Cell type-specific expression of endogenous cardiac Troponin I antisense RNA in the neonatal rat heart

Since the number of detected natural antisense RNA is growing, investigations upon the expression pattern of the antisense RNA become more important. As we focused our work on natural occurring antisense transcripts in human and rat heart tissues, we were interested in the question, whether the expression pattern of antisense and sense RNA can vary in different cell types of the same tissue. In our previous analysis of total neonatal rat heart tissue, we demonstrated the co-expression of both cTnI RNA species in this tissue. Now we investigated the expression of antisense and sense RNA quantitatively in neonatal cardiomyocytes (NCMs) and neonatal cardiac fibroblasts (NCFs). Performing northern blot as well as RT-PCR, we could detect natural antisense and sense RNA transcripts of cTnI in NCM and NCF implying that these transcripts are co-expressed in both cell types. The absolute amounts of the RNA transcripts were higher in NCM. Both RNA species showed identical sizes in the northern blot. Quantification by real-time PCR revealed a higher relative level of natural antisense RNA in NCF compared to NCM which points out to a cell type-specific expression of sense and antisense RNA. Our observations suggest that antisense RNA transcription may contribute to a cell type-specific regulation of the cTnI gen

Left ventricular apical thrombus after systemic thrombolysis with recombinant tissue plasminogen activator in a patient with acute ischemic stroke

BACKGROUND: Thrombolysis with recombinant tissue plasminogen activator (rtPA) is an established treatment in acute stroke. To prevent rethrombosis after rtPA therapy, secondary anticoagulation with heparin is commonly performed. However, the recommended time-point and extent of heparin treatment vary and are not well investigated. CASE PRESENTATION: We report a 61-year-old man who developed an acute global aphasia and right-sided hemiparesis. Cranial CT was normal and systemic thrombolytic therapy with tPA was started 120 minutes after symptom onset. Low-dose subcutaneous heparin treatment was initiated 24 hours later. Transthoracic echocardiography (TTE) 12 hours after admission showed slightly reduced left ventricular ejection fraction (LVEF) but was otherwise normal. 48 hours later the patient suddenly deteriorated with clinical signs of dyspnea and tachycardia. TTE revelead a large left ventricular apical thrombus as well as a reduction of LVEF to 20 %. Serial further TTE investigations demonstrated a complete resolution of the thrombus and normalisation of LVEF within two days. CONCLUSION: Our case demonstrates an intracardiac thrombus formation following rtPA treatment of acute stroke, probably caused by secondary hypercoagulability. Rethrombosis or new thrombus formation might be an underestimated complication of rtPA therapy and potentially explain cases of secondary stroke progression

Early right ventricular systolic dysfunction in patients with systemic sclerosis without pulmonary hypertension: a Doppler Tissue and Speckle Tracking echocardiography study

<p>Abstract</p> <p>Background</p> <p>Isovolumetric acceleration (IVA) is a novel tissue Doppler parameter for the assessment of systolic function. The aim of this study was to evaluate IVA as an early parameter for the detection of right ventricular (RV) systolic dysfunction in patients with systemic sclerosis (SSc) without pulmonary hypertension.</p> <p>Methods</p> <p>22 patients and 22 gender- and age-matched healthy subjects underwent standard echocardiography with tissue Doppler imaging (TDI) and speckle tracking strain to assess RV function.</p> <p>Results</p> <p>Tricuspid annular plane systolic excursion (TAPSE) (23.2 ± 4.1 mm vs. 26.5 ± 2.9 mm, p < 0.006), peak myocardial systolic velocity (Sm) (11.6 ± 2.3 cm/s vs. 13.9 ± 2.7 cm/s, p = 0.005), isovolumetric contraction velocity (IVV) (10.3 ± 3 cm/s vs. 14.8 ± 3 cm/s, p < 0.001) and IVA (2.3 ± 0.4 m/s²vs. 4.1 ± 0.8 m/s², p < 0.001) were significant lower in the patient group. IVA was the best parameter to predict early systolic dysfunction with an area under the curve of 0.988.</p> <p>Conclusion</p> <p>IVA is a useful tool with high-predictive power to detect early right ventricular systolic impairment in patients with SSc and without pulmonary hypertension.</p

