Bewegungsparcours, Sturzrisiko und gesundheitsbezogene Lebensqualität

Background

The purpose was to evaluate the interventional effects of activity trails (courses) on fall risk factors and health-related quality of life (hrQoL).

Materials and methods

A total of 94 subjects (67.7?±?5.7 years; 29 men, 65 women) completed the following measurements prior to and 12 weeks after the initiation of the activity trail intervention: maximum isometric leg extensors force (F_max, m3 diagnoses©), gait velocity (GV), and static postural stability (STAB, Zebris FDM©), fall-associated self-efficacy (FALL, FES-I), and hrQoL (SF-36).

Results

During the 12-week intervention period, the participants increased F_max (1.63?±?0.6 vs. 1.70?±?0.6 N?kg^-1) and GV (1.06?±?0.25 vs. 1.11?±?0.18m?s^-1; p?<?0.05). Neither FALL (19.44?±?3.6 vs. 19.41?±?4.3 points) nor STAB (84.3?±?56.4 vs. 79.7?±?63.1 mm²) changed. Additionally, significant improvements in hrQoL regarding vitality (56.3?±?17.2 vs. 63.2?±?18.3 points) and mental health (69.4?±?18.7 vs. 75.5?±?16.5 points; p?<?0.05) were found.

Conclusion

The improvements in fall-related risk factors and hrQoL may be expected to contribute to fall prevention and psychosocial quality of life.     

Insulin-mediated suppression of lipolysis in adipose tissue and skeletal muscle of obese type 2 diabetic men and men with normal glucose tolerance

Aims/hypothesis

Impaired regulation of lipolysis and accumulation of lipid intermediates may contribute to obesity-related insulin resistance and type 2 diabetes mellitus. We investigated insulin-mediated suppression of lipolysis in abdominal subcutaneous adipose tissue (AT) and skeletal muscle (SM) of obese men with normal glucose tolerance (NGT) and obese type 2 diabetic men.

Methods

Eleven NGT men and nine long-term diagnosed type 2 diabetic men (7?±?1 years), matched for age (58?±?2 vs 62?±?2 years), BMI (31.4?±?0.6 vs 30.5?±?0.6 kg/m²) and V ? O 2 max $ \overset{\cdot }{V}{\mathrm{O}}_{2 \max } $ (28.9?±?1.5 vs 29.5?±?2.4 ml kg^?1 min^?1) participated in this study. Interstitial glycerol concentrations in AT and SM were assessed using microdialysis during a 1 h basal period and a 6 h stepwise hyperinsulinaemic–euglycaemic clamp (8, 20 and 40 mU m^?2 min^?1). AT and SM biopsies were collected to investigate underlying mechanisms.

Results

Hyperinsulinaemia suppressed interstitial SM glycerol concentrations less in men with type 2 diabetes (?7?±?6%, ?13?±?9% and ?27?±?9%) compared with men with NGT (?21?±?7%, ?38?±?8% and ?53?±?8%) (p?=?0.014). This was accompanied by increased circulating fatty acid and glycerol concentrations, a lower glucose infusion rate (21.8?±?3.1 vs 30.5?±?2.0 μmol kg body weight^?1 min^?1; p?<?0.05), higher hormone-sensitive lipase (HSL) serine 660 phosphorylation, increased saturated diacylglycerol (DAG) lipid species in the muscle membrane and increased protein kinase C (PKC) activation in type 2 diabetic men vs men with NGT. No significant differences in insulin-mediated reduction in AT interstitial glycerol were observed between groups.

Conclusions/interpretation

Our results suggest that a blunted insulin-mediated suppression of SM lipolysis may promote the accumulation of membrane saturated DAG, aggravating insulin resistance, at least partly mediated by PKC. This may represent an important mechanism involved in the progression of insulin resistance towards type 2 diabetes. Trial registration: ClinicalTrials.gov NCT01680133     

Commonly used bowel preparations have significant and different effects upon cell proliferation in the colon: a pilot study

Background

Acute pancreatitis is an inflammatory disease characterized by local tissue injury and systemic inflammatory response leading to massive nitric oxide (NO) production and haemodynamic disturbances. Therefore, the aim of this work was to evaluate the vascular reactivity of pulmonary and mesenteric artery rings from rats submitted to experimental pancreatitis. Male Wistar rats were divided into three groups: saline (SAL); tauracholate (TAU) and phospholipase A₂ (PLA₂). Pancreatitis was induced by administration of TAU or PLA₂ from Naja mocambique mocambique into the common bile duct of rats, and after 4 h of duct injection the animals were sacrificed. Concentration-response curves to acetylcholine (ACh), sodium nitroprusside (SNP) and phenylephrine (PHE) in isolated mesenteric and pulmonary arteries were obtained. Potency (pEC₅₀) and maximal responses (E_MAX) were determined. Blood samples were collected for biochemical analysis.

