Deficiency of cyclase-associated protein 2 promotes arrhythmias associated with connexin43 maldistribution and fibrosis

Introduction

Cyclase-associated protein 2 (CAP2) plays a major role in regulating the actin cytoskeleton. Since inactivation of CAP2 in a mouse model by a gene trap approach (Cap2^gt/gt) results in cardiomyopathy and increased mortality, we hypothesized that CAP2 has a major impact on arrhythmias and electrophysiological parameters.

Material and methods

We performed long-term-ECG recordings in transgenic CAP2 deficient mice (C57BL/6) to detect spontaneous arrhythmias. In vivo electrophysiological studies by right heart catheterization and ex vivo epicardial mapping were used to analyze electrophysiological parameters, the inducibility of arrhythmias, and conduction velocities. Expression and distribution of cardiac connexins and the amount of cardiac fibrosis were evaluated.

Results

Spontaneous ventricular arrhythmias could be detected in Cap2^gt/gt during the long-term-ECG recording. Cap2^gt/gt showed marked conduction delays at atrial and ventricular levels, including a reduced heart rate (421.0 ±40.6 bpm vs. 450.8 ±27.9 bpm; p < 0.01), and prolongations of PQ (46.3 ±4.1 ms vs. 38.6 ±6.5 ms; p < 0.01), QRS (16.2 ±2.6 ms vs. 12.6 ±1.4 ms; p < 0.01), and QTc interval (55.8 ±6.0 ms vs. 45.2 ±3.3 ms; p = 0.02) in comparison to wild type mice. The PQ prolongation was due to an infra-Hisian conduction delay (HV: 9.7 ±2.1 ms vs. 6.5 ±3.1 ms; p = 0.02). The inducibility of ventricular tachycardias during the electrophysiological studies was significantly elevated in the mutant mice (inducible animals: 88% vs. 33%; p = 0.04). Cap2^gt/gt showed more abnormal distribution of connexin43 compared to WT (23.0 ±4.7% vs. 2.9 ±0.8%; p < 0.01). Myocardial fibrosis was elevated in Cap2^gt/gt hearts (9.1 ±6.7% vs. 5.5 ±3.3%; p < 0.01).

Conclusions

Loss of CAP2 results in marked electrophysiological disturbances including impaired sinus node function, conduction delays, and susceptibility to malignant arrhythmias. Structural changes in Cap2^gt/gt are associated with alterations in myocardial connexins and fibrosis.     

Heart rate variability in children with aortic valve stenosis – a pilot study

Introduction

The aim of our prospective study was to evaluate heart rate variability (HRV) in children with aortic valve stenosis (AS) and its relationship with left ventricular mass and peak transaortic valve pressure gradient (PG).

Material and methods

Sixty children with AS divided into 3 groups according to their PG and 60 healthy controls were studied. Holter ECG monitoring with time domain HRV analysis was performed. Left ventricular mass was calculated by echocardiography.

Results

Mean values of all HRV parameters were statistically significantly lower (p < 0.001) in children with AS than in controls (respectively: SDNN 127.8 ±28.2 ms; 162.6 ±38.0 ms, SDNN day 99.7 ±26.6 ms; 134.1 ±36.1 ms, SDNN night 99.9 ±32.8 ms; 123.4 ±45.7 ms, SDANN 112.2 ±27.7 ms; 142.4 ±34.6, SDNNi 62.2 ±16.2 ms; 75.9 ±21.6, RMSSD 39.6 ±12.1 ms; 50.3 ±16.7 ms, rMSSD day 33.6 ±10.9 ms; 43.1 ±14.7 ms, rMSSD night 49.8 ±18.1 ms; 64.4 ±24.9 ms, pNN50 16.4 ±9.5%; 23.5 ±11.7%, pNN50 day 12.0 ±8.5%; 18.4 ±10.7%, pNN50 night; 26.5 ±14.8%; 36.4 ±17.4%. No significant differences between the mean values of HRV parameters in children with different PG and with and without myocardial hypertrophy were found. In children with AS and ventricular arrhythmia SDNN day was significantly lower (p < 0.05) compared to patients without arrhythmia (94.9 ±22.1 ms vs. 109.3 ±22.5 ms).

