Evaluation of exercise capacity with cardiopulmonary exercise testing and BNP levels in adult patients with single or systemic right ventricles

Introduction

The aim of the study was to evaluate exercise capacity using cardiopulmonary exercise test (CpET) and serum B-type natriuretic peptide (BNP) levels in patients with single or systemic right ventricles.

Material and methods

The study group included 40 patients (16 males) – 17 with transposition of the great arteries after Senning operation, 13 with corrected transposition of the great arteries and 10 with single ventricle after Fontan operation, aged 19–55 years (mean 28.8 ±9.5 years). The control group included 22 healthy individuals (10 males) aged 23–49 years (mean 30.6 ±6.1 years).

Results

The majority of patients reported good exercise tolerance – accordingly 27 were classified in NYHA class I (67.5%), 12 (30%) in class II, and only 1 (0.5%) in class III. Cardiopulmonary exercise test revealed significantly lower exercise capacity in study patients than in control subjects. In the study vs. control group VO_2max was 21.7 ±5.9 vs. 34.2 ±7.4 ml/kg/min (p = 0.00001), maximum heart rate at peak exercise (HRmax) 152.5 ±32.3 vs. 187.2 ±15.6 bpm (p = 0.00001), VE/VCO₂ slope 34.8 ±7.1 vs. 25.7 ±3.2 (p = 0.00001), forced vital capacity (FVC) 3.7 ±0.9l vs. 4.6 ±0.3 (p = 0.03), forced expiratory volume in 1 s (FEV₁) 3.0 ±0.7 vs. 3.7 ±0.9l (p = 0.0002) respectively. Serum BNP concentrations were higher in study patients than in control subjects; 71.8 ±74.4 vs. 10.7 ±8.1 (pg/ml) respectively (p = 0.00001). No significant correlations between BNP levels and CpET parameters were found.

Conclusions

Patients with a morphological right ventricle serving the systemic circulation and those with common ventricle physiology after Fontan operation show markedly reduced exercise capacity. They are also characterized by higher serum BNP concentrations, which do not however correlate with CpET parameters.     

Calcium-phosphate metabolism parameters and erythrocyte Ca2+ concentration in autosomal dominant polycystic kidney disease patients with normal renal function

Introduction

The aim of this study was to assess calcium-phosphate metabolism of autosomal dominant polycystic kidney disease (ADPKD) patients with a special consideration to the following serum parameters: calcium (Ca²⁺), inorganic phosphate (Pi), parathyroid hormone (PTH) and intracellular erythrocyte calcium ([Ca²⁺]_i) concentrations.

Material and methods

The study included 49 adult ADPKD patients (19 males, 30 females) aged 36 ±11 years with normal renal function and no diagnosis of diabetes as well as 50 healthy controls (22 males, 28 females) matched for age and gender. Serum concentrations of sodium (Na⁺), potassium (K⁺) and magnesium (Mg²⁺) ions and Pi were determined with an indirect ion-selective method, while Ca2+ concentration was measured with a direct ion-selective method. The PTH was detected using a radioimmunometric method. [Ca²⁺]_i concentration was determined with the Ca²⁺ sensitive fluorescent dye Fura-2 method.

Results

In the ADPKD group, when compared to controls, the following concentrations were significantly higher: serum Ca²⁺ (1.18 ±0.06 mmol/l vs. 1.15 ±0.06 mmol/l, p = 0.0085), [Ca²⁺]_i (146.9 ±110.0 nmol/l vs. 96.5 ±52.7 nmol/l, p = 0.0075), serum Na+ (139.4 ±2.7 mmol/l vs. 138.5 ±2.1 mmol/l, p = 0.060, borderline significance), and PTH (15.5 ±6.8 pg/ml vs. 13.6 ±5.3 pg/ml, p = 0.066, borderline significance), while serum Mg²⁺ was significantly lower (0.81 ±0.09 mmol/l vs. 0.85 ±0.05 mmol/l, p = 0.021). In the ADPKD group we observed significant negative correlations of PTH with Ca²⁺ serum concentrations (Rs = –0.32, p = 0.025) and with estimated glomerular filtration rate (Rs = –0.31, p = 0.033).

Conclusions

The erythrocyte Ca²⁺ concentration is elevated in ADPKD patients with normal renal function. It may result from a dysfunction of mutated polycystins which can affect various aspects of electrolyte metabolism.     

Peripheral blood lymphocyte subsets (CD4+, CD8+ T cells), leptin level and weight loss after laparoscopic greater curvature plication in morbidly obese patients

Introduction

The aim of the study was to detect the effect of laparoscopic greater curvature plication (LGCP) on peripheral blood lymphocyte subsets (helper and cytotoxic T lymphocytes – CD4+ and CD8+ T cells respectively), leptin level and weight loss in morbidly obese patients.

