Hidradenitis suppurativa is associated with childhood and lifetime traumatic events: a case-control study.

BACKGROUND: Negative life events in childhood can increase the susceptibility to autoimmune and inflammatory diseases. Hidradenitis suppurativa (HS) is a systemic inflammatory disease affecting the apocrine sweat glands, characterized by abscesses, fistulas and inflammatory nodules. It is unknown whether adult HS is associated with traumatic events. OBJECTIVE: To investigate the association between childhood and total lifetime traumatic events and the presence of HS. METHODS: We conducted a matched (1 : 3) case-control study with 71 HS patients and 213 controls. Patients were matched on age, gender and level of education. Questionnaires on general and demographic information, as well as the Traumatic Experience Checklist and the Hospital Anxiety and Depression Scale, were completed. RESULTS: The number of traumatic events (OR: 1.20 per trauma, P value < 0.05), and childhood traumatic events (yes vs. no, OR 3.59, P value < 0.05) and the number of childhood traumatic events (OR 1.35 per trauma, P value < 0.05) were correlated with an increased risk of developing HS. Detailed analysis showed that childhood emotional traumatic events (OR 5.03, P value < 0.05) were significantly associated with the development of HS. CONCLUSION: Number of lifetime traumatic events and childhood traumatic events are associated with HS. This association is strongest for emotional childhood traumas. The increased prevalence of childhood traumas in HS patients can be one of the underlying mechanisms leading to systemic inflammation in these patients.

The Year in Cardiology 2013: cardiovascular disease prevention.

The decline in cardiovascular mortality in Europe by nearly 50% over the last three decades resulted in particular from improved risk factor control and prevention interventions in addition to improved treatment. This review provides an overview of key studies in epidemiology, hypertension control, lipidology, diabetology, and lifestyle changes published in 2013. EXAMINE in diabetology and AIM-High and HPS-2-THRIVE in lipidology failed to demonstrate an event reduction. According to EUROASPIRE IV clinical implementation of secondary prevention treatments is still suboptimal. The 2013 study highlights in prevention prove the dynamic progress of knowledge in the field;, however, knowledge alone is futile without implementation.

Inter-hospital transfer of ECMO-assisted patients with a portable miniaturized ECMO device: 4 years of experience.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) in patients with severe pulmonary failure is able to keep patients alive until organ regeneration, until shunting out for further diagnostic and therapeutic options or until transportation to specialized centers. Nonetheless, extracorporeal techniques require a high degree of expertise, so that a confinement to specialized centers is meaningful. Following from this requirement, the need for inter-hospital transfer of patients with severely compromised pulmonary function is rising. METHODS: We report about our experience with a portable ECMO system during inter-hospital air or ground transfer of patients with cardiopulmonary failure. RESULTS: The portable ECMO system was used for transportation to the center and in-hospital treatment in 36 patients with an average age of 53 years suffering from respiratory failure. Accordingly, the ECMO system was implanted as a veno-venous extracorporeal system. Pre-ECMO ventilation time was 5.2 (2-9) days. Twelve patients were transported to our institution by ground and 24 patients by air ambulance over a median distance of 46 km. With the assistance of the ECMO device, prompt stabilization of cardiopulmonary function could be achieved in all patients without any technical complications. Post-ECMO ventilation was 9.8 days. Weaning from the ECMO system was successful in 61% of all patients after a median device working period of 12.7 days; median ICU stay was 34 days and a survival rate of 64% of patients was achieved. Technical (8%) and device-associated bleeding (11%)/thromboembolic (8%) complication rates showed very acceptable levels. CONCLUSION: Our experience demonstrates that miniaturized, portable ECMO therapy allows location-independent, out-of-center stabilization of pulmonary compromised patients with consecutive inter-hospital transfer and further in-house treatment, so that sophisticated ECMO therapy can be offered to every patient, even in hospitals with primary healthcare.

Gaze is driven by an internal goal trajectory in a visuomotor task.