Conclusions

In children with AS the balance of the autonomic nervous systemic disturbed which manifests in an increase in sympathetic and decrease in parasympathetic activity. Transaortic valve pressure gradient and myocardial hypertrophy do not influence the HRV. The SDNN reduction during the day period may indicate the risk of ventricular arrhythmia in children with AS.     

Heart function disturbances in chronic kidney disease – echocardiographic indices

Introduction

In chronic kidney disease (CKD) patients left ventricular (LV) diastolic dysfunction occurs frequently and is associated with heart failure (HF) and higher mortality. Left ventricular systolic dysfunction is associated with coronary artery disease (CAD) and is a major determinant of prognosis. The aim of this study was to assess indices of LV diastolic dysfunction in CKD patients.

Material and methods

Study included 118 CKD patients. All patients underwent transthoracic echocardiography. Diastolic function based on E and A, E/A ratio and pulmonary vein flow velocities as well as EF%, deceleration time, RA, LA volume were assessed. In dialysis patients examination was carried out before and after dialysis.

Results

In CKD patients the stage of renal failure was associated with the significant increase in LV mass (268.0 ±47.6 CKD I/II vs. 432.7 ±122.4 CKD V/dialysis, p < 0.0001), systolic LV (37.3 ±4.5 vs. 51.2 ±8.9, p < 0.0001) and diastolic LV (CKD I–II 44.7 ±4.1 vs. CKD III 48.5 ±6.7 vs. CKD IV 47.1 ±5.6; p = 0.004) dimensions and in the size of the LA (40.4 ±2.0 vs. 41.9 ±2.7 vs. 42.3 ±3.2 vs. 44.8 ±3.1; p < 0.0001). The increase the E/E’ ratio between groups of patients (6.7 ±1.5 vs. 8.9 ±2.4 vs. 11.5 ±4.0 vs. 13.5 ±5.0; p < 0.0001) was seen in this study. The reduction in deceleration time (247.2 ±34.5 in CKD I/II vs. 197.4 ±61.0 in CKD IV, p = 0.0005) along with the decrease in estimated glomerular filtration rate was also observed in this study.

Conclusions

Early identification of factors involved is necessary to prevent this devastating process. Many indexes of contractility are used and each of them has imperfections. It seems that TVI, E, E/A and E/E’ are good instruments for the early detection of left ventricular hypertrophy and diastolic dysfunction.     

Changes in left ventricular ejection fraction and coronary flow reserve after coronary microembolization

Introduction

Although coronary microembolization (CME) is a frequent phenomenon in patients undergoing percutaneous coronary intervention, few data are available on the changes in left ventricular ejection fraction (LVEF) and coronary flow reserve (CFR) after CME.

Material and methods

In this study, six miniature swine of either sex (body weight 21-25 kg) were used to prepare a CME model. After coronary angiography, 1.2 × 10⁵ microspheres (42 µm) were selectively infused into the left anterior descending artery via an infusion catheter. Left ventricular ejection fraction was evaluated using transthoracic echocardiography; myocardial blood flow was measured using coloured microspheres; and CFR and coronary pressure were measured using Doppler and a pressure wire.

Results

Left ventricular ejection fraction was 0.77 ±0.08 at baseline, 0.69 ±0.08 at 2 h, 0.68 ±0.08 at 6 h, and 0.76 ±0.06 at 1 week (2 h vs. baseline p < 0.05; 6 h vs. baseline p < 0.01). After CME, left ventricular end systolic volume (LVESV) and end diastolic volume (LVEDV) were significant larger 1 week later (p < 0.01 for both), while CFR was significantly reduced at 6 h (1.24 ±0.10 at 6 h vs. 1.77 ±0.30 at baseline, p < 0.01) and myocardial blood flow remained unchanged. Serum ET-1 level was significantly higher only at 6 h after CME (6 h vs. baseline p < 0.05).

