ResearchPad - systolic-pressure https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Right ventricular pressure overload directly affects left ventricular torsion mechanics in patients with precapillary pulmonary hypertension]]> https://www.researchpad.co/article/elastic_article_8470 This study examined the impact of septal flattening on left ventricular (LV) torsion in patients with precapillary pulmonary hypertension (PH). Fifty-two patients with proven precapillary PH and 13 healthy controls were included. Ventricular function was assessed including 4D-measurements, tissue velocity imaging, and speckle tracking analysis. Increased eccentricity index (1.39 vs. 1.08, p<0.001), systolic pulmonary artery pressure (64 vs. 29mmHg, p<0.001) and right ventricular Tei index (0.55 vs. 0.28, p = 0.007), and reduced tricuspid annular plane systolic excursion (19.0 vs. 26.5mm, p<0.001) were detected in PH patients as compared to controls. With increasing eccentricity of left ventricle, LV torsion was both decreased and delayed. Torsion rate paralleled this pattern of change during systole, but not during diastole. In conclusion, right ventricular pressure overload directly affects LV torsion mechanics. The echocardiographic methodology applied provides novel insights in the interrelation of right- and left ventricular function.

]]>
<![CDATA[Elevated pulmonary arterial pressure in Zucker diabetic fatty rats]]> https://www.researchpad.co/article/5c58d612d5eed0c484031535

Diabetes is a very strong predictor of chronic systemic vascular diseases and acute cardiovascular events. Recently, associations between metabolic disorders and pulmonary hypertension have also been reported in both humans and animal models. In order to get some further insight into the relationship of pulmonary hypertension with obesity, insulin resistance and hyperglycemia, herein we have used the Zucker diabetic fatty rats (ZDF/clr-lepr fa) at 20 weeks fed a standard diet and compared to their lean Zucker littermates (ZL). ZDF rats were obese, had elevated plasma glucose levels and insulin resistance, i.e. a clinically relevant model of type 2 diabetes. They presented elevated systolic, diastolic and mean pulmonary arterial pressures and a parallel increase in the Fulton index. Systemic arterial pressures were also increased but the left ventricle plus septum weight was similar in both groups and the heart rate was reduced. Wall media thickening was observed in the small pulmonary arteries from the ZDF rats. Isolated pulmonary arteries mounted in a wire myograph showed similar vasoconstrictor responses to phenylephrine and 5-HT and similar responses to the endothelium-dependent vasodilator acetylcholine. However, the iNOS inhibitor 1400W enhanced the vasoconstrictor responses in ZDF but not in ZL rats. The protein expression of eNOS and iNOS was not significantly different in the lungs of the two groups. The lung expression of Bmpr2 mRNA was downregulated. However, the mRNA expression of Kcna5, Kcnk3, Kcnq1, Kcnq4 or Kcnq5, which encode for the potassium channels Kv1.5, TASK-1, Kv7.1, Kv7.4 and Kv7.5, respectively, was similar in ZL and ZDF rats. In conclusion, ZDF rats show increased pulmonary arterial pressure, right ventricular hypertrophy, pulmonary arterial medial thickening and downregulated lung Bmpr2 despite leptin resistance. These changes were mild but are consistent with the view that diabetes is a risk factor for pulmonary hypertension.

]]>
<![CDATA[Impact of hemodialysis on cardiovascular system assessed by pulse wave analysis]]> https://www.researchpad.co/article/5be5fb88d5eed0c484f6cf3f

Valuable information about cardiovascular system can be derived from the shape of aortic pulse wave being the result of reciprocal interaction between heart and vasculature. Pressure profiles in ascending aorta were obtained from peripheral waveforms recorded non-invasively (SphygmoCor, AtCor Medical, Australia) before, during and after hemodialysis sessions performed after 3-day and 2-day interdialytic intervals in 35 anuric, prevalent hemodialysis patients. Fluid status was assessed by Body Composition Monitor (Fresenius Medical Care, Bad Homburg, Germany) and online hematocrit monitoring device (CritLine, HemaMetrics, Utah). Systolic pressure and ejection duration decreased during dialysis. Augmentation index remained stable at 30 ± 13% throughout hemodialysis session despite the decrease of augmented pressure and pulse height. Subendocardial viability ratio (SEVR) determined after 3-day and 2-day interdialytic intervals increased during the sessions by 43.8 ± 26.6% and 26.1 ± 25.4%, respectively. Hemodialysis performed after 3-day and 2-day interdialytic periods reduced significantly overhydration by 2.4 ± 1.0 L and 1.8 ± 1.2 L and blood volume by 16.3 ± 9.7% and 13.7 ± 8.9%, respectively. Intradialytic increase of SEVR correlated with ultrafiltration rate (R = 0.39, p-value < 0.01), reduction in overhydration (R = -0.57, p-value < 0.001) and blood volume drop (R = -0.38, p-value < 0.01). The strong correlation between the decrease of overhydration during hemodialysis and increase in SEVR confirmed that careful fluid management is crucial for proper cardiac function. Hemodialysis affected cardiovascular system with the parameters derived from pulse-wave-analysis (systolic and augmented pressures, pulse height, ejection duration, SEVR) being significantly different at the end of dialysis from those before the session. Combination of pulse-wave-analysis with the monitoring of overhydration provides a new insight into the impact of hemodialysis on cardiovascular system.