When we make hand movements to visual targets, gaze usually leads hand position by a series of saccades to task-relevant locations. Recent research suggests that the slow smooth pursuit eye movement system may interact with the saccadic system in complex tasks, suggesting that the smooth pursuit system can receive non-retinal input. We hypothesise that a combination of saccades and smooth pursuit guides the hand movements towards a goal in a complex environment, using an internal representation of future trajectories as input to the visuomotor system. This would imply that smooth pursuit leads hand position, which is remarkable, as the general idea is that smooth pursuit is driven by retinal slip. To test this hypothesis, we designed a video-game task in which human subjects used their thumbs to move two cursors to a common goal position while avoiding stationary obstacles. We found that gaze led the cursors by a series of saccades interleaved with ocular fixation or pursuit. Smooth pursuit was correlated with neither cursor position nor cursor velocity. We conclude that a combination of fast and slow eye movements, driven by an internal goal instead of a retinal goal, led the cursor movements, and that both saccades and pursuit are driven by an internal representation of future trajectories of the hand. The lead distance of gaze relative to the hand may reflect a compromise between exploring future hand (cursor) paths and verifying that the cursors move along the desired paths.

[Bed capacity analysis for an intensive care unit : Retrospective analysis and projection for need of intensive care beds in over 65 year olds with selected cardiovascular diseases]. / Bettenkapazitätsanalyse für eine internistische Intensivstation : Retrospektive Analyse und Projektion des Intensivbettenbedarfs bei über 65-Jährigen mit ausgewählten kardiovaskulären Erkrankungen.

BACKGROUND: The increasing number of elderly individuals in the population and the simultaneous increase of the intensive care demand emphasizes the relevance of an efficient bed capacity analysis. Particularly, cardiovascular diseases represent a frequently occurring disease in the population group over 65 years of age. The objective of the following paper is the analysis of the retrospective and prospective intensive care demand by patients over 65 years with 6 selected (cardiovascular) codes of the International Statistical Classification of Diseases and Related Health Problems (ICD-10). METHODS: For the retrospective analysis, data from 2015-2017 were analyzed applying descriptive and bivariate methods. The analysis of the intensive care bed demand was based on the queuing theory. RESULTS: The monthly capacity utilization rates were constantly higher than the target capacity utilization rate of a maximum of 80% and in some cases even higher than 100%. In particular, the demand of patients with I50.14 was very high throughout the entire hospital. The bed demand analysis shows an increase from 9 needed beds in 2017 to 11 beds by 2030 for the 6 diagnosis groups. Regarding the 5 diagnosis groups without I50.14, only approximately half of the required beds were needed, retrospectively and in future. CONCLUSION: The effect of demographic change on the intensive care demand already exists, and a continuing, prospective increase of the demand is expected. The results underline the need of effective and demand-oriented intensive care capacity planning. However, prior to expanding bed capacities, the analysis of admission criteria of intensive care unit patients is necessary to reserve capacities primarily for patients with real intensive care needs.

Is home-based monitoring of ovulation to time frozen embryo transfer a cost-effective alternative for hospital-based monitoring of ovulation? Study protocol of the multicentre, non-inferiority Antarctica-2 randomised controlled trial.