Conclusions

Reduction of CFR and LVEF is significant at 6 h after CME and recovers 1 week later with left ventricular dilation.     

Echocardiographic assessment of right ventricular function in responders and non-responders to cardiac resynchronization therapy

Introduction

The aim of this study was to determine whether baseline right ventricular (RV) function assessed by standard echocardiography may indicate patients who will respond to cardiac resynchronization therapy (CRT).

Material and methods

The data of 57 patients (54 men, 95%), aged 66.4 ±8.7 years with heart failure (HF) having a CRT device implanted were collected. All patients had left ventricular ejection fraction (LVEF) ≤ 35% and QRS complex duration ≥ 120 ms. Echocardiographic examination with tissue Doppler imaging techniques and complex RV evaluation were performed at baseline and three months after CRT onset.

Results

Three months after CRT implantation, patients responding to CRT, defined as a reduction of left ventricle end-systolic volume (LVESV) of at least 10% (n = 34), compared to patients with a reduction of LVESV of less than 10% (n = 23), had at baseline a smaller right atrium diameter (47.85 ±11.33 mm vs. 52.65 ±8.69 mm; p = 0.028), higher TAPSE (14.56 ±2.57 mm vs. 13.04 ±2.93 mm; p = 0.030) and lower grade of tricuspid valve regurgitation (1.82 ±0.97 vs. 2.3 ±0.88; p = 0.033).

Conclusions

This study showed that there are differences in baseline right ventricular function between responders and non-responders to CRT. Yet in our study, none of the baseline RV parameters provided any value in identifying patients who would respond to CRT.     

Potential drug-drug interactions in hospitalized patients with chronic heart failure and chronic obstructive pulmonary disease

Introduction

Polypharmacy is common in patients with chronic heart failure (HF) and/or chronic obstructive pulmonary disease (COPD), but little is known about the prevalence and significance of drug-drug interactions (DDIs). This study evaluates DDIs in hospitalized patients.

Material and methods

We retrospectively screened medical charts over a 6-month period for diagnosis of chronic HF and/or COPD. Potential DDIs were evaluated using Lexi-Interact software.

Results

Seven hundred and seventy-eight patients were included in the study (median age 75 years, 61% men). The median number of drugs on admission and discharge was 6 (interquartile range (IQR) 4–9) and 7 (IQR 5–), respectively (p = 0.10). We recorded 6.5 ±5.7 potential DDIs per patient on admission and 7.2 ±5.6 on discharge (p = 0.2). From admission to discharge, type-C and type-X potential DDIs increased (p < 0.05 for both). Type X interactions were rare (< 1%), with the combination of a β-blocker and a β₂ agonist being the most common (64%). There were significantly more type-C and type-D potential DDIs in patients with chronic HF as compared to patients with COPD (p < 0.001). Patients with concomitant chronic HF and COPD had more type-C and type-X potential DDIs when compared to those with individual disease (p < 0.005). An aldosterone antagonist and ACE inhibitor/ARB were prescribed to 3% of chronic HF patients with estimated glomerular filtration rate < 30 ml/(min × 1.73 m²).

Conclusions

The DDIs are common in patients with chronic HF and/or COPD, but only a few appear to be of clinical significance. The increase in potential DDIs from admission to discharge may reflect better guideline implementation rather than poor clinical practice.     

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.     

Heart rate variability in overactive bladder experimental model

Introduction

Two main pathophysiological concepts of overactive bladder (OAB) are postulated: the neurogenic and myogenic theories. Autonomic nervous system (ANS) dysfunction is also involved in OAB pathophysiology. The purpose of our study was to estimate ANS activity by heart rate variability (HRV) assessment in two OAB experimental models evoked by cyclophosphamide administration: acute (AOAB) and chronic (COAB) overactive ones.

Material and methods

In the AOAB model, an i.p. dose of cyclophosphamide was administered (200 mg/kg body weight) while the COAB model received 4 times the i.p. administration of cyclophosphamide (75 mg/kg body weight). In each subject, after urethane anaesthesia (1.2 g/kg body weight), 20-minute ECG recordings (PowerLab) were performed with subsequent HRV analysis.