Fundamental aspects of cardiovascular regulation in predisposition to atrial fibrillation

Background: Atrial fibrillation is the most common sustained arrhythmia in cardiology. The structural factors leading to atrial fibrillation are well known, but there should be also regarded the functional factors. In 2014, the Task Force published guidelines for atrial fibrillation describing the importance of the vegetative nervous system in creating predisposition to atrial fibrillation although it describes that the mechanism is not completely clear. Furthermore, it is important to understand this mechanism, regarding the increasing number of patients affected by atrial fibrillation without any structural heart diseases. The aim of this work is to understand the physiological background of the predisposition to the appearance and recurrence of atrial fibrillation regarding the role of neural regulatory systems of the heart, especially when no structural heart diseases are present. Therefore, the following is a fundamental analysis of the neural regulation of heart rhythm, including the vegetative nervous system at its medullar and central levels and also the cerebral cortex input in heart regulation. Conclusions: The predisposition to atrial fibrillation regarding the neural regulatory systems of the heart can be pinpointed to three key factors: 1. Central over-activity; 2. Sympathetic efferent overflow towards the heart in rest state; 3. Parasympathetic exhaustion and break-down of the parasymphatetic protective function

New approach to heart rate variability analysis based on cardiophysiological biomarkers

Background: The heart rate variability (HRV) analysis is a well-known method demonstrating its value over the years in different medical fields. However, it still has its known limitations. Material and methods: The new approach to HRV analysis is based on a complementary HRV standard analysis with new cardiophysiological biomarkers. The biomarkers are assessed on cardiorhythmograms obtained by a 5-minute ECG recording using a specialized hardware (Polyspectrum-HRV-device, Neurosoft). Results: A possible applicative value of the biomarkers is shown on examples of how a prognosis for recurrence of atrial fibrillation (AFib) could be made. When in a rest-state cardiorhythmogram are observed LF drops and are followed by a pathological counterregulation, prognostically, recurrence of atrial fibrillation is expected. When in a cardiorhythmogram LF drops are observed and are followed by a physiological counterregulation, prognostically, sinus rhythm is expected. Physiological background of the biomarkers: increased central modulation of the heart in rest state of a patient, a sympathetic overflow of the heart in calm state and insufficiency of compensatory parasymphatetic counteractivation. Limitations of the paper: this is a methodological paper without description of patients. This paper will be followed by a clinical paper in which we are going to describe the validation of these cardiophysiological biomarkers on patients with AFib. Conclusions: Complementary to the standard HRV analysis, cardiophysiological biomarkers should be assessed: LF drops and HF counterregulation could be used for prognosis construction in cardiology

Implementation of seven echocardiographic parameters of myocardial asynchrony to improve the long-term response rate of cardiac resynchronization therapy (CRT)