Results

In mesenteric rings, the potency for ACh was significantly decreased from animals treated with TAU (about 4.2-fold) or PLA₂ (about 6.9-fold) compared to saline group without changes in the maximal responses. Neither pEC₅₀ nor E_MAX values for Ach were altered in pulmonary rings in any group. Similarly, the pEC₅₀ and the E_MAX values for SNP were not changed in both preparations in any group. The potency for PHE was significantly decreased in rat mesenteric and pulmonary rings from TAU group compared to SAL group (about 2.2- and 2.69-fold, for mesenteric and pulmonary rings, respectively). No changes were seen in the E_MAX for PHE. The nitrite/nitrate (NO_x ^-) levels were markedly increased in animals submitted to acute pancreatitis as compared to SAL group, approximately 76 and 68% in TAU and PLA₂ protocol, respectively.

Conclusion

Acute pancreatitis provoked deleterious effects in endothelium-dependent relaxing response for ACh in mesenteric rings that were strongly associated with high plasma NO_x ^- levels as consequence of intense inflammatory responses. Furthermore, the subsensitivity of contractile response to PHE in both mesenteric and pulmonary rings might be due to the complications of this pathological condition in the early stage of pancreatitis.     

Verteilung der karotidalen Intima-Media-Dicke bei Männern und Frauen mit und ohne koronare Herzerkrankung

Purpose

The aim of this study was to introduce population-based sex and age-stratified distributions of carotid intima media thickness (CIMT), to compare fixed cut-off and percentile values for subjects with and without known coronary heart disease (CHD) and to describe CIMT percentiles.

Methods

Between 2000 and 2003, a total of 4,814 subjects aged 45–75 years were recruited into the Heinz Nixdorf recall study (HNR). Ultrasound examination of extracranial arteries was performed and the CIMT was measured manually over a distance of 1 cm proximal to the bulb in the common carotid artery (CCA). Both sides were measured and the average of the right and left artery were calculated (mean CIMT).

Results

The CIMT was measured for 1,749 men and 1,802 women without prevalent CHD and 177 men and 50 women with prevalent CHD. Mean CIMT values were higher in men compared to women (men 0.71?±?0.14 mm vs. women 0.65?±?0.11 mm, p?≤?0.0001) and in subjects with CHD compared to those without (men with and without CHD: 0.76?±?0.14 mm and 0.70?±?0.14 mm, p?≤?0.0001, respectively; women with and without CHD: 0.73?±?0.15 mm and 0.64?±?0.11 mm, p?≤?0.0001, respectively). In men the mean CIMT increased from 0.62?±?0.10 mm in the youngest (45–49 years old) up to 0.79?±?0.13 mm in the highest age group (≥?70 years) (0.57?±?0.08 mm up to 0.71?±?0.12 mm in women, p?≤?0.0001 for both).

Conclusions

Compared to international studies similar CIMT distributions were found in this study using both continuous and percentile distributions. However, lower CIMT values were observed in older participants, which can be explained by exclusion of carotid plaque formation in CIMT measurements.     

Feasibility of multiple short, 40-s, intra-procedural ECG recordings to detect immediate changes in heart rate variability during catheter ablation for arrhythmias

Purpose

This study aims to evaluate a method to detect heart rate variability (HRV) changes using short ECG segments during ablation for arrhythmias.

Methods

HRV was averaged from sequentially shorter time windows from 5-min ECG recordings in 15 healthy volunteers. The 40-s window was identified as the shortest duration that yielded reproducible values in high frequency (HF) and low frequency (LF) HRV. This method was validated in patients undergoing tilt table testing to see if the expected modulation in HRV that occurs prior to syncope could be detected from multiple 40-s recordings. Lastly, this method was used to assess HRV changes in 75 patients undergoing ablation for atrial fibrillation (AF) and other arrhythmias, to see if autonomic modulation as a result of ablation could be detected. A further 14 patients had stepwise HRV measurements at different stages of the AF ablation procedure to determine whether intra-procedural HRV changes could be detected.

Results

HRV, averaged from multiple 40-s recordings, demonstrated the expected increase immediately preceding syncope compared with baseline (LF: 341?±?311?C1,536?±?1,368 ms², p?<?0.05; HF: 342?±?339?C1,628?±?1,755 ms², p?<?0.05). AF ablation, particularly following right pulmonary vein circumferential ablation, produced immediately detectable reductions in LF (153?±?251?C50?+?116 ms², p?<?0.001) and HF (86?±?195?C33?±?83 ms², p?<?0.001) without any change in RR interval (877?±?191?C843?±?220 ms, p?=?0.261). Ablation for atrial flutter did not change the mean RR interval, LF or HF HRV.

Conclusion

Averaging multiple 40-s windows give valid HF and LF HRV measurements that enable detection of intra-procedural changes. Left atrial ablation around the right-sided pulmonary veins is unique in producing reductions in HRV. This method has the potential for use as an endpoint marker for adjunctive autonomic ablation procedures.     

Glucagon responses to increasing oral loads of glucose and corresponding isoglycaemic intravenous glucose infusions in patients with type 2 diabetes and healthy individuals

Aims/hypothesis

Type 2 diabetes is associated with hypersecretion of glucagon during an OGTT, whereas i.v. glucose suppresses glucagon levels. This suggests that type 2 diabetic hyperglucagonaemia may result from glucose stimulation of the gastrointestinal tract. We evaluated glucagon responses to increasing amounts of glucose given orally and corresponding isoglycaemic i.v. glucose infusions (IIGIs) in patients with type 2 diabetes and in healthy controls.

