Response of B-type natriuretic pepticle to exercise in hypertensive patients with suspected diastolic heart failure: Correlation with cardiac function, hemodynamics, and workload

Background Diastolic heart failure (DHF) is characterized by dyspnea due to increased left ventricular (LV) filling pressures during stress. We sought the relationship of exercise-induced increases in B-type natriuretic peptide (BNP) to LV filling pressures and parameters of cardiovascular performance in suspected DHF. Methods Twenty-six treated hypertensive patients with suspected DHF (exertional dyspnea, LV ejection fraction >50%, and diastolic dysfunction) underwent maximal exercise echocardiography using the Bruce protocol. BNP, transmitral Doppler, and tissue Doppler for systolic (So) and early (Ea) and late (Aa) diastolic mitral annular velocities were obtained at rest and peak stress. LV filling pressures were estimated with E/Ea ratios. Results Resting BNP correlated with resting pulse pressure (r=0.45, P=0.02). Maximal exercise performance (4.6 +/- 2.5min) was limited by dyspnea. Blood pressure increased with exercise (from 143 +/- 19/88 +/- 8 to 191 +/- 22/90 +/- 10 mm Hg); 13 patients (50%) had a hypertensive response. Peak exercise BNP correlated with peak transmitral E velocity (r = 0.41, P <.05) and peak heart rate (r = -0.40, P <.05). BNP increased with exercise (from 48 57 to 74 97 pg/mL, P =.007), and the increment of BNP with exercise was associated with maximal workload and peak exercise So, Ea, and Aa (P <.01 for all). Filling pressures, approximated by lateral E/Ea ratio, increased with exercise (7.7 +/- 2.0 to 10.0 +/- 4.8, P <.01). BNP was higher in patients with possibly elevated filling pressures at peak exercise (E/Ea >10) compared to those with normal pressures (123 +/- 124 vs 45 +/- 71 pg/mL, P =.027). Conclusions Augmentation of BNP with exercise in hypertensive patients with suspected DHF is associated with better exercise capacity, LV systolic and diastolic function, and left atrial function. Peak exercise BNP levels may identify exercise-induced elevation of filling pressures in DHF.

Prediction of functional capacity in chronic heart failure patients using myocardial tissue Doppler

Background. Exercise therapy improves functional capacity in CHF, but selection and individualization of training would be helped by a simple non-invasive marker of peak VO2. Peak VO2 in these pts is difficult to predict without direct measurement, and LV ejection fraction is a poor predictor. Myocardial tissue velocities are less load-dependent, and may be predictive of the exercise response in CHF pts. We sought to use tissue velocity as a predictor of peak VO2 in CHF pts. Methods. Resting 2D-echocardiography and tissue Doppler imaging were performed in 182 CHF pts (159 male, age 62±10 years) before and after metabolic exercise testing. The majority of these patients (129, 71%) had an ischemic cardiomyopathy, with resting EF of 35±13% and a peak VO2 of 13.5±4.7 ml/kg/min. Results. Neither resting EF (r=0.15) nor peak EF (r=0.18, both p=NS) were correlated with peak VO2. However, peak VO2 correlated with peak systolic velocity in septal (Vss, r=0.31) and lateral walls (Vsl, r=0.26, both p=0.01). In a general linear model (r2 = 0.25), peak VO2 was calculated from the following equation: 9.6 + 0.68*Vss - 0.09*age + 0.06*maximum HR. This model proved to be a superior predictor of peak VO2 (r=0.51, p=0.01) than the standard prediction equations of Wasserman (r= -0.12, p=0.01). Conclusions. Resting tissue Doppler, age and maximum heart rate may be used to predict functional capacity in CHF patients. This may be of use in selecting and following the response to therapy, including for exercise training.

Constitutive glycogen synthase kinase-3α/β activity protects against chronic β-adrenergic remodelling of the heart

