Naringenin and interindividual variability in interaction of coumarin with grapefruit juice.

Grapefruit juice has been shown to enhance oral bioavailability of several drugs including coumarin. The degree of the interaction is highly variable among the individuals. OBJECTIVE: The aim of the study was to evaluate the interindividual variability in the pharmacokinetic profile of three components of grapefruit juice (naringin/naringenin, scopoletin, umbelliferone) and to compare it with the pattern of coumarin-grapefruit juice interaction. STUDY DESIGN: A two-set clinical study with the participation of 18 healthy volunteers was designed. In the first set of the experiment the total renal recovery of naringenin, scopoletin and umbelliferone within 13 hours after the intake of 1L grapefruit juice was estimated. Four individuals, who had demonstrated extremely high or extremely low excretion of the metabolites in the first set, were selected for the second set. The subjects took 10 mg coumarin with 1L grapefruit juice vs 10 mg coumarin with 1 L water in a cross-over manner. The interaction pattern was evaluated according to the time-course curves of 7-hydroxycoumarin (main metabolite of coumarin) excreted with urine. The detailed time-course excretory profiles of naringenin and scopoletin from grapefruit juice were also obtained. RESULTS: The screening demonstrated a significant interindividual variability in the renal excretion of naringenin (max/min > 15), scopoletin (max/min = 6.2), umbelliferone (max/min = 3.3). The interaction between coumarin and grapefruit juice has been observed by increase in the total recovery of 7-hydroxycoumarin up to 3 mg and by delay in time of its excretion by 2-3 hours. This interaction has been observed in 3 of 4 subjects and correlated with naringenin amounts in the urine. The mechanism and the sites of the interaction, as well as the causes for its wide interindividual variability are discussed in the paper.     

Cardiac loading conditions modify the ventricular repolarization in conscious dogs with heart failure

Changes in myocardial loading conditions influence the ventricular action potential via mechanoelectric feedback, a mechanism impaired in pathology. In vivo the QT interval of the electrocardiogram which reflects the action potential duration allows appropriate determination of its modifications. The effects of changes in cardiac loading conditions (load reduction with trinitrin; volume loading with Plasmion) on regional function and ventricular local electrogram were investigated in conscious dogs before (control) and after 4 weeks of rapid pacing (dilated cardiomyopathy, DCM). In controls both interventions increased heart rate. Trinitrin increased end-diastolic wall thickness (EDWth, P<0.001) and reduced absolute QT interval duration (P<0.05). Plasmion decreased EDWth (P<0.001) and increased left ventricular end diastolic pressure (LVEDP, P<0.001) without QT interval alteration. However, the corrected QT interval was unchanged in both interventions. In DCM, trinitrin did not change the QT interval. Plasmion increased LVEDP (P<0.01) and prolonged QT and corrected QT intervals (P<0.01) despite the tachycardia. In controls the changes in cardiac loading conditions did not modify the QT interval, suggesting intact endogenous regulation of repolarization. The impaired adaptation observed in DCM contributed to an increase in QT interval following volume loading. In this model, a prolonged repolarization after abrupt volume loading may result from enhanced or disclosed mechanoelectric feedback.     

Age and QT variability index during free breathing, controlled breathing and tilt in patients with chronic heart failure and healthy control subjects

The QT variability index (QTVI) indicates temporal dispersion in myocardial repolarization, and a high QTVI is associated with a propensity for sudden death from malignant ventricular arrhythmias in subjects at high risk. In this study, the authors assessed the effects of free breathing, controlled breathing, and sympathetic stress (tilt) on the QTVI in patients with chronic heart failure (CHF) and healthy control subjects. The authors also examined the influence of age on the same variables. To obtain normative data, they calculated 95% confidence intervals for healthy subjects grouped according to age. Under all experimental conditions, the QTVI was larger in the CHF group overall and in the age subsets than in controls. In patients and controls, the QTVI increased significantly during tilt, although no differences were found between the QTVI measured during free and controlled breathing. In healthy controls, the following variables correlated significantly with the QTVI: age and baseline heart rate (P < 0.001). In patients with CHF, aging had no influence on the QTVI. Conclusion: Age, sympathetic stress, and CHF all tend to increase the QTVI and could potentially induce sudden death. Further studies should assess the usefulness of the QTVI as a marker predicting sudden cardiac death under the various conditions of risk.     