STUDY QUESTION: The objective of this trial is to compare the effectiveness and costs of true natural cycle (true NC-) frozen embryo transfer (FET) using urinary LH tests to modified NC-FET using repeated ultrasound monitoring and ovulation trigger to time FET in the NC. Secondary outcomes are the cancellation rates of FET (ovulation before hCG or no dominant follicle, no ovulation by LH urine test, poor embryo survival), pregnancy outcomes (miscarriage rate, clinical pregnancy rates, multiple ongoing pregnancy rates, live birth rates, costs) and neonatal outcomes (including gestational age, birthweight and sex, congenital abnormalities or diseases of babies born). WHAT IS KNOWN ALREADY: FET is at the heart of modern IVF. To allow implantation of the thawed embryo, the endometrium must be prepared either by exogenous oestrogen and progesterone supplementation (artificial cycle (AC)-FET) or by using the NC to produce endogenous oestradiol before and progesterone after ovulation to time the transfer of the thawed embryo (NC-FET). During an NC-FET, women visit the hospital repeatedly and receive an ovulation trigger to time FET (i.e. modified (m)NC-FET or hospital-based monitoring). From the woman's point of view, a more natural approach using home-based monitoring of the ovulation with LH urine tests to allow a natural ovulation to time FET may be desired (true NC-FET or home-based monitoring). STUDY DESIGN SIZE DURATION: This is a multicentre, non-inferiority prospective randomised controlled trial design. Consenting women will undergo one FET cycle using either true NC-FET or mNC-FET based on randomisation. PARTICIPANTS/MATERIALS SETTING METHODS: Based on our sample size calculation, the study group will consist of 1464 women between 18 and 45 years old who are scheduled for FET. Women with anovulatory cycles, women who need ovulation induction and women with a contra indication for pregnancy will be excluded. The primary outcome is ongoing pregnancy. Secondary outcomes are cancellation rates of FET, pregnancy outcomes (including miscarriage rate, clinical pregnancy, multiple pregnancy rate and live birth rate). Costs will be estimated by counting resource use and calculating unit prices. STUDY FUNDING/COMPETING INTERESTS: The study received a grant from the Dutch Organisation for Health Research and Development (ZonMw 843002807; www.zonmw.nl). ZonMw has no role in the design of the study, collection, analysis, and interpretation of data or writing of the manuscript. F.B. reports personal fees from member of the external advisory board for Merck Serono, grants from Research support grant Merck Serono, outside the submitted work. A.E.P.C. reports and Unrestricted grant of Ferring B.V. to the Center for Reproductive medicine, no personal fee. Author up-to-date on Hyperthecosis. Congress meetings 2019 with Ferring B.V. and Theramex B.V. M.G. reports Department research and educational grants from Guerbet, Merck and Ferring (location VUMC) outside the submitted work. E.R.G. reports personal fees from Titus Health Care, outside the submitted work. C.B.L. reports grants from Ferring, grants from Merck, from Guerbet, outside the submitted work. The other authors have none to declare. TRIAL REGISTRATION NUMBER: Dutch Trial Register (Trial NL6414 (NTR6590), https://www.trialregister.nl/). TRIAL REGISTRATION DATE: 23 July 2017. DATE OF FIRST PATIENT'S ENROLMENT: 10 April 2018.

[Acute iron poisoning : Successful treatment of a potentially fatal suicidal attempt]. / Akute Eisenintoxikation : Erfolgreiche Therapie einer potenziell tödlichen parasuizidalen Geste.

We present the case of a patient who took 150 mg per kg bodyweight of iron in a suicidal attempt. We illustrate the diagnostic and therapeutic procedures required to successfully cope with this poisoning, which is, by surprise, potentially lethal.

Exercise-based cardiac rehabilitation in patients with reduced left ventricular ejection fraction: The Cardiac Rehabilitation Outcome Study in Heart Failure (CROS-HF): A systematic review and meta-analysis.