]]>
<![CDATA[A Computational Study on the Relation between Resting Heart Rate and Atrial Fibrillation Hemodynamics under Exercise]]> https://www.researchpad.co/article/5989dad9ab0ee8fa60bb945f

Aims

Clinical data indicating a heart rate (HR) target during rate control therapy for permanent atrial fibrillation (AF) and assessing its eventual relationship with reduced exercise tolerance are lacking. The present study aims at investigating the impact of resting HR on the hemodynamic response to exercise in permanent AF patients by means of a computational cardiovascular model.

Methods

The AF lumped-parameter model was run to simulate resting (1 Metabolic Equivalent of Task—MET) and various exercise conditions (4 METs: brisk walking; 6 METs: skiing; 8 METs: running), considering different resting HR (70 bpm for the slower resting HR—SHR—simulations, and 100 bpm for the higher resting HR—HHR—simulations). To compare relative variations of cardiovascular variables upon exertion, the variation comparative index (VCI)—the absolute variation between the exercise and the resting values in SHR simulations referred to the absolute variation in HHR simulations—was calculated at each exercise grade (VCI4, VCI6 and VCI8).

Results

Pulmonary venous pressure underwent a greater increase in HHR compared to SHR simulations (VCI4 = 0.71, VCI6 = 0.73 and VCI8 = 0.77), while for systemic arterial pressure the opposite is true (VCI4 = 1.15, VCI6 = 1.36, VCI8 = 1.56).

Conclusions

The computational findings suggest that a slower, with respect to a higher resting HR, might be preferable in permanent AF patients, since during exercise pulmonary venous pressure undergoes a slighter increase and systemic blood pressure reveals a more appropriate increase.

]]>
<![CDATA[Vital Sign Prediction of Adverse Maternal Outcomes in Women with Hypovolemic Shock: The Role of Shock Index]]> https://www.researchpad.co/article/5989d9dbab0ee8fa60b67a9a

Objective

To determine the optimal vital sign predictor of adverse maternal outcomes in women with hypovolemic shock secondary to obstetric hemorrhage and to develop thresholds for referral/intensive monitoring and need for urgent intervention to inform a vital sign alert device for low-resource settings.

Study Design

We conducted secondary analyses of a dataset of pregnant/postpartum women with hypovolemic shock in low-resource settings (n = 958). Using receiver-operating curve analysis, we evaluated the predictive ability of pulse, systolic blood pressure, diastolic blood pressure, shock index, mean arterial pressure, and pulse pressure for three adverse maternal outcomes: (1) death, (2) severe maternal outcome (death or severe end organ dysfunction morbidity); and (3) a combined severe maternal and critical interventions outcome comprising death, severe end organ dysfunction morbidity, intensive care admission, blood transfusion ≥ 5 units, or emergency hysterectomy. Two threshold parameters with optimal rule-in and rule-out characteristics were selected based on sensitivities, specificities, and positive and negative predictive values.

Results

Shock index was consistently among the top two predictors across adverse maternal outcomes. Its discriminatory ability was significantly better than pulse and pulse pressure for maternal death (p<0.05 and p<0.01, respectively), diastolic blood pressure and pulse pressure for severe maternal outcome (p<0.01), and systolic and diastolic blood pressure, mean arterial pressure and pulse pressure for severe maternal outcome and critical interventions (p<0.01). A shock index threshold of ≥ 0.9 maintained high sensitivity (100.0) with clinical practicality, ≥ 1.4 balanced specificity (range 70.0–74.8) with negative predictive value (range 93.2–99.2), and ≥ 1.7 further improved specificity (range 80.7–90.8) without compromising negative predictive value (range 88.8–98.5).

Conclusions

For women with hypovolemic shock from obstetric hemorrhage, shock index was consistently a strong predictor of all adverse outcomes. In lower-level facilities in low resource settings, we recommend a shock index threshold of ≥ 0.9 indicating need for referral, ≥ 1.4 indicating urgent need for intervention in tertiary facilities and ≥ 1.7 indicating high chance of adverse outcome. The vital sign alert device incorporated values 0.9 and 1.7; however, all thresholds will be prospectively validated and clinical pathways for action appropriate to setting established prior to clinical implementation.

]]>
<![CDATA[The Effect of High Dose Cholecalciferol on Arterial Stiffness and Peripheral and Central Blood Pressure in Healthy Humans: A Randomized Controlled Trial]]> https://www.researchpad.co/article/5989db3aab0ee8fa60bd475f

Background

Low levels of serum 25-hydroxy vitamin D are associated with increased arterial stiffness and hypertension. Supplementation with vitamin D precursors has been proposed as a treatment option for these conditions. We examined the effect of oral cholecalciferol on arterial stiffness and blood pressure in healthy normotensive adults.

