Heart Rate‐Dependence of QTc Intervals Assessed by Different Correction Methods in Patients with Normal or Prolonged Repolarization

Background: There is a continuing debate about the optimal method for QT interval adjustment to heart rate changes. We evaluated the heart rate dependence of QTc intervals derived from five different QT correction methods. Methods: Study patients (n = 123, age 68 ± 11 years) were dual‐chamber device recipients with baseline normal or prolonged QT interval who had preserved intrinsic ventricular activation with narrow QRS complexes. Patients were classified to either Normal‐QT (n = 69) or Prolonged‐QT (n = 54) groups. Serial QT intervals were recorded at baseline (52 ± 3 beats per minute) and following atrial pacing stages at 60, 80, and 100 beats per minute. The QTc formulae of Bazett, Fridericia, Sagie‐Framingham, Hodges, and Karjalainen‐Nomogram were applied to assess the effect of heart rate on the derived QTc values by using linear mixed‐effects models. Results: Heart rate had a significant effect on QTc regardless of the formula used (P < 0.05 for all formulae). The Bazett's formula demonstrated the highest QTc variability across heart rate stages (highest F values) in both patient groups (in the total cohort, F = 175.9). In the following rank order, the formulae Hodges, Karjalainen‐Nomogram, Sagie‐Framingham, and Fridericia showed similar QTc heart rate dependence at both slower and faster heart rates in both patient groups (F = 21.8, 25.6, 28.8, 36.9, in the total cohort, respectively). Conclusions: Of the studied QTc formulae, the Bazett appeared the most heart rate dependent. Our results suggest the use of Hodges and the Karjalainen‐Nomogram secondly to ensure least heart rate dependence of QTc intervals in patients with either normal or prolonged repolarization. (PACE 2010; 553–560)     

Morpho‐functional response of the elbow extensor muscles to twelve‐week self‐perceived maximal resistance training

The aim of this study was to determine morphological and functional changes of the elbow extensor muscles in response to a 12‐week self‐perceived maximal resistance training (MRT). Twenty‐one healthy sedentary young men were engaged in elbow extensor training using isoacceleration dynamometry for 12 weeks with a frequency of five sessions per week (five sets of ten maximal voluntarily contractions, 1‐min rest period between each set). Prior to, at 6 weeks and after the training, a series of cross‐sectional magnetic resonance images of the upper arm were obtained and muscle volumes were calculated. Maximal and endurance strength increased (P<0·01) by 15% and 45% at 6 weeks, and by 29% and 70% after 12 weeks compared with baseline values, while fatigue rate of the elbow extensors decreased by 67%. The volume of triceps brachii increased in both arms (P<0·01) by 4% at 6 weeks, and by 8% after 12 weeks compared with baseline values (right arm – from 487·4 ± 72·8 cm³ to 505·8 ± 72·3 cm³ after 6 weeks and 525·3 ± 73·7 cm³ after 12 weeks; left arm – from 475·3 ± 79·1 cm³ to 493·2 ± 72·7 cm³ after 6 weeks and 511·3 ± 77·0 cm³ after 12 weeks). A high correlation was found between maximal muscle strength and muscle volume prior (r² = 0·62) and after (r² = 0·69) the training (P≤0·05). A self‐perceived MRT resulted in an increase in maximal and endurance strength. Morphological adaptation changes of triceps brachii as a result of 12‐week specific strength training can explain only up to 26% of strength gain.     

Influence of long‐term oxygen therapy on heart rate and QT time‐series in hypoxic patients with chronic obstructive pulmonary disease

