The QT interval during wake and sleep in patients with ventricular arrhythmias

Eight patients with frequent ventricular ectopy underwent continuous electrocardiographic (ECG) and polygraphic monitoring for 4 days. A complex protocol consisted of normal day-night, activity-nonactivity, cycles for 48 h (nine patients); followed by a 24-h awake bedrest; and finally by a very delayed sleep and inactivity phase in the morning before returning to a normal day-night cycle (eight patients only). ECG tracings showed that the QT intervals during rapid eye movement sleep and nonrapid eye movement sleep increased significantly when compared with active wakefulness. The Bazett's corrected QT (QTc) interval also increased from active wakefulness to rapid eye movement sleep and nonrapid eye movement sleep. Adjusted mean QT intervals computed using the RR [corrected] interval as a covariate were significantly longer during non-rapid-eye-movement (407 ms) and rapid-eye-movement (408 ms) sleep than during active wakefulness (386 ms). The RR-adjusted mean QT intervals during inactive wake were also longer (400 ms) but this clear trend did not reach statistical significance (p = 0.08). Although prolongation of the QT interval during sleep reflects inactivity that may be related to withdrawal of sympathetic tone, we postulate that sleep per se also has an effect on the interval.     

Association of corrected QT interval with long-term mortality in patients with syncope

Introduction

The electrocardiographic parameters QRS duration, QRS-T angle and QTc can predict mortality in patients with cardiovascular disease. The prgnostic value of these parameters in hospitalized patients with syncope needs investigation.

Material and methods

We retrospectively studied 590 consecutive patients hospitalized with syncope. After excluding patients with baseline abnormal rhythm, QT- prolonging medications, and missing data, 459 patients were analyzed. Baseline demographic characteristics, co-morbidities, medication use, San Francisco Syncope Rule (SFSR) and Osservatorio Epidemiologico sulla Sincope nel Lazio (OESIL) score and data on mortality were collected. The categorical variables and continuous variables of the 2 groups of patients with prolonged QTc and normal QTc interval were analyzed by Fischer''s exact test and Mann-Whitney Test. A stepwise Cox regression model was used for time to death analysis.

Results

Of 459 patients, prolonged QTc interval was observed in 122 (27%). Mean follow-up was 41 months. Patients with prolonged QTc interval had higher prevalence of cardiovascular disease, OESIL score, high risk SFSR, hypertension, dyslipidemia, coronary artery disease, congestive heart failure, and increased mortality. Stepwise Cox regression analysis showed that significant independent prognostic factors for time to death were prolonged QTc interval (p = 0.005), age (p = 0.001), diabetes mellitus (p = 0.001) and history of malignancy (p = 0.006). QRS duration and QRS-T angle were not independent predictors of mortality.

Conclusions

A prolonged QTc interval is an independent predictor of long-term mortality in hospitalized patients with syncope.     

Effect of sertindole on QTc interval in patients with schizophrenia

Sertindole has been marketed and offered daily clinical practice only for 9 months in our country, so no data has been its QTc prolongation potential. In the present study, we performed a clinical trial to investigate the effects of sertindole on QTc in patients with schizophrenia. The study comprised 21 patients with schizophrenia. Sertindole was administered in the following dosing regime: treatment was initiated with 4 mg/day sertindole. From day 3 to day 6, the dose was increased to 8 mg/day, and up to day 9, it was raised to 12 mg/day. The protocol allowed up to dose of 20 mg/day according to effectiveness and tolerability. QTc values were determined at beginning, months 3 and 6. In addition, Positive and Negative Syndrome Scale (PANSS) were scored concomitantly. At the beginning of 6-month period, the mean QTc interval of patients was 391.7 ± 19.2 ms. At the end of this period, it was 402.8 ± 23.8 ms. Although the mean QTc interval changing was significant throughout 6-month period, of the patients, at any evaluation point, only 1 female (451 ms) and 1 male (433 ms) had borderline prolongation at month 3 for both, without any exceeding the dangerous limits. In summary, our results suggest that sertindole is tolerable and despite dose-related QT prolongation, sertindole had not the proarrhythmic profile. Future studies with larger sample evaluating the effects of treatment are required.     