<p>Abstract</p> <p>Background</p> <p>Cardiac resynchronization Therapy (CRT) is an effective therapy for chronic heart failure with beneficial hemodynamic effects leading to a reduction of morbidity and mortality. The responder rates, however, are low. There are various and contentious echocardiographic parameters of myocardial asynchrony. Patient selection by echocardiographic assessment of asynchrony is thought to improve responder rates.</p> <p>Methods</p> <p>In this small single-center pilot-study, seven established parameters of myocardial asynchrony were used to select patients for CRT: (1) interventricular electromechanical delay (IMD, cut-off ≥ 40 ms), (2) Septal-to-posterior wall motion delay (SPWMD, ≥ 130 ms), (3) maximal difference in time-to-peak velocities between any two of twelve LV segments (Ts-12 ≥ 104 ms), (4) standard deviation of time to peak myocardial velocities (Ts-12-SD, ≥ 34.4 ms), (5) difference between the septal and basal time-to-peak velocity (TDId, ≥ 60 ms), (6) left ventricular electromechanical delay (LVEMD, > 140 ms) and (7) delayed longitudinal contraction (DLC, > 2 segments).</p> <p>16 chronic heart failure patients (NYHA III–IV, LVEF < 0.35, QRS ≥ 120 ms) at least two out of seven parameters of myocardial asynchrony received cardiac resynchronization therapy (CRT-ICD). Follow-up echo examination was after 6 months. The control group was a historic group of CRT patients (n = 38) who had not been screened for echocardiographic signs of myocardial asynchrony prior to device implantation.</p> <p>Results</p> <p>Based on reverse remodeling (relative reduction of LVESV > 15%, relative increase of LVEF > 25%), the responder rate to CRT was 81.2% in patients selected for CRT according to our protocol as compared to 47.4% in the control group (p = 0.04). At baseline, there were on average 4.1 ± 1.6 positive parameters of asynchrony (follow-up: 3.7 [± 1.6] parameters positive, p = 0.52). Only the LVEMD decreased significantly after CRT (p = 0.027). The remaining parameters showed a non-significant trend towards reduction of myocardial asynchrony.</p> <p>Conclusion</p> <p>The implementation of different markers of asynchrony in the selection process for CRT improves the hemodynamic response rate to CRT.</p

Hypoxic Induction of Receptor Activity-Modifying Protein 2 Alters Regulation of Pulmonary Endothelin-1 by Adrenomedullin: Induction under Normoxia Versus Inhibition under Hypoxia

ABSTRACT The vasodilator adrenomedullin (AM) is up-regulated in pulmonary hypertension, and inhaled AM is beneficial in patients. Therefore, we investigated the effects of AM on pulmonary endothelin-1 (ET-1). In normoxic isolated rat lungs (IRL) and rat pulmonary artery endothelial cells (RPAEC), the calcitonin gene-related peptide type-1 receptor (CGRP1R) antagonist human (h)CGRP(8-37) decreased ET-1 secretion, and the AM receptor antagonist hAM(22-52) had no effect. Exogenous AM (1 and 10 pM) increased ET-1 levels, which was abolished by hCGRP(8-37) and protein kinase A (PKA) inhibition. At 50 and 100 pM, AM decreased ET-1, an effect sensitive to hAM(22-52), NO inhibition, and protein kinase G (PKG) inhibition. In RPAEC, these results were attributed to altered ET-1 gene expression; low exogenous AM also promoted activity of endothelin-converting enzyme, and high AM increased the number of endothelin type-B (ETB) receptor sites. Hypoxia significantly elevated AM and ET-1 levels in IRL and RPAEC, and hAM(22-52), NO inhibition, or PKG inhibitors caused a further ET-1 rise. These interventions also prevented the hypoxia-related increase in ETB sites in RPAEC. In RPAEC, both high AM and hypoxia down-regulated receptor activity-modifying protein (RAMP)1, but they up-regulated RAMP2 protein and AM receptor sites, and RAMP2 silencing by small interference RNA proved its pivotal role for signal switching. In conclusion, endogenous pulmonary AM up-regulates ET-1 and endothelinconverting enzyme activity under physiological conditions, via CGRP1R and PKA. In contrast, hypoxia-induced high AM levels, via AM1 receptor and NO/PKG, down-regulate ET-1 gene expression and promote expression of ETB receptors. This hypoxia-related switch of AM signaling can be attributed to up-regulation of the RAMP2/AM1 receptor system. Adrenomedullin (AM), first discovered b

Interventional Pneumology in Pulmonary Bleeding; A Review: From the Bronchus to the Vessel