Methods

Plasma glucagon responses were measured during three 4 h OGTTs with increasing loads of glucose (25 g, 75 g and 125 g) and three corresponding IIGIs in eight patients with type 2 diabetes (age [mean?±?SEM] 57?±?4 years; BMI 29.5?±?1.0 kg/m²; HbA_1c 7.0?±?0.3% [53?±?2 mmol/mol]) and eight healthy individuals (age 57?±?4 years; BMI 28.9?±?0.7 kg/m²; HbA_1c 5.4?±?0.1% [36?±?1 mmol/mol]).

Results

In healthy controls no difference in glucagon suppression during the first 45 min of the 25 g OGTT and the corresponding IIGI (?153?±?35 vs ?133?±?24 min?×?pmol/l; p?=?NS) was observed, whereas patients with type 2 diabetes only exhibited significant glucagon suppression following IIGI (29?±?27 vs ?144?±?20 min?×?pmol/l; p?=?0.005). At higher oral glucose loads this difference increased and also became evident in healthy controls.

Conclusions/interpretation

In patients with type 2 diabetes increasing amounts of oral glucose elicit hypersecretion of glucagon, whereas corresponding IIGIs result in significant glucagon suppression; a phenomenon that is also observed in healthy individuals when larger glucose loads are ingested orally. This suggests that the hyperglucagonaemic response to oral glucose in type 2 diabetes may represent a pathological version of a gut-derived physiological phenomenon. Trial registration: ClinicalTrials.gov NCT00529048     

Bolus injection of newly synthesized vitamin E derivative ETS-GS for the treatment of acute severe ulcerative colitis in a mouse model

Purpose

Vitamin E with its antioxidant action has therapeutic effects on ulcerative colitis (UC), but use of vitamin E is limited because of its insolubility in water. We developed ETS-GS (γ-l-glutamyl-S-[2-[[[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltri-decyl)-2?H-1-benzopyran-6-yl]oxy]carbonyl]-3-oxo-3-[(2-sulfoethyl)amino]propyl]-l-cysteinylglycine sodium salt), a newly synthesized soluble vitamin E derivative with strong antioxidant action. We evaluated the therapeutic effects of bolus injection of ETS-GS on acute severe UC in a mouse model.

Methods

An animal model of acute severe UC was induced by feeding mice 5 % dextran sulfate sodium (DSS) for 5 days, followed by 1 % DSS on days 5–8, the experimental period. ETS-GS or saline was administered by subcutaneous bolus injection during the experimental period. We examined disease activity index (DAI) score, histological score, colon length, colon weight, and serum cytokines in the mice.

Results

The following results at day 8 in the DSS + ETS-GS group were significantly lower than those in the DSS + Saline group: DAI score, 2.6?±?0.6 vs. 3.1?±?0.5; histological score, 2.1?±?1.0 vs. 3.1?±?0.8; serum interleukin (IL)-6, 15?±?9.4 vs. 39?±?23 pg/ml; and keratinocyte-derived chemokine (KC), 122?±?61 vs. 228?±?66 pg/ml (P?<?0.05). Colon length, colon weight, and serum IL-10 in the DSS + ETS-GS group were significantly higher than those in the DSS + Saline group (88?±?12 vs. 75?±?5.7 mm, 0.48?±?0.09 vs. 0.38?±?0.05 g, and 55?±?18 vs. 31?±?10 pg/ml, respectively; P?<?0.05).

Conclusions

Bolus injection of ETS-GS may be one therapeutic modality for acute severe UC. Its effects are associated with suppression of serum IL-6 and serum KC and promotion of serum IL-10.     

Glucocorticoid treatment impairs microvascular function in healthy men in association with its adverse effects on glucose metabolism and blood pressure: a randomised controlled trial

Aims/hypothesis

Glucocorticoids (GCs) are widely used anti-inflammatory agents that frequently induce side effects, including insulin resistance, diabetes and hypertension. Here, we investigated the contribution of microvascular dysfunction to the development of these adverse effects in healthy men.

Methods

In a randomised, placebo-controlled, dose–response intervention study, 32 healthy normoglycaemic men (age: 21?±?2 years; BMI: 21.9?±?1.7 kg/m²) were allocated to receive prednisolone 30 mg once daily (n?=?12), prednisolone 7.5 mg once daily (n?=?12) or placebo (n?=?8) for 2 weeks using block randomisation. A central office performed the treatment allocation, and medication was dispersed by the hospital pharmacy that was also blinded. Treatment allocation was kept in concealed envelopes. Participants, study personnel conducting the measures and assessing the outcome were blinded to group assignment. The study was conducted at a university hospital. Primary endpoint was prednisolone-induced changes in microvascular function, which was assessed by capillary microscopy. Insulin sensitivity was determined by hyperinsulinaemic–euglycaemic clamp and postprandial glycaemic excursions by standardised meal tests.