Effect of ECG-derived respiration (EDR) on modeling ventricular repolarization dynamics in different physiological and psychological conditions

Ventricular repolarization dynamics is an important predictor of the outcome in cardiovascular diseases. Mathematical modeling of the heart rate variability (RR interval variability) and ventricular repolarization variability (QT interval variability) is one of the popular methods to understand the dynamics of ventricular repolarization. Although ECG derived respiration (EDR) was previously suggested as a surrogate of respiration, but the effect of respiratory movement on ventricular repolarization dynamics was not studied. In this study, the importance of considering the effect of respiration and the validity of using EDR as a surrogate of respiration for linear parametric modeling of ventricular repolarization variability is studied in two cases with different physiological and psychological conditions. In the first case study, we used 20 young and 20 old healthy subjects’ ECG and respiration data from Fantasia database at Physionet to analyze a bivariate QT–RR and a trivariate \({\text{QT}}{-}{\text{RR}}{-}{\text{RESP}}\,{\text{or}}\,{\text{QT}}{-}{\text{RR}}{-}{\text{EDR}}\) model structure to study the aging effect on cardiac repolarization variability. In the second study, we used 16 healthy subjects’ data from drivedb (stress detection for automobile drivers) database at Physionet to do the same analysis for different psychological condition (i.e., in stressed and no stress condition). The results of our study showed that model having respiratory information (QT–RR–RESP and QT–RR–EDR) gave significantly better fit value (p < 0.05) than that of found from the QT–RR model. EDR showed statistically similar (p > 0.05) performance as that of respiration as an exogenous model input in describing repolarization variability irrespective of age and different mental conditions. Another finding of our study is that both respiration and EDR-based models can significantly (p < 0.05) differentiate the ventricular repolarization dynamics between healthy subjects of different age groups and with different psychological conditions, whereas models without respiration or EDR cannot distinguish between the groups. These results established the importance of using respiration and the validity of using EDR as a surrogate of respiration in the absence of respiration signal recording in linear parametric modeling of ventricular repolarization variability in healthy subjects.     

Cardiac repolarization abnormalities and increased sympathetic activity in scleroderma

BACKGROUND: Cardiac involvement in scleroderma is a poor prognostic sign and is usually underdiagnosed, particularly in asymptomatic patient. This paper focuses on QT dynamicity and heart rate variability (HRV) in patients with scleroderma and controls in an attempt to investigate the cardiac autonomic system and ventricular repolarization. METHODS: Sixty patients with scleroderma and 30 age- and sex-matched healthy controls who had no cardiovascular risk factors were included in this study. All patients and the controls underwent a 24-hour holter recording as well as a transthoracic echocardiography. HRV and QT dynamicity parameters were calculated. RESULTS: In HRV analysis, autonomic balance was changed in favor of the sympathetic system in patients with diffuse scleroderma. In QT dynamicity analysis, QT/RR slopes were significantly steeper in patients with diffuse scleroderma compared to patients with limited scleroderma and controls (QTapex/RR: 0.24 +/- 0.16, 0.15 +/- 0.03, 0.14 +/- 0.03 respectively p < 0.001; QTend/RR: 0.26 +/- 0.17, 0.14 +/- 0.04, 0.13 +/- 0.05, respectively p < 0.001). CONCLUSIONS: Patients with diffuse scleroderma may have asymptomatic cardiac repolarization abnormalities and autonomic dysfunction. Our results may indicate that QT dynamicity and HRV can be useful noninvasive methods that may detect impaired state of autonomic balance and cardiac repolarization in patients with diffuse scleroderma.     