Material and methods

Morbidly obese patients (n = 20, age range: 25–50 years, body mass index (BMI) range: 37–45 kg/m²) who underwent LGCP were enrolled in a prospective study to determine the percentages of their peripheral blood T cells (CD4+ and CD8+) before and 4 months postoperatively using flow cytometry. Also, the level of their leptin before and 4 months postoperatively was established using enzyme-linked immunosorbent assay (ELISA). The data are expressed as the percentage of total lymphocytes ± the standard error of the mean.

Results

A decrease in the BMI and loss of weight (31.20 ±1.2%) were confirmed 4 months postoperatively since BMI was 44.71 ±4.3 (range: 37–45) kg/m² preoperatively, and decreased to 31.80 ±1.1 (range: 24–33) kg/m² after surgery. The mean percentage of CD4+ and CD8+ T lymphocytes significantly decreased postoperatively (38.2 ±1.5 before and 29.3 ±2.6 after operation for CD4+, 17.3 ±1.8 preoperatively and 9.5 ±1.7 postoperatively for CD8+, p < 0.05). The mean leptin level was 43.01 ±22.01 preoperatively while postoperatively it was 24.8 ±11.1 (p < 0.05), so the leptin level substantially decreased compared to its preoperative values.

Conclusions

This study found that weight loss after LGCP in morbidly obese patients led to decreases in levels of leptin and circulating immune cells compared to their preoperative values.     

Early hemodynamic response to the tilt test in patients with syncope

Introduction

Our aim was to evaluate the differences in the early hemodynamic response to the tilt test (HUTT) in patients with and without syncope using impedance cardiography (ICG).

Material and methods

One hundred twenty-six patients (72 female/48 male; 37 ±17 years) were divided into a group with syncope (HUTT(+), n = 45 patients) and a group without syncope (HUTT(–), n = 81 patients). ECG and ICG signals were continuously recorded during the whole examination, allowing the calculation of heart rate (HR), stroke volume (SV), and cardiac output (CO) for every beat. The hemodynamic parameters (averaged over 1 min) were analyzed at the following points of the HUTT: the last minute of resting, the period immediately after the tilt (0 min), 1 min and 5 min after the maneuver. The absolute changes of HR, SV and CO were calculated for 0, 1, and 5 min after the maneuver in relation to the values at rest (ΔHR, ΔSV, ΔCO). Also, the percentage changes were calculated (HRi, SVi, COi).

Results

There were no differences between the groups in absolute and percentage changes of hemodynamic parameters immediately after and 1 min after tilting. Significant differences between the HUTT(+) and HUTT(–) groups were observed in the 5^th min of tilting: for ΔSV (–27.2 ±21.2 ml vs. –9.7 ±27.2 ml; p = 0.03), ΔCO (–1.78 ±1.62 l/min vs. –0.34 ±2.48 l/min; p = 0.032), COi (–30 ±28% vs. –0.2 ±58%; p = 0.034).

Conclusions

In the 5^th min the decrease of hemodynamic parameters (ΔSV, ΔCO, COi) was significantly more pronounced in HUTT(+) patients in comparison to the HUTT(–) group.     

Circulating visfatin level and visfatin/insulin ratio in obese women with metabolic syndrome

Introduction

Visfatin is an adipokine secreted by visceral adipose tissue with insulin-mimetic properties. Higher circulating visfatin levels were reported in type 2 diabetes. The aim of this study was to analyse circulating visfatin and insulin levels and the visfatin/insulin ratio in obese women with and without metabolic syndrome (MetS).

Material and methods

The study involved 92 obese women. Subjects were diagnosed with MetS according to IDF 2005 criteria. The MetS group consisted of 71 subjects (age: 52.8 ±9.4 years, body mass index [BMI]: 39.1 ±5.6 kg/m², waist circumference: 109.6 ±11.4 cm and fat mass: 52.0 ±12.8 kg) while the non-MetS group consisted of 21 subjects (age: 51.7 ±9.5 years, BMI: 36.3 ±5.2 kg/m², waist circumference: 104.7 ±11.0 cm and fat mass: 45.2 ±10.7 kg). In addition to anthropometric measurements and assessment of serum glucose and lipids, plasma concentrations of visfatin were estimated by enzyme-linked immunosorbent assay (ELISA) and of insulin by radioimmunoassay (RIA). Homeostatic model assessment insulin resistance (HOMA-IR) and visfatin/insulin ratio were calculated.