Results

Compared with placebo, prednisolone 7.5 mg and 30 mg decreased insulin-stimulated capillary recruitment by 9?±?4% and 17?±?3%, respectively (p?<?0.01). In addition, prednisolone 7.5 mg and 30 mg reduced insulin sensitivity (M value) by ?11.4?±?4.5 μmol kg^?1 min^?1 and ?25.1?±?4.1 μmol kg^?1 min^?1 (p?<?0.001) and increased postprandial glucose levels by 11?±?5% and 27?±?9% (p?<?0.001), respectively. Only high-dose prednisolone increased systolic blood pressure (6?±?1.2 mmHg, p?=?0.006). Prednisolone-induced changes in insulin-stimulated capillary recruitment were associated with insulin sensitivity (r?=?+0.76; p?<?0.001), postprandial glucose concentrations (r?=??0.52; p?<?0.03) and systolic blood pressure (r?=??0.62; p?<?0.001). Prednisolone increased resistin concentrations, which were negatively related to insulin-stimulated capillary recruitment (r?=??0.40; p?=?0.03). No effects were noted on adiponectin and leptin concentrations. Prednisolone treatment was well tolerated; none of the participants left the study.

Conclusions/interpretation

Prednisolone-induced impairment of insulin-stimulated capillary recruitment was paralleled by insulin resistance, increased postprandial glucose levels, hypertension and increased circulating resistin concentrations in healthy men. We propose that GC-induced impairments of microvascular function may contribute to the adverse effects of GC treatment on glucose metabolism and blood pressure.

Trial registration

isrctn.org ISRTCN 78149983

Funding

The study was funded by the Dutch Top Institute Pharma T1-106.     

Cytochrome P450 Pathway Contributes to Methanandamide-induced Vasorelaxation in Rat Aorta

Purpose

The generation of hyperpolarising vasorelaxant endothelial cytochrome P450 epoxygenase (CYP)—derived metabolites of arachidonic may provide beneficial effects for the treatment of cardiovascular diseases in which the bioavailability of NO is impaired. The cannabinoid methanandamide has vasodilatory properties linked to hyperpolarisation. The aim of the present work was to investigate the vasorelaxant effects of methanandamide in rat aorta, focusing on the role of cytochrome P450 pathway.

Methods

Changes in isometric tension in response to a cumulative concentration-response curve of methanandamide (1 nM–100 μM) were recorded in aortic rings from male Wistar rats. The involvement of cannabinoid receptors, endothelial nitric oxide (NO)-, prostacyclin- and some hyperpolarising-mediated pathways were investigated. The activation of large-conductance Ca²⁺-activated K⁺ (BKCa) channels have also been evaluated.

Results

Methanandamide provoked an endothelium-dependent vasorelaxation in rat aorta, reaching a maximal effect (Rmax) of 67%?±?2.6%. This vasorelaxation was clearly inhibited by the combination of CB₁ and CB₂ cannabinoid antagonists (Rmax: 21.6%?±?1.3%) and by the combination of guanylate cyclase and CYP inhibitors (Rmax: 16.7%?±?1.1%). The blockade induced separately by guanylate cyclase (31.3%?±?2.8%) or CYP (36.3%?±?6.6%) inhibitors on methanandamide vasorelaxation was not significantly modified by either CB₁ or CB₂ inhibition. BKCa channels inhibition caused a partial and significant inhibition of the methanandamide vasorelaxation (Rmax: 39.9%?±?3.3%).

Conclusions

Methanandamide endothelium-dependent vasorelaxation is mediated by CB₁ and CB₂ cannabinoid receptors. The NO- and CYP-mediated pathways contribute in a concurrent manner in this vascular effect. Stimulation of both cannabinoid receptor subtypes is indistinctly linked to NO or CYP routes to cause vasorelaxation.     

Incidence,predictors, and clinical course of atrial tachyarrhythmias in patients with pulmonary hypertension

Background

The prevalence and predictors of atrial tachyarrhythmias (ATa) in patients with pulmonary hypertension (PH) is less well understood.

Methods

We performed a retrospective study including 311 patients with PH, confirmed by right heart catheterization in our center between 2007 and 2011. Baseline characteristics, clinical, echocardiographic, and hemodynamic data were collected and compared between patients with and without ATa.

Results

The mean age was 61?±?13 years with 64 % females. The mean pulmonary artery pressure (mPAP) was 46?±?20 mmHg, mean left ventricular ejection fraction (LVEF) was 55?±?13 %, and mean pulmonary capillary wedge pressure (PCWP) was 19?±?9 mmHg. Of the 311 patients with PH, 121 (39 %) patients had ATa. Patients with ATa were older (p?p?=?0.03), diabetes (p?=?0.015), coronary artery disease (p?p?p?=?0.001), impaired LVEF (p?=?0.02), and left atrial enlargement (p?p?=?0.022). In multivariate analysis using Cox-proportional hazard model, the independent predictors of mortality were age (HR 1.05; p?=?0.003), coronary artery disease (HR 2.34; p?=?0.047), LVEF (HR 0.793; p?=?0.023), and mPAP (HR 1.023; p?=?0.003).

Conclusion

ATa are common in patients with PH. Left heart disease, left atrial enlargement, and elevated PCWP but not right atrial enlargement or mPAP predict the occurrence of ATa in patients with PH.     