BACKGROUND: In heart failure with reduced left ventricular ejection fraction (HFrEF) patients the effects of exercise-based cardiac rehabilitation on top of state-of-the-art pharmacological and device therapy on mortality, hospitalization, exercise capacity and quality-of-life are not well established. DESIGN: The design of this study involved a structured review and meta-analysis. METHODS: Evaluation of randomised controlled trials of exercise-based cardiac rehabilitation in HFrEF-patients with left ventricular ejection fraction ≤40% of any aetiology with a follow-up of ≥6 months published in 1999 or later. RESULTS: Out of 12,229 abstracts, 25 randomised controlled trials including 4481 HFrEF-patients were included in the final evaluation. Heterogeneity in study population, study design and exercise-based cardiac rehabilitation-intervention was evident. No significant difference in the effect of exercise-based cardiac rehabilitation on mortality compared to control-group was found (hazard ratio 0.75, 95% confidence interval 0.39-1.41, four studies; 12-months follow-up: relative risk 1.29, 95% confidence interval 0.66-2.49, eight studies; six-months follow-up: relative risk 0.91, 95% confidence interval 0.26-3.16, seven studies). In addition there was no significant difference between the groups with respect to 'hospitalization-for-any-reason' (12-months follow-up: relative risk 0.79, 95% confidence interval 0.41-1.53, four studies), or 'hospitalization-due-to-heart-failure' (12-months follow-up: relative risk 0.59, 95% confidence interval 0.12-2.91, four studies; six-months follow-up: relative risk 0.84, 95% confidence interval 0.07-9.71, three studies). All studies show improvement of exercise capacity. Participation in exercise-based cardiac rehabilitation significantly improved quality-of-life as evaluated with the Kansas City Cardiomyopathy Questionnaire: (six-months follow-up: mean difference 1.94, 95% confidence interval 0.35-3.56, two studies), but no significant results emerged for quality-of-life measured by the Minnesota Living with Heart Failure Questionnaire (nine-months or more follow-up: mean difference -4.19, 95% confidence interval -10.51-2.12, seven studies; six-months follow-up: mean difference -5.97, 95% confidence interval -16.17-4.23, four studies). CONCLUSION: No association between exercise-based cardiac rehabilitation and mortality or hospitalisation could be observed in HFrEF patients but exercise-based cardiac rehabilitation is likely to improve exercise capacity and quality of life.

[Prevention of coronary artery disease]. / Prävention der koronaren Herzerkrankung.

Coronary artery disease is still the leading cause of premature death, reduction in physical work capacity and diminished quality of life in western civilizations. Given the fact that coronary artery disease is a preventable disease in most of the cases, its prevalence remains unacceptably high. Consequent application of preventive recommendations with regards to life-style aspects like tobacco use, nutrition, overweight and physical activity could help to reduce the prevalence of atherosclerotic diseases by half. Aim of this review is to focus the reader's attention to the most important risk factors, their influence on progression of atherosclerotic lesions and ways to reduce risk factor burden.

Movement dynamics.

Recently, several reports have suggested that the control of multi-joint limbs is mediated by reducing the number of degrees of freedom in redundant limbs. In addition, more insight has been gained into the constraints that are imposed on muscle activation patterns and joint rotations.

[Acute colitis in Wegener's disease: a case report]. / Colite aiguë révélant une maladie de Wegener.

We report the case of a 52 year old man who was hospitalized within a context of a persistent deterioration of his general condition. He was suspected of having a chronic inflammatory colitis. A pulmonary radiography revealed the presence of voluminous bilateral excavated masses with hydro-aerical levels. After having refuted among others a suspicion of tuberculosis, the results of a thoracic percutaneous transpleural lung aspiration by needle under tomodensitometric control steered our diagnosis towards a vascularitis of the Wegener disease type. A treatment with corticotherapy in large doses completed with cyclophosphamid allowed for clinical, biological and radiological improvement. Wegener's granulomatosis usually starts in an insidious manner with febrile episodes and an impairment of the general condition associated with inflammatory biological signs, as observed in our patient. After these warning symptoms, come ORL and/or pulmonary and/or renal impairment, which represent the classical triad of diffused GW. However a certain number of particularities unusual for that diagnosis characterized our patient and prompted the discussion of this case.

Phytotoxicity of tolylfluanid in tomatoes.

The use of Euparen Multi (tolylfluanid) for controlling Botrytis cinerea in tomatoes has been decreased the last decade for several reasons. Because of the lack of different fungicides with a good efficacy it is important that growers can use different fungicides to prevent development of resistance of Botrytis cinerea against many fungicides. Tolylfluanid has negative side effects on some insect populations that are used for biological control. It is known that Euparen Multi and Euparen can have a negative effect on some predatory mites (Schmidt and Zeller, 1998) such as Phytoseiulus persimilis and some parasitic wasps like Encarsia formosa, Eretmocerus eremicus, Diglyphus isaea and Dacnusa sibirica. Recently investigation indicates that this fungicide is harmless for the predatory bug Macrolophus caliginosus (Biobest, 2006) frequently used in the cultivation of tomatoes as a predator for whitefly (Trialeurodes vaporariorum). To investigate if tolylfluanid has a phytotoxic effect on tomato plants an experiment was performed. Young tomato plants were used, who are more sensitive. These plants were subdivided in different groups, from which each one was sprayed with a different concentration of tolylfluanid. The highest concentrations of tolylfluanid were used to stimulate the visibility of the possible phytotoxic effects. Results of this experiment demonstrate that there wasn't a difference between the different groups that were sprayed with tolylfluanid or the control group. This indicates that tolylfluanid doesn't seem to be phytotoxic. It is also important to mention that this experiment was done in the fall when the intensity of the sunlight was decreasing. There still exists the possibility that extreme irradiation in combination with tolylfluanid can provoke a phototoxic effect on young tomato plants.