Results

Most of the differences in time domain analysis parameters were insignificant, except those concerning SDNN and rMSSD (p < 0.05). In frequency analysis, a power decrease of all standard spectral components was revealed in both OAB groups. In AOAB, TP (1.43 ±1.21 vs. 7.92 ±6.22 in control; p < 0.05) and VLF (0.95 ±1.08 vs. 6.97 ±5.99 in control; p < 0.05) showed significant power decrease, whereas the COAB group was mostly characterized by LF (0.09 ±0.15 vs. 0.34 ±0.33 in control; p < 0.05) and HF (0.25 ±0.29 vs. 0.60 ±0.41 in control; p < 0.05) decrease.

Conclusions

The ANS disturbances, found as standard spectral parameter abnormalities, were demonstrated in both AOAB and COAB. When this finding is analysed, together with the lack of statistically significant differences in normalized nLF and nHF powers, the VLF changes seem to play an essential role, probably reflecting the progression in bladder inflammatory changes.     

Contractile reserve assessed by dobutamine test identifies super-responders to cardiac resynchronization therapy

Introduction

In this study, we sought to determine whether myocardial contractile reserve (CR) assessed by dobutamine stress echocardiography (DSE) can identify patients who experience nearly complete normalization of left ventricular (LV) function after the implantation of a cardiac resynchronization therapy (CRT) pacemaker.

Material and methods

The study group consisted of 55 consecutive patients with non-ischemic dilated cardiomyopathy, LV ejection fraction (LVEF) < 35%, and prolonged QRS complex duration, who were scheduled for CRT pacemaker implantation. The DSE (20 µg/kg/min) was performed in all patients. The CR assessment was based on a change in the wall motion score index (ΔWMSI) and ΔLVEF during DSE. Super-response was defined as an increase in LVEF to > 50% and reduction in left ventricular end-systolic dimension to < 40 mm 12 months following the CRT implantation.

Results

A total of 7 patients (12.7%) were identified as super-responders to CRT. When compared to non-super-responders, these patients had significantly higher values of the dobutamine-induced change in ΔWMSI (1.031 ±0.120 vs. 0.49 ±0.371, p < 0.01), and ΔEF (17.9 ±2.2 vs. 8.8 ±6.2, p < 0.01). Receiver operating characteristic analysis showed that dobutamine-induced changes in ΔWMSI ≥ 0.7 and ≥ 14% for ΔEF are the best discriminators for a super-response. Patients with ΔWMSI ≥ 0.7 and ΔEF ≥ 14% are significantly less often hospitalized (p < 0.01) for worsening of heart failure during 28.5 ±3.0 months of the follow-up.

Conclusions

Contractile reserve assessed by DSE can identify patients with dilated cardiomyopathy who are likely to experience near normalization of LV function following CRT.     

The effect of diabetic autonomic neuropathy on P-wave duration,dispersion and atrial fibrillation

Introduction

Atrial fibrillation (AF) is the most common sustained arrhythmia. Diabetic autonomic neuropathy (DAN) is a frequent complication of diabetes mellitus and has a negative impact on the cardiovascular system. There are no data about the occurrence of paroxysmal atrial fibrillation (PAF) in the population with DAN.

Material and methods

We analysed the data of 100 patients with PAF. The study population was divided into three groups: group I: 28 patients with diabetes mellitus (DM) and DAN, group II: 34 patients with DM without DAN, and group III: 38 patients without DM. P-wave duration (FPD) and dispersion (PWD) were measured during sinus rhythm and AF episodes were counted during 12 months of follow-up.

Results

Recurrence of PAF was higher in group I (47 episodes/year) compared to groups II and III (26 and 22 episodes/year) – p<0.01. The FPD was longer in group I (137.4 ±12.0 ms vs. 126 ±23.0 ms in II group and 129 ±18.3 ms in group III; p<0.001). The PWD was longer in patients with DAN (53 ±19 ms vs. 36 ±18 ms and 34 ± 20 ms, p<0.001).