Effect of beta adrenergic stimulation and blockade on immediate hypersensitivity skin test reactions

The effects of isoproterenol (a β-adrenergic stimulating agent) and propranolol (a β-adrenergic blocking agent) were studied on immediate hypersensitivity skin test reactions in 15 atopic subjects. Forearm skin of these subjects was pretreated with these agents by local iontophoretic application and compared to areas locally pretreated with saline or diphenhydramine hydrochloride. Following pretreatment of skin, scratch or intradermal tests were performed with the most reactive antigen for each patient. A significant increase of skin reactivity occurred in areas of skin pretreated with propranolol. A significant decrease in reactivity followed pretreatment with isoproterenol. Thus the iontophoresis of β-adrenergic agents can alter the immediate hypersensitivity skin test reactions of atopic patients. This alteration is consistent with a modification of the local synthesis of cyclic adenosine monophosphate (CAMP) induced by these pharmacologic agents. It is not clear whether this presumed alteration in CAMP is exerting its effect on mediator release from dermal mast cells or directly on the dermal blood vessels or both.     

Effect of beta adrenergic stimulation and blockade on cutaneous reactivity to histamine.

It has been previously demonstrated that iontophoresis of beta adrenergic agents will alter the size of immediate hypersensitivity skin tests. It was unclear whether this alteration was due to an effect on the dermal mast cell (inhibition of histamine release) or on the cutaneous vasculature (inhibition of capillary permeability). For this reason isoproterenol, propranolol, diphenhydramine as a positive control, and saline as a negative control were iontophoresed onto the forearm of 10 atopic and 10 nonatopic adult subjects. In order to bypass histamine release from mast cells the patients were then challenged directly with histamine by the "prick" technique. The size of the resultant wheals was noted. The data obtained allowed the following conclusions: (1) The atopic group responded to histamine with greater wheal size than the nonatopic group. (2) Iontophoresis of diphyenhydramine effectively reduced the magnitude of the histamine wheal in both groups. (3) Isoproterenol decreased the wheal size in both groups. (4) Propranolol increased the wheal size in only the nonatopic group. (5) The successful modulation of the histamine-induced wheal and flare indicated that these drugs, regardless of their effect on the dermal mast cell, exert a measurable effect on the target organ (vasculature).     

The effect of 25-hydroxyvitamin D levels on QT interval duration and dispersion in type 2 diabetic patients

Aim

To assess the relationship between corrected QT (QTc) interval and vitamin 25-hydroxyvitamin D levels (25-OHD) deficiency in type 2 diabetic patients.

Methods

The study included 253 patients with type 2 diabetes and 170 age-matched controls treated between October and December 2013. QTc duration and QTc dispersion were measured on ECG recordings and 25-OHD, calcium, phosphorus, and blood glucose levels were determined.

Results

Patients with diabetes had significantly longer QTc duration and QTc dispersion than controls (P < 0.001 and P < 0.001 respectively). Diabetic patients with prolonged QTc duration were older and had longer diabetes duration and higher HbA1c levels than patients with normal QTc interval. They significantly more frequently had 25-OHD deficiency (P < 0.001), but had similar calcium and phosphorus levels. Diabetic patients with prolonged QTc dispersion were of similar age and had similar diabetes duration and HbA1c levels as patients with normal QTc dispersion. They significantly more frequently had 25-OHD deficiency (P = 0.010), but had similar calcium and phosphorus levels.

Conclusion

This study showed prolonged QTc duration and QTc dispersion in patients with type 2 diabetes, especially those with 25-OHD deficiency.Worldwide prevalence of type 2 diabetes mellitus (T2DM) is 7.7%, and is expected to further increase. The principal cause of death in patients with T2DM are cardiovascular diseases, with the annual mortality of 5.4% (1). Cardiac mortality and morbidity rate can be reduced by disease detection at the time when overt cardiac disease is still not present. This requires novel screening strategies, one of which is QT interval analysis. QT abnormalities can predict cardiac death in several diseases, including chronic heart failure, systemic hypertension, and peripheral vascular disease (2). In diabetic patients QT abnormalities can be detected at diagnosis and are better predictors of cardiac death than autonomic function tests (3). Moreover, in diabetic patients increased QT dispersion was shown to predict cardiovascular mortality (4).Calcium-phosphorus metabolism disorders and 25 hydroxyvitamin D (25-OHD) deficiency are known risk factors for cardiovascular events (5-7). Also, disturbances that lead to decreased 25-OHD levels have been shown to result in structural and ionic channel remodeling, which may increase the susceptibility to cardiac arrhythmias. In addition, they induce cardiac hypertrophy and fibrosis, which are known risk factors for sudden cardiac death (7,8).Altered 25-OHD and calcium homeostasis may also play a role in the development of T2DM. Vitamin D has been shown to affect the synthesis and secretion of insulin (9) and predict the increased risk of all-cause and cardiovascular mortality in T2DM patients independent of conventional risk factors (10). However, there are limited data on the relationship between 25-OHD and QT parameters in diabetic patients. The aim of this study was to investigate the relationship between the 25-OHD deficiency and the corrected QT (QTc) interval duration and dispersion in patients with diabetes.     