Lung protective ventilation and hospital survival of cardiac intensive care patients.

OBJECTIVE: To detect connections between parameters of ventilation and outcomes of cardiac intensive care patients. DESIGN AND SETTING: Noninterventional study. Between 05/11 and 05/12 all patients with acute heart failure and post cardiopulmonary resuscitation were registered. Lung protective ventilation was defined as peak inspiratory pressure (PIP) < 30 mmHg and tidal volume (Vt) < = 6 ml/kg. RESULTS: In total, 129 patients were included in the study, 68.2 % male, age 67.9 ± 13.4 years, weight 71.4 ± 37.2 kg, predictive body weight 66.9 ± 8.8 kg, mortality 47.3 %. Lung protective ventilated patients at day 1: 17.3 % with a significant difference between surviving and nonsurviving patients (24.1 % vs. 9.6 %; p < 0.05). Logistic regression models showed a strong connection between PIP and survival (odds ratio 1.13; p < 0.05). Vt showed no significant influence on survival. CONCLUSION: Our data recommends a strict observance of a low PIP for cardiac intensive care patients, whereas Vt seems to be of secondary importance.

Tamoxifen treatment for breast cancer enforces a distinct gene-expression profile on the human endometrium: an exploratory study.

Tamoxifen treatment for breast cancer increases proliferation of the endometrium, resulting in an enhanced prevalence of endometrial pathologies, including endometrial cancer. An exploratory study was performed to begin to understand the molecular mechanism of tamoxifen action in the endometrium. Gene-expression profiles were generated of endometrial samples of tamoxifen users and compared with matched controls. The pathological classification of samples from both groups included atrophic/inactive endometrium and endometrial polyps. Unsupervised clustering revealed that samples of tamoxifen users were, irrespective of pathological classification, fairly similar and consequently form a subgroup distinct from the matched controls. Using SAM analysis (a statistical method to select genes differentially expressed between groups), 256 differentially expressed genes were selected between the tamoxifen and control groups. Upon comparing these genes with oestrogen-regulated genes, identified under similar circumstances, 95% of the differentially expressed genes turned out to be tamoxifen-specific. Finally, construction of a gene-expression network of the differentially expressed genes revealed that 69 genes centred around five well-known genes: TP53, RELA, MYC, epidermal growth factor receptor and beta-catenin. This could indicate that these well-known genes, and the pathways in which they function, are important for tamoxifen-controlled proliferation of the endometrium.

Exercise training in coronary artery disease and coronary vasomotion.

Exercise training has assumed a major role in cardiac rehabilitation, mostly because of its positive effects on myocardial perfusion in patients with coronary artery disease. The mechanisms involved in mediating this key effect have long been debated: both regression of coronary artery stenosis and improvement of collateralization have been suggested as potential adaptations. However, the comparatively minute changes in luminal diameter and myocardial contrast staining do not fully explain the significant changes in myocardial perfusion. During the last decade, endothelial dysfunction was identified as a trigger of myocardial ischemia. The impaired production of endothelium-derived nitric oxide (NO) in response to acetylcholine and flow leads to paradoxic vasoconstriction and exercise-induced ischemia. Recently, it was confirmed in humans that training attenuates paradoxic vasoconstriction in coronary artery disease and increases coronary blood flow in response to acetylcholine. Data from cell-culture and animal experiments suggest that shear stress acts as a stimulus for the endothelium to increase the transport capacity for L-arginine (the precursor molecule for NO), to enhance NO synthase activity and expression, and to increase the production of extracellular superoxide dismutase, which prevents premature breakdown of NO. Exercise also affects the microcirculation, where it sensitizes resistance arteries for the vasodilatory effects of adenosine. These novel findings provide a pathophysiological framework to explain the improvement of myocardial perfusion in the absence of changes in baseline coronary artery diameter. Because endothelial dysfunction has been identified as a predictor of coronary events, exercise may contribute to the long-term reduction of cardiovascular morbidity and mortality.

