ResearchPad - cardiac-ventricles 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[Furin, a transcriptional target of NKX2-5, has an essential role in heart development and function]]> https://www.researchpad.co/article/5c897793d5eed0c4847d307a

The homeodomain transcription factor NKX2-5 is known to be essential for both normal heart development and for heart function. But little is yet known about the identities of its downstream effectors or their function during differentiation of cardiac progenitor cells (CPCs). We have used transgenic analysis and CRISPR-mediated ablation to identify a cardiac enhancer of the Furin gene. The Furin gene, encoding a proprotein convertase, is directly repressed by NKX2-5. Deletion of Furin in CPCs is embryonic lethal, with mutant hearts showing a range of abnormalities in the outflow tract. Those defects are associated with a reduction in proliferation and premature differentiation of the CPCs. Deletion of Furin in differentiated cardiomyocytes results in viable adult mutant mice showing an elongation of the PR interval, a phenotype that is consistent with the phenotype of mice and human mutant for Nkx2-5. Our results show that Furin mediate some aspects of Nkx2-5 function in the heart.

]]>
<![CDATA[Cardiovascular magnetic resonance imaging feature tracking: Impact of training on observer performance and reproducibility]]> https://www.researchpad.co/article/5c57e6d2d5eed0c484ef3edd

Background

Cardiovascular magnetic resonance feature tracking (CMR-FT) is increasingly used for myocardial deformation assessment including ventricular strain, showing prognostic value beyond established risk markers if used in experienced centres. Little is known about the impact of appropriate training on CMR-FT performance. Consequently, this study aimed to evaluate the impact of training on observer variance using different commercially available CMR-FT software.

Methods

Intra- and inter-observer reproducibility was assessed prior to and after dedicated one-hour observer training. Employed FT software included 3 different commercially available platforms (TomTec, Medis, Circle). Left (LV) and right (RV) ventricular global longitudinal as well as LV circumferential and radial strains (GLS, GCS and GRS) were studied in 12 heart failure patients and 12 healthy volunteers.

Results

Training improved intra- and inter-observer reproducibility. GCS and LV GLS showed the highest reproducibility before (ICC >0.86 and >0.81) and after training (ICC >0.91 and >0.92). RV GLS and GRS were more susceptible to tracking inaccuracies and reproducibility was lower. Inter-observer reproducibility was lower than intra-observer reproducibility prior to training with more pronounced improvements after training. Before training, LV strain reproducibility was lower in healthy volunteers as compared to patients with no differences after training. Whilst LV strain reproducibility was sufficient within individual software solutions inter-software comparisons revealed considerable software related variance.

Conclusion

Observer experience is an important source of variance in CMR-FT derived strain assessment. Dedicated observer training significantly improves reproducibility with most profound benefits in states of high myocardial contractility and potential to facilitate widespread clinical implementation due to optimized robustness and diagnostic performance.

]]>
<![CDATA[Dynamical anchoring of distant arrhythmia sources by fibrotic regions via restructuring of the activation pattern]]> https://www.researchpad.co/article/5c254501d5eed0c48442bcd2

Rotors are functional reentry sources identified in clinically relevant cardiac arrhythmias, such as ventricular and atrial fibrillation. Ablation targeting rotor sites has resulted in arrhythmia termination. Recent clinical, experimental and modelling studies demonstrate that rotors are often anchored around fibrotic scars or regions with increased fibrosis. However, the mechanisms leading to abundance of rotors at these locations are not clear. The current study explores the hypothesis whether fibrotic scars just serve as anchoring sites for the rotors or whether there are other active processes which drive the rotors to these fibrotic regions. Rotors were induced at different distances from fibrotic scars of various sizes and degree of fibrosis. Simulations were performed in a 2D model of human ventricular tissue and in a patient-specific model of the left ventricle of a patient with remote myocardial infarction. In both the 2D and the patient-specific model we found that without fibrotic scars, the rotors were stable at the site of their initiation. However, in the presence of a scar, rotors were eventually dynamically anchored from large distances by the fibrotic scar via a process of dynamical reorganization of the excitation pattern. This process coalesces with a change from polymorphic to monomorphic ventricular tachycardia.