Background: There is increasing interest in the cardiovascular pathology independently associated with chronic obstructive pulmonary disease (COPD). We examined the influence of long‐term oxygen therapy (LTOT) on heart rate (RR) and QT time‐series in COPD. Methods: Ten hypoxic stable COPD patients underwent Holter ECG monitoring for 24 h and physical activity/energy expenditure monitoring for 5 days before and after LTOT. Variability of RR and QT time‐series was quantified using standard statistics and their structural (correlation/scaling) properties were assessed using multifractal analysis. Pre‐ and post‐LTOT cardiac/activity parameters were compared to examine the influence of oxygen therapy and circadian variation. Results: PaO₂ increased (P = 0·0004) whilst PaCO₂ was unchanged (P = 0·56) following LTOT. Activity/energy expenditure estimates were also unchanged following LTOT (P = 0·64–0·99), but RR variability was increased during the morning (P < 0·05) and night (P < 0·1, trend only). Multifractality of RR and QT time‐series was not significantly changed following LTOT, although QT multifractality showed some time‐dependent fluctuations. Trends in RR and QT time‐series over 24‐h were similar pre‐ and post‐LTOT, indicating a generally normal circadian response. Conclusions: An increase in HRV following LTOT (but notably in the absence of altered activity levels) provides tentative evidence that LTOT has a direct effect on heart rate control in COPD. This beneficial influence was expressed mainly during the morning, and the relevance of this diurnal variation in response requires further investigation. It was also confirmed that both RR and (to a lesser degree) QT time‐series in COPD have a multifractal structure, and this is not affected appreciably by LTOT.     

Reverse Electrical Remodeling of the Ventricles Following Successful Restoration of Sinus Rhythm in Patients with Persistent Atrial Fibrillation

Background: Atrial fibrillation (AF) has been shown to be associated with reduced survival and increased ventricular arrhythmogenesis. The purpose of this study was to assess the effects of AF with adequate rate control on the electrophysiologic properties of the ventricles. We hypothesized that AF results in increased ventricular arrhythmogenic risk and that reverse remodeling occurs postsuccessful cardioversion. Methods: In nine patients with persistent AF, we recorded 12‐lead electrocardiograms (ECGs) and 1‐hour high‐resolution Holter ECGs (H12+, Mortara Instrument, Inc. Milwaukee, WI, USA; recorders [1000 sps] immediately following cardioversion (Day 1) and after 30 days of maintaining sinus rhythm (Day 30). We measured QTc, QT dispersion, and calculated estimates of mean ventricular action potential duration (RT), diastolic interval (DI), T‐wave width (TW), T‐wave peak‐to‐end, and their respective scatter on Day 1 and Day 30. Maintenance of normal sinus rhythm was confirmed with a weekly trans‐telephonic ECG transmission. Results: The average QTc interval decreased from 449 ± 28 ms on Day 1 to 422 ± 36 ms on Day 30 (P = 0.04). There was no significant difference in the average QT dispersion. A significant decrease was also noted in DI and TW scatter at Day 30 when compared with Day 1 (P = 0.03 and 0.04, respectively). A decrease in RT scatter was also noted albeit not statistically significant (P = 0.07). Conclusion: Our results suggest a greater propensity to ventricular arrhythmogenesis in the immediate period following restoration of sinus rhythm and reverse electrical remodeling of the ventricles during the first month after successful maintenance of sinus rhythm. (PACE 2010; 33:1198–1202)     

Nateglinide and glibenclamide metabolic effects in naïve type 2 diabetic patients treated with metformin