Results

In the MetS group significantly higher (p < 0.01) plasma concentrations of insulin and HOMA-IR values but similar visfatin levels were observed than in the non-MetS group. As a consequence of the significantly higher plasma insulin concentration the visfatin/insulin ratio was significantly lower in the MetS group (p < 0.05). The visfatin/insulin ratio correlated inversely with anthropometric parameters such as body mass, BMI, body fat and waist circumference (r = –0.41, p = 0.0003; r = –0.42, p = 0.0002; r = –0.29, p = 0.01; r = –0.23, p = 0.04, respectively).

Conclusions

We conclude that the visfatin/insulin ratio declining with increasing visceral obesity may predispose to the development of insulin resistance.     

Prognostic factors of mid-term clinical outcome in congestive heart failure patients discharged after acute decompensation

Introduction

Risk stratification in congestive heart failure (CHF) patients is based on a variety of clinical and laboratory variables. We analysed renal function, BNP, water composition, echocardiographic and functional determinations in predicting mid-term outcome in CHF patients discharged after decompensation.

Material and methods

All subjects with NYHA class II-IV were enrolled at hospital discharge. NYHA class, BNP, water body composition, non-invasive cardiac output and echocardiogram were analysed. Death, cardiac transplantation and hospital readmission for CHF were scheduled.

Results

Two-hundred and thirty-seven (64.5% males, age 71.1±10.1) patients were discharged after obtaining normal hydration; left ventricular ejection fraction (LVEF) was 43.2±16.2%, cardiac output was 3.8±1.1 l/min and BNP at discharge resulted 401.3±501.7 pg/ml. During the 14-month follow-up 15 patients (6.3%) died, 1 (0.4%) underwent cardiac transplantation and 18 (7.6%) were readmitted for CHF (event group); in 203 (85.6%) no events were observed (no-event group). Higher NYHA class (2.1±0.7 vs. 1.9±0.4, p=0.01), BNP at discharge (750.2±527.3 pg/ml vs. 340.7±474.3 pg/ml, p=0.002) and impaired LVEF (33.7±15.7% vs. 44.5±15.8%, p=0.0001) and creatinine (1.7±0.6 vs. 1.2±0.8 mg/dl, p=0.004) were noticed in the event group. At multivariate Cox analysis LVEF (p=0.0009), plasma creatinine (p=0.006) and BNP at discharge (p=0.001) were associated with adverse mid-term outcome. Kaplan-Meier survival curves demonstrated that adding cut-off points for creatinine 1.5 mg/dl and discharged BNP of 250 pg/ml discriminated significantly prognosis (p=0.0001; log rank 21.09).

Conclusions

In predicting mid-term clinical prognosis in CHF patients discharged after acute decompensation, BNP at discharge ≥ 250 pg/ml added with plasma creatinine > 1.5 mg/dl are strong adverse predictors.     

Influence of home-based telemonitored Nordic walking training on autonomic nervous system balance in heart failure patients

Introduction

Rehabilitation positively affects the modulation of the autonomic nervous system (ANS). There are no papers evaluating the influence of Nordic walking training (NW) on ANS activity among chronic heart failure (CHF) patients. The aim of study was to assess the influence of NW on ANS activity measured by heart rate variability (HRV) and heart rate turbulence (HRT) in CHF patients and its correlation with physical capacity improvement measured by peak oxygen consumption (peak VO₂ [ml/kg/min]) in the cardiopulmonary exercise treadmill test (CPET).

Material and methods

The study group comprised 111 CHF patients (NYHA class II–III; ejection fraction (EF) ≤ 40%). Patients were randomized (2 : 1) to 8-week NW (five times weekly) at 40–70% of maximal heart rate (training group – TG) (n = 77), or to a control group (CG) (n = 34). The effectiveness of NW was assessed by changes (delta (Δ)) in peak VO₂, HRV and HRT as a result of comparing these parameters from the beginning and the end of the programme.

Results

Eventually, 36 TG patients and 15 CG patients were eligible for HRV and HRT analysis. In the TG low/high frequency ratio (LF/HF) decreased (1.9 ±1.11 vs. 1.7 ±0.63, p = 0.0001) and peak VO₂ increased (16.98 ±4.02 vs. 19.70 ±4.36 ml/kg/min, p < 0.0001). Favourable results in CG were not observed. The differences between TG and CG were significant: Δpeak VO₂ (p = 0.0081); ΔLF/HF (p = 0.0038). An inverse correlation was found between the decrease in ΔLF/HF and the increase in Δpeak VO₂ (R = –0.3830, p = 0.0211) only in the TG. Heart rate variability did not change significantly in either group.

Conclusions

Nordic walking positively affects the parasympathetic-sympathetic balance in CHF patients, which correlates with the improvement in Δpeak VO₂. No significant influence of NW on HRT was observed.     