Regular physical activity improves endothelial function in patients with coronary artery disease by increasing phosphorylation of endothelial nitric oxide synthase.

BACKGROUND: In stable coronary artery disease (CAD), exercise training has well-documented positive effects on arterial endothelial function. NO derived from endothelial NO synthase (eNOS) is regarded as a protective factor against atherosclerosis. The aim of the present study was to investigate the effects of exercise training on the endothelial function in relation to the expression of eNOS and Akt-dependent eNOS phosphorylation in the left internal mammary artery (LIMA) of patients with stable CAD. METHODS AND RESULTS: In 17 training patients (T) and 18 control patients (C), endothelium-dependent vasodilation and average peak flow velocity (APV) in response to acetylcholine were measured invasively at study beginning and after 4 weeks in the LIMA. In LIMA tissue sampled during bypass surgery, eNOS expression and content of pospho-eNOS-Ser1177, Akt, and phospho-Akt were determined by Western blot and quantitative reverse transcriptase-polymerase chain reaction. After exercise training, LIMA APV in response to acetylcholine was increased by 56+/-8% (from +48+/-8% at beginning to +104+/-11% after 4 weeks, P<0.001). Patients in T had a 2-fold higher eNOS protein expression (T 1.0+/-0.7 versus C 0.5+/-0.3 arbitrary units, P<0.05) and 4-fold higher eNOS Ser1177-phosphorylation levels in LIMA-endothelium (1.2+/-0.9 versus 0.3+/-0.2 arbitrary units, P<0.01). A linear correlation was confirmed between Akt phosphorylation and phospho-eNOS levels (R=0.80, P<0.05) and between phospho-eNOS and Delta APV (R=0.59, P<0.05). CONCLUSIONS: Exercise training in stable CAD leads to an improved agonist-mediated endothelium-dependent vasodilatory capacity. The change in acetylcholine-induced vasodilatation was closely related to a shear stress-induced/Akt-dependent phosphorylation of eNOS on Ser1177.

Molecular portrait of the progestagenic and estrogenic actions of tibolone: behavior of cellular networks in response to tibolone.

Tibolone is a synthetic steroid with estrogenic effects on brain, vagina, and bone without stimulating the endometrium. During tibolone treatment, it is thought that the progestagenic properties of tibolone stimulate cell differentiation, which effectively counterbalances the growth-stimulating effects of the estrogenic properties of tibolone. The objective of this study was to characterize the expression profile that reflects the endometrial responses to the separated estrogenic (growth-inducing) and progestagenic (growth-inhibiting) actions of tibolone, thus gaining insight into the counteracting effect of these properties of tibolone on the endometrium. The estrogenic action of tibolone was studied in the estrogen-responsive ECC1 cell line (expressing estrogen receptor alpha), and the progestagenic action was studied in the progesterone-responsive cell line Ishikawa PRAB-36 (expressing PRA and PRB). The data showed that the progestagenic and estrogenic effects of tibolone produce different expression profiles with a narrow overlap in genes; however, both properties modulate the same biological processes. The final genetic network analysis indicated that the estrogenic effect of tibolone is potentially counterbalanced by the progestagenic metabolite of tibolone via differential regulation of similar cellular processes. For example, both progestagenic and estrogenic properties stimulate proliferation, but they exert the opposite effect on apoptosis. The apoptosis network was stimulated by the progestagenic properties of tibolone; in contrast, the estrogenic effect of tibolone suppressed the apoptosis network. The current results indicate that this differential regulation is realized through modulation of a different group of genes and rarely via contraregulation of the same set of genes.