Methods

40 healthy adults were randomised in this double-blinded study to either oral cholecalciferol 3000 IU/day or matching placebo and were followed for 16 weeks to examine any effects on pulse wave velocity (PWV), augmentation index (AIx), peripheral and central blood pressure and 24-hour ambulatory blood pressure.

Results

22 subjects in the cholecalciferol arm and 18 subjects in the placebo arm completed the 16 weeks of follow-up. There was no difference in changes in PWV, AIx corrected for heart rate or central or peripheral blood pressure between the two groups. There was no correlation between serum 25-hydroxy vitamin D and any of these parameters.

Conclusions

Oral cholecalciferol 3000 IU/day does not affect arterial stiffness or blood pressure after 16 weeks of treatment in healthy normotensive adults.

Trial Registration

ClinicalTrials.gov NCT00952562

]]>
<![CDATA[Inhibition of Interleukin-6 Receptor in a Murine Model of Myocardial Ischemia-Reperfusion]]> https://www.researchpad.co/article/5989dae6ab0ee8fa60bbda60

Background

Interleukin-6 (IL-6) levels are upregulated in myocardial infarction. Recent data suggest a causal role of the IL-6 receptor (IL-6R) in coronary heart disease. We evaluated if IL-6R blockade by a monoclonal antibody (MR16-1) prevents the heart from adverse left ventricular remodeling in a mouse model of ischemia-reperfusion (I/R).

Methods

CJ57/BL6 mice underwent I/R injury (left coronary artery ligation for 45 minutes) or sham surgery, and thereafter received MR16-1 (2mg/mouse) 5 minutes before reperfusion and 0.5mg/mouse weekly during four weeks, or control IgG treatment. Cardiac Magnetic Resonance Imaging (CMR) and hemodynamic measurements were performed to determine cardiac function after four weeks.

Results

I/R caused left ventricular dilatation and a decrease in left ventricular ejection fraction (LVEF). However, LVEF was significantly lower in the MR16-1 treatment group compared to the IgG group (28±4% vs. 35±6%, p = 0.02; sham 45±6% vs. 43±4%, respectively; p = NS). Cardiac relaxation (assessed by dP/dT) was not significantly different between the MR16-1 and IgG groups. Also, no differences were observed in histological myocardial fibrosis, infarct size and myocyte hypertrophy between the groups.

Conclusion

Blockade of the IL-6R receptor by the monoclonal MR16-1 antibody for four weeks started directly after I/R injury did not prevent the process of cardiac remodeling in mice, but rather associated with a deterioration in the process of adverse cardiac remodeling.

]]>
<![CDATA[Altered vasoreactivity in neonatal rats with pulmonary hypertension associated with bronchopulmonary dysplasia: Implication of both eNOS phosphorylation and calcium signaling]]> https://www.researchpad.co/article/5989db4fab0ee8fa60bdbbaa

Bronchopulmonary dysplasia (BPD) consists of an arrest of pulmonary vascular and alveolar growth, with persistent hypoplasia of the pulmonary microvasculature and alveolar simplification. In 25 to 40% of the cases, BPD is complicated by pulmonary hypertension (BPD-PH) that significantly increases the risk of morbidity. In vivo studies suggest that increased pulmonary vascular tone could contribute to late PH in BPD. Nevertheless, an alteration in vasoreactivity as well as the mechanisms involved remain to be confirmed. The purpose of this study was thus to assess changes in pulmonary vascular reactivity in a murine model of BPD-PH. Newborn Wistar rats were exposed to either room air (normoxia) or 90% O2 (hyperoxia) for 14 days. Exposure to hyperoxia induced the well-known features of BPD-PH such as elevated right ventricular systolic pressure, right ventricular hypertrophy, pulmonary vascular remodeling and decreased pulmonary vascular density. Intrapulmonary arteries from hyperoxic pups showed decreased endothelium-dependent relaxation to acetylcholine without any alteration of relaxation to the NO-donor sodium nitroprusside. This functional alteration was associated with a decrease of lung eNOS phosphorylation at the Ser1177 activating site. In pups exposed to hyperoxia, serotonin and phenylephrine induced exacerbated contractile responses of intrapulmonary arteries as well as intracellular calcium response in pulmonary arterial smooth muscle cells (PASMC). Moreover, the amplitude of the store-operated Ca2+ entry (SOCE), induced by store depletion using a SERCA inhibitor, was significantly greater in PASMC from hyperoxic pups. Altogether, hyperoxia-induced BPD-PH alters the pulmonary arterial reactivity, with effects on both endothelial and smooth muscle functions. Reduced activating eNOS phosphorylation and enhanced Ca2+ signaling likely account for alterations of pulmonary arterial reactivity.