Background and objective: Most antidiabetic agents target only one of several underlying causes of diabetes. The complementary actions of the glinides and the biguanides may give optimal glycemic control in patients with type 2 diabetes mellitus. The aim of the present study was to compare the effects of nateglinide plus metformin with glibenclamide plus metformin on glucose and lipid metabolism, and haemodynamic parameters in patients with type 2 diabetes mellitus. Methods: We enrolled 248 type 2 diabetic patients. Patients were randomly assigned to receive nateglinide (n = 124) or glibenclamide (n = 124), after 6 months of run‐in, in which we titrated nateglinide (starting dose 180 mg/day), glibenclamide (starting dose 7·5 mg/day), and metformin (starting dose 1500 mg/day). The final doses were (mean ± standard deviation), 300 ± 60, 12·5 ± 2·5, and 2500 ± 500 mg/day, respectively. We followed these patients for 1 year after titration. We assessed body mass index (BMI), fasting (FPG) and post‐prandial (PPG) plasma glucose, glycosylated haemoglobin (HbA_1c), fasting (FPI) and post‐prandial (PPI) plasma insulin, homeostasis model assessment (HOMA) index, and lipid profile [total cholesterol (TC), low density lipoprotein‐cholesterol (LDL‐C), high density lipoprotein‐cholesterol (HDL‐C), triglycerides (Tg), apolipoprotein A‐I (Apo A‐I), and apolipoprotein B (Apo B)], systolic blood pressure (SBP), and diastolic blood pressure (DBP). All variables were evaluated at baseline and after 3 and 6 months in the run‐in period, and at baseline, and after 3, 6, 9 and 12 months for both treatment groups. Results and discussion: Body mass index did not show any significant change during the study. We observed a significant improvement from baseline to 1 year on HbA_1c (P < 0·01 vs. baseline and vs. glibenclamide group, respectively), FPG (P < 0·01 vs. baseline), PPG (P < 0·01 vs. baseline), and on HOMA index (P < 0·05 vs. baseline) in the nateglinide group. In the glibenclamide group, we found significant changes in HbA_1c (P < 0·05 vs. baseline), FPG (P < 0·01 vs. baseline), PPG (P < 0·05 vs. baseline), and HOMA index (P < 0·05 vs. baseline). No significant change was observed in TC, LDL‐C, HDL‐C, Tg, Apo A‐I, Apo B, SBP, DBP and HR in either group after 3, 6, 9 and 12 months. These effects of nateglinide and glibenclamide on insulin‐resistance parameters are in agreement with previous reports. Contrarily to previous reports, we did not observe any significant BP change in patients treated with glibenclamide. Although both nateglinide and glibenclamide attenuated PPG and HOMA index, they did not have significant effects on lipid metabolism, as already shown in subjects with type 2 diabetes and good glycemic control. Conclusion: Nateglinide improved glycemic control better than glibenclamide in combination with metformin.     

A Simple Electrocardiographic Algorithm for Detecting Ventricular Tachycardia

The purpose of this study wus to determine whether a simple ECG algorithm could be developed for predicting susceptibility to ventricular tachyarrhythmias (VT) as defined by sustained spontaneous or inducible VT. Two different QT dispersion algorithms were determined by the difference between the longest and shortest QT interval measured in three orthogonal leads (I, aVF, V1; QTD3), and at least 11 of 12 leads (QTDl2) from the 12-lead ECG. These QT dispersion algorithms were investigated (with and without the QRS duration from the 12-lead EGG) and compared to the signal-averaged ECG (SAEGG) in order to determine their sensitivity and specificity for detecting VT. Only patients who underwent SAECC and were referred for programmed electrical stimulation were included in this study. A positive SAECG was defined by filtered QRS duration > 114 ms, and/or low amplitude signal duration > 38 ms, and/or root mean square voltage in the last 40 ms of < 20 μV. Sixty patients were enrolled in this study with a mean age of 63 ± 2 years. Eifty-five percent of the patients had coronary artery disease. A simple ECG algorithm consisting of the sum of QTD3 plus the QBS duration had a sensitivity and specificity of 90% and 63%. respectively, whereas the SAECG had a sensitivity and specificity of 60% and 63%. respectively (P = 0.022). We conclude that a simple EGG algorithm is more sensitive than the SAEGG for predicting VT. This algorithm combines two easily measured variables obtained from the 12-lead EGG, and can easily be performed without expensive computer equipment.     

Acute effect of methylphenidate on QT interval duration and dispersion in children with attention deficit hyperactivity disorder

Among childhood psychiatric disorders, attention deficit hyperactivity disorder (ADHD) is of greatest interest to practitioners. Methylphenidate (MPH) is a drug that is widely used in the treatment of children in whom ADHD has been diagnosed. Although this treatment has been used for years, its effects on the heart remain the subject of debate. The QT interval comprises the ventricular activation and recovery periods as seen on electrocardiogram (ECG). The acute effect of MPH on QT interval dispersion is unknown. Researchers in the present study sought to investigate the acute effects of MPH on QT interval as seen on ECG. A total of 25 patients with ADHD (mean age, 9.4±2.1 y) who were treated with MPH were enrolled in the study. Twelve-lead derivation ECGs were taken before and 2 h after administration of 10 mg of MPH. Maximum QT interval, minimum QT interval, and interval durations were measured, and QT dispersion was calculated, for each ECG. QT dispersion measured after medication administration decreased significantly from 59.6±16.3 ms to 50.8±10.9 ms (P=.016); corrected QT dispersion decreased significantly from 70.9±17.6 ms to 61.3±13.3 ms (P=.011). Maximum QT interval duration decreased from 373.7±21.8 ms to 361.8±29.0 ms (P=.006); minimum QT interval duration rose from 317.0±23.3 ms to 322.3±21.6 ms (P=.312). In conclusion, the findings of this study show that MPH reduces QT dispersion during the acute period shortly after its administration.     