Interventional pneumology includes both bronchological and vascular methods of diagnosis and therapy, especially in emergency situations such as pulmonary hemorrhage. In massive pulmonary hemorrhage bronchological diagnosis is required to determine the site and extent of bleeding, as well as angiography of bronchial arteries, and of pulmonary arteries. Bronchus occlusion by aid of balloon catheter or double lumen tube are holding measures until definitive surgery or embolization of bronchial or pulmonary arteries can be performed. The paper suggests a close relationship between bronchoscopic and angiographic diagnosis and therapy in case of severe pulmonary bleeding

No role for epigallocatechin gallate (EGCG)

Consumption of tea is inversely associated with cardiovascular diseases. However, the active compound(s) responsible for the protective effects of tea are unknown. Although many favorable cardiovascular effects in vitro are mediated by epigallocatechin gallate (EGCG), its contribution to the beneficial effects of tea in vivo remains unresolved. In a randomised crossover study, a single dose of 200 mg EGCG was applied in three different formulas (as green tea beverage, green tea extract (GTE), and isolated EGCG) to 50 healthy men. Flow-mediated dilation (FMD) and endothelial-independent nitro-mediated dilation (NMD) was measured before and two hours after ingestion. Plasma levels of tea compounds were determined after each intervention and correlated with FMD. FMD significantly improved after consumption of green tea containing 200 mg EGCG (p < 0.01). However, GTE and EGCG had no significant effect on FMD. NMD did not significantly differ between interventions. EGCG plasma levels were highest after administration of EGCG and lowest after consumption of green tea. Plasma levels of caffeine increased after green tea consumption. The results show that EGCG is most likely not involved in improvement of flow-mediated dilation by green tea. Instead, other tea compounds, metabolites or combinations thereof may play a role

Noninvasive monitoring of cardiac function in a chronic ischemic heart failure model in the rat: Assessment with tissue Doppler and non-Doppler 2D strain echocardiography

<p>Abstract</p> <p>Objectives</p> <p>Feasibility of noninvasive monitoring of cardiac function after surgically induced ischemic cardiomyopathy with tissue Doppler and non-Doppler 2D strain echocardiography in rats.</p> <p>Background</p> <p>The optimal method for quantitative assessment of global and regional ventricular function in rats with chronic heart failure for research purposes remains unclear.</p> <p>Methods</p> <p>20 rats underwent suture ligation of the left anterior descending coronary artery via a left thoracotomy to induce ischemic cardiomyopathy. Echocardiographic examination with estimation of left ventricular wall thickness, diameters, fractional shortening, ejection fraction, wall velocities as well as radial strain were performed before and 4 weeks after surgery.</p> <p>Results</p> <p>Mean LVEF decreased from 70 ± 6% to 40 ± 8% (p < 0.0001) one month after the operation. LVEDD increased from 7 ± 1 mm to 9 ± 1 mm (p < 0.0001), systolic anterior velocity decreased from 0.79 ± 0.25 cm/s to 0.18 ± 0.19 cm/s (p < 0.0001). Radial 2D strain was significantly reduced after myocardial infarction of the septal (18.2 ± 6.6% vs 7.0 ± 5.9%, p < 0.001), anteroseptal (17.3 ± 5.2% vs 4.6 ± 3.0%, p < 0.0001), anterior (18.9 ± 5.9% vs 5.6 ± 2.5%, p < 0.0001), lateral (21.4 ± 4.9% vs 8.1 ± 3.5%, p < 0.0001) as well as posterior myocardial segments (19.3 ± 5.2% vs 15.4 ± 5.5%, p < 0.01). Inferior segments (19.2 ± 7.9% vs 17.8 ± 7.9%, ns) did not change at all.</p> <p>Conclusion</p> <p>It is feasible to assess dimensions, global function, and regional contractility with echocardiography in rats suffering from chronic heart failure after myocardial infarction. Particularly regional function can be exactly evaluated if tissue Doppler and 2D strain is used.</p