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.     

Fear and the startle reflex: Blink modulation and autonomic response patterns in animal and mutilation fearful subjects

The present study was designed to examine the pattern of startle reflex modulation and autonomic responses for individuals high in animal or blood-injury fear when viewing pictures of their feared objects. Sixteen individuals in each fear group and 16 low-fear control individuals viewed 32 color slides depicting fear-relevant, unpleasant but fear-unrelated, neutral, and pleasant scenes. Free viewing times were assessed in a second phase of the procedure as an index of avoidance behavior. Exposure to pictures of feared objects resulted in a consistent startle reflex potentiation and behavioral avoidance in both fear groups. This activation of the basic aversive system was independent of the autonomic pattern of the fear responses, which differed for the high-fear groups. These results suggest that the probe startle response indexes the organism's basic motivational disposition and add new information to the assessment of fear.     

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.     

Age-Dependent Prevalence of Cardioembolic Sources Detected by TEE: Diagnostic and Therapeutic Implications

To define the prevalence of cardioembolic sources found by transesophageal echocardiography (TEE) in different age groups of patients with and without cryptogenic systemic embolism, TEE risk factors for cardiogenic embolism were identified from 341 consecutive patients referred for TEE. One hundred and thirty-five had cryptogenic cerebral or systemic peripheral embolic events (CEE) and 206 other indications for TEE (CTR). Cardioembolic sources were found in 40% of CEE and in 29% of CTR (P < 0.02). Specifically, left atrial (LA) thrombi (P < 0.0001), atrial septal aneurysm with right-to-left shunt (P < 0.002), and atherosclerotic aortic plaques (P < 0.02) were more frequent. The prevalence of potential cardioembolic sources was significantly higher in patients ≥ 70-years old than in younger patients (P < 0.03), specifically LA thrombi (P < 0.004) and atherosclerotic aortic plaques (P < 0.0001). In patients ≥ 70-years old, potential cardioembolic sources were found in 63% and in 40% in CEE and CTR (P = 0.073), respectively. However, LA thrombi were more frequent in CEE (P < 0.003). Thus, potential cardioembolic sources observed by TEE are found more frequently in patients ≥ 70-years old than in younger patients. LA thrombi were more frequent in CEE than in CTR patients ≥ 70-years old. In patients ≥ 70-years old with CEE who are eligible for an anticoagulant regimen, a search for potential cardioembolic sources by TEE should be considered.     

The Effects of Allyl Isovalerate on the Hematopoietic and Immunologic Systems in Rodents

The Effects of Allyl Isovalerate on the Hempatopoietic and ImmunologicSystems in Rodents. HONG, H. L., HUFF, J. E., LUSTER, M. I.,MARONPOT, R. R., DIETER, M. P., HAVES, H. T., AND BOORMAN, G.A. (1988). Fundam. Appl. Toxicol. 10, 655–663. FemaleB6C3F1 mice plus male and female Fischer 344/N rats were gavagedwith allyl isovalerate (AIV) in corn oil at 0, 31,62, or 125(mice) and 0, 31. 62, 125, or 250 (rats) mg/kg body weight forfive daily exposures per week for a 2-week period. Hematologic,immunologic, and histopathologic studies were performed 48 to72 hr following the final treatment. AIV exposure had no effecton hematology or bone marrow cellularity in mice or rats. AIVexposure at 250 mg/kg was toxic to rats causing reduced weightgain and hepatotoxicity. In vivo and in vitro studies revealedthat pluripotent hematopoietic stem cells (CFU-S) and granulocyte-macrophageprogenitors (CFU-GM) in the bone marrow were decreased in thetreated mice. Hematopoietic suppression was correlated withthe reduction in the hexose monophosphate shunt metabolism ofbone marrow cells but the Embden-Meyerhof pathway and tncarboxylicacid pathway enzymes did not appear to be affected. Examinationof host resistance following Plasmodium and Listeria challengedid not demonstrate significant differences between treatedand control mice, nor were there other effects on the immunesystem. This suggests that the myelotoxic effects were minimaland of a degree that would not alter host resistance.