Adipose tissue is inflamed in NAFLD due to obesity but not in NAFLD due to genetic variation in PNPLA3

Aims/hypothesis

The rs738409 C>G single-nucleotide polymorphism in PNPLA3 leads to a missense mutation (I148M) which increases liver fat but does not cause insulin resistance. We hypothesised that patients with non-alcoholic fatty liver disease (NAFLD) due to the PNPLA3 variant (‘PNPLA3 NAFLD’?=?PNPLA3-148MM) do not have adipose tissue (AT) inflammation in contrast with those with NAFLD due to obesity (‘obese NAFLD’).

Methods

Biopsy specimens of AT were taken, and PNPLA3 genotype and liver fat (¹H-magnetic resonance spectroscopy) were determined in 82 volunteers, who were divided into groups based on either median BMI (obese 36.2?±?0.7 kg/m²; non-obese 26.0?±?0.4 kg/m²) or PNPLA3 genotype. All groups were similar with respect to age and sex. The PNPLA3 subgroups were equally obese (PNPLA3-148MM, 31.1?±?1.3 kg/m²; PNPLA3-148II, 31.2?±?0.8 kg/m²), while the obese and non-obese subgroups had similar PNPLA3 genotype distribution. Gene expression of proinflammatory (MCP-1, CD68) and anti-inflammatory (Twist1, ADIPOQ) markers was measured using quantitative real-time RT-PCR.

Results

Liver fat was similarly increased in obese NAFLD (9.5?±?1.3% vs 5.1?±?0.9%, obese vs non-obese, p?=?0.007) and PNPLA3 NAFLD (11.4?±?1.7% vs 5.3?±?0.8%, PNPLA3-148MM vs PNPLA3-148II, p?<?0.001). Fasting serum insulin was higher in the obese than the non-obese group (76?±?6 vs 47?±?6 pmol/l, p?<?0.001), but similar in PNPLA3-148MM and PNPLA3-148II (60?±?8 vs 62?±?5 pmol/l, NS). In obese vs non-obese, MCP-1 and CD68 mRNAs were upregulated, whereas those of Twist1 and ADIPOQ were significantly downregulated. AT gene expression of MCP-1, CD68, Twist1 and ADIPOQ was similar in PNPLA3-148MM and PNPLA3-148II groups.

Conclusions/interpretation

PNPLA3 NAFLD is characterised by an increase in liver fat but no insulin resistance or AT inflammation, while obese NAFLD has all three of these features.     

H-FABP, cardiovascular risk factors, and functional status in asymptomatic spinal cord injury patients

Background

This was a cross-sectional study in the setting of a rehabilitation hospital.

Objective

The aim of the study was to determine the serum levels of heart-type fatty acid-binding protein (H-FABP) in patients with spinal cord injury (SCI). A further goal was to examine whether there is a relationship between H-FABP levels and Functional Ambulation Classification (FAC) scale, Functional Independence Measure (FIM) score, American Spinal Injury Association (ASIA) status, and metabolic syndrome (MetS).

Methods

The study included 56 SCI patients and 37 age- and sex-matched healthy control subjects who had not been diagnosed with coronary artery disease in the past.

Results

Serum H-FABP levels were significantly higher in patients with SCI than in control subjects: paraplegia group, 18.5?±?11.4; tetraplegia group, 16.3?±?9.1; control group, 6.7?±?5.1 ng/ml (p?<?0.001). There was no difference between the other cardiac enzymes (troponin I, AST, ALT, CK, CK-MB, and LDH) among the groups. The relationship between the serum H-FABP levels and FAC status was examined. There was a negative correlation between FAC status and H-FABP levels (p?<?0.001, r?=???0.581). Patients with complete SCI were divided into two groups according to the level of the lesion: (lesion levels in C6–T6, n?=?25; lesion levels in T7–L2, n?=?11). In patients with complete motor injury, H-FABP levels were higher in subjects with injuries above T6 than in those with injuries below T6 (24.21?±?10.1 and 14.1?±?10.4, respectively; p?=?0.011). Serum levels of H-FABP were higher in SCI patients with MetS (n?=?10) than in those without MetS (n?=?46; 25.8?±?11.6 ng/ml vs. 16.42?±?10.3 ng/ml, respectively; p?=?0.014). Patients were then divided into two groups according to SCI duration: <?12 months (n?=?27) and >?12 months (n?=?29). H-FABP levels showed statistically significant differences between the two groups (14.8?±?11.7 ng/dl and 20.9?±?9.9 ng/dl, respectively; p?=?0.036).

Conclusion

H-FABP is related to MetS and FAC status in asymptomatic SCI patients.     

Fibrosis and electrophysiological characteristics of the atrial appendage in patients with atrial fibrillation and structural heart disease

Purpose

This study was conducted to investigate the degree of fibrosis in atrial appendages of patients with and without atrial fibrillation (AF) undergoing cardiac surgery. In addition, we hypothesized that areas of atrial fibrosis can be identified by electrogram fractionation and low voltage for potential ablation therapy.