Evaluation of PR, RR, QT Intervals and QT Dispersion Following Stellate Ganglion Block in Chronic Shoulder–Hand Pain Patients

Abstract: Right stellate ganglion block (SGB) can increase QT interval, rate‐corrected QT interval (QTc), QT dispersion (QTD), rate‐corrected QTD (QTcD), and RR interval while left SGB can decrease these intervals in healthy volunteers. No such studies have been conducted in patients with chronic pain, hence this study was designed to investigate the effects of left and right SGB on these variables in chronic shoulder–hand pain patients. In this study, 28 patients with chronic shoulder–hand pain of at least 6 months duration were given right or left SGB depending on the shoulder affected. A 12‐lead electrocardiogram (ECG) was recorded before the block, 30 minutes and 60 minutes after the block. PR interval, RR interval, QT interval were recorded in all 12 leads while QTc, QTD, and QTcD were calculated. Right SGB was performed in 21 patients. A significant decrease (P < 0.05) in PR interval and a significant increase (P < 0.05) in RR interval, QT interval, and QTc interval were observed. QTD showed a significant increase (P < 0.05) only at 30 minutes after right SGB. Left SGB was performed in seven patients. A significant decrease (P < 0.05) in QT interval was observed throughout the study period, while QTc showed a significant decrease (P < 0.05) only at 60 minutes after the block. We conclude that right SGB induces significant increase of QT interval, RR interval, QTc interval, QTD, and a significant decrease of PR interval while left SGB produces a significant decrease in QT and QTc intervals in patients with chronic shoulder–hand pain.     

Temporal age‐related changes in spectral,fractal and complexity characteristics of heart rate variability

Cross‐sectional studies have suggested that heart rate (HR) variability, analysed using traditional time and frequency domain methods, is related to ageing, but no longitudinal studies have estimated the age dependence of HR fluctuation. This study evaluated temporal age‐related changes in 12‐h measures of HR variability among 109 patients with coronary artery disease (CAD), who underwent repeat Holter recordings at 32‐month intervals. Time and frequency domain measures, along with fractal and complexity measures of HR variability, were determined at the baseline and after 32 months. Changes in HR dynamics were compared with various laboratory variables, exercise data and angiographic progression of CAD. Traditional time and frequency domain measures of HR variability did not change significantly during the follow‐up, but the power‐law scaling slope decreased from ?1·29 ± 0·20 to ?1·36 ± 0·23 (P<0·01) and the short‐term fractal exponent (α₁) of HR dynamics from 1·29 ± 0·14–1·22 ± 0·18 (P<0·001). The approximate entropy value also decreased from 1·00 ± 0·19 to 0·95 ± 0·18 (P<0·05). The changes in HR behaviour were not related to demographic data, laboratory values or angiographic progression of CAD. Only a weak correlation was observed between the change in the power‐law slope and the baseline glucose value (P<0·05). This longitudinal study shows that the fractal characteristics of HR dynamics and the complexity properties of R‐R intervals undergo rapid changes along with ageing, and that fractal and complexity analysis techniques are more sensitive than traditional analysis methods in documenting temporal age‐related changes in HR behaviour.     