]]>
<![CDATA[Diagnostic Accuracy Study of an Oscillometric Ankle-Brachial Index in Peripheral Arterial Disease: The Influence of Oscillometric Errors and Calcified Legs]]> https://www.researchpad.co/article/5989db0eab0ee8fa60bcb617

Background

Peripheral arterial disease (PAD) is an indicator of widespread atherosclerosis. However, most individuals with PAD, in spite of being at high cardiovascular risk, are asymptomatic. This fact, together with the limitations of the Doppler ankle-brachial index (ABI), contributes to PAD underdiagnose. The aim of this study was to compare oscillometric ABI and Doppler ABI to diagnose peripheral arterial disease, and also to examine the influence of oscillometric errors and calcified legs on the PAD diagnoses.

Methods and Findings

We measured the ankle-brachial indexes of 90 volunteers (n = 180 legs, age 70 ± 14 years, 43% diabetics) using both oscillometer OMRON-M3 and Doppler. For concordance analyses we used the Bland and Altman method, and also estimated the intraclass correlation coefficient. Receiver Operating Characteristic Curves were used to examine the diagnostic performance of both methods. The ABI means were 1.06 ± 0.14 and 1.04 ± 0.16 (p = 0.034) measured by oscillometer and Doppler ABIs respectively, with limits of agreement of ± 0.20 and intraclass correlation coefficient = 0.769. Oscillometer yielded 23 “error” measurements, and also overestimated the measurements in low ankle pressures. Using Doppler as gold standard, oscillometer performance for diagnosis of PAD showed an Area Under Curve = 0.944 (sensitivity: 66.7%, specificity: 96.8%). Moreover, when considered calcified legs and oscillometric “error” readings as arteriopathy equivalents, sensitivity rose to 78.2%, maintaining specificity in 96%. The best oscillometer cut-off point was 0.96 (sensitivity: 87%, specificity: 91%, positive likelihood ratio: 9.66 and negative likelihood ratio: 0.14).

Conclusion

Despite its limitations, oscillometric ABI could be a useful tool for the diagnosis of PAD, particularly when considering calcified legs and oscillometric “errors” readings as peripheral arterial disease equivalents.

]]>
<![CDATA[Minimally invasive estimation of ventricular dead space volume through use of Frank-Starling curves]]> https://www.researchpad.co/article/5989db59ab0ee8fa60bdf1f6

This paper develops a means of more easily and less invasively estimating ventricular dead space volume (Vd), an important, but difficult to measure physiological parameter. Vd represents a subject and condition dependent portion of measured ventricular volume that is not actively participating in ventricular function. It is employed in models based on the time varying elastance concept, which see widespread use in haemodynamic studies, and may have direct diagnostic use. The proposed method involves linear extrapolation of a Frank-Starling curve (stroke volume vs end-diastolic volume) and its end-systolic equivalent (stroke volume vs end-systolic volume), developed across normal clinical procedures such as recruitment manoeuvres, to their point of intersection with the y-axis (where stroke volume is 0) to determine Vd. To demonstrate the broad applicability of the method, it was validated across a cohort of six sedated and anaesthetised male Pietrain pigs, encompassing a variety of cardiac states from healthy baseline behaviour to circulatory failure due to septic shock induced by endotoxin infusion. Linear extrapolation of the curves was supported by strong linear correlation coefficients of R = 0.78 and R = 0.80 average for pre- and post- endotoxin infusion respectively, as well as good agreement between the two linearly extrapolated y-intercepts (Vd) for each subject (no more than 7.8% variation). Method validity was further supported by the physiologically reasonable Vd values produced, equivalent to 44.3–53.1% and 49.3–82.6% of baseline end-systolic volume before and after endotoxin infusion respectively. This method has the potential to allow Vd to be estimated without a particularly demanding, specialised protocol in an experimental environment. Further, due to the common use of both mechanical ventilation and recruitment manoeuvres in intensive care, this method, subject to the availability of multi-beat echocardiography, has the potential to allow for estimation of Vd in a clinical environment.

]]>
<![CDATA[Right Ventricular Systolic Dysfunction Is Common in Hypertensive Heart Failure: A Prospective Study in Sub-Saharan Africa]]> https://www.researchpad.co/article/5989da79ab0ee8fa60b97b0d

Introduction

Right ventricular (RV) systolic dysfunction is now recognized widely as a strong and independent predictor of adverse outcomes in patients with heart failure (HF). Reduction of RV systolic function more closely predicts impaired exercise tolerance and poor survival than does left ventricular (LV) systolic function. In spite of this, there is a dearth of data on RV function in hypertensive HF which is the commonest form of HF in sub-Saharan Africa. We therefore conducted a prospective cohort study of hypertensive HF patients presenting to the University of Abuja Teaching Hospital, Abuja, Nigeria over an 8 year period.