Heart rate turbulence in patients with poorly controlled diabetes mellitus type 2

Introduction

Cardiac autonomic neuropathy (CAN) causes substantial morbidity and increased mortality in patients with diabetes mellitus (DM). Besides heart rate variability (HRV), heart rate turbulence (HRT) is an important method of assessment of cardiac autonomic regulation. The aim of the study was to assess the correlation between HRT and diabetic control.

Material and methods

Fifty-nine patients met the inclusion criteria – 38 males and 21 females, age 64.4 ±7.6. The patients included had inadequately controlled DM type 2 defined as glycated haemoglobin (HbA_1c) > 9% (mean 11.8 ±2.7%). In all patients, intensive insulin treatment had been applied for 6 months. After 6 months, HbA_1c was measured. ECG Holter monitoring was performed before and after insulin treatment to evaluate the time domain HRV and HRT parameters (turbulence onset (TO) and turbulence slope (TS)).

Results

After 6 months of intensive insulin treatment, HbA_1c concentrations ranged from 6.3% (45 mmol/mol) to 11.2% (99 mmol/mol) – mean 8.5 ±3.8% (69 ±18 mmol/mol). Significant improvement of TO, TS and SDNN was observed. The TO and TS significantly correlated with HbA_1c (r = 0.35, p = 0.006 and r = –0.31, p = 0.02 respectively). Among analyzed HRV time domain parameters such as SDNN, rMSSD and pNN50, only SDNN correlated with HbA_1c (r = –0.41, p = 0.001). It was further concluded that intensive insulin therapy led to better glycemic control, resulting in improvement of HRT.

Conclusions

Heart rate turbulence may be useful in monitoring changes of the autonomic nervous system functions in patients with DM, similarly to HRV parameters.     

Serum creatine phosphokinase as predictor of intermediate syndrome in organophosphorus poisoning

Background:

Organophosphorus (OP) compounds are commonly used pesticides. In OP poisoning, intermediate syndrome (IMS) manifests between the end of the acute cholinergic crisis and delayed neuropathy. Respiratory paralysis in IMS, if identified early can reduce the need for ventilator support, morbidity, and mortality. Serum creatine phosphokinase (CPK) is elevated in IMS. The objectives of our study were to measure serum CPK level, correlate CPK levels with severity of poisoning and estimate atropine dose used.

Materials and Methods:

A prospective, observational study was conducted for 1-year. Patients diagnosed with OP poisoning were included. Demographic characteristics, type of poison, time since poisoning, Peradeniya Organophosphorus Poisoning (POP) score, serum pseudocholinesterase, CPK levels, atropine dose, and outcome of treatment were documented.

Results:

Seventy-five patients were recruited of which 57% and 43% were males and females, respectively, with a mean age of 31.48 ± 11.76 years. The most common OP compound was chlorpyriphos followed by triazophos and methylparathion. The time required to reach hospital was 181.26 ± 89.53 min. About 73.3% and 26.7% of patients had mild and moderate poisoning, respectively, as per POP scale. Pseudocholinesterase level was 364 (205–2168) IU. The amount of atropine used was 190.66 ± 78.83 mg. Serial serum CPK values were 279.72 ± 350.21 IU, 389.78 ± 376.33 IU and 163.13 ± 155.15 IU at admission, 48 h, and 96 h after admission, respectively. A weak positive correlation between serum CPK levels and severity of poisoning (r = 0.352) was observed. All patients recovered completely within 10.69 ± 5.57 days. Three patients developed IMS, and their serial CPK levels were 1837.33 ± 243.19 IU/L, 1935 ± 97.41 IU/L, and 714.66 ± 394.82 IU/L; and recovered in 17 ± 5.6 days.

Conclusion:

Increased serum CPK levels at 48 h after poisoning was observed in all the patients, but three patients had more than 1500 IU/L, who manifested with IMS. Early diagnosis of IMS by serial estimation of CPK may help in timely intervention and reduce further life-threatening complications.     

Dynamic Valgus Alignment and Functional Strength in Males and Females During Maturation

Context:

Sex differences in dynamic measures have been established in physically mature populations. Gaining information on maturation''s effect on dynamic performance measures implicated in injury risk may enable us to better design injury prevention programs.

Objective:

To examine sex differences in dynamic valgus alignment and triple-hop distance measures across maturational stages in males and females. A secondary purpose was to determine if a field test of strength and power predicts dynamic valgus alignment.

Design:

Cross-sectional study.

Setting:

Laboratory.

Patients or Other Participants:

157 young athletes (78 females, 79 males) aged 9 to 18 years.

Intervention(s):

Subjects performed drop-jump landings and single-leg triple-hop tests as part of a broader injury screening.