Inhibition of 17β-estradiol metabolism by grapefruit juice in ovariectomized women

In an open, randomized, cross-over study the concentrations of 17β-estradiol and estrone in serum were measured over 192 hours in 8 ovariectomized women after a single oral dose intake of 2 mg micronized 17β-estradiol. The subjects were studied with and without grapefruit juice intake containing the three natural flavonoids, naringenin, quercetin and kaempherol, which are found as glycosides in citrus fruit. These flavonoids interact with the metabolism of drugs such as 17β-estradiol and other steroids that are extensively metabolised through the P-450NF (P-450 IIIA4) enzyme or closely related P-450 systems. After administration of grapefruit juice, peak estrone (between 2–6 hours after tablet intake) concentrations increased significantly. The AUC_0–48 and AUC_0–192 for estrone but not 17β-estradiol, resulting from a single administration of micronized 17β-estradiol, were significantly altered. Combined measured estrogens (i.e. 17β-estradiol and estrone) also increased significantly. The relationship between the ADCs for 17β-estradiol and estrone was not altered by juice intake indicating that a metabolic step after estrone, i.e. further A and/or D ring conversion was inhibited. This study demonstrates that grapefruit juice may alter the metabolic degradation of estrogens, and increase the bioavailable amounts of 17β-estradiol and its metabolite estrone, presumably by affecting the oxidative degradation of estrogens. This food interaction may be one factor behind the interindividual variability in 17β-estradiol, estrone and estriol serum concentrations after exogenous administration of 17β-estradiol to patients.     

Increased QT interval variability in 3 recently concussed athletes: an exploratory observation

Context:

The QT interval variability index (QTVI) is a noninvasive measure of beat-to-beat fluctuations of the QT interval as seen from a single electrocardiographic lead. It represents the relationship between the respective variabilities of the QT and R-R intervals. Recently, the QTVI was demonstrated to be an index of vagal cardiac autonomic modulation in resting conditions.

Objective:

To determine whether QTVI varied in athletes at 48 hours, 1 week, and 2 weeks after a concussive head injury.

Design:

Case series.

Setting:

Testing facility.

Patients or Other Participants:

Three athletes with recent concussions and 3 uninjured athletes with similar demographic factors.

Main Outcome Measure(s):

Continuous 3-lead electrocardiograms were obtained in a seated, resting position over 2 successive weeks. Separate, unpaired t tests were performed to determine whether group-visit differences were present in the QTVI at 48 hours, 1 week, or 2 weeks.

Results:

No demographic differences were present between groups. At 48 hours, the QTVI was greater in the concussion group than in the matched controls. At weeks 1 and 2, the QTVI in the concussion group was lower than at 48 hours and not different from that of the control group.

Conclusions:

Vagal cardiac autonomic modulation, as quantified by the QTVI, appeared to be negatively affected in concussed athletes within 48 hours of injury, resolved within 1 week, and remained at control group levels 2 weeks later. Serial assessments of QTVI may be of clinical utility in identifying suspected cases of acute concussion and may provide helpful information for determining when an athlete can return to play safely.     

快速心房起搏兔肺静脉心肌袖细胞膜钾通道基因表达及胺碘酮的影响

目的： 观察快速心房起搏对兔肺静脉心肌袖细胞膜钾通道及其亚型(Kv4.3、Kir6.2)基因表达的影响及胺碘酮的干预作用。方法： 新西兰兔30只，随机分为3组(n=10)，Ⅰ组：对照组；Ⅱ组：快速心房起搏组；Ⅲ组：心房快速起搏+胺碘酮组。3组均经颈内静脉将电极置入右心房，其中Ⅰ组不予心房起搏，Ⅱ组和Ⅲ组以600 beats/min连续起搏右心房7 d；同时Ⅲ组按100 mg·kg^-1·d^-1给予胺碘酮灌胃，Ⅰ组和Ⅱ组则给予等量无药物成分的糖片(安慰剂)7 d。剪取3组兔的肺静脉心肌袖组织，应用逆转录-聚合酶链反应技术(RT-PCR)以3-磷酸甘油醛脱氢酶(GAPDH)为内参照，测定肺静脉心肌袖细胞Kv4.3、Kir6.2的mRNA表达水平。结果： Ⅱ组Kv4.3钾通道mRNA表达低于Ⅰ组45%(P<0.01)，Ⅲ组低于Ⅰ组73％（P<0.01),Ⅲ组低于Ⅱ组51%(P<0.01),Kir6.2mRNA的表达Ⅱ组比Ⅰ组高32%(P<0.01)，Ⅲ组与Ⅰ组无明显差异（P>0.05)，Ⅲ组低于Ⅱ组22%(P<0.05)。结论： 快速心房起搏可引起兔肺静脉心肌袖细胞钾通道基因表达变化，后者可能是肺静脉心肌袖接受电刺激后钾离子通道重构的分子基础，肺静脉心肌袖钾通道可能是胺碘酮的作用靶点之一。     