Aims - Glycogen synthase kinase 3 (GSK-3) signalling is implicated in the growth of the heart during development and in response to stress. However, its precise role remains unclear. We set out to characterize developmental growth and response to chronic isoproterenol (ISO) stress in knockin (KI) mice lacking the critical N-terminal serines, 21 of GSK-3 and 9 of GSK-3 respectively, required for inactivation by upstream kinases. Methods and results - Between 5 and 15 weeks, KI mice grew more rapidly, but normalized heart weight and contractile performance were similar to wild-type (WT) mice. Isolated hearts of both genotypes responded comparably to acute ISO infusion with increases in heart rate and contractility. In WT mice, chronic subcutaneous ISO infusion over 14 days resulted in cardiac hypertrophy, interstitial fibrosis, and impaired contractility, accompanied by foetal gene reactivation. These effects were all significantly attenuated in KI mice. Indeed, ISO-treated KI hearts demonstrated reversible physiological remodelling traits with increased stroke volume and a preserved contractile response to acute adrenergic stimulation. Furthermore, simultaneous pharmacological inhibition of GSK-3 in KI mice treated with chronic subcutaneous ISO recapitulated the adverse remodelling phenotype seen in WT hearts. Conclusion - Expression of inactivation-resistant GSK-3/does not affect eutrophic myocardial growth but protects against pathological hypertrophy induced by chronic adrenergic stimulation, maintaining cardiac function and attenuating interstitial fibrosis. Accordingly, strategies to prevent phosphorylation of Ser-21/9, and consequent inactivation of GSK-3/, may enable a sustained cardiac response to chronic-agonist stimulation while preventing pathological remodelling. © 2010 The Author.

PSD modifications of FHRV due to interpolation and CTG storage rate

Cardiotocographic data provide physicians information about foetal development and permit to assess conditions such as foetal distress. An incorrect evaluation of the foetal status can be of course very dangerous. To improve interpretation of cardiotocographic recordings, great interest has been dedicated to foetal heart rate variability spectral analysis. It is worth reminding, however, that foetal heart rate is intrinsically an uneven series, so in order to produce an evenly sampled series a zero-order, linear or cubic spline interpolation can be employed. This is not suitable for frequency analyses because interpolation introduces alterations in the foetal heart rate power spectrum. In particular, interpolation process can produce alterations of the power spectral density that, for example, affects the estimation of the sympatho-vagal balance (computed as low-frequency/high-frequency ratio), which represents an important clinical parameter. In order to estimate the frequency spectrum alterations of the foetal heart rate variability signal due to interpolation and cardiotocographic storage rates, in this work, we simulated uneven foetal heart rate series with set characteristics, their evenly spaced versions (with different orders of interpolation and storage rates) and computed the sympatho-vagal balance values by power spectral density. For power spectral density estimation, we chose the Lomb method, as suggested by other authors to study the uneven heart rate series in adults. Summarising, the obtained results show that the evaluation of SVB values on the evenly spaced FHR series provides its overestimation due to the interpolation process and to the storage rate. However, cubic spline interpolation produces more robust and accurate results. © 2010 Elsevier Ltd. All rights reserved.

Effects of hydrogen sulphide on the isolated perfused rat heart

Objectives: Hydrogen sulphide has been identified as a gas signalling molecule in the body, and has previously been shown to have vasorelaxant properties. The aim of the study was to investigate the effects of sodium hydrosulphide (NaHS), a hydrogen sulphide donor, on heart rate (HR), left ventricular developed pressure (LVDP) and coronary flow (CF) in the isolated perfused rat heart. Methods: A Langendorff isolated heart preparation was used to investigate the effect of a dose range of sodium hydrosulphide, in the presence and absence of inhibitors, on heart rate, left ventricular developed pressure and coronary flow. Results: Sodium hydrosulphide caused a significant decrease in heart rate at a concentration of 10-3 M (P <0.001). This decrease was partially inhibited by glibenclamide, a K ATP channel blocker (P <0.05); L-NAME, a nitric oxide synthase inhibitor (P <0.001), and methylene blue (P <0.001), but not by H-89, a protein kinase A inhibitor. Sodium hydrosulphide significantly increased coronary flow at concentrations of 10-4 - 10-3M (P <0.05). This response was significantly increased in the presence of L-NAME (P <0.001) and methylene blue (P <0.001), whereas H-89 inhibited the increase in coronary flow due to sodium hydrosulphide (P <0.001). Sodium hydrosulphide significantly decreased LVDP at all concentrations (P <0.001). In the presence of glibenclamide and H-89, the time period of the decrease in LVDP due to sodium hydrosulphide was extended (P <0.001), whereas methylene blue and L-NAME caused a significant reduction in the response to sodium hydrosulphide (P <0.05, P <0.01 respectively). Conclusion: Sodium hydrosulphide reduced heart rate and LVDP, and increased coronary flow in the isolated perfused rat heart; however, the mechanisms of action could not be fully elucidated.

Preservation of myocardial beta-adrenergic receptor signaling delays the development of heart failure after myocardial infarction.