Semi‐quantitative tracking of intra‐airway fluids by computed tomography

Background: Airway secretions are a source of complications for patients with acute and chronic lung diseases, yet lack of techniques to quantitatively track secretions hampers research into clinical measures to reduce their pathologic consequences. Methods: In a preserved swine lung model, we tracked a contrasted mucus simulant (CMS) using sequential computed tomography (CT). Known drivers of secretion movement – gravity and ventilation – were tested. Ten millilitres of CMS were unilaterally introduced (1 ml min^?1) into the airways of 12 lung sets. After instillation, six lung sets were maintained prone and six were rotated 180°. Subsequently, all were mechanically ventilated for 10 min. CTs were obtained before infusion, after infusion and after ventilation ± rotation. For CT analysis, the lungs were partitioned into eight sub‐cuboids using anatomic landmarks. The volumes of two CT number ranges representing CMS and poor aeration/collapse were computed in every sub‐cuboid for each CT acquisition. Volume differences between study time points were used to quantify changes. Results: CMS and poor aeration/collapse volume change distributed gravitationally after infusion. After ventilation without rotation, the CMS and poor aeration/collapse volumes remained within the originally injected sub‐cuboid, although the poor aeration/collapse volume expanded (27·3 ± 6·1→50·5 ± 7·4 ml, P<0·05). After ventilation + rotation, there was a reduction in the CMS and poor/aeration collapse volumes in the originally injected sub‐cuboid (14·4 ± 1·7→4·4 ± 0·6 ml, P<0·05 and 18·3 ± 3·8→11·9 ± 2·7 ml, P<0·05, respectively) accompanied by increases in the gravitationally opposite sub‐cuboid (1·7 ± 0·2→11·1 ± 1·1 ml, P<0·05 and 0·8 ± 0·5→40·6 ± 3·5 ml, P<0·05, respectively). Conclusion: Movement of fluids within the bronchial tree can be semi‐quantitatively tracked with analysis of sequential CT acquisitions. In this isolated swine lung model, gravity had an important and brisk effect on movement of a viscous fluid, whereas ventilation tended to embed it peripherally.     

Increased heterogenity of ventricular repolarization in obese nonhypertensive children

Objective: Obese children, without arterial hypertension, may be a unique clinical opportunity to evaluate the effect of obesity, per se, on ventricular repolarization, excluding the influence of possible comorbidities. The QTc dispersion (QTc‐d), JTc dispersion (JTc‐d), and transmural dispersion of repolarization (TDR) have been suggested to be electrocardiographic indexes reflecting the physiological variability of regional ventricular repolarization. The aim of our study is to define the effects of obesity on the ventricular repolarization in obese children who have no other clinically appreciable cause of heart disease. Methods: The study involved 70 subjects (48 male, 22 female), with a mean age (± standard deviation) of 13 ± 2 years. A total of 35 individuals were obese (Group A: 24 male, 11 female, mean body mass index [BMI] of 38.2 ± 5.8 kg/m²), and 35 participants were healthy lean children (Group C: 24 male, 11 female, mean BMI of 22.3 ± 0.3 kg/m²). Heart rate; QRS duration; maximum and minimum QT interval; and QTc‐d, JTc‐d, and TDR measurement were performed. Results: Compared with the healthy control group, obese children presented increased values of the QTc‐d, JTc‐d, and TDR (31.1 ± 10.6 vs 46.2 ± 15.3 ms, P < 0.003; 29.8 ± 8.5 vs 40.1 ± 10.3 ms, P < 0.04; 83.2 ± 13.5 vs 100.7 ± 16.3 ms, P < 0.05). A statistically significant correlation was found between the values of QTc‐d, insulin serum concentration (r = 0.46, P = 0.04), and homeostasis model assessment of insulin resistance (r = 0.34, P = 0.03). Conclusions: Our data suggest that obese nonhypertensive children have an increased ventricular repolarization heterogeneity in relation to controls. (PACE 2010; 33:1533–1539)     

Lower limb vascular conductance and resting popliteal blood flow during head‐up and head‐down postural challenges

This study hypothesized that central and local reflex mechanisms affecting vascular conductance (VC) through the popliteal artery compensated for the reduction in muscle perfusion pressure (MPP) to maintain popliteal blood flow (PBF) during head‐down tilt (35? HDT), but not in head‐up tilt (45? HUT). Resting measurements were made on 15 healthy men in prone position to facilitate the access to the popliteal artery, on two separate days in random order during horizontal (HOR), HDT or HUT. In each body position, the body was supported, and the ankles were maintained in relaxed state so that there was no muscle tension, as with normal standing. Popliteal blood flow velocity and popliteal arterial diameter were measured by ultrasound, and PBF was calculated. MPP was corrected to mid‐calf from measured finger cuff pressure, and VC was estimated by dividing PBF by MPP. The MPP in HDT (48 ± 2 mmHg) was ~100mmHg less than in HUT (145 ± 2 mmHg). PBF was similar between HOR (51 ± 18 ml min^?1) and HDT (47 ± 13 ml min^?1), but was lower in HUT (30 ± 9 ml min^?1). VC was different between HDT (1·0 ± 0·3 ml min^?1 mmHg^?1), HOR (0·6 ± 0·2 ml min^?1 mmHg^?1) and HUT (0·2 ± 0·1 ml min^?1 mmHg^?1). In conclusion, the interactions of central and local regulatory mechanisms resulted in a disproportionate reduction of VC during HUT lowering PBF even though MPP was higher, while in HDT, increased VC contributed to maintain PBF at the same level as the HOR control condition.     

