infusion. There wasa significant prolongation of the QT interval [QT (corrected),417 ± 22 to 502 ± 35 ms, P<0·05; QT(atrial pacing at 600 ms), 374 ±17 to 419 ± 23ms, P<0·05; QT (ventricular pacing at 600 ms), 409± 37 to 449 ± 30 ms, P<0·05]. The ventriculareffective refractory period significantly prolonged during DPI201–106 administration (242 ± 21 to 287 ±56 ms, P < 0·05), but the supernormal-period durationdecreased. The atrial effective refractory period was shortenedin four patients and prolonged in one (261 ± 67 to 240± 53 ms, NS). The corrected atrial repolarization time(PT_ac) shortened significantly during DPI 210–106 infusion(479 ± 26 to 445 ± 22 ms at 20 min of the maintenancedose, P<0·05). Atrial fibrillation was initiated infive patients during DPI infusion, but no ventricular arrhythmiawas provoked. These findings suggest that DPI 201–106has novel differential electrophysiological effects on atriaand ventricles.