When the heart fails, there is often a constellation of biochemical alterations of the beta-adrenergic receptor (betaAR) signaling system, leading to the loss of cardiac inotropic reserve. betaAR down-regulation and functional uncoupling are mediated through enhanced activity of the betaAR kinase (betaARK1), the expression of which is increased in ischemic and failing myocardium. These changes are widely viewed as representing an adaptive mechanism, which protects the heart against chronic activation. In this study, we demonstrate, using in vivo intracoronary adenoviral-mediated gene delivery of a peptide inhibitor of betaARK1 (betaARKct), that the desensitization and down-regulation of betaARs seen in the failing heart may actually be maladaptive. In a rabbit model of heart failure induced by myocardial infarction, which recapitulates the biochemical betaAR abnormalities seen in human heart failure, delivery of the betaARKct transgene at the time of myocardial infarction prevents the rise in betaARK1 activity and expression and thereby maintains betaAR density and signaling at normal levels. Rather than leading to deleterious effects, cardiac function is improved, and the development of heart failure is delayed. These results appear to challenge the notion that dampening of betaAR signaling in the failing heart is protective, and they may lead to novel therapeutic strategies to treat heart disease via inhibition of betaARK1 and preservation of myocardial betaAR function.

Cardioprotective effects of Dan-Yang-Fu-Xin decoction on chronic heart failure in rats

Purpose: To evaluate the cardioprotective effects and possible mechanisms of Dan-Yang-Fu-Xin decoction (DYFX) in a rat chronic heart failure (CHF). Methods: A CHF rat model induced by ligation of the left anterior descending coronary artery was used to investigate the cardioprotective effects of DYFX. After intragastric administration for 8 weeks, several functional cardiac indices, including fractional shortening (FS), ejection fraction (EF), heart rate (HR) and cardiac output (CO) were assessed by ultrasound examination. Subsequently, inflammatory markers, viz, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), myocardial enzymes, namely, lactate dehydrogenase (LDH) and creatine kinase (CK), were also assessed by enzyme-linked immunosorbent assay (ELISA). Results: Intragastric administration of DYFX (200, 400 and 600 mg/kg) significantly reversed the decrease in body weight and increase in cardiac weight (p < 0.05) induced by CHF. Treatment with DYFX also significantly reversed EF, FS, HR, and CO changes in CHF rats. In addition, DYFX inhibited the two inflammatory cytokines (TNF-α and IL-6) and myocardial enzymes (CK and LDH), suggesting that these effects may include the mechanisms of cardioprotectiion involved in attenuation of CHF. Conclusion: DYFX possesses cardioprotective effects involving CHF. The protective mechanisms may include the suppression of expression of inflammatory mediators and myocardial enzymes.

Physiological and symptomatic responses to cycling and walking in intermittent claudication

To shed light on the potential efficacy of cycling as a testing modality in the treatment of intermittent claudication (IC), this study compared physiological and symptomatic responses to graded walking and cycling tests in claudicants. Sixteen subjects with peripheral arterial disease (resting ankle: brachial index (ABI) < 0.9) and IC completed a maximal graded treadmill walking (T) and cycle (C) test after three familiarization tests on each mode. During each test, symptoms, oxygen uptake (VO2), minute ventilation (VE), respiratory exchange ratio (RER) and heart rate (HR) were measured, and for 10 min after each test the brachial and ankle systolic pressures were recorded. All but one subject experienced calf pain as the primary limiting symptom during T; whereas the symptoms were more varied during C and included thigh pain, calf pain and dyspnoea. Although maximal exercise time was significantly longer on C than T (690 +/- 67 vs. 495 +/- 57 s), peak VO2, peak VE and peak heart rate during C and T were not different; whereas peak RER was higher during C. These responses during C and T were also positively correlated (P < 0.05) with each other, with the exception of RER. The postexercise systolic pressures were also not different between C and T. However, the peak decline in ankle pressures from resting values after C and T were not correlated with each other. These data demonstrate that cycling and walking induce a similar level of metabolic and cardiovascular strain, but that the primary limiting symptoms and haemodynamic response in an individual's extremity, measured after exercise, can differ substantially between these two modes.