Conclusions

The results showed that the presence of DAN caused a significant increase in P-wave duration and dispersion, which might be responsible for the recurrence of AF.     

Expression of COX-2, IL-1β, TNF-α and IL-4 in epithelium of serrated adenoma,adenoma and hyperplastic polyp

Introduction

Colon polyps and inflammatory process play the key role in neoplasia of colorectal cancer. In recent years there have been many publications on the malignancy of hyperplastic polyp (HP) which according to the WHO classification is a non-neoplastic polyp. The aim of this study is to determine the expression of inflammatory proteins COX-2, IL-1β, TNF-α and IL-4 in the epithelium of colorectal polyps.

Material and methods

In the study, 144 colorectal polyps were analyzed. The groups of HP, classical (A) and serrated adenomas (SA) and normal mucosa (control) according to histopathological studies were selected. Immunohistochemical examinations Rusing antibodies against COX-2, IL-1β, TNF-α and IL-4 were performed. The expression of analyzed protein was evaluated using modified Remmele-Stegner scale (0-16).

Results

Statistical analysis revealed higher expression of TNF-α (16 ±3.87 vs. 1 ±5.06), IL-1β (12 ±4 vs 8 ±2.72), COX-2 (9 ±2.54 vs. 8 ±3.14) and IL-4 (12 ±3.45 vs. 4 ±3.35) in SA polyps compared to the control (p < 0.001). The HP had an increased level of expression of TNF-α (12 ±3.72 vs. 1 ±5.06, p < 0.005), COX-2 (8.5 ±1.97 vs. 8 ±3.14, p < 0.012) and IL-4 (12 ±3.46 vs. 4 ±3.35, p < 0.001). Significantly higher expression of IL-4 (12 ±2.32 vs. 4 ±3.35, p < 0.001) and IL-1β (16 ±4.32 vs. 8 ±2.72, p < 0.044) in A compared to the control were observed.

Conclusions

Expression of inflammatory factors differed between polyps. Inflammation accompanied the serrated structures which occur in polyps. The inflammatory process affects the development of colorectal polyps. The HP may predispose to malignancy.     

Usefulness of patient's history and non-invasive electrocardiographic parameters in prediction of ajmaline test results in patients with suspected Brugada syndrome

Introduction

The aim of the work was to assess the usefulness of patient''s history and non-invasive electrocardiographic parameters in the prediction of ajmaline test results in patients with suspected Brugada syndrome.

Material and methods

The study involved a group of 59 patients (37 men) at average age of 31.6 ±12.2 years with suspected concealed form of Brugada syndrome. Pharmacological provocation with intravenous ajmaline administration was performed. The patients were divided into two groups depending on ajmaline test results. Individual and total predictive value for ajmaline test was based on the analysis of medical anamnesis and non-invasive electrocardiographic examination.

Results

The analysis carried out within the work indicated a special predictive value of 2 parameters which constituted the study inclusion criteria – family history of Brugada syndrome (28.6% vs. 3.8%; p = 0.0477) and occurrence of saddleback electrocardiographic changes in ECG curve (42.9% vs. 0.0%; p = 0.0002). Non-invasive electrocardiographic parameters which showed significant predictive value for ajmaline test were as follows: dispersion of QTc interval (prior to the provocation test 54.43 ±24.77 ms vs. 32.70 ±12.98 ms; p = 0.0005 and during daytime activity 46.81 ±27.16 ms vs. 32.07 ±13.19 ms; p = 0.0198), corrected QT intervals, Tpeak-Tend intervals in particular leads, QTpeak intervals, dispersion of Tpeak-Tend interval assessed from precordial leads (V1–V6) (42.86 ±13.80 ms vs. 26.54 ±11.70 ms; p = 0.001) and J-point elevation in V2 and V3 leads.

Conclusions

Both interview and non-invasive electrocardiographic parameters which reflect cardiomyocyte repolarization disorders are of high predictive value in anticipating ajmaline pharmacological provocation results in patients with suspected Brugada syndrome.     