Methods

Interstitial fibrosis from right (RAA) and/or left atrial appendages (LAA) was studied in patients with sinus rhythm (SR, n?=?8), paroxysmal (n?=?21), and persistent AF (n?=?20) undergoing coronary artery bypass and/or aortic or mitral valve surgery. Atrial fibrosis quantification was performed with Masson trichrome staining. Intraoperative bipolar epicardial electrophysiological measurements were performed to correlate fibrosis to electrogram fractionation, voltage, and AF cycle length.

Results

The average degree of fibrosis was 11.2?±?7.2 % in the LAA and 22.8?±?7.6 % in the RAA (p?<?0.001). Fibrosis was not significantly higher in paroxysmal AF patients compared to SR subjects (18.2?±?8.7 versus 20.7?±?5.3 %). Persistent AF patients had a higher degree of LAA and RAA fibrosis compared to paroxysmal AF patients (LAA 14.6?±?8.7 versus 8.6?±?4.7 %, p?=?0.02, and RAA 28.2?±?7.9 versus 18.2?±?8.7 %, respectively, p?=?0.04). The left atrial end diastolic volume index was higher in persistent AF patients compared to SR controls (38.3?±?16.4 and 28?±?11 ml/m², respectively, p?=?0.04). No correlation between atrial fibrosis and electrogram fractionation or voltage was found.

Conclusion

Patients with structural heart disease undergoing cardiac surgery have more fibrosis in the RAA than in the LAA. Furthermore, RAA fibrosis is increased in persistent AF but not paroxysmal AF patients compared to control subjects. Electrogram fractionation and low voltage did not provide accurate identification of the fibrotic substrate.     

Simultaneous assessment of contact pressure and local electrical coupling index using robotic navigation

Purpose

Contact with cardiac tissue is a determinant of lesion efficacy during atrial fibrillation (AF) ablation. The Sensei®X Robotic Catheter System (Hansen Medical, CA) has been validated for contact force sensing. The electrical coupling index (ECI) from the EnSite Contact? system (St. Jude Medical, MN) has been validated as an indicator of tissue contact. We aimed at analyzing ECI behavior during radiofrequency (RF) pulses maintaining a stable contact through the robotic navigation contact system.

Methods

In 15 patients (age, 59?±?12) undergoing AF ablation, pulmonary vein (PV) isolation was guided by the Sensei®X System, employing the Contact? catheter.

Results

During the procedure, we assessed ECI changes associated with adequate contact based on the IntelliSense® force-sensing technology (Hansen Medical, CA. Baseline contact (27?±?8 g/cm²) ECI value was 99?±?13, whereas ECI values in a noncontact site (0 g/cm²) and in a light contact site (1–10 g/cm²) were respectively 66?±?12 and 77?±?10 (p?<?0.0001). Baseline contact ECI values were not different depending on AF presentation (paroxysmal AF, 98?±?9; persistent AF, 100?±?9) or on cardiac rhythm (sinus rhythm, 97?±?7; AF,101?±?10). In all PVs, ECI was significantly reduced during and after ablation (ECI during RF, 56?±?15; ECI after RF, 72?±?16; p?<?0.001). A mean reduction of 32.2 % during RF delivery and 25.4 % immediately after RF discontinuation compared with baseline ECI was observed.

Conclusions

Successful PV isolation is associated with a significant decrease in ECI of at least 20 %. This may be used as a surrogate marker of effective lesion in AF ablation.     

Cerebral blood flow and cerebrovascular reactivity at rest and during sub-maximal exercise: Effect of age and 12-week exercise training

Chronic reductions in cerebral blood flow (CBF) and cerebrovascular reactivity to CO₂ are risk factors for cerebrovascular disease. Higher aerobic fitness is associated with higher CBF at any age; however, whether CBF or reactivity can be elevated following an exercise training intervention in healthy individuals is unknown. The aim of this study was to assess the effect of exercise training on CBF and cerebrovascular reactivity at rest and during exercise in young and older individuals. Ten young (23?±?5 years; body mass index (BMI), 26?±?3 kg m^?2; $ {\mathop{V}\limits^{ \cdot }{_{\text{O2}}}}\max $ , 35?±?5 ml kg^?1 min^?1) and 10 older (63?±?5 years; BMI, 25?±?3.0 kg m^?2; $ {\mathop{V}\limits^{ \cdot }{_{\text{O2}}}}\max $ , 26?±?4 ml kg^-1 min^?1) previously sedentary individuals breathed 5 % CO₂ for 3 min at rest and during steady-state cycling exercise (30 and 70 % heart rate range (HRR)) prior to and following a 12-week aerobic exercise intervention. Effects of training on middle cerebral artery blood velocity (MCAv) at rest were unclear in both age groups. The absolute MCAv response to exercise was greater in the young (9 and 9 cm s^?1 (30 and 70 % HRR, respectively) vs. 5 and 4 cm s^?1 (older), P?<?0.05) and was similar following training. Cerebrovascular reactivity was elevated following the 12-week training at rest (2.87?±?0.76 vs. 2.54?±?1.12 cm s^?1 mm Hg^?1, P?=?0.01) and during exercise, irrespective of age. The finding of a training-induced elevation in cerebrovascular reactivity provides further support for exercise as a preventative tool in cerebrovascular and neurological disease with ageing.     