Amiodarone to prevent recurrence of atrial fibrillation. Canadian Trial of Atrial Fibrillation Investigators

BACKGROUND: The restoration and maintenance of sinus rhythm is a desirable goal in patients with atrial fibrillation, because the prevention of recurrences can improve cardiac function and relieve symptoms. Uncontrolled studies have suggested that amiodarone in low doses may be more effective and safer than other agents in preventing recurrence, but this agent has not been tested in a large, randomized trial. METHODS: We undertook a prospective, multicenter trial to test the hypothesis that low doses of amiodarone would be more efficacious in preventing recurrent atrial fibrillation than therapy with sotalol or propafenone. We randomly assigned patients who had had at least one episode of atrial fibrillation within the previous six months to amiodarone or to sotalol or propafenone, given in an open-label fashion. The patients in the group assigned to sotalol or propafenone underwent a second randomization to determine whether they would receive sotalol or propafenone first; if the first drug was unsuccessful the second agent was prescribed. Loading doses of the drugs were administered and electrical cardioversion was performed (if necessary) within 21 days after randomization for all patients in both groups. The follow-up period began 21 days after randomization. The primary end point was the length of time to a first recurrence of atrial fibrillation. RESULTS: Of the 403 patients in the study, 201 were assigned to amiodarone and 202 to either sotalol (101 patients) or propafenone (101 patients). After a mean of 16 months of follow-up, 71 of the patients who were assigned to amiodarone (35 percent) and 127 of those who were assigned to sotalol or propafenone (63 percent) had a recurrence of atrial fibrillation (P<0.001). Adverse events requiring the discontinuation of drug therapy occurred in 18 percent of the patients receiving amiodarone, as compared with 11 percent of those treated with sotalol or propafenone (P=0.06). CONCLUSIONS: Amiodarone is more effective than sotalol or propafenone for the prevention of recurrences of atrial fibrillation.     

Analysis of the QT-RR variability interactions using the NARMAX model

In this paper a new approach is used in order to evaluate and quantify the interactions between the QT and RR intervals. This is achieved after the identification of the RR and QT series with a hybrid model (the non-linear autoregressive moving average with exogenous input (NARMAX)). This identification follows two steps: the first is a linear parametric identification corresponding to the MA model, whereas the second is a non-linear identification using the NARX model. The power spectral density PSD of RR and QT is computed by using the monovariate part of this model (MA model). The QT-related RR series is obtained by using the bivariate part corresponding to the NARX model and its PSD is determined by using the autoregressive method. Then a cross-spectral and the coherence function were determined in order to confirm the obtained results. Different heart pathology cases were selected to evaluate the approach: the normal case, the cases which represent long QT intervals and some other cases which represent short QT intervals. They were taken from the MIT BIH database. The results show that every case illustrates two frequencies; the first in the low frequency band LF and the second in the high frequency band HF. In the normal case and long QT interval cases, the LF was predominating in the QT, RR and in QT-related RR power spectral density PSD. In the short QT interval cases the HF was much larger in all cases. The obtained results were compared to the poincaré plot method which confirms it; however, the NARMAX model can distinguish between normal and pathologic cases with a great precision (p < 0.001). In addition, the QT variability index QTVI is computed and represented by a box plot which expresses the relationship between QT and RR intervals. The QTVI shows a large variability in the short QT interval cases, whereas it shows a small and a negative variability in the long QT interval case.     