Clinical effects of sevoflurane anesthesia induction with a portable inhalational anesthetic circuit in pediatric patients

Introduction

Pediatric anesthesia induction with sevoflurane usually needs a special vaporizer and gas source, which limits its use to the operating room (OR). Many children feel anxious and cry when entering the OR because of being separated from their parents, which impairs anesthesia safety and their physical and mental health. In this study, we used a portable circuit to perform sevoflurane anesthesia induction outside the OR, assessed its effects and compared them with those of ketamine anesthesia in pediatric patients.

Material and methods

One hundred children had anesthesia induced with either sevoflurane (sevoflurane group) through the portable inhalational anesthetic circuit, or ketamine by intramuscular injection (ketamine group), then were transferred to the OR. Peak inspired concentration (Cp) and steady state concentration (Cs) of sevoflurane were measured. Heart rate (HR) and saturation of peripheral oxygen (SpO₂) were monitored. Time for anesthesia induction, awakening, leaving the OR and duration of the operation were recorded. The patients’ reaction during anesthesia was also analyzed.

Results

The Cp and Cs of sevoflurane were correlated with bodyweight. Compared with the ketamine group, the sevoflurane group showed shorter time for anesthesia induction (28 ±7 s vs. 195 ±34 s, p < 0.0001), awakening (11.2 ±3.6 s vs. 63.5 ±6.7 s, p < 0.0001) and leaving the OR (20.5 ±5.6 s vs. 43.4 ±10.6, p < 0.0001), less noncooperation during anesthesia induction (10% vs. 80%, p < 0.0001), lower HR (130 ±16 beats/min vs. 143 ±19 beats/min, p = 0.0004) and higher SpO₂ (98.9 ±0.9% vs. 96.1 ±2.5%, p < 0.0001) on arrival at the OR.

Conclusions

Pediatric anesthesia induction by sevoflurane with the portable inhalational anesthetic circuit is convenient, safe and effective outside the OR.     

Patients with heart failure and concomitant chronic obstructive pulmonary disease participating in the Heart Failure Pilot Survey (ESC-HF Pilot) – Polish population

Introduction

There is an increasing interest in comorbidities in heart failure patients. Data about chronic obstructive pulmonary disease (COPD) in the Polish population of heart failure (HF) patients are scarce. The aim of this study was to investigate the clinical characteristics, treatment differences and outcome according to COPD occurrence in the Polish population of patients participating in the ESC-HF Pilot Survey Registry.

Material and methods

We analyzed the data of 891 patients with HF recruited in 2009–2011 in Poland: 648 (72.7%) hospitalized patients and 243 (27.3%) patients included as outpatients.

Results

The COPD was documented in 110 (12.3%) patients with HF in the analyzed population. Patients with – compared to those without COPD were older, more often smokers, had higher NYHA class, and higher prevalence of hypertension. Ejection fraction (EF) was higher in hospitalized patients with COPD compared to patients without COPD (40.5 ±14.6% vs. 37.2 ±13.7%, p < 0.04), without a significant difference in the outpatient group. There was a significant difference in β-blocker use between patients with and without COPD (81.8% vs. 94.7%, p < 0.0001). Most patients received them below target doses. At the end of the 12-month follow-up, there was no significant difference in mortality between COPD and no-COPD patients (10.9% vs. 11.1%, p = 0.66).

Conclusions

The findings from the Polish part of the ESC-HF registry indicate that COPD in patients with HF is associated with older age, smoker status, hypertension and higher NYHA class. The use of β-blockers was significantly lower in patients with than without COPD. There were no significant differences in mortality between groups.     

Enhanced connexin 43 expression following neural stem cell transplantation in a rat model of traumatic brain injury

Introduction

Reestablishment of functional networks after traumatic brain injury (TBI) has been proffered as one of the goals of neural stem cell (NSC) transplantation therapeutics. Gap junctions provide essential means for direct cellular communication by transferring small molecules and ions, which may provide insights into the interplay between grafted NSCs and host cells.