Methods

Each subject had transthoracic echocardiography performed on them according to the guidelines of American Society of Echocardiography. RV systolic function was defined as a tricuspid annular plane systolic excursion (TAPSE) <15mm using M-mode echocardiography.

Results

RV systolic dysfunction was identified in 272 (44.5%) of the 611 subjects that were studied. Subjects with TAPSE less than 15mm had worse prognosis compared to those with TAPSE ≥15mm.There was a significant correlation between TAPSE and other adverse prognostic markers including left and right atrial area, LV size, LV mass, LV ejection fraction, restrictive mitral inflow and RV systolic pressure (RVSP). However, LV ejection fraction and right atrial area were the only independent determinants of RV systolic dysfunction.

Conclusions

Hypertensive HF is a major cause of RV systolic dysfunction even in a population with a low prevalence of coronary artery disease, and RV systolic dysfunction is associated with poor prognosis in hypertensive HF. Detailed assessment of RV function should therefore be part of the echocardiography evaluation of patients with hypertensive HF.

]]>
<![CDATA[Heart Rate Dependence of the Pulmonary Resistance x Compliance (RC) Time and Impact on Right Ventricular Load]]> https://www.researchpad.co/article/5989da64ab0ee8fa60b918d4

Background

The effect of heart rate (HR) and body surface area (BSA) on pulmonary RC time and right ventricular (RV) load is unknown.

Methods

To determine the association of HR and BSA with the pulmonary RC time and measures of RV load, we studied three large patient cohorts including subjects with 1) known or suspected pulmonary arterial hypertension (PAH) (n = 1008), 2) pulmonary hypertension due to left heart disease (n = 468), and 3) end-stage heart failure with reduced ejection fraction (n = 150). To corroborate these associations on an individual patient level, we performed an additional analysis using high-fidelity catheters in 22 patients with PAH undergoing right atrial pacing.

Results

A faster HR inversely correlated with RC time (p<0.01 for all), suggesting augmented RV pulsatile loading. Lower BSA directly correlated with RC time (p<0.05) although the magnitude of this effect was smaller than for HR. With incremental atrial pacing, cardiac output increased and total pulmonary resistance (TPR) fell. However, effective arterial elastance, its mean resistive component (TPR/heart period; 0.60±0.27 vs. 0.79±0.45;p = 0.048), and its pulsatile component (0.27±0.18 vs 0.39±0.28;p = 0.03) all increased at faster HR.

Conclusion

Heart rate and BSA are associated with pulmonary RC time. As heart rate increases, the pulsatile and total load on the RV also increase. This relationship supports a hemodynamic mechanism for adverse effects of tachycardia on the RV.

]]>
<![CDATA[Cardiac Time Intervals by Tissue Doppler Imaging M-Mode: Normal Values and Association with Established Echocardiographic and Invasive Measures of Systolic and Diastolic Function]]> https://www.researchpad.co/article/5989daa8ab0ee8fa60ba8342

Purpose

To define normal values of the cardiac time intervals obtained by tissue Doppler imaging (TDI) M-mode through the mitral valve (MV). Furthermore, to evaluate the association of the myocardial performance index (MPI) obtained by TDI M-mode (MPITDI) and the conventional method of obtaining MPI (MPIConv), with established echocardiographic and invasive measures of systolic and diastolic function.

Methods

In a large community based population study (n = 974), where all are free of any cardiovascular disease and cardiovascular risk factors, cardiac time intervals, including isovolumic relaxation time (IVRT), isovolumic contraction time (IVCT), and ejection time (ET) were obtained by TDI M-mode through the MV. IVCT/ET, IVRT/ET and the MPI ((IVRT+IVCT)/ET) were calculated. We also included a validation population (n = 44) of patients who underwent left heart catheterization and had the MPITDI and MPIConv measured.

Results

IVRT, IVRT/ET and MPI all increased significantly with increasing age in both genders (p<0.001 for all). IVCT, ET, IVRT/ET, and MPI differed significantly between males and females, displaying that women, in general exhibit better cardiac function. MPITDI was significantly associated with invasive (dP/dt max) and echocardiographic measures of systolic (LVEF, global longitudinal strain and global strainrate s) and diastolic function (e’, global strainrate e)(p<0.05 for all), whereas MPIConv was significantly associated with LVEF, e’ and global strainrate e (p<0.05 for all).

Conclusion

Normal values of cardiac time intervals differed between genders and deteriorated with increasing age. The MPITDI (but not MPIConv) is associated with most invasive and established echocardiographic measures of systolic and diastolic function.