Endothelial dysfunction in patients with chronic heart failure: systemic effects of lower-limb exercise training.

OBJECTIVES: We sought to analyze the systemic effects of lower-limb exercise training (ET) on radial artery endothelial function in patients with chronic heart failure (CHF). BACKGROUND: Local ET has the potential to improve local endothelial dysfunction in patients with CHF. However, it remains unclear whether the systemic effects can be achieved by local ET. METHODS: Twenty-two male patients with CHF were prospectively randomized to either ET on a bicycle ergometer (ET group, n = 11; left ventricular ejection fraction [LVEF] 26 +/- 3%) or an inactive control group (group C, n = 11; LVEF 24 +/- 2%). At the beginning of the study and after four weeks, endothelium-dependent and -independent vasodilation of the radial artery was determined by intra-arterial infusion of acetylcholine (ACh-7.5, 15 and 30 microg/min) and nitroglycerin (0.2 mg/min). The mean internal diameter (ID) of the radial artery was assessed using a high resolution ultrasound system (NIUS-02, Asulab Research Laboratories, Neuchâtel, Switzerland) with a 10-MHz probe. RESULTS: After four weeks of ET, patients showed a significant increase in the baseline-corrected mean ID in response to ACh (30 microg/min), from 33 +/- 10 to 127 +/- 25 microm (p < 0.001 vs. control group at four weeks). In the control group, the response to ACh (30 microg/min) remained unchanged. Endothelium-independent vasodilation was similar in both groups at the beginning of the study and at four weeks. In the training group, increases in agonist-mediated, endothelium-dependent vasodilation correlated to changes in functional work capacity (r = 0.63, p < 0.05). CONCLUSIONS: In patients with stable CHF, bicycle ergometer ET leads to a correction of endothelial dysfunction of the upper extremity, indicating a systemic effect of local ET on endothelial function.

Correction of endothelial dysfunction in chronic heart failure: additional effects of exercise training and oral L-arginine supplementation.

OBJECTIVES: The aim of this study was to analyze whether L-arginine (L-arg.) has comparable or additive effects to physical exercise regarding endothelium-dependent vasodilation in patients with chronic heart failure (CHF). BACKGROUND: Endothelial dysfunction in patients with CHF can be corrected by both dietary supplementation with L-arg. and regular physical exercise. METHODS: Forty patients with severe CHF (left ventricular ejection fraction 19 +/- 9%) were randomized to an L-arg. group (8 g/day), a training group (T) with daily handgrip training, L-arg. and T (L-arg. + T) or an inactive control group (C). The mean internal radial artery diameter was determined at the beginning and after four weeks in response to brachial arterial administration of acetylcholine (ACh) (7.5, 15, 30 microg/min) and nitroglycerin (0.2 mg/min) with a transcutaneous high-resolution 10 MHz A-mode echo tracking system coupled with a Doppler device. The power of the study to detect clinically significant differences in endothelium-dependent vasodilation was 96.6%. RESULTS: At the beginning, the mean endothelium-dependent vasodilation in response to ACh, 30 microg/min was 2.54 +/- 0.09% (p = NS between groups). After four weeks, internal radial artery diameter increased by 8.8 +/- 0.9% after ACh 30 microg/min in L-arg. (p < 0.001 vs. C), by 8.6 +/- 0.9% in T (p < 0.001 vs. C) and by 12.0 +/- 0.3% in L-arg. +/- T (p < 0.005 vs. C, L-arg. and T). Endothelium-independent vasodilation as assessed by infusion of nitroglycerin was similar in all groups at the beginning and at the end of the study. CONCLUSIONS: Dietary supplementation of L-arg. as well as regular physical exercise improved agonist-mediated, endothelium-dependent vasodilation to a similar extent. Both interventions together seem to produce additive effects with respect to endothelium-dependent vasodilation.