Seasonal covariation of the circadian phases of rectal temperature and slow wave sleep onset

There is a scarcity of well-controlled studies of the seasonal variation in circadian rhythmicity. In the present study, the circadian phase of rectal temperature and the onset of slow wave sleep were studied in a series of twelve 24-h experiments, one each month of the year, for six healthy subjects under controlled conditions in a climatic chamber. In winter, as compared with summer, the average circadian rhythm of rectal temperature was phase delayed by 45 min, and the average onset of slow wave sleep was phase delayed by 40 min. The temporal relationship between the circadian phase of rectal temperature and the timing of slow wave sleep was maintained throughout the year. Habitual rising and retiring times covaried as well. Furthermore, the circadian rhythm of rectal temperature followed the timing of the photoperiod across the year, but had a much smaller range of seasonal variation. Apparently, the seasonal variation in the photoperiodic zeitgeber is largely compensated for by the stabilizing influence of secondary zeitgebers. However, in healthy subjects some effect of photoperiodic variation can still be observed.     

Radiofrequency Catheter Ablation of the Anterosuperior and Posteroinferior Atrial Approaches to the AV Node for Treatment of AV Nodal Reentrant Tachycardia

Catheter Ablation Techniques in AVNRT. Radiofrequency catheter ablation has been established as a first-line curative treatment modality in patients with symptomatic AV nodal reentrant tachycardia (AVNRT). The successful sites of stepwise catheter ablation approaches of the so-called fast and slow pathways strongly suggest that AVNRT involves the atrial approaches to the AV node. The typical fast pathway ablation sites are located anterosuperior toward the apex of the triangle of Koch, which also contains the compact AV node, whereas the usual slow pathway ablation sites are located posteroinferior toward the base of the triangle of Koch at a greater distance to the compact AV node and bundle of His. Accordingly, ablation studies with large patient cohorts have demonstrated that fast pathway ablation carries a higher risk of inadvertent complete AV block. Thus, the slow pathway is clearly the primary target site, and fast pathway ablation is rarely necessary. Different approaches for slow pathway ablation have been elaborated: anatomically oriented stepwise techniques, ablation guided by double potentials recorded within the area of the slow pathway insertion, and combined techniques. The modern concept of AVNRT suggests that this arrhythmia involves the highly complex three-dimensional nonuniform anisotropic AV junctional area. Accordingly, mapping and ablation studies demonstrated that the anterior approach is not identical with fast pathway ablation, and the posterior approach is not identical with slow pathway ablation. Therefore, it is essential for interventional electrophysiologists to familiarize themsdves with the anatomic and electrophysiologic details of this complex and variable specialized AV junctional region. In this review, the anatomic and pathophysiologic aspects of the AV junctional area as they relate to interventional therapy are summarized briefly, and the catheter techniques for ablation of the so-called fast and slow AV nodal pathways for the treatment of AVNRT are described.     

Electrocardiographic and Clinical Predictors of Torsades de Pointes Induced by Almokalant Infusion in Patients with Chronic Atrial Fibrillation or Flutter: A Prospective Study

The aim of this study was to identify predictors of torsades de pointes (TdP) in patients with atrial fibrillation (AF) or flutter exposed to the Class III antiarrhythmic drug almokalant. TdP can be caused by drugs that prolong myocardial repolarization. One hundred patients received almokalant infusion during AF (infusion 1) and 62 of the patients during sinus rhythm (SR) on the following day (infusion 2). Thirty-two patients converted to SR. Six patients developed TdP. During AF, T wave alternans was more common prior to infusion (baseline) in patients developing TdP (50% vs 4%, P < 0.01). After 30 minutes of infusion 1, the TdP patients exhibited a longer QT interval (493 ± 114 vs 443 ± 54 ms [mean ± SD], P < 0.01), a larger precordial QT dispersion (50 ± 74 vs 27 ± 26 ms, P < 0.05), and a lower T wave amplitude (0.12 ± 0.22 vs 0.24 ± 0.16 mV. P < 0.01). After 30 minutes of infusion 2, they exhibited a longer QT interval (672 ± 26 vs 489 ± 74 ms, P < 0.001), a larger QT dispersion in precordial (82 ± 7 vs 54 ± 52 ms, P < 0.01) and extremity leads (163 ± 0 vs 40 ± 34 ms, P < 0.001), and T wave alternans was more common (100% vs 0%, P < 0.001). Risk factors for development of TdP were at baseline: female gender, ventricular extrasystoles, and treatment with diuretics; and, after 30 minutes of infusion: sequential bilateral bundle branch block, ventricular extrasystoles in bigeminy, and a biphasic T wave. Patients developing TdP exhibited early during almokalant infusion a pronounced QT prolongation, increased QT dispersion, and marked morphological T wave changes.     