Main Outcome Measure(s):

Maturational status was ascertained from self-report questionnaires and grouped according to Tanner stages 1 and 2 (MatGrp1), 3 and 4 (MatGrp2), and 5 (MatGrp3). Frontal-plane knee valgus displacement, which served as a measure of dynamic valgus alignment, and single-leg triple-hop distance were assessed.

Results:

Males demonstrated less dynamic valgus alignment during drop jumps in the latter maturational stages (MatGrp1  =  13.1° ± 8.7°, MatGrp2  =  9.0° ± 6.2°, MatGrp3  =  9.2° ± 9.4°), whereas females increased dynamic valgus alignment throughout maturation (MatGrp1  =  11.5° ± 6.9°, MatGrp2  =  12.8° ± 8.8°, MatGrp3  =  15.5° ± 8.7°). Thus, in the more mature groups, males had less dynamic valgus alignment than females. Both males (MatGrp1  =  393.5 ± 63.7 cm, MatGrp2  =  491.8 ± 95.1 cm, MatGrp3  =  559.3 ± 76.3 cm) and females (MatGrp1  =  360.3 ± 37.1 cm, MatGrp2  =  380.1 ± 44.3 cm, MatGrp3  =  440.0 ± 66.2 cm) increased triple-hop distance, but males increased more. Within each subgroup of MatGrp and sex, triple-hop distance had no predictive ability for dynamic malalignment.

Conclusions:

When dynamic valgus alignment and strength were assessed, sex and maturational status displayed an interaction. However, functional strength did not predict degree of dynamic valgus alignment.     

Differences in metabolic parameters and cardiovascular risk between American Diabetes Association and World Health Organization definition of impaired fasting glucose in European Caucasian subjects: a cross-sectional study

Introduction

The American Diabetes Association (ADA) defines impaired fasting glucose (IFG) as fasting plasma glucose concentration of 100–125 mg/dl, whereas the World Health Organization (WHO) and the International Diabetes Federation (IDF) define IFG as fasting plasma glucose levels of 110–125 mg/dl. We identified differences in metabolic parameters and cardiovascular disease (CVD) risk according to the ADA or WHO/IDF definition of IFG.

Material and methods

Healthy drug-naive Caucasian (Greek) subjects (n = 396; age 55 ±12 years) participated in this cross-sectional study.

Results

Diastolic blood pressure (DBP) and uric acid levels were higher in the subjects with glucose 100–109 mg/dl compared with those with glucose < 100 mg/dl (87 ±9 mm Hg vs. 84 ±11 mm Hg, p = 0.004 for DBP, 5.6 ±1.5 mg/dl vs. 5.0 ±1.0 mg/dl, p = 0.002 for uric acid), whereas triglyceride levels were lower in subjects with glucose 100–109 mg/dl compared with those with glucose ≥ 110 mg/dl (169 mg/dl (interquartile range (IQR) = 102–186) vs. 186 mg/dl (IQR = 115–242), p = 0.002). Only the ADA definition recognized subjects with significantly increased 10-year CVD risk estimation (SCORE risk calculation) compared with their respective controls (5.4% (IQR = 0.9–7.3) vs. 4.1% (IQR = 0.7–5.8), p = 0.002).

Conclusions

The ADA IFG definition recognized more subjects with significantly increased CVD risk (SCORE model) compared with the WHO/IDF definition.     

Left atrial mechanical functions in chronic primary mitral regurgitation patients: a velocity vector imaging-based study

Introduction

Assessment of the left atrium (LA) mechanical function provides further information on the level of cardiac compensation. We aimed to evaluate LA function using a strain imaging method: velocity vector imaging (VVI) in chronic primary mitral regurgitation (MR).

Material and methods

We recruited 48 patients with chronic, isolated, moderate to severe MR (54.70 ±15.35 years and 56% male) and 30 age- and sex-matched healthy controls (56.52 ±15.95 years and 56% male). The LA volumes during reservoir (RV), conduit (CV) and contractile phases (AV) were measured. Global strain (S), systolic strain rate (SRs), early diastolic (ESRd) and late diastolic strain rate (LSRd) were calculated.

Results

LA RV (50 ±18.7 to 37.9 ±5.9; p = 0.0001), CV (43.1 ±29 to 21 ±2.56; p = 0.0001), and AV (17.9 ±13.5 to 10.9 ±1.9; p = 0.006) were increased in MR patients. The LA reservoir phase strain was 16.2 ±8.1% in the MR group and 51.1 ±5.7% in the control group (p = 0.0001). The LA SRs (1.01 ±0.52 s^–1 for MR and 2.1 ±0.22 s^–1 for controls; p = 0.0001), LA ESRd (0.83 ±0.34 s^–1 for MR and 2.26 ±0.17 s^–1 for controls; p = 0.0001) and LA LSRd (0.76 ±0.24 s^–1 for MR and 2.2 ±0.26 s^–1 for controls; p = 0.0001) were impaired in MR patients.