The relationship between cephalometric carotid artery calcification and Framingham Risk Score profile in patients with obstructive sleep apnea

Purpose

The morbidity rate of arteriosclerosis becomes clinically manifested as acute cardiovascular events. In the progress of atherosclerosis, the carotid artery calcifies and sometimes appears as a calcified mass on a cephalometric radiograph. This study was designed to evaluate cardiovascular risks according to the Framingham Risk Score (FRS) between subjects with and without visible carotid artery calcification on a cephalogram.

Methods

Subjects diagnosed with obstructive sleep apnea (OSA) were divided into two groups according to whether or not calcification was visible on a cephalometric radiograph in the carotid artery area, and the characteristic differences between the two groups were analyzed. The evaluated variables included age, BMI, apnea–hypopnea index (AHI), SpO₂, ESS, blood pressure, medication history, diabetes mellitus (DM), drinking, smoking, and lipid-related measurements. FRSs for stroke, general cardiovascular disease (GCD), and coronary heart disease (CHD) were calculated. Statistical analyses were performed (SPSS 18.0) with significance defined as a two-tailed p value less than 0.05.

Results

A total of 811 subjects completed the data collection (727 males, age 53.0?±?12.5 years, AHI 31.7?±?22.6, times/h). From FRSs, probabilities of a GCD, stroke, and CHD within 10 years were 16.0?±?9.7, 9.8?±?6.7, and 11.9?±?8.3 %, respectively. Some 84 subjects exhibited calcification in the carotid arterial area. Calcification subjects were higher GCD risk and older than subjects who had no identified calcification (20.3?±?10.1 vs 15.6?±?20.3 %, p?=?0.013, 58.8?±?11.4 vs. 52.3?±?12.5 years, p?<?0.001). Although there is no significant difference in OSA-related variables and FRSs, subjects with visible calcifications have higher prevalence of high blood pressure medication and DM (p?<?0.01).

Conclusion

While the presence of a calcified mass on a cephalometric radiograph is not diagnostic of atherosclerosis, this information indicates some cardiovascular risk.     

Lack of Effect of Nitrates on Exercise Stress Test Results in Patients with Microvascular Angina

Purpose

To assess the effects of short-acting nitrates on exercise stress test (EST) results and the relation between EST results and coronary blood flow (CBF) response to nitrates in patients with microvascular angina (MVA).

Methods

We completed 2 symptom/sign limited ESTs on 2 separate days, in a random sequence and in pharmacological washout, in 29 MVA patients and in 24 patients with obstructive coronary artery disease (CAD): one EST was performed without any intervention (control EST, C-EST), and the other after sublingual isosorbide dinitrate, 5 mg (nitrate EST, N-EST). CBF response to nitroglycerin (25 μg) was assessed in the left anterior descending coronary artery by transthoracic Doppler-echocardiography.

Results

At C-EST. ST-segment depression ≥1 mm (STD) was induced in 26 (90 %) and 23 (96 %) MVA and CAD patients, respectively (p?=?0.42), whereas at N-EST, STD was induced in 25 (86 %) and 14 (56 %) MVA and CAD patients, respectively (p?=?0.01). Time and rate pressure product at 1 mm STD increased during N-EST, compared to C-EST, in CAD patients (475?±?115 vs. 365?±?146 s, p?<?0.001; and 23511?±?4352 vs. 20583?±?6234 bpm?mmHg, respectively, p?=?0.01), but not in MVA patients (308?±?160 vs. 284?±?136 s; p?=?0.19; and 21290?±?5438 vs. 20818?±?4286 bpm?mmHg, respectively, p?=?0.35). In MVA patients, a significant correlation was found between heart rate at STD during N-EST and CBF response to nitroglycerin (r?=?0.40, p?=?0.04).

Conclusions

Short-acting nitrates improve EST results in CAD, but not in MVA patients. In MVA patients a lower nitrate-dependent coronary microvascular dilation may contribute to the lack of effects of nitrates on EST results.     

Does bariatric surgery change olfactory perception? Results of the early postoperative course

Purpose

Changes of food preference toward foods with low caloric density have been demonstrated after bariatric surgery and may contribute to sustained body weight loss. It has been hypothesized that olfactory perception as an integral part of food selection might be altered after bariatric surgery.

Methods

Sniffin’ Sticks® were used to investigate the olfactory perception of morbidly obese patients undergoing either Roux-en-Y gastric bypass (RYGB, n?=?15) or sleeve gastrectomy (SG, n?=?15) before 1, 6, 12, and 24 weeks after surgery. Obese patients without surgical intervention served as controls (CG, n?=?12). Results are presented using the testing odor threshold, discrimination, and identification score (TDI; higher scores indicate better olfactory perception). Body weight loss was recorded.

Results

Initial BMI of the SG group (56.04?±?7.096 kg m^?2) was higher compared to the BMI of the RYGB (48.71?±?6.49 kg m^?2) and CG (50.35?±?6.78 kg m^?2); p?=?0.011. Body weight loss among the surgical groups was not different (p?=?0.011) while controls did not lose weight. Mean baseline TDI scores were significantly lower in the SG group 27.1?±?3.9 vs. 32.6?±?3.6 (RYGB) and 32.1?±?5.3 (CG), respectively, whereas there were after 24 weeks no changes in RYGB and CG patients; the TDI score in the SG group increased significantly to 31.1?±?3.5 (p?<?0.01).