TNF-α早期表达在大鼠急性心肌梗死室性心律失常发生中的作用及机制研究

目的:通过大鼠急性心肌梗死(AMI)模型和离体心脏灌流模型探讨AMI后TNF-α早期表达在室性心律失常发生中的作用,并初步探讨其机制.方法:结扎大鼠左前降支,建立AMI模型,设手术组(MI组)和假手术组(S组).分10、20、30、60分钟、3、6、12小时共7个时间点记录大鼠心电图.用实时荧光定量PCR法和免疫组化法检测AMI后各时间点TNF-α的mRNA和蛋白表达水平.大鼠离体心脏灌流模型观察TNF-α致室性心律失常的作用.激光共聚焦技术观察TNF-α对单个心肌细胞胞内钙浓度的影响.结果:与S组相比,MI组心肌组织中TNF-α从10分钟起mRNA和蛋白表达水平均出现表达明显升高(P<0.05).MI组大鼠室性心律失常发生次数在各时间点均高于S组(P<0.05),并且与TNF-α分泌的时间窗重叠.200 U/ml TNF-α灌流能够引起离体心脏室性心律失常,经2 mg/ks依那西普(TNF-α受体螯合剂)预处理后同等浓度的TNF-α引起的室性心律失常较前明显地减少(P<0.05).200 U/ml的TNF-α可使大鼠心肌细胞胞内钙荧光强度短时间内增加121.0%±13.3%.结论:大鼠急性梗死后TNF-α表达与室性心律失常发生相关,其机制可能与TNF-α使心肌细胞胞内钙短时间内大量增加有关.     

Quantitative effect of vagal stimulation on heart interval in newborn and older rabbits

Summary In two groups of young rabbits, aged 0–5 and 9–23 days, the effect on the heart interval of stimulation of the right and left vagal nerves separately was investigated at frequencies of 1, 2, 4, 8 and 16 stimuli per second. Up to and including 8 stimuli per second, this is well described by log₁₀ (I _f /I _o )=Hf, orI _f =I _o L ^f =I _o e ^hf , whereI _o andI _f are the heart intervals before and during stimulation respectively at frequencyf, L is a lengthening factor,H=log₁₀ L andh=2.3026 H. Thus each increase in vagal stimulation multiplies the heart interval by a constant factor.the response as defined by H were estimated for both right and left vagal nerves in 15 rabbits, and right or left only in 7 others. The responses varied considerably in individual rabbits and were much larger for almost all in the younger group.The effects of right compared with left stimulation, and of deviations of observed from fitted interval ratios, are studied in detail. Some other mathematical forms given in the literature for the response curves are discussed.This work was supported in part by grants from the Netherlands Organisation for the Advancement of Pure Research (Z.W.O.), received through the Foundation for Basic Medical Research (FUNGO).     

The effect of beta adrenergic blockade on bronchial sensitivity to acetyl-beta-methacholine in normal and allergic rhinitis subjects.

The effect of propranolol inhalation on sensitivity to methacholine inhalation was studied in normal and allergic rhinitis subjects to determine whether beta adrenergic blockade alters sensitivity to mediators in nonasthmatic atopic individuals. A partial beta adrenergic blockade is suggested as being instrumental in asthma. Hay fever patients studied showed similar effects and also developed asthma for the first time.     

The effect of beta adrenergic receptor blockade on the vasodilator response in the forearm to voluntary hyperventilation

1. Blood flow was simultaneously measured by venous-occlusion plethysmography in both forearms of ten healthy men. 2. Voluntary overbreathing to produce about 8 times the resting ventilation caused a vasodilatation similar in both forearms. 3. When one forearm was treated with an intra-arterialinfusion of propranolol, a beta adrenergic blocking agent, the vasodilator response was reduced by an average of 28%, the reduction was significant (P < 0-01). 4. The failure of propranolol to abolish the vasodilator response was not due to incomplete block of beta adrenergic receptors since the dose of propranolol used reversed the vasodilator response to an intravenous infusion of adrenaline. 5. The results suggest that the vasodilator response to voluntary hyperventilation can be explained partly, but not entirely, by the release to the circulation of an adrenaline-like substance.     