QT dispersion in adult hypertensives

Increased QT dispersion is associated with sudden cardiac death in congestive cardiac failure, hypertrophic cardiomyopathy and following myocardial infarction. Patients with hypertension--in particular, those with left ventricular hypertrophy (LVH)--are also at greater risk of sudden cardiac death. We examined whether QT dispersion, which is easily obtained from a routine ECG, correlates with LVH. One-hundred untreated patients with systemic hypertension and 78 normotensives had QT dispersion measured manually from a surface 12-lead electrocardiogram and two-dimensional echocardiography performed to measure interventricular septal thickness, posterior wall thickness and left ventricular internal diameter. Office blood pressure was also recorded. Multivariate analysis demonstrated significant relationships between QT dispersion and office systolic blood pressure, and left ventricular mass index. Manual measurement of QT dispersion might be a simple, noninvasive screening procedure to identify those hypertensives at greatest risk of sudden cardiac death in a third-world country.     

柚皮素对心肌缺血/再灌注损伤大鼠PI3K/AKT信号通路和内质网应激及其相关凋亡通路的影响

目的:观察柚皮素对缺血/再灌注(I/R)大鼠心脏损伤的影响,并探讨柚皮素的作用是否涉及PI3K/AKT信号通路和内质网应激及其相关凋亡通路.方法:48只SD大鼠按随机数字表法分成假手术组(sham组)、模型组(I/R组)、柚皮素处理组(NAR组)和柚皮素处理+LY294002组(NL组).结扎大鼠冠状动脉左前降支30 ...     

The effect of paracetamol on peritoneal reflex after single and multiple grapefruit ingestion.

In the last few years, more attention has been paid to the influence of grapefruit juice on metabolism on many drugs. It has been reported that grapefruit juice increases the plasma concentrations of orally administrated drugs, that undergo metabolism in liver. However, all these experiments were done with a single dose of grapefruit juice. The primary aim of this study was to evaluate if the chronical ingestion of grapefruit juice could also cause these effects. Paracetamol is metabolized by reactions of oxidation and conjugation to nontoxic ineffective metabolites. These reactions, partly catalyzed by cytochrome P450 izoenzymes, take place in liver. The analgesic effect of paracetamol was examined by Writhing tests, where we used acetic acid as an irritating agent. We used three groups of male mice: the control group, the group which was administrated 0.2 mL of grapefruit juice per os 10 days (GPOch) and the group which was administrated single dose of 0.5 mL grapefruit juice per os 90 min. before the experiment (GPOac). Dose of 50 mg/kg of paracetamol was applicated s.c. 5 min. before i.p. application of 3 % acetic acid. The writhing phenomenon was observed in periods of 5-15 min. and 15-30 min. after the application of paracetamol. The results show that paracetamol in GPOch group significantly decreases irritant effect of acetic acid in the period of 15-30 min. after the application in relation to the control group. However, the acetic acid shows stronger irritant effect in GPOch group than in the control group and less irritant effect in GPOac group than in the control group. In the period of 5-15 min. after the application, paracetamol shows analgesic effect neither in the control nor in the other groups.     

Electrophysiological tests in clinical laboratory]

We briefly described recently developed methods for testing cardiac electrophysiological phenomena such as 24-hour Ambulatory ECG, high resolution ECG, body surface mapping ECG, heart rate variability, QT and QT dispersion, and T wave alternans. Of these methods ambulatory ECG monitoring is important and useful for detecting malignant arrhythmias and ischemia attacks, especially in cases of vasospastic angina. Using this method, it is possible to quantitatively analyze arrhythmia and elucidate the pathophysiology of vasospastic angina. The monitoring system is useful not only for diagnosis, but also for assessing treatment efficacy. Heart rate variability is currently used for analyzing the autonomic nervous system; however, the exact meaning of each index still remains to be confirmed. The concept of QT dispersion was recently introduced as an index for detecting dispersion of ventricular repolarization and QT dispersion is still controversial. T wave alternans monitoring has been recently introduced as a new method of assessing the microvolt level of T wave alternans, which has been hypothesized to correlate with the occurrence of arrhythmic events in myocardial infarction. The possible roles of these methods and their applications for clinical practice are discussed.     