A Decrease in Pulmonary Vein Diameter After Radiofrequency Ablation Predicts the Development of Severe Stenosis

A decrease in ostial pulmonary vein (PV) diameter was observed in patients on the day after radiofrequency ablation of atrial fibrillation (AF). This study examined whether a relative reduction in PV diameter on day 1 (RRPVD1) after the procedure predicts the late development of severe PV stenosis (PVS). The study included 104 consecutive patients (mean age = 55 years, range 46–61, 34 women) with drug refractory AF. Pulmonary vein diameter was measured using MR angiography (MRA) on the day before and on day 1 after the ablation procedure. The MRA was repeated every 3 months after the procedure. Severe PVS was defined as a >70% diameter reduction from the initial ostial diameter. The cut-off of RRPVD1 was prespecified as 25% decrease in initial diameter. The data are presented as medians and interquartile range. A total of 357 PV were treated. The RRPVD1 was 0.0% (0.0–11.1%). Severe PVS was found in 18 PV during a follow-up of 12 months (range 6–13). The log-rank analysis confirmed a strong association between a RRPVD1 ≥25% and the development of PVS (hazard ratio: 7.1; 95% confidence interval 3.8–13.5, P < 0.0001). By multivariate Cox regression model, after adjustment of procedure variables, RRPVD1 was the strongest predictor of development of severe PVS. RRPVD1 ≥25% was a strong independent predictor of development of severe PVS.     

Balloon Electrode Catheter for Transesophageal Atrial Pacing and Transesophageal EGG Recording

A new balloon electrode catheter (10 French) with five or six balloon electrodes placed on the cardiac side was developed for transesophageal atrial pacing and bipolar ECG recording. The diameter of the hemispheric electrodes is 6 mm and the length of the esophageal balloon is 10 cm. The transesophageal atrial pacing threshold was measured with the balloon electrode catheter by transesophageal programmed atrial stimulation (TPS) (n = 54). At the onset of TPS, the feeling, capture fn = 54), and pain voltage threshold (n = 6) were measured by increasing the amplitude of the pacing voltage during high rate bipolar atrial pacing and bipolar atrial ECG recording. In 38 TPS, the capture threshold was lower than the feeling threshold (n = 28). In 16 TPS, the capture threshold was higher than the feeling threshold. In conclusion, painless atrial pacing and excellent ECG recording can be achieved with a multipolar esophageal balloon electrode catheter with a low pacing voltage amplitude and a high P wave amplitude.     

Concentration- and Region-dependent Intestinal Permeability of Fluvastatin in the Rat

The purpose of this study was to investigate the mechanisms of transport of fluvastatin across the intestinal mucosa in various regions of the intestine in the rat. In-situ single-pass perfusions of the jejunum, ileum and colon were performed and the effective permeability (P_eff) of fluvastatin, antipyrine and D-glucose were assessed in each region, at three different perfusate fluvastatin concentrations (1.6, 16 and 160 μM). The effect of lovastatin acid on the bi-directional transport of fluvastatin across the ileal mucosa was also studied. The P_eff of fluvastatin was found to be dependent both on the intestinal region and on the concentration in the intestinal lumen (P < 0.001). Fluvastatin had the lowest P_eff (0.55±0.10 times 10^?4 cm s^?1) in the jejunum at 1.6 μM, and the highest P_eff (1.0±0.16 times 10^?4 cm s^?1) in the colon at 160 μM. The highest concentration of fluvastatin increased the average absorption of water from the intestine by 209% (P < 0.05), and the average P_eff of D-glucose by 29% (P < 0.05). The presence of excess lovastatin acid (100 μM, compared with fluvastatin 1.6 μM) at the luminal side increased the average absorption of water by 218% (P < 0.001), and the P_eff of fluvastatin in the ileum and the colon by 44 and 50%, respectively (P < 0.05). The presence of lovastatin acid on the luminal side in the ileum also increased the blood-to-lumen transport (exsorption) of fluvastatin by 43% (P < 0.001). The increased intestinal absorption of fluvastatin at higher concentrations does not suggest that substantial absorption occurs by any carrier-mediated process in the absorptive direction. The increased bi-directional transport when lovastatin acid was added to the lumen suggests that fluvastatin is not a P-glycoprotein substrate. Instead, the concentration-dependent increase in the absorption of fluvastatin, water and D-glucose suggests a direct effect of fluvastatin on the transcellular passive transport.     