The effect of experimental frost-bite on the responses of the rabbit ear-artery to adrenergic and electrical stimulation

The aim of the present investigation was to study the effect of sub-zero temperatures on the adrenergic activated, smooth muscle-contraction of a peripheral blood-vessel. The central ear-artery of the rabbit was used for this purpose. The artery was stimulated to contract in vitro by activation of phentolamine sensitive, post-junctional, a-adrenoceptors by use of noradrenaline, or by noradrenaline released from noradrenergic nerves in the blood-vessel following electrical field stimulation. The effect of freezing the tissue in vivo for 15 min at sub-zero temperatures (–4, - 6 and – 9 ^oC) was studied in vitro. Exposure to – 4 and – 6 ^oC did not alter the apparent affinity (ED₆₀) of noradrenaline significantly, when measured immediately, or 2 or 6 days after exposure. The maximal response to noradrenaline was reduced by approximately 54, 74 and 100% following exposure to – 4 , – 6 and – 9 ^oC, respectively. The response was completely restored after 2 and 6 days of regeneration in vivo following exposure to – 6 ^oC, whereas the response after exposure to – 9 ^oC was restored by only about 8 and 30% after 2 and 6 days regeneration, respectively. The maximal response to electrical field stimulation, which was completely inhibited by tetrodotoxin and phentolamine, was reduced by approximately 92% after exposure for 15 min to –4 and – 6 ^oC, while it was completely inhibited after exposure to – 9 ^oC. The response was restored by only 15–20% following 2 and 6 days in vivo after exposure to – 6 ^oC. No regeneration of the contraction induced by the electrical stimulation was observed after 2 or 6 days following exposure to –9 ^oC. The results of the present study suggest that noradrenergic nerves in the central ear-artery of the rabbit are more sensitive to subzero temperatures than are the post-junctional, noradrenergic α-receptors and the smooth muscle of the blood-vessel. The damage induced by freezing appeared to be both time and temperature dependent and there was only limited restoration of the nervous function 6 days after severe freezing.     

Protective effect of interval exercise on psychophysiological stress reactivity in children

Two studies determined whether interval exercise reduces children's stress reactivity. For Experiment 1 children completed interval exercise ( n =14) or watched TV ( n =14) for 25 min. After 20 min rest children completed a speech task. Speech-induced diastolic blood pressure (DBP) reactivity was dampened in the exercise group ( p <.05). For Experiment 2 children ( n =22) completed interval exercise-speech and TV-speech conditions on separate days. Physical activity was assessed by accelerometry and aerobic fitness estimated by submaximal exercise. DBP, systolic BP, and heart rate (HR) reactivity to the speech stressor were dampened ( p <.05) after exercise compared to TV watching. Fitness was positively associated with HR reactivity. Interval exercise that mimics usual patterns of physically active play dampens cardiovascular reactivity to interpersonal stress.     

The effects of volatile induction and maintenance of anesthesia and selective spinal anesthesia on QT interval, QT dispersion, and arrhythmia incidence

OBJECTIVE:

The effects of sevoflurane general anesthesia and bupivacaine selective spinal anesthesia on QT dispersion (QTd) and corrected QT (QTc) interval were investigated.

METHODS AND MATERIALS:

This prospective, randomized, double-blind study was conducted between July and September 2009 in the Urology and General Surgery operating rooms. Forty ASA I–II patients undergoing noncardiac surgery were randomized into two groups: Group R (n = 20) and Group V (n = 20). In Group R, 5 mg bupivacaine was administered into the spinal space. Anesthesia induction in Group V was established with sevoflurane + 0.1 mg/kg vecuronium using the maximum vital capacity technique. Anesthesia was maintained with 2–3% sevoflurane + 50% N₂O/O₂ inhalation. All patients were tested with a 24-hour Holter ECG device. QT, QTc, and QTd intervals were measured using 12-lead ECG records at 1 and 3 minutes during preinduction, postinduction, postincision and postextubation periods. Mean arterial pressure (MAP), heart rate and ECG records were measured simultaneously.

RESULTS:

None of the patients displayed arrhythmia. There was no significant difference between the groups with regard to QTd values (p>0.05). However, QTc was longer in Group V than in Group R after the induction of anesthesia at 3 minutes, after the intubation at 1 and 3 minutes, and after the incision at 1 and 3 minutes. MAP and heart rate were generally higher in Group V (p<0.05).

CONCLUSION:

Although Volatile Induction and Maintenance of Anesthesia (VIMA) with sevoflurane might prolong the QTc interval and did not result in arrhythmia, selective spinal anesthesia with bupivacaine was not associated with alterations in the QT interval or arrhythmia.     