应用定量组织多普勒成像技术评价家族性高胆固醇血症患者的左室功能

目的探讨定量组织多普勒成像技术(quantitative tissue velocity imaging,QTVI)在评价家族性高胆固醇血症(familial hypercholesterolemia,FH)患者左心室功能方面的临床应用价值。方法运用QTVI对24例FH患者和25例健康人心肌各节段速度曲线进行分析,测量后室间隔、侧壁、前壁、下壁、前室间隔、后壁六个壁的瓣环、基底段和中间段三个位置的心肌收缩峰值速度(Vs),左室舒张早期的运动速度(Ve)和舒张晚期的运动速度(Va),计算Ve/Va值;常规超声心动图脉冲多普勒检测二尖瓣口E、A峰流速,计算E/A值;利用M型超声测量左室射血分数(EF);计算左室Tei指数。结果FH组与对照组常规超声心动图测值均在正常范围内,差别无统计学意义;QTVI方法测得的侧壁瓣环、侧壁基底段的Ve,侧壁瓣环、侧壁基底段、后间隔基底段、后壁基底段的Ve/Va,FH组均小于对照组,差别有统计学意义(P0.05)。结论QTVI为临床检测FH患者左室功能变化提供一种无创性方法。     

Apocynin抑制慢性心力衰竭兔心肌纤维化的实验研究

目的:探讨NADPH氧化酶抑制剂Apocynin对心衰兔心肌纤维化的影响及其机制。方法:32只兔随机分为假手术安慰剂组、假手术Apocynin组、心衰安慰剂组、心衰Apocynin组。通过容量超负荷联合压力超负荷建立家兔心衰模型。安慰剂或Apocynin以15mg/天口服。8周后,行超声心动图检查,观察动物的心脏结构和功能变化。通过细胞色素C还原试验测定心肌NADPH氧化酶活性。通过组织形态学分析心肌纤维化程度。运用Real-timePCR检测心肌转化生长因子β(TGF-β)、结缔组织生长因子(CTGF)、基质金属蛋白酶-2(MMP-2)和MMP-9基因表达。结果:与假手术安慰剂组比较,心衰安慰剂组心脏明显扩大,心功能明显降低(P<0.05),心肌NADPH氧化酶活性增加(P<0.05),心肌纤维化显著(P<0.05),TGF-β、CTGF、MMP-2和MMP-9表达上调(P<0.05)。与心衰安慰剂组比较,心衰Apocynin组心功能显著改善(P<0.05),心肌NADPH氧化酶活性明显降低(P<0.05),心肌纤维化显著减轻(P<0.05),心肌TGF-β、CTGF、MMP-2和MMP-9表达明显降低(P<0.05)。结论:Apocynin可通过下调心肌TGF-β、CTGF、MMP-2和MMP-9基因表达,改善心衰兔心肌纤维化。     

QT离散度与心自主神经的关系

ＱＴ离散度 (ＱＴｄｉｓｐｅｒｓｉｏｎ ,ＱＴｄ)定义为同步记录 1 2导联心电图中测量的最大ＱＴ间期 (ＱＴｍａｘ)与最小ＱＴ间期 (ＱＴｍｉｎ)之差[1 ] ,反映了心室肌复极不同步性和电不稳定性[2 - 4 ] 。这一概念已得到了心内膜和心外膜单相动作电位与体表心电图的对照研究[4,5] 及动物实验[6] 证实 ,大量临床研究也证明了ＱＴｄ与心室肌复极不同步性的高度相关[7- 9] 。近年来 ,对于ＱＴｄ的电生理基础及其本质引起广泛关注 ,人们认识到自主神经系统与心性猝死密切相关 ,交感过度激活可导致致命性心律失常发作 ,而迷走激活却有保护和抗…     

The activity of liver oxidative enzymes after single and multiple grapefruit juice ingestion.