Conclusions

The LA deformation indices may be used as adjunctive parameters to determine LA dysfunction in chronic primary MR.     

Prognostic value of tissue factor in patients with abdominal aortic and iliac arterial aneurysms – preliminary study

Introduction

The decision on the time and choice of strategy of treatment of abdominal aortic aneurysm must be especially carefully balanced. The aim of the study was to evaluate the tissue factor (TF) plasma level as a potential factor useful in anticipation of abdominal aortic aneurysm and/or iliac arterial aneurysm via comparison of plasma TF level in patients with ruptured and non-ruptured aneurysms.

Material and methods

The study included 33 patients with aneurysm (17 operated on electively because of non-ruptured aneurysm and 16 operated on emergently due to ruptured aneurysm), 33 claudicant patients with atherosclerosis of the abdominal aorta and iliac arteries with normal diameter of arteries, and 30 healthy controls. Plasma TF level was assessed by ELISA method using the IMUBIND Tissue Factor ELISA Kit (American Diagnostica Inc.).

Results

The study showed an increased TF level in patients with aneurysm (134 ±54 pg/ml) and in patients with atherosclerosis without concomitant aneurysm (91 ±30 pg/ml) in comparison with the control group (62 ±20 pg/ml), respectively p < 0.001 and p = 0.008. A significantly higher TF plasma level was observed in patients with ruptured abdominal aortic aneurysms (160 ±57 pg/ml) as compared to patients with non-ruptured aortic aneurysms (109 ±39 pg/ml) or peripheral arterial occlusive disease (91 ±30 pg/ml), respectively p < 0.001 and p < 0.001. The difference in TF level between the group with non-ruptured aortic aneurysms (109 ±39 pg/ml) and the patients with atherosclerosis without aneurysm (91 ±30 pg/ml) was not statistically significant.

Conclusions

No difference in TF level between patients with non-ruptured AAA/IAA and patients with aortic and iliac atherosclerosis without aneurysm indicates that an increased TF plasma level is not specific for any of the above-mentioned vascular pathologies.     

Thrombin inhibition by dabigatran attenuates atherosclerosis in ApoE deficient mice

Introduction

Atherosclerosis is a chronic inflammatory disease characterized by endothelial cell damage, infiltration, proliferation and accumulation of macrophages, lymphocytes and transformed vascular smooth muscle cells within the vascular wall and procoagulation processes involving activation of plasmatic coagulation events and platelets. Numerous studies suggested a close interaction between thrombin action and atherogenesis, but possibly underlying mechanisms are multiple and specific treatment options were missing until now.

Material and methods

Atherosclerosis prone 12 weeks old ApoE^–/– mice were fed a cholesterol rich diet for 4 weeks and were concomitantly treated orally with placebo or the thrombin inhibitor dabigatran (1.2 g/kg/day).

Results

The thrombin time (HEMOCLOT^®) was significant extended in dabigatran treated animals. Vascular oxidative stress was significantly reduced during thrombin inhibition, as assessed by L012 chemiluminescence in aortic segments (212 ±84 vs. 69 ±21 RLU/s/mg dry weight, p = 0.048). Organ chamber experiments of isolated aortic rings showed that dabigatran treatment significantly improved endothelium-derived vasorelaxation (p < 0.001). Dabigatran treated mice developed less atherosclerotic lesions (6.2 ±0.2% vs. 9 ±1.1%, p = 0.037) and showed less infiltration of atherosclerotic lesions with macrophages (2.59 ±0.3% vs. 5.14 ±0.7%, p = 0.0046), as determined by systematic histological and immunohistological analyses of the aortic root. Blood pressure, body weight and food intake were not altered by the treatment.

Conclusions

The thrombin inhibitor dabigatran reduces vascular oxidative stress and inflammation, improves endothelial function and decreases atherosclerosis in mice.     

The effects of botulinum toxin type A on improvement and dynamic spastic equinus correction in children with cerebral palsy – preliminary results

Introduction

We evaluated the effects of botulinum toxin type A (BTA) with physical therapy on dynamic foot equinus correction and higher motor functional outcome in children with spastic type of cerebral palsy (CP).

Material and methods

Ankle joint active and passive movement, gastrocnemial muscle spasticity levels (Modified Ashworth Scale (MAS)), and higher motor functional status (Gross Motor Function Classification System (GMFCS) and Gross Motor Function Measure (GMFM) (GMFM-D – standing and GMFM-E – walking) were assessed before treatment and 3, 8, 16 weeks and 6 months after BTA administration in 12 children.