]]>
<![CDATA[Ursodeoxycholic Acid Ameliorates Fructose-Induced Metabolic Syndrome in Rats]]> https://www.researchpad.co/article/5989dabaab0ee8fa60bae882

The metabolic syndrome (MS) is characterized by insulin resistance, dyslipidemia and hypertension. It is associated with increased risk of cardiovascular diseases and type-2 diabetes. Consumption of fructose is linked to increased prevalence of MS. Ursodeoxycholic acid (UDCA) is a steroid bile acid with antioxidant, anti-inflammatory activities and has been shown to improve insulin resistance. The current study aims to investigate the effect of UDCA (150 mg/kg) on MS induced in rats by fructose administration (10%) in drinking water for 12 weeks. The effects of UDCA were compared to fenofibrate (100 mg/kg), an agonist of PPAR-α receptors. Treatment with UDCA or fenofibrate started from the 6th week after fructose administration once daily. Fructose administration resulted in significant increase in body weight, elevations of blood glucose, serum insulin, cholesterol, triglycerides, advanced glycation end products (AGEs), uric acid levels, insulin resistance index and blood pressure compared to control rats. Moreover, fructose increased oxidative stress in aortic tissues indicated by significant increases of malondialdehyde (MDA), expression of iNOS and reduction of reduced glutathione (GSH) content. These disturbances were associated with decreased eNOS expression, increased infiltration of leukocytes and loss of aortic vascular elasticity. Treatment with UDCA successfully ameliorated the deleterious effects of fructose. The protective effect of UDCA could be attributed to its ability to decrease uric acid level, improve insulin resistance and diminish oxidative stress in vascular tissues. These results might support possible clinical application of UDCA in MS patients especially those present with liver diseases, taking into account its tolerability and safety. However, further investigations on human subjects are needed before the clinical application of UDCA for this indication.

]]>
<![CDATA[Presence of ´isolated´ tricuspid regurgitation should prompt the suspicion of heart failure with preserved ejection fraction]]> https://www.researchpad.co/article/5989db52ab0ee8fa60bdc731

Background

Diastolic dysfunction of the left ventricle is common but frequently under-diagnosed. Particularly in advanced stages affected patients may present with significant functional tricuspid regurgitation (TR) as the most prominent sign on echocardiography. The underlying left ventricular pathology may eventually be missed and symptoms of heart failure are attributed to TR, with respective therapeutic consequences.

The aim of the present study was to determine prevalence and mechanisms underlying TR evolution in heart failure with preserved ejection fraction (HFpEF).

Methods and results

Consecutive HFpEF patients were enrolled in this prospective, observational study. Confirmatory diagnostic tests including echocardiography and invasive hemodynamic assessments were performed.

Of the 175 patients registered between 2010 and 2014, 51% had significant (moderate or severe) TR without structural abnormalities of the tricuspid valve. Significant hemodynamic differences between patients with and without relevant TR were encountered. These included elevated pulmonary vascular resistance (p = 0.038), reduced pulmonary arterial compliance (PAC, p = 0.005), and elevated left ventricular filling pressures (p = 0.039) in the TR group. Multivariable binary logistic regression analysis revealed diastolic pulmonary artery pressure (p = 0.029) and PAC (p = 0.048) as independent determinants of TR.

Patients were followed for 18.1±14.1 months, during which 32% had a cardiac event. While TR was associated with outcome in the univariable analysis, it failed to predict event-free survival in the multivariable model.

Conclusions

The presence of ´isolated´ functional TR should prompt the suspicion of HFpEF. Our data show that significant TR is a marker of advanced HFpEF but neither an isolated entity nor independently associated with event-free survival.

]]>
<![CDATA[Incidences and Risk Factors of Organ Manifestations in the Early Course of Systemic Sclerosis: A Longitudinal EUSTAR Study]]> https://www.researchpad.co/article/5989da79ab0ee8fa60b97b2a

Objective

Systemic sclerosis (SSc) is a rare and clinically heterogeneous autoimmune disorder characterised by fibrosis and microvascular obliteration of the skin and internal organs. Organ involvement mostly manifests after a variable period of the onset of Raynaud's phenomenon (RP). We aimed to map the incidence and predictors of pulmonary, cardiac, gastrointestinal (GI) and renal involvement in the early course of SSc.

Methods

In the EUSTAR cohort, patients with early SSc were identified as those who had a visit within the first year after RP onset. Incident SSc organ manifestations and their risk factors were assessed using Kaplan-Meier methods and Cox regression analysis.

Results

Of the 695 SSc patients who had a baseline visit within 1 year after RP onset, the incident non-RP manifestations (in order of frequency) were: skin sclerosis (75%) GI symptoms (71%), impaired diffusing capacity for monoxide<80% predicted (65%), DU (34%), cardiac involvement (32%), FVC<80% predicted (31%), increased PAPsys>40mmHg (14%), and renal crisis (3%). In the heart, incidence rates were highest for diastolic dysfunction, followed by conduction blocks and pericardial effusion. While the main baseline risk factor for a short timespan to develop FVC impairment was diffuse skin involvement, for PAPsys>40mmHg it was higher patient age. The main risk factors for incident cardiac manifestations were anti-topoisomerase autoantibody positivity and older age. Male sex, anti-RNA-polymerase-III positivity, and older age were risk factors associated with incident renal crisis.