In the recent time, several in vitro and in vivo studies have shown the inhibitory effect of grapefruit juice on metabolism of xenobiotics catalyzed by liver oxidative enzymes including cytochrome P450 izoenzymes. However, all these experiments were done with a single dose of grapefruit juice. The primary aim of this study was to evaluate if the chronical ingestion of grapefruit juice can cause enzyme activity alteration as well as a single dose. Three groups of male mice were used: the control group, the group which was administered 0.2 mL of grapefruit juice per os 10 days and the group which was administered single dose of 0.5 mL grapefruit juice per os 90 min. before the sacrificing. After the sacrificing of animals, liver was homogenized with appropriate buffer, and the activity of oxidative liver enzymes: xanthine oxidase (XOD), peroxidase (Px), catalase (CAT), lipid peroxidase (LPx), glutathion peroxidase (GSH-Px) and liver glutathion contents (GSH) were detected by standard methods. The results show that the enzyme activity of liver MFO was changed according to a single or multiple grapefruit juice ingestion. The grapefruit juice in a single oral dose significantly decreases the activity of xanthine oxidase, glutathion peroxidase, lipid peroxidase and liver glutathion contents, and has no effect on activity of catalase and peroxidase. The multiple grapefruit ingestion increases the activity of XOD, GSH-Px, LPx, Px and GSH, while the activity of CAT enzyme is unchanged. The chronical and single grapefruit ingestion has no effect on relative liver weight, but the liver protein content is significantly decreased after the multiple oral grapefruit juice ingestion.     

QT interval dispersion changes according to the vessel involved during percutaneous coronary angioplasty

Increased QT dispersion (QTd) is a noninvasive marker of an electrophysiologic abnormality associated with high mortality in coronary artery disease. The purposes of this study were to measure changes in QTd and ST-segment changes immediately before, during and after intracoronary balloon inflation and to determine whether the coronary artery vessel involved and/or the duration of inflation affect(s) QTd. A total of 45 patients (32 men, 13 women, mean age 58 +/- 11 years) who were referred for elective percutaneous transluminal coronary angioplasty were included. The mean QT interval dispersions for all patients before the inflation, during the balloon inflation at 60 sec and after the balloon deflation at 5 min were 68 +/- 13 ms, 82 +/- 16 ms and 71 +/- 13 ms, respectively. There was no significant difference between baseline and 5 min after deflation. The increase in QTd during the balloon inflation was significant (p<0.01). There was no significant QTd change in patients with left circumflex artery (Cx) lesions during inflation and after deflation compared with baseline. The differences were statistically significant only in patients with left anterior descending (LAD) lesions and right coronary artery (RCA) lesions at 60 sec during balloon inflation (p=0.001 vs. p=0.04). Acute reversible myocardial ischemia induced by balloon inflation causes an increase in QTd limited to the LAD and RCA vessels. Therefore, when using QTd as a marker of myocardial repolarization abnormality due to acute reversible ischemia, the involved coronary artery vessel must be taken into account.     

Within-subject electrocardiographic differences at equal heart rates: role of the autonomic nervous system

Various combinations of sympathetic and vagal tone can yield the same heart rate, while ventricular electrophysiology differs. To demonstrate this in humans, we studied healthy volunteers in the sitting position with horizontal legs. First, heart rate was increased by lowering the legs to 60 degrees and back. Thereafter, heart rate was increased by handgrip. In each subject, a leg-lowering angle was selected at which heart rate matched best with heart rate in the third handgrip minute. Thirteen subjects had a heart rate match better than 1%. Heart rate (control: 65.2+/-9.0 bpm) increased to 72.1+/-8.7 (leg lowering) and to 72.1+/-8.8 (handgrip) bpm. QRS azimuth, QRS duration, maximal T vector, T azimuth, T elevation, ST duration, QRS-T angle and QT interval differed significantly (P<0.05) between leg lowering and handgrip (QT interval 418+/-15 versus 435+/-21 ms). Also, septal dispersion of repolarization, assessed as the time difference between the apex and the end of the T wave in the V2 and V3 leads, differed significantly (V2: 96.7+/-19.3 versus 110.0+/-23.3 ms, P<0.01; V3: 88.7+/-19.3 versus 97.3+/-23.3 ms; P<0.01). Hence, leg lowering and handgrip cause different ventricular depolarization and repolarization. The hypertensive handgrip manoeuvre entails a longer QT interval and probably an increased septal dispersion of repolarization.