Results

There was a significant improvement of active (initial – (–)13.07 ±5.78; 6 months – (–)10.64 ±4.77; p < 0.001) and passive (initial – 4.21 ±2.29; 6 months – 4.71 ±2.16; p < 0.05) ankle joint foot dorsiflexion. GMFM-D and GMFM-E were significantly higher after 3, 8, 16 weeks (p < 0.001) and GMFM-D after 6 months (p < 0.001).

Conclusions

Botulinum toxin type A administration and physical therapy in patients with spastic CP improves the motion range of dynamic foot equinus after 3 weeks and higher motor functional outcome (standing and walking).     

Concomitant administration of simvastatin with ivabradine in contrast to metoprolol intensifies slowing of heart rate in normo- and hypercholesterolemic rats

Introduction

β-Blockers play a significant role in therapeutic heart rate (HR) management and angina control. In patients who are unable to tolerate β-blockers ivabradine could be particularly useful. The aim of the study was to establish whether concomitant administration of simvastatin with ivabradine or metoprolol had any effect on rat HR and blood pressure (BP).

Material and methods

The experiments were performed in hyper- and normocholesterolemic outbred Wistar rats. Animals were divided into 2 groups: receiving during 4 weeks normal diet (normocholesterolemic rats) or diet with 5% cholesterol and 2.5% cholic acid (hypercholesterolemic rats). Then rats received placebo (0.1% methylcellulose), 2) metoprolol 30 mg/kg bw; 3) ivabradine 10 mg/kg bw; 4) simvastatin 10 mg/kg bw; 5) simvastatin 10 mg/kg bw + metoprolol 30 mg/kg bw; 6) simvastatin 10 mg/kg bw + ivabradine 10 mg/kg bw. Drugs were given during a 4-week period. HR and BP measure were provided by an Isotec pressure transducer connected to a direct current bridge amplifier. For the further lipid profile examination, 0.25 ml of blood samples were taken.

Results

After administration of ivabradine with simvastatin to normocholesterolemic and hypercholesterolemic rats the mean HR was significantly reduced as compared to rats receiving simvastatin (312.0 ±30.2 min⁻¹ vs. 430.7 ±27.8 min⁻¹, p<0.05); (329.8 ±24.2 min⁻¹ vs. 420.5 ±9.2 min⁻¹, p<0.05) or ivabradine alone (312.0 ±30.2 min⁻¹ vs. 350.2 ±16.0 min⁻¹, p<0.05); (329.8 ±24.2 min⁻¹ vs. 363.0 ±21.7 min⁻¹, p<0.05).

Conclusions

Concomitant administration of simvastatin with ivabradine intensified slowing of HR, although it did not influence BP in normo-and hypercholesterolemic rats. Statin-induced intensification of HR deceleration after metoprolol administration was not observed.     

Total IgE plasma levels vary according to gender and age in Brazilian patients with allergic rhinitis

OBJECTIVE:

Allergic rhinitis is a disease that affects the upper airways and causes inflammation of the nasal mucosa and it is mediated by IgE antibodies produced after sensitization to environmental allergens. Previous reports have indicated that this disease affects males more often than females. The objective of this study was to verify whether total IgE plasma levels vary between genders in patients suffering from allergic rhinitis.

METHODS:

A total of 171 adult patients suffering from allergic rhinitis (55 males and 116 females) were enrolled. Total IgE plasma levels were determined using commercial kits, with 140 IU/mL considered as a reference value. The mean total IgE plasma levels were compared according to gender and age.

RESULTS:

The mean age of the overall patient group with allergic rhinitis was 38.4±19.0 years and a significant difference in age was observed between genders (males: 32.2±17.8 years; females: 41.4±18.9 years; p = 0.0027). Additionally, the mean total IgE plasma levels were higher in males (413.0±143.0 IU/mL) than in females (147.9±98.0 IU/mL) (p<0.0001). These differences persisted even when males and females were stratified by age (up to or older than 20 years of age).

CONCLUSIONS:

In conclusion, total IgE plasma levels are higher in young adult males than in females suffering from allergic rhinitis. Evaluating total IgE plasma levels can be useful to identify patients at risk of allergic rhinitis in areas with low industrial pollution.     

Use of macular thickness parameters for the diagnosis of primary open-angle glaucoma

Introduction

Retinal thickness in primary open-angle glaucoma patients was determined to establish its correlation with advancement of glaucoma neuropathy.

Material and methods

One hundred ninety-four patients (371 eyes, age 30–65 years) were divided in 3 groups including 50 patients with confirmed primary open-angle glaucoma, 67 primary open-angle glaucoma-suspected patients and 77 healthy persons (control group). The retinal foveola, foveal, peri-foveal and posterior pole average thickness values were determined with an RTA analyzer. For comparison, linear cup-to-disc diameter ratio (C/D), nerve fiber index (NFI) and mean defect of the retina sensitivity (MD) were also determined.