Beneficial effects of exercise : shifting the focus from body weight to other markers of health

Background: Exercise is widely promoted as a method of weight management, while the other health benefits are often ignored. The purpose of this study was to examine whether exercise-induced improvements in health are influenced by changes in body weight. Methods: Fifty-eight sedentary overweight/obese men and women (BMI 31.8 (SD 4.5) kg/m2) participated in a 12-week supervised aerobic exercise intervention (70% heart rate max, five times a week, 500 kcal per session). Body composition, anthropometric parameters, aerobic capacity, blood pressure and acute psychological response to exercise were measured at weeks 0 and 12. Results: The mean reduction in body weight was −3.3 (3.63) kg (p<0.01). However, 26 of the 58 participants failed to attain the predicted weight loss estimated from individuals’ exercise-induced energy expenditure. Their mean weight loss was only −0.9 (1.8) kg (p<0.01). Despite attaining a lower-than-predicted weight reduction, these individuals experienced significant increases in aerobic capacity (6.3 (6.0) ml/kg/min; p<0.01), and a decreased systolic (−6.00 (11.5) mm Hg; p<0.05) and diastolic blood pressure (−3.9 (5.8) mm Hg; p<0.01), waist circumference (−3.7 (2.7) cm; p<0.01) and resting heart rate (−4.8 (8.9) bpm, p<0.001). In addition, these individuals experienced an acute exercise-induced increase in positive mood. Conclusions: These data demonstrate that significant and meaningful health benefits can be achieved even in the presence of lower-than-expected exercise-induced weight loss. A less successful reduction in body weight does not undermine the beneficial effects of aerobic exercise. From a public health perspective, exercise should be encouraged and the emphasis on weight loss reduced.

Exercise alone is not enough : weight loss also needs a healthy (Mediterranean) diet?

Objective: In the majority of exercise intervention studies, the aggregate reported weight loss is often small. The efficacy of exercise as a weight loss tool remains in question. The aim of the present study was to investigate the variability in appetite and body weight when participants engaged in a supervised and monitored exercise programme. ---------- Design: Fifty-eight obese men and women (BMI = 31·8 ± 4·5 kg/m2) were prescribed exercise to expend approximately 2092 kJ (500 kcal) per session, five times a week at an intensity of 70 % maximum heart rate for 12 weeks under supervised conditions in the research unit. Body weight and composition, total daily energy intake and various health markers were measured at weeks 0, 4, 8 and 12. ---------- Results: Mean reduction in body weight (3·2 ± 1·98 kg) was significant (P < 0·001); however, there was large individual variability (−14·7 to +2·7 kg). This large variability could be largely attributed to the differences in energy intake over the 12-week intervention. Those participants who failed to lose meaningful weight increased their food intake and reduced intake of fruits and vegetables. ---------- Conclusion: These data have demonstrated that even when exercise energy expenditure is high, a healthy diet is still required for weight loss to occur in many people.

Acute compensatory eating following exercise is associated with implicit hedonic wanting for food

The efficacy of exercise to promote weight loss could potentially be undermined by its influence on explicit or implicit processes of liking and wanting for food which in turn alter food preference. The present study was designed to examine hedonic and homeostatic mechanisms involved in the acute effects of exercise on food intake. 24 healthy female subjects were recruited to take part in two counterbalanced activity sessions; 50 min of high intensity (70% max heart rate) exercise (Ex) or no exercise (NEx). Subjective appetite sensations, explicit and implicit hedonic processes, food preference and energy intake (EI) were measured immediately before and after each activity session and an ad libitum test meal. Two groups of subjects were identified in which exercise exerted different effects on compensatory EI and food preference. After exercise, compensators (C) increased their EI, rated the food to be more palatable, and demonstrated increased implicit wanting. Compensators also showed a preference for high-fat sweet food compared with non-compensators (NC), independent of the exercise intervention. Exercise-induced changes in the hedonic response to food could be an important consideration in the efficacy of using exercise as a means to lose weight. An enhanced implicit wanting for food after exercise may help to explain why some people overcompensate during acute eating episodes. Some individuals could be resistant to the beneficial effects of exercise due to a predisposition to compensate for exercise-induced energy expenditure as a result of implicit changes in food preferences.

Tesofensine : a novel potent weight loss medicine

Background: The incidence of obesity is increasing; this is of major concern, as obesity is associated with cardiovascular disease, stroke, type 2 diabetes, respiratory tract disease, and cancer. Objectives/methods: This evaluation is of a Phase II clinical trial with tesofensine in obese subjects. Results: After 26 weeks, tesofensine caused a significant weight loss, and may have a higher maximal ability to reduce weight than the presently available anti-obesity agents. However, tesofensine also increased blood pressure and heart rate, and may increase psychiatric disorders. Conclusions: It is encouraging that tesofensine 0.5 mg may cause almost double the weight loss observed with sibutramine or rimonabant. As tesofensine and sibutramine have similar pharmacological profiles, it would be of interest to compare the weight loss with tesofensine in a head-to-head clinical trial with sibutramine, to properly assess their comparative potency. Also, as teso fensine 0.5 mg increases heart rate, as well as increasing the incidence of adverse effects such as nausea, drug mouth, flatulence, insomnia, and depressed mode, its tolerability needs to be further evaluated in large Phase III clinical trials.