Conclusion

In SSc patients presenting early after RP onset, approximately half of all incident organ manifestations occur within 2 years and have a simultaneous rather than a sequential onset. These findings have implications for the design of new diagnostic and therapeutic strategies aimed to ‘widen' the still very narrow ‘window of opportunity'. They may also enable physicians to counsel and manage patients presenting early in the course of SSc more accurately.

]]>
<![CDATA[Postsystolic Shortening Is Associated with Altered Right Ventricular Function in Children after Tetralogy of Fallot Surgical Repair]]> https://www.researchpad.co/article/5989daf7ab0ee8fa60bc35c2

The aim of the study was to determine whether segmental interactions, as expressed by postsystolic shortening (PSS), affects RV mechanics and are connected with impaired systolic and diastolic function in rTOF children. Patients and Methods: 55 rTOF adolescent (study group), and 34 healthy volunteers (control group) were examined using classical Doppler flow (Doppler), Tissue Doppler Imaging (TDI) and Speckle Tracking Echocardiography (STE). PSS was found to occur when time to peak (TTP) was longer than pulmonary valve closure time (PVCT). TTP and strain were derived from RV lateral segments—basal (BL), medial (ML) and apical (AL) in STE. PVCT was measured from the beginning of QRS complex in the ECG to the termination of Doppler flow at the pulmonary valve. TDI was obtained at the lateral tricuspid annulus site and the systolic (S′), early (E′) and late diastolic (A’) peak velocities were measured along with isovolumic contraction (IVCT), and relaxation (IVRT) time. PW was used to measure early tricuspid inflow velocity (E) for calculating the E/E’ ratio. The TDI data in patients with PSS presence (TTP>PVCT) and those in whom it did not occur (TTP≤PVCT) were compared. Results: PSS in BL, ML and AL were observed respectively in: 27(51,9%), 9 (18%), and 8 (16,7%) patients. Mean values of TTP in BL, ML, and AL were respectively: 420.6±55.5ms, 389.8±50.0ms and 366.7±59.0ms. PVCT mean value was 396.6±33.5ms. In the study group, the mean E’ in TTP>PVCT was significantly lower (4.8±1.8 cm/s) compared to mean E’ in TTP≤PVCT (8.4±2.6 cm/s), p<0.01. The average E/E’ was significantly higher in TTP>PCVT than in TTP≤PVCT, respectively 21.6±7.3 vs 12.2±5.1, p<0.05. IVRT was significantly prolonged in TTP>PVCT compared to IVRT in TTP≤PVCT, respectively 95.9±38.7 vs 77.0±35.1, p<0.05. Furthermore, in TTP>PVCT, significantly higher strain in BL (-28.8±8.7%) was observed when compared to that parameter in TTP≤PVCT (-35.3±13.1%), p <0.05. Conclusions: Tissue Doppler Echocardiography and Speckle Tracking Echocardiography are useful techniques for detecting regional systolic and diastolic dysfunction in children after Tetralogy of Fallot surgical repair. Postsystolic shortening in the basal lateral segment is commonly seen in children after the Tetralogy of Fallot surgical repair, and is associated with altered right ventricular systolic and diastolic function.

]]>
<![CDATA[Computational Investigation of Cerebrospinal Fluid Dynamics in the Posterior Cranial Fossa and Cervical Subarachnoid Space in Patients with Chiari I Malformation]]> https://www.researchpad.co/article/5989dacbab0ee8fa60bb4352

Purpose

Previous computational fluid dynamics (CFD) studies have demonstrated that the Chiari malformation is associated with abnormal cerebrospinal fluid (CSF) flow in the cervical part of the subarachnoid space (SAS), but the flow in the SAS of the posterior cranial fossa has received little attention. This study extends previous modelling efforts by including the cerebellomedullary cistern, pontine cistern, and 4th ventricle in addition to the cervical subarachnoid space.

Methods

The study included one healthy control, Con1, and two patients with Chiari I malformation, P1 and P2. Meshes were constructed by segmenting images obtained from T2-weighted turbo spin-echo sequences. CFD simulations were performed with a previously verified and validated code. Patient-specific flow conditions in the aqueduct and the cervical SAS were used. Two patients with the Chiari malformation and one control were modelled.

Results

The results demonstrated increased maximal flow velocities in the Chiari patients, ranging from factor 5 in P1 to 14.8 in P2, when compared to Con1 at the level of Foramen Magnum (FM). Maximal velocities in the cervical SAS varied by a factor 2.3, while the maximal flow in the aqueduct varied by a factor 3.5. The pressure drop from the pontine cistern to the cervical SAS was similar in Con1 and P1, but a factor two higher in P2. The pressure drop between the aqueduct and the cervical SAS varied by a factor 9.4 where P1 was the one with the lowest pressure jump and P2 and Con1 differed only by a factor 1.6.