Results

Statistically highly significant differences in the retinal thickness and glaucoma parameters between the individual groups were observed. In the peri-foveal region, the retinal thickness in glaucoma patients was only 173.0 ±11.4 µm while in the healthy patients 201.1 ±13.1 µm. In the posterior pole region, the thickness values were only 168.1 ±11.3 µm and 195.7 ±12.3 µm, respectively. A moderate correlation between retinal thickness in peri-foveal and posterior pole regions and the C/D, NFI and MD parameters was also established (Pearson coefficients below –0.351 or above 0.284).

Conclusions

The retinal thickness in the peri-foveal and posterior pole regions depends on the degree of glaucoma advancement. This original observation may be a basis for acceptance of this method as a quite new tool in glaucoma diagnosis.     

Two-dimensional speckle-tracking echocardiography assessment of left ventricular remodeling in patients after myocardial infarction and primary reperfusion

Introduction

Left ventricular remodeling (LVR) is the most prognostically important consequence of acute myocardial infarction (AMI). The aim of the study was to assess the value of speckle tracking echocardiography in the prediction of left ventricular remodeling in patients after AMI and primary coronary angioplasty (PCI).

Material and methods

Eighty-eight patients (F/M = 31/57 patients; 63.6 ±11 years old) with coronary artery disease (CAD) and successful PCI were enrolled and divided into group I with ST-elevation myocardial infarction or non-ST elevation myocardial infarction and group II with stable angina pectoris. Conventional and speckle tracking echocardiography was performed 3 days (baseline), 30 days and 90 days after PCI. Patients were divided into 2 groups based on the presence of LVR (increase of LV end-diastolic and/or end-systolic volume > 20%) at 3 months follow-up.

Results

At initial presentation, 2-chamber longitudinal strain (9.4 ±3.5% vs. –11.6 ±3.6%, p < 0.04) and 4-chamber transverse strain (10.4 ±8.2% vs. 15.6 ±8%, p < 0.003) were lower in the LVR+ group compared to the LVR– group. LV wall motion score index did not differ between the two groups. After 30 days, circumferential apical and basal strain (–15.58 ±8.9% vs. –25.53 ±8.8%, p < 0.001; –15.02 ±5.6 vs. –19.78 ±6.3, p < 0.008), radial apical strain (9.96 ±8.4% vs. 14.15 ±5.5%, p < 0.03), 4-chamber longitudinal strain (–8.7 ±5.8% vs. –13.47 ±3.9%, p < 0.005), 4-chamber transverse strain (10.5 ±8.1% vs. 16.7 ±8.3%, p < 0.03), apical rotation (3.84 ±2.5° vs, 5.66 ±3.2°, p < 0.04) and torsion (6.15 ±4.1° vs. 8.98 ±4.6°, p < 0.03) were significantly decreased in the LVR+ group compared to the LVR– group. According to ROC analysis, circumferential apical strain > –15.92% (sensitivity 93%, specificity 59%, positive predictive value 90%) was the most powerful predictor of remodeling after primary PCI in AMI.

Conclusions

Our results suggest that impaired indices of LV deformation detected 3 days and 30 days after AMI may provide important predictive value in LV remodeling and patients’ follow-up.     

Anthropometric indices in relation to overweight and obesity among Turkish medical students

Introduction

The aim of this study was to present the reference anthropometric data associated with obesity for cardiovascular risk and metabolic diseases for healthy young adults in a Turkish population.

Material and methods

The study group consisted of 1163 second-year medical students (650 women, 513 men) aged 20-25 years from Çukurova University in Adana and the measurements were made using a flexible standard measuring tape. The data were collected during the period 2007-2011.

Results

From 1163 medical students, the mean values of body mass index, circumferences of waist, hip, neck, mid-arm, thigh and calf were 20.89 ±1.6 kg/m², 73.15 ±5.1 cm, 95.35 ±4.8 cm, 30.32 ±1.37 cm, 24.12 ±1.75 cm, 47.23 ±3.26 cm and 34.36 ±2.19 cm respectively in women, while the same measurements were 21.98 ±1.67 kg/m², 77.73 ±5.81 cm, 95.64 ±4.81 cm, 35.61 ±1.43 cm, 25.60 ±1.84 cm, 44.10 ±3.26 cm and 34.92 ±2.08 cm respectively in men. Moreover, waist to hip ratio, waist to height ratio and neck to height ratio were respectively 0.76, 0.44 and 0.18 in women and 0.81, 0.43 and 0.19 in men.

Conclusions

The precise knowledge of anthropometric data could be used as reference values for evaluating the body composition and fat distribution of Turkish young people.