Within- and between-day repeatability and variability in children's physiological responses during submaximal treadmill exercise

The purpose of this study was to verify within- and between-day repeatability and variability in children's oxygen uptake (VO^sub 2^), gross economy (GE; VO^sub 2^ divided by speed) and heart rate (HR) during treadmill walking based on self-selected speed (SS). Fourteen children (10.1 ± 1.4 years) undertook three testing sessions over 2 days in which four walking speeds, including SS were tested. Within- and between-day repeatability were assessed using the Bland and Altman method, and coefficients of variability (CV) were determined for each child across exercise bouts and averaged to obtain a mean group CV value for VO^sub 2^, GE, and HR per speed. Repeated measures analysis of variance showed no statistically significant differences in within- or between-day CV for VO^sub 2^, GE, or HR at any speed. Repeatability within- and between-day for VO^sub 2^, GE, and HR for all speeds was verified. These results suggest that submaximal VO^sub 2^ during treadmill walking is stable and reproducible at a range of speeds based on children's SS.

Driving performance on monotonous roads

Driving on motorways has largely been reduced to a lane-keeping task with cruise control. Rapidly, drivers are likely to get bored with such a task and take their attention away from the road. This is of concern in terms of road safety – particularly for professional drivers - since inattention has been identified as one of the main contributing factors to road crashes and is estimated to be involved in 20 to 30% of these crashes. Furthermore, drivers are not aware that their vigilance level has decreased and that their driving performance is impaired. Intelligent Transportation System (ITS) intervention can be used as a countermeasure against vigilance decrement. This paper aims to identify a variety of metrics impacted during monotonous driving - ranging from vehicle data to physiological variables - and relate them to two monotonous factors namely the monotony of the road design (straightness) and the monotony of the environment (landscape, signage, traffic). Data are collected in a driving simulator instrumented with an eye tracking system, a heart rate monitor and an electrodermal activity device (N=25 participants). The two monotonous factors are varied (high and low) leading to the use of four different driving scenarios (40 minutes each). We show with Generalised Linear Mixed Models that driver performance decreases faster when the road is monotonous. We also highlight that road monotony impairs a variety of driving performance and vigilance measures, ranging from speed, lateral position of the vehicle to physiological measurements such as heart rate variability, blink frequency and electrodermal activity. This study informs road designers of the importance of having a varied road environment. It also provides a range of metrics that can be used to detect in real-time the impairment of driving performance on monotonous roads. Such knowledge could result in the development of an in-vehicle device warning drivers at early signs of driving performance impairment on monotonous roads.

The effects of exercise-induced weight loss on appetite-related peptides and motivation to eat

Context: The magnitude of exercise-induced weight loss depends on the extent of compensatory responses. An increase in energy intake is likely to result from changes in the appetite control system toward an orexigenic environment; however, few studies have measured how exercise impacts on both orexigenic and anorexigenic peptides. ---------- Objective: The aim of the study was to investigate the effects of medium-term exercise on fasting/postprandial levels of appetite-related hormones and subjective appetite sensations in overweight/obese individuals. ---------- Design and Setting: We conducted a longitudinal study in a university research center. ---------- Participants and Intervention: Twenty-two sedentary overweight/obese individuals (age, 36.9 ± 8.3 yr; body mass index, 31.3 ± 3.3 kg/m2) took part in a 12-wk supervised exercise programme (five times per week, 75% maximal heart rate) and were requested not to change their food intake during the study. ---------- Main Outcome Measures: We measured changes in body weight and fasting/postprandial plasma levels of glucose, insulin, total ghrelin, acylated ghrelin (AG), peptide YY, and glucagon-like peptide-1 and feelings of appetite. ---------- Results: Exercise resulted in a significant reduction in body weight and fasting insulin and an increase in AG plasma levels and fasting hunger sensations. A significant reduction in postprandial insulin plasma levels and a tendency toward an increase in the delayed release of glucagon-like peptide-1 (90–180 min) were also observed after exercise, as well as a significant increase (127%) in the suppression of AG postprandially. ---------- Conclusions: Exercise-induced weight loss is associated with physiological and biopsychological changes toward an increased drive to eat in the fasting state. However, this seems to be balanced by an improved satiety response to a meal and improved sensitivity of the appetite control system.