Effects of electrical or chemical stimulation of the prefrontal cortex on arrhythmias induced in cats by electrical stimulation of the anteromedial hypothalamus

When the anteromedial hypothalamus is stimulated with a chronically implanted electrode in conscious cats, negative emotional behaviors such as restlessness and escape occur during stimulation and ventricular extrasystoles occur in rapid succession immediately after the end of stimulation. It has been shown in the lightly anesthetized cat that the activity of the sympathetic nervous system becomes predominant during stimulation of the anteromedial hypothalamus thereby causing the rises in blood pressure and heart rate. However, immediately after the cessation of the stimulation, this 'sympathetic dominant' state was observed to be switched to the 'parasympathetic dominant' state with falls in blood pressure and heart rate which was very frequently followed by the appearance of the ventricular extrasystoles (Poststimulus Arrhythmia: PSA). The purpose of this experiment was to examine how the electric and pharmacological stimulation of the prefrontal cortex modulate the rise in the blood pressure and heart rate and PSA caused by electric stimulation of the anteromedial hypothalamus. When the prefrontal cortex was electrically stimulated simultaneously with stimulation of the anteromedial hypothalamus in 24 lightly anesthetized cats, PSA was inhibited or facilitated or remained unchanged depending on the site of stimulation in the prefrontal cortex. When dopamine or noradrenaline was microinjected into the site of prefrontal cortex where PSA was inhibited, PSA was suppressed and this effect was blocked by microinjection of haloperidol or phenoxybenzamine, respectively. Dopamine was ineffective when injected in the site where PSA was facilitated; PSA was facilitated by microinjection of noradrenaline and this effect was inhibited by microinjection of propranolol. Although changes in blood pressure and heart rate were observed when the inhibition or facilitation of PSA was elicited by prefrontal injection of noradrenaline, no changes in cardiovascular parameters occurred when dopamine injection caused the inhibition of PSA. These results suggest (1) that activation of the dopamine receptor or alpha adrenoceptor in the prefrontal cortex is involved in the inhibition of PSA, and activation of beta adrenoceptor is concerned with facilitation of PSA and (2) that the mechanisms of dopamine receptor mediated inhibition of PSA appear to be different from those of inhibition of PSA by activation of the alpha adrenoceptor in the prefrontal cortex.     

Flow cytometric detection of neutrophil-associated immunoglobulin in patients with or without neutropenia and establishment of the reference interval

We measured neutrophil-associated immunoglobulin (NAIg) levels using flow cytometry to establish the reference interval for NAIg and to estimate NAIg in patients with or without neutropenia. Peripheral blood from 152 individuals was analyzed for NAIg detection by flow cytometry. Using fluorescescent-conjugated anti-CD10 monoclonal antibody and anti-human immunoglobulins, proportions of NAIgG, NAIgA, and NAIgM bound to neutrophils were measured. Reference intervals for NAIg were set as NAIgG <2.6%, NAIgA <3.2%, and NAIgM <3.4%, representing the 95th percentile of data from 40 healthy individuals. 63 patients with neutropenia showed positivities of 49.2% (31/63) for NAIgG, 50.0% (19/38) for NAIgA, and 42.9% for (27/63) NAIgM. The proportion of NAIgA-bound neutrophils was higher in females (median 10.7% vs 3.0%, P=0.024), and NAIgA positivity rates were increased in patients aged less than 10 years (83.3%, P=0.043). NAIg was associated with the severity of neutropenia. In particular, NAIgM levels were significantly increased in patients with severe neutropenia (P=0.019). In addition, NAIg was commonly detected in patients with autoimmune diseases, solid organ tumors, hematologic disorders, and lymphoma. Flow cytometry permitted rapid detection of NAIg in small samples. Using this method, and using the reference intervals defined herein, patients with neutropenia or adverse transfusion reactions may be evaluated in a clinically relevant manner.     

The effect of lignocaine on sperm phagocytosis in the peritoneal fluid from women with or without endometriosis

The study was undertaken to investigate a possible mechanism for reducing the phagocytosis of spermatozoa by leukocytes in the peritoneal fluid from women suffering from endometriosis. Peritoneal fluids were collected during laparoscopy from women undergoing laparoscopic sterilization or from women under investigation for cause of infertility where the laparoscopic findings were endometriosis. Prepared spermatozoa from one healthy man were incubated in vitro with peritoneal fluid with or without lignocaine. Samples from the incubations were studied daily and the number of viable and dead spermatozoa were counted. The number of free spermatozoa, not adhered to leukocytes, was significantly increased when incubated in human peritoneal fluid supplemented with lignocaine. Thus lignocaine contributes to increasing the number of free spermatozoa and maintaining the possibility of fertilizing an oocyte. For patients with endometriosis, treatment with lignocaine might be a means of increasing the chances of conception. A clinical study is in progress to evaluate this effect in vivo and to search for alternative methods of assisting the fertilization process.