Functional near‐infrared spectroscopy to probe sensorimotor region activation during electrical stimulation‐evoked movement

This study used non‐invasive functional near‐infrared spectroscopy (fNIRS) neuroimaging to monitor bilateral sensorimotor region activation during unilateral voluntary (VOL) and neuromuscular electrical stimulation (NMES)‐evoked movements. Methods. In eight healthy male volunteers, fNIRS was used to measure relative changes in oxyhaemoglobin (O₂Hb) and deoxyhaemoglobin (HHb) concentrations from a cortical sensorimotor region of interest in the left (LH) and right (RH) hemispheres during NMES‐evoked and VOL wrist extension movements of the right arm. Results. NMES‐evoked movements induced significantly greater activation (increase in O₂Hb and concomitant decrease in HHb) in the contralateral LH than in the ipsilateral RH (O₂Hb: 0·44 ± 0·16 μM and 0·25 ± 0·22 μM, P = 0·017; HHb: ?0·19 ± 0·10 μM and ?0·12 ± 0·09 μM, P = 0·036, respectively) as did VOL movements (0·51 ± 0·24 μΜ and 0·34 ± 0·21 μM, P = 0·031; HHb: ?0·18 ± 0·07 μΜ and ?0·12 ± 0·04 μΜ, P = 0·05, respectively). There was no significant difference between conditions for O₂Hb (P = 0·144) and HHb (P = 0·958). Conclusion. fNIRS neuroimaging enables quantification of bilateral sensorimotor regional activation profiles during voluntary and NMES‐evoked wrist extension movements.     

Effect of epirubicin-based chemotherapy and dexrazoxane supplementation on QT dispersion in non-Hodgkin lymphoma patients

BACKGROUND AND OBJECTIVE: Aim of the present study was to assess the effect of epirubicin-based chemotherapy on QT interval dispersion in patients with aggressive non-Hodgkin lymphoma (NHL), and the effect of dexrazoxane supplementation. Prolongation of QT dispersion may not only represent a sensitive tool in identifying the first sign of anthracycline-induced cardiotoxicity, but it may serve also in identifying patients who are at risk of arrhythmic events. METHODS: Twenty untreated patients, 相似文献   

Myocardial perfusion defects in Bartter and Gitelman syndromes

Background Normotensive hypokalaemic tubulopathies (Bartter and Gitelman syndromes (BS/GS)) are genetic diseases that are considered benign. However, QT prolongation, left ventricular dysfunction and reduction of cardiac index upon exercise leading to arrhythmias and sudden cardiac death have been reported in these patients. Hence, we aimed to verifying whether an isometric exercise could represent a useful tool for the identification of patients at risk for future cardiac events. Patients and methods Myocardial function (MF) and perfusion, evaluated as myocardial blood flow (MBF) of 10 BS/GS patients and 10 healthy controls, were investigated at rest and during isometric exercise. MF and MBF were evaluated using quantitative two‐dimensional and myocardial contrast echocardiography. Results BS/GS patients had normal baseline MF and MBF. During exercise in BS/GS patients, corrected QT (QTc) was prolonged to peak value of 494 ± 9·1 ms (P < 0·001). In controls, MF increased from resting to peak exercise (left ventricular ejection fraction: 65 ± 4% to 78 ± 5%, P < 0·003) while in seven BS/GS patients (Group 1) it declined (64 ± 5% to 43 ± 9%, P < 0·001). Myocardial perfusion increased upon exercise in controls as shown by changes of its markers: β (a measure of myocardial flow velocity; 0·89 ± 0·12 vs. 0·99 ± 0·12, P < 0·001) and myocardial blood volume (14·4 ± 2 vs. 20·2 ± 0·25, P < 0·001), while in Group 1 BS/GS it decreased (0·87 ± 0·15 vs. 0·67 ± 0·15, P < 0·001; and 14·5 ± 1·9 vs. 8·3 ± 0·22, P < 0·001, respectively). Conclusions Our results document for the first time that exercise induce coronary microvascular and myocardial defects in BS/GS patients. Therefore, this may challenge the idea that BS/GS are benign diseases. In addition, the diagnostic approach to these syndromes should include an in‐depth cardiac assessment in order to identify patients at higher risk.     