EFFECTS OF THE EXTRADURAL ADMINISTRATION OF MORPHINE OR BUPIVACAINE, ON THE METABOLIC RESPONSE TO UPPER ABDOMINAL SURGERY

The influence of thoracic extradural local anaesthetics (0.5%bupivacaine) or extradural morphine on the metabolic responseto upper abdominal surgery was compared with the administrationof morphine i.v. in the period after operation. The extradurallocal anaesthetic group had significantly lower blood glucoseand plasma FFA concentrations and consistently, but not significantly,lower blood glycerol and lactate concentrations than both theother groups. At 4 h both extradural groups had significantlylower plasma FFA and blood 3-hydroxybutyrate concentrationsthan the control group. Blood alanine concentration decreasedin all three groups with a minimum at 24 h. There were no differencesin serum insulin concentrations between the groups. It is concludedthat thoracic extradural morphine differs from thoracic extradurallocal anaesthetics in being much less able to suppress the metabolicresponse associated with upper abdominal surgery.     

Temperature-controlled Radiofrequency Catheter Ablation of Accessory Pathways and Atrioventricular Nodal Reentrant Tachycardia: The 5-French Catheter Approach

Ablation with Temperature-Controlled 5-French Catheters. Introduction: In the present study, we assessed the feasibility of radiofrequency (RF) ablation of accessory pathways and AV nodal reentrant tachycardias with novel 5-French catheters with 4-mm tip electrodes using established mapping criteria and temperature-controlled power output control. Methods and Results: In this prospective study, 60 consecutive adult patients (mean age 36 ± 20 years) with accessory pathways (n = 37; 24 left-sided) or AV nodal reentrant tachycardia (n = 23) underwent RF catheter ablation. A 5-French catheter with a 4-mm tip electrode and an embedded thermistor was used for RF application. The surface of the tip electrodes was 26 mm2 compared to 38 mm² of 7-French catheters with 4-mm tip electrodes from the same catheter series. Power output was automatically and continuously adjusted according to the preset catheter tip temperature of 60° to 70°C. Pulse duration was 90 seconds. For left-sided accessory pathways, the retrograde route via the femoral artery was used. After removing the 5-French sheaths, only 4 hours of bed rest were advised. For ablation of AV nodal reentrant tachycardia, the so-called slow pathway was targeted for ablation. Acute success was achieved in 34 (92%) of 37 patients with accessory pathways and 23 (100%) of 23 patients with AV nodal reentrant tachycardia. A mean of 3 ± 4 RF pulses (median 2 pulses; range 1 to 20 pulses) was applied. The mean fluoroscopy time was 26 ± 21 minutes. No complete AV block or other procedure-related complications were observed. Recurrences occurred in 2 patients with accessory pathways and in 2 patients with AV nodal reentrant tachycardia during a follow-up of 9 ± 4 months. Conclusions: Temperature-controlled RF ablation of accessory pathways and AV nodal reentrant tachycardia in adults using 5-French catheters is feasible, effective, and safe. Ablation with 5-French catheters might help to reduce the complication rate of catheter ablation techniques.     

Evidence for a light chain restriction of glycoprotein Ib/IX and Ilb/IIIa reactive antibodies in chronic idiopathic thrombocytopenic purpura (ITP)

To address the assumption of clonally restricted antibodies in immune thrombocytopenias we studied sera from 19 patients with chronic ITP known to possess antibodies reactive with glycoprotein (GP) Ib/IX and/or GPIIb/IIIa. These sera were re-analysed using the standard monoclonal antibody immobilization of platelet antigens (MAIPA) assay and 16 patients exhibited IgG antibodies reactive with GPIIb/IIIa; seven patients showed also a reactivity with GPIb/IX. Employing a light-chain-specific MAIPA assay, 75% (12/16) of these sera displayed GPHb/ Ilia-specific antibodies that were light chain restricted; only 13% (2/16) of the GPIIb/IHa reactive sera showed a mixed kappa and lambda phenotype. A light-chain-restricted phenotype was also seen for the GPIb/IX reactive antibodies. To further substantiate these findings, the MAIPA assay was modified in order to avoid interference from human anti-mouse antibodies. A high frequency of light-chain restricted platelet antibodies was also found using the modified MAIPA technique. These results support the hypothesis of a clonal B-cell expansion in immune thrombocytopenias, producing antibodies with a restricted idiotype repertoire and reacting with a limited number of epitopes.