Material and methods

Thirty-six adult male Wister rats were used in this study. The controlled cortical impact (CCI) model of brain injury has been performed. Seventy-two hours after CCI injury, animals were randomly assigned to two groups: PBS- and NSC- transplanted group. NSCs-transplanted group received delivery of the NSCs suspension to the cortex below the injury cavity in the ipsilateral hemisphere. At 1, 2, and 4 weeks post-transplantation, we investigated the expression patterns of gap junction-associated connexin 43 (Cx43) in the transplant site and the border of CCI by immunohistochemistry, Western blot and RT-PCR.

Results

Our findings showed that Cx43 staining was significantly greater in the transplant site and the border of CCI in the NSCs-transplanted rats compared to the control rats at different time points (p < 0.01 at 1 week, p < 0.05 at 2 and 4 weeks). Significantly higher gene and protein expression of Cx43 was found in NSCs-transplanted rats compared to the control rats in the period of 4 weeks post-transplantation (p < 0.01), and remained at a higher level until 2 weeks with or without NSC transplantation.

Conclusions

It is proposed that gap junction-associated Cx43 might participate in NSCs’ beneficial effects via gap-junctional coupling by which grafted NSCs integrate into host neural tissue following transplantation after TBI.     

Disturbances in apoptosis of lamina propria lymphocytes in Crohn's disease

Introduction

The aim of this study was to assess the potential mechanisms providing resistance to apoptosis of lamina propria lymphocytes (LPL) directlyin intestinal tissues from patients with Crohn''s disease (CD).

Material and methods

Fifty CD patients were enrolled in the study. The control group consisted of healthy patients who underwent surveillance colonoscopy after endoscopic polypectomy. Each CD patient underwent colonoscopy with tissue sampling from inflamed areas of the colon with the assessment of immunohistochemical expression of active caspase 3, Fas, tumour necrosis factor receptor 1 (TNFR1), Bcl-2, Bax, CD4 and CD8. This was compared with healthy intestinal mucosa.

Results

The expression of active caspase 3 was significantly lower in LPL in CD (0.4 ±0.3 vs. 2.8 ±1.5; p = 0.0002). A statistically significant increase of CD4 and CD8 positive cells was noted in CD (2.3 ±0.5 vs. 1.2 ±0.2, p < 0.0001; 2.1 ±0.3 vs. 1.1 ±0.3, p < 0.0001, respectively). It was associated with a significant increase of the Bcl-2 (6.7 ±2.7 vs. 2.9 ±0.8; p < 0.0001) and a decrease of the Bax protein expression (3.4 ±2.1 vs. 5.5 ±1.8; p < 0.0001) in CD. The expression of Fas and TNFR1 did not differ between the study groups.

Conclusions

LPL in CD are resistant to apoptosis when compared with physiological conditions. This is probably due to an imbalance in Bcl-2 family proteins. TNFR1-related pathway is probably not involved in disturbances of LPL apoptosis in CD.     

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).     

Cardiac complications associated with trastuzumab in the setting of adjuvant chemotherapy for breast cancer overexpressing human epidermal growth factor receptor type 2 – a prospective study

Introduction

Trastuzumab, a recombinant humanized monoclonal antibody, is targeted against the external domain of the human epidermal growth factor receptor type 2 (HER2). It improves efficacy of HER2-positive breast cancer treatment. The authors present their experience with patients (pts) treated with trastuzumab in the aspects of cardiac complications.

Material and methods

We observed prospectively 253 women with early positive HER2 breast cancer treated with trastuzumab. Assessment of cardiovascular status, ECG and echocardiography was performed initially and every 3 months until 6^th month during follow-up.

Results

Cardiac complications developed in 52 pts (20.55%) and included: asymptomatic left ventricle dysfunction (43), symptomatic heart failure (6), new asymptomatic LBBB (1); new negative T-waves in ECG (2). There was a progressive decline in left ventricular ejection fraction (LVEF) during treatment. It was more enhanced in pts with cardiac complications. Following trastuzumab termination/discontinuation LVEF increased but at month 18 still remained significantly lower than initially in both groups (61.07 ±4.84 vs. 59.97 ±5.23 – no cardiac complications; p < 0.05; 58.14 ±4.08% vs. 53.08 ±5.74% – cardiac complications; p < 0.05). During 6-month follow-up 33 out of 46 pts experienced an improvement in left ventricular status. In 13 pts in whom trastuzumab was discontinued, it was restarted; 6 of them successfully completed total therapy. Univariate analysis revealed no association between any cardiovascular risk factor and the development of cardiotoxicity.