Maintained cerebral metabolic ratio during exercise in patients with β‐adrenergic blockade

Background: Decreased cerebral metabolic ratio (CMR) [molar uptake of O₂ versus molar uptake of (glucose + ½ lactate)] during exercise is attenuated by intravenous administration of the non‐selective β‐adrenergic receptor antagonist propranolol. We evaluated to what extent cirrhotic patients in oral treatment with propranolol are able to mobilize brain non‐oxidative carbohydrate metabolism. Methods: Incremental cycle ergometry to exhaustion (86 ± 4·2 W; mean ± SD) was performed in eight cirrhotic patients instrumented with a catheter in the brachial artery and one retrograde in the right internal jugular vein. Healthy subjects form the control group. Results: In β‐blocked cirrhotic patients arterial lactate increased from 1·5 ± 0·3 to 5·1 ± 0·8 mM (P<0·05) and the arterial–jugular venous difference (a–v diff) from ?0·01 ± 0·03 to 0·30 ± 0·05 mM (P<0·05) at rest and during exercise, respectively. During exercise the glucose a–v diff of 0·46 ± 0·06 mM remained at a level similar to rest (0·54 ± 0·03 mM) and at exhaustion the CMR was not significantly changed (5·8 ± 1·1 versus 6·0 ± 0·6). In controls, CMR decreased from 5·6 ± 0·9 at rest to 3·4 ± 0·7 (P<0·05) during maximal exercise and at a lactate level comparable to that achieved by the patients it was 3·8 ± 0·4. Conclusion: During exhaustive exercise in cirrhotic patients the CMR is maintained and a significant cerebral uptake of lactate is demonstrated. The data suggest that oral treatment with a non‐selective β‐adrenergic receptor antagonist attenuates cerebral non‐oxidative metabolism.     

Simultaneous quantification of myocardial perfusion,oxidative metabolism,cardiac efficiency and pump function at rest and during supine bicycle exercise using 1‐11C‐acetate PET – a pilot study

Background: PET using 1‐¹¹C‐acetate (ACE‐PET) applied at rest is used for measuring absolute myocardial blood flow (MBF) and oxidative metabolic rate (k_mono). We evaluated the feasibility of quantitative ACE‐PET during exercise. Methods: Five endurance athletes underwent dynamic PET scanning at rest and during supine bicycle stress. Exercise was maintained at a workload of 120 Watt for 17 min. The rate‐pressure product (RPP) was recorded repeatedly. MBF, k_mono in left (LV) and right (RV) ventricular wall, cardiac output (CO), cardiac efficiency and a lung uptake value reflecting left heart diastolic pressures were calculated from the PET data using previously validated models. Results: MBF increased from 0·71 ± 0·17 to 2·48 ± 0·25 ml min^?1 per ml, LV‐k_mono from 0·050 ± 0·005 to 0·146 ± 0·021 min^?1, RV‐k_mono from 0·023 + 0·006 to 0·087 + 0·014 min^‐1, RPP from 4·7 ± 0·8 to 13·2 ± 1·4 mmHg × min^?1 × 10³ and Cardiac Output from 5·2 ± 1·1 to 12·3 ± 1·2 l min ^?1 (all P < 0·001). Cardiac efficiency was unchanged (P = 0·99). Lung uptake decreased from 1·1 ± 0·2 to 0·6 ± 0·1 ml g^?1 (P < 0·001). Discussion: A number of important parameters related to cardiac function can be quantified non‐invasively and simultaneously with a short scanning protocol during steady state supine bicycling. This might open up new opportunities for studies of the integrated cardiac physiology in health and early asymptomatic disease.     