Conclusion

This pilot study demonstrates that including the posterior cranial fossa is feasible and suggests that previously found flow differences between Chiari I patients and healthy individuals in the cervical SAS may be present also in the SAS of the posterior cranial fossa.

]]>
<![CDATA[The Effect of Gender on Mesenchymal Stem Cell (MSC) Efficacy in Neonatal Hyperoxia-Induced Lung Injury]]> https://www.researchpad.co/article/5989d9e0ab0ee8fa60b69273

Background

Mesenchymal stem cells (MSC) improve alveolar and vascular structures in experimental models of bronchopulmonary dysplasia (BPD). Female MSC secrete more anti-inflammatory and pro-angiogenic factors as compared to male MSC. Whether the therapeutic efficacy of MSC in attenuating lung injury in an experimental model of BPD is influenced by the sex of the donor MSC or recipient is unknown. Here we tested the hypothesis that female MSC would have greater lung regenerative properties than male MSC in experimental BPD and this benefit would be more evident in males.

Objective

To determine whether intra-tracheal (IT) administration of female MSC to neonatal rats with experimental BPD has more beneficial reparative effects as compared to IT male MSC.

Methods

Newborn Sprague-Dawley rats exposed to normoxia (RA) or hyperoxia (85% O2) from postnatal day (P) 2- P21 were randomly assigned to receive male or female IT bone marrow (BM)-derived green fluorescent protein (GFP+) MSC (1 x 106 cells/50 μl), or Placebo on P7. Pulmonary hypertension (PH), vascular remodeling, alveolarization, and angiogenesis were assessed at P21. PH was determined by measuring right ventricular systolic pressure (RVSP) and pulmonary vascular remodeling was evaluated by quantifying the percentage of muscularized peripheral pulmonary vessels. Alveolarization was evaluated by measuring mean linear intercept (MLI) and radial alveolar count (RAC). Angiogenesis was determined by measuring vascular density. Data are expressed as mean ± SD, and analyzed by ANOVA.

Results

There were no significant differences in the RA groups. Exposure to hyperoxia resulted in a decrease in vascular density and RAC, with a significant increase in MLI, RVSP, and the percentage of partially and fully muscularized pulmonary arterioles. Administration of both male and female MSC significantly improved vascular density, alveolarization, RVSP, percent of muscularized vessels and alveolarization. Interestingly, the improvement in PH and vascular remodeling was more robust in the hyperoxic rodents who received MSC from female donors. In keeping with our hypothesis, male animals receiving female MSC, had a greater improvement in vascular remodeling. This was accompanied by a more significant decrease in lung pro-inflammatory markers and a larger increase in anti-inflammatory and pro-angiogenic markers in male rodents that received female MSC. There were no significant differences in MSC engraftment among groups.

Conclusions

Female BM-derived MSC have greater therapeutic efficacy than male MSC in reducing neonatal hyperoxia-induced lung inflammation and vascular remodeling. Furthermore, the beneficial effects of female MSC were more pronounced in male animals. Together, these findings suggest that female MSC maybe the most potent BM-derived MSC population for lung repair in severe BPD complicated by PH.

]]>
<![CDATA[Rodent heart failure models do not reflect the human circulating microRNA signature in heart failure]]> https://www.researchpad.co/article/5989db5aab0ee8fa60bdf52c

Introduction

We recently identified a set of plasma microRNAs (miRNAs) that are downregulated in patients with heart failure in comparison with control subjects. To better understand their meaning and function, we sought to validate these circulating miRNAs in 3 different well-established rat and mouse heart failure models, and correlated the miRNAs to parameters of cardiac function.

Methods

The previously identified let-7i-5p, miR-16-5p, miR-18a-5p, miR-26b-5p, miR-27a-3p, miR-30e-5p, miR-199a-3p, miR-223-3p, miR-423-3p, miR-423-5p and miR-652-3p were measured by means of quantitative real time polymerase chain reaction (qRT-PCR) in plasma samples of 8 homozygous TGR(mREN2)27 (Ren2) transgenic rats and 8 (control) Sprague-Dawley rats, 6 mice with angiotensin II-induced heart failure (AngII) and 6 control mice, and 8 mice with ischemic heart failure and 6 controls. Circulating miRNA levels were compared between the heart failure animals and healthy controls.

Results

Ren2 rats, AngII mice and mice with ischemic heart failure showed clear signs of heart failure, exemplified by increased left ventricular and lung weights, elevated end-diastolic left ventricular pressures, increased expression of cardiac stress markers and reduced left ventricular ejection fraction. All miRNAs were detectable in plasma from rats and mice. No significant differences were observed between the circulating miRNAs in heart failure animals when compared to the healthy controls (all P>0.05) and no robust associations with cardiac function could be found.

Conclusions

The previous observation that miRNAs circulate in lower levels in human patients with heart failure could not be validated in well-established rat and mouse heart failure models. These results question the translation of data on human circulating miRNA levels to experimental models, and vice versa the validity of experimental miRNA data for human heart failure.

]]>