Conclusions

Our data suggest that a substantial body weight loss per se does not affect olfactory perception. However, our results point towards improved olfactory perception after sleeve gastrectomy but not Roux-en-Y gastric bypass.     

Tetramethylpyrazine Attenuates Atherosclerosis Development and Protects Endothelial Cells from ox-LDL

Purpose

We assessed whether tetramethylpyrazine (TMP), an active ingredient of Ligusticum wallichii Franchat, attenuates atherosclerosis (AS) development in rabbits and protects endothelial cells injured by ox-LDL.

Methods

In vivo, rabbits subjected to atherosclerosis were treated with TMP (75 and 150 mg/kg) by oral gavage for 12 weeks. In vitro, rat aortic endothelial cells (RAECs) were stimulated by ox-LDL.

Results

TMP treatment with 75 and 150 mg/kg significantly reduced the relative atherosclerosis area ratio in the aorta (0.41?±?0.042, 0.27?±?0.047 vs. 0.66?±?0.058 in AS), the ratio of intimal/medial thickness (0.54?±?0.09, 0.39?±?0.07 vs. 1.1?±?0.3 in AS) and the number of monocytes in intimal (10.1?±?2.8, 8.2?±?2.0 vs. 14.1?±?4.9 counts/mm² in AS). TMP also decreased levels of TC (15?±?4.2 to 6.1?±?1.2 mmol/L), TG (1.8?±?0.3 to 1.08?±?0.24 mmol/L), LDL-C (20.1?±?4.3 to 10.2?±?1.6 mmol/L) and increased HDL-C levels (0.40?±?0.08 to 0.85?±?0.17 mmol/L) in atherosclerosis rabbit plasma. TMP decreased the MCP-1 (187.3?±?38.4 to 86.1?±?17.2 pg/ml) and ICAM-1 (350.6?±?43.7 to 260.6?±?46.1 pg/ml) levels in plasma and inhibited LOX-1 expression in the rabbit aortas. Moreover, our in vitro study revealed that TMP suppressed monocyte adhesion to RAECs, inhibited RAEC migration, and down-regulated MCP-1 and ICAM-1 expression in ox-LDL-injured RAECs. Likewise, TMP inhibited LOX-1 and 5-LOX expression, and prevented nuclear accumulation of RelA/p65 and IκB degradation in ox-LDL-injured RAECs. Furthermore, TMP suppressed ox-LDL-induced activations of p-ERK, p-p38, and p-JNK MAPK.

Conclusion

TMP produces a tangible protection in atherosclerosis and endothelial cells. TMP might be a potential protective agent for atherosclerosis.     

The effect of a single 2 h bout of aerobic exercise on ectopic lipids in skeletal muscle,liver and the myocardium

Aims/hypothesis

Ectopic lipids are fuel stores in non-adipose tissues (skeletal muscle [intramyocellular lipids; IMCL], liver [intrahepatocellular lipids; IHCL] and heart [intracardiomyocellular lipids; ICCL]). IMCL can be depleted by physical activity. Preliminary data suggest that aerobic exercise increases IHCL. Data on exercise-induced changes on ICCL is scarce. Increased IMCL and IHCL have been related to insulin resistance in skeletal muscles and liver, whereas this has not been documented in the heart. The aim of this study was to assess the acute effect of aerobic exercise on the flexibility of IMCL, IHCL and ICCL in insulin-sensitive participants in relation to fat availability, insulin sensitivity and exercise capacity.

Methods

Healthy physically active men were included. $ \overset{\cdot }{V}{\mathrm{O}}_{2 \max } $ was assessed by spiroergometry and insulin sensitivity was calculated using the HOMA index. Visceral and subcutaneous fat were separately quantified by MRI. Following a standardised dietary fat load over 3 days, IMCL, IHCL and ICCL were measured using MR spectroscopy before and after a 2 h exercise session at 50–60% of $ \overset{\cdot }{V}{\mathrm{O}}_{2 \max } $ . Metabolites were measured during exercise.

Results

Ten men (age 28.9?±?6.4 years, mean ± SD; $ \overset{\cdot }{V}{\mathrm{O}}_{2 \max } $ 56.3?±?6.4 ml kg^?1 min^?1; BMI 22.75?±?1.4 kg/m²) were recruited. A 2 h exercise session resulted in a significant decrease in IMCL (?17?±?22%, p?=?0.008) and ICCL (?17?±?14%, p?=?0.002) and increase in IHCL (42?±?29%, p?=?0.004). No significant correlations were found between the relative changes in ectopic lipids, fat availability, insulin sensitivity, exercise capacity or changes of metabolites during exercise.

Conclusions/interpretation

In this group, physical exercise decreased ICCL and IMCL but increased IHCL. Fat availability, insulin sensitivity, exercise capacity and metabolites during exercise are not the only factors affecting ectopic lipids during exercise.