Conclusions

One out of five treated patients discontinues trastuzumab in an adjuvant setting due to cardiac complications. LV dysfunction is the most frequent. Routine cardiac monitoring should be obligatory.     

Exhaled eicosanoids and biomarkers of oxidative stress in exacerbation of chronic obstructive pulmonary disease

Introduction

Eicosanoids and oxidants play an important role in inflammation, but their role in chronic obstructive pulmonary disease (COPD) is uncertain. In this study we hypothesized that levels of exhaled leukotrienes, prostaglandins and biomarkers of oxidative stress are increased in infectious exacerbations of COPD and that they decrease after antibiotic therapy.

Material and methods

Cysteinyl-leukotrienes (LTs), leukotriene B₄ (LTB₄), prostaglandin E₄, hydrogen peroxide (H₂O₂) and 8-isoprostane were measured in exhaled breath condensate (EBC) in 16 COPD patients with infectious exacerbations (mean age 64 ±12 years, 13 male) on day 1, during antibiotic therapy (days 2-4), 2-4 days after therapy and at a follow-up visit when stable (21-28 days after therapy).

Results

There was a significant fall in concentration of cys-LTs, LTB₄ and 8-isoprostane at visit 3 compared to day 1 (cys-LTs: 196.5 ±38.4 pg/ml vs. 50.1 ±8.2 pg/ml, p < 0.002; LTB₄: 153.6 ±25.5 pg/ml vs. 71.9 ±11.3 pg/ml, p < 0.05; 8-isoprostane: 121.4 ±14.6 pg/ml vs. 56.1 ±5.2 pg/ml, p < 0.03, respectively). Exhaled H₂O₂ was higher on day 1 compared to that at visits 2 and 3 (0.74 ±0.046 µM vs. 0.52 ±0.028 µM and 0.35 ±0.029 µM, p < 0.01 and p < 0.01, respectively). Exhaled PGE₂ levels did not change during exacerbations of COPD. Exhaled eicosanoids and H₂O₂ in EBC measured at the follow-up visit (stable COPD) were significantly higher compared to those from healthy subjects.

Conclusions

We conclude that eicosanoids and oxidants are increased in infectious exacerbations of COPD. They are also elevated in the airways of stable COPD patients compared to healthy subjects.     

The sound of a mobile phone ringing affects the complex reaction time of its owner

Introduction

Mobile phone conversation decreases the ability to concentrate and impairs the attention necessary to perform complex activities, such as driving a car. Does the ringing sound of a mobile phone affect the driver''s ability to perform complex sensory-motor activities? We compared a subject''s reaction time while performing a test either with a mobile phone ringing or without.

Material and methods

The examination was performed on a PC-based reaction time self-constructed system Reactor. The study group consisted of 42 healthy students. The protocol included instruction, control without phone and a proper session with subject''s mobile phone ringing. The terms of the study were standardised.

Results

There were significant differences (p < 0.001) in reaction time in control (597 ms), mobile (633 ms) and instruction session (673 ms). The differences in female subpopulation were also significant (p < 0.01). Women revealed the longest reaction time in instruction session (707 ms), were significantly quicker in mobile (657 ms, p < 0.01) and in control session (612 ms, p < 0.001). In men, the significant difference was recorded only between instruction (622 ms) and control session (573 ms, p < 0.01). The other differences were not significant (p > 0.08). Men proofed to complete significantly quicker than women in instruction (p < 0.01) and in mobile session (p < 0.05). Differences amongst the genders in control session was not significant (p > 0.05).

Conclusions

The results obtained proofed the ringing of a phone exerts a significant influence on complex reaction time and quality of performed task.