Comparison of SSRIs and SNRIs in major depressive disorder: a meta‐analysis of head‐to‐head randomized clinical trials

Context: Controversy exists whether serotonin–norepinephrine reuptake inhibitors (SNRIs) have improved efficacy compared with selective serotonin reuptake inhibitors (SSRIs). Objective: To compare clinical outcomes of adults treated with SSRIs or SNRIs for major depressive disorder (MDD) under ideal clinical condition, research design, and outcome measure. Data sources: Electronic databases searched were Medline, Embase and Cochrane Library from inception to July 2007. Study selection: Included studies were those head‐to‐head randomized trials comparing remission (HAMD‐17 ≤7–8, MADRS ≤10–12) after 8–12 weeks of therapeutic doses of SSRIs or SNRIs in patients diagnosed with MDD were targeted for analysis. Reviews, letters, commentaries, economic studies, etc. were excluded. Studies were reviewed by two independent researchers. Where disagreements occurred in study selection, a consensus approach was used. Data extraction and analysis: Targeted outcome data included number of patients achieving remission, withdrawing from therapy due to lack of efficacy (LoE) and/or adverse drug reactions (ADRs), and total patients in trial. A random effects model combined intent‐to‐treat (ITT) and per‐protocol (PP) odds ratio (OR), and remission and dropout rates. Chi‐square assessed heterogeneity. Quality assessment was done using Downs‐Black checklist. Results: Thirty‐three studies were identified; 18 were rejected (patients had co‐morbidities in 7, outcomes differed in 5, different follow‐up in 3, and three reviews). Fifteen head‐to‐head trials of 3094 patients, average age was 41·9 ± 11·9 years (for SNRIs) and 41·6 ± 12·1 years (for SSRIs), P = 0·941. All analyses displayed non‐heterogeneity (P > 0·05). The OR (under ITT) was 1·27 (1·06–1·52 95% CI) favoring SNRIs. Meta‐analytic remission rates were 48·5 ± 3·2% and 41·9 ± 4·2% for SNRIs and SSRIs, respectively. The meta‐analytic difference in remission rates between drugs was 5·7% (P = 0·007). Dropout rates due to ADRs were higher with SNRIs than SSRIs (3·2% difference, P < 0·001). Dropout rates due to LoE were non‐significant between studied groups (P > 0·05). Conclusions: Serotonin and norepinephrine reuptake inhibitors showed statistical but not clinical significance when compared with SSRIs in treating MDD.     

Effects of hypocaloric very‐low‐carbohydrate diet vs. Mediterranean diet on endothelial function in obese women*

Background Obesity is a cardiovascular risk factor associated with endothelial dysfunction, but the effect of different weight loss strategies on endothelial function is not known. The effect of diet on endothelial function in two hypocaloric diets, a very‐low‐carbohydrate diet (A) and a Mediterranean diet (M), was measured by brachial artery flow‐mediated dilation (FMD). Design Using a longitudinal, randomized, open study design, subjects were engaged in a 2‐month weight loss diet. FMD, inflammatory cytokines [interleukin‐6 (IL‐6) and tumour necrosis factor‐α] and a marker of oxidative stress [8‐iso‐prostaglandin F2α (8‐iso‐PGF2α)] were measured in subjects on three occasions: before initiating the diet (T0), after 5–7 days of dieting (T5) and after 2 months of dieting (T60). The very short‐ and medium‐term time points were established to discriminate respectively the effect of the diet itself (T5) from that of weight loss (T60). Twenty overweight/obese but otherwise healthy women (BMI: 27–34·9 kg m^?2; age 30–50 years) completed the study. Results Group A lost more weight (mean ± SEM; ?7·6 ± 0·8 kg) than group M (?4·9 ± 0·6 kg, P = 0·014) at T60. The FMD was not significantly different between the two groups at T0 (group A: 12·2 ± 2·9% vs. group B: 10·3 ± 2·3%, P = ns). In group A, FMD was significantly reduced at T5 and returned to baseline at T60; in group M, FMD increased at T5 and returned to baseline at T60 (P = 0·007 for diet × time interaction). Serum concentrations of IL‐6 and 8‐iso‐PGF2α were not significantly different between the two groups at T0 and increased significantly at T5 only in group A (P < 0·001 and P < 0·005 respectively). Conclusion As endothelial dysfunction is known to be associated with acute cardiovascular events, this study suggests that the cardiovascular risk might be increased in the first days of a very‐low‐carbohydrate diet.