]]>
<![CDATA[Deletion of Nkx2-5 in trabecular myocardium reveals the developmental origins of pathological heterogeneity associated with ventricular non-compaction cardiomyopathy]]> https://www.researchpad.co/article/5b4a28c7463d7e4513b8982a

Left ventricular non-compaction (LVNC) is a rare cardiomyopathy associated with a hypertrabeculated phenotype and a large spectrum of symptoms. It is still unclear whether LVNC results from a defect of ventricular trabeculae development and the mechanistic basis that underlies the varying severity of this pathology is unknown. To investigate these issues, we inactivated the cardiac transcription factor Nkx2-5 in trabecular myocardium at different stages of trabecular morphogenesis using an inducible Cx40-creERT2 allele. Conditional deletion of Nkx2-5 at embryonic stages, during trabecular formation, provokes a severe hypertrabeculated phenotype associated with subendocardial fibrosis and Purkinje fiber hypoplasia. A milder phenotype was observed after Nkx2-5 deletion at fetal stages, during trabecular compaction. A longitudinal study of cardiac function in adult Nkx2-5 conditional mutant mice demonstrates that excessive trabeculation is associated with complex ventricular conduction defects, progressively leading to strain defects, and, in 50% of mutant mice, to heart failure. Progressive impaired cardiac function correlates with conduction and strain defects independently of the degree of hypertrabeculation. Transcriptomic analysis of molecular pathways reflects myocardial remodeling with a larger number of differentially expressed genes in the severe versus mild phenotype and identifies Six1 as being upregulated in hypertrabeculated hearts. Our results provide insights into the etiology of LVNC and link its pathogenicity with compromised trabecular development including compaction defects and ventricular conduction system hypoplasia.

]]>
<![CDATA[Loss of ATP-Sensitive Potassium Channel Surface Expression in Heart Failure Underlies Dysregulation of Action Potential Duration and Myocardial Vulnerability to Injury]]> https://www.researchpad.co/article/5989da9bab0ee8fa60ba3dbc

The search for new approaches to treatment and prevention of heart failure is a major challenge in medicine. The adenosine triphosphate-sensitive potassium (KATP) channel has been long associated with the ability to preserve myocardial function and viability under stress. High surface expression of membrane KATP channels ensures a rapid energy-sparing reduction in action potential duration (APD) in response to metabolic challenges, while cellular signaling that reduces surface KATP channel expression blunts APD shortening, thus sacrificing energetic efficiency in exchange for greater cellular calcium entry and increased contractile force. In healthy hearts, calcium/calmodulin-dependent protein kinase II (CaMKII) phosphorylates the Kir6.2 KATP channel subunit initiating a cascade responsible for KATP channel endocytosis. Here, activation of CaMKII in a transaortic banding (TAB) model of heart failure is coupled with a 35–40% reduction in surface expression of KATP channels compared to hearts from sham-operated mice. Linkage between KATP channel expression and CaMKII is verified in isolated cardiomyocytes in which activation of CaMKII results in downregulation of KATP channel current. Accordingly, shortening of monophasic APD is slowed in response to hypoxia or heart rate acceleration in failing compared to non-failing hearts, a phenomenon previously shown to result in significant increases in oxygen consumption. Even in the absence of coronary artery disease, failing myocardium can be further injured by ischemia due to a mismatch between metabolic supply and demand. Ischemia-reperfusion injury, following ischemic preconditioning, is diminished in hearts with CaMKII inhibition compared to wild-type hearts and this advantage is largely eliminated when myocardial KATP channel expression is absent, supporting that the myocardial protective benefit of CaMKII inhibition in heart failure may be substantially mediated by KATP channels. Recognition of CaMKII-dependent downregulation of KATP channel expression as a mechanism for vulnerability to injury in failing hearts points to strategies targeting this interaction for potential preventives or treatments.

]]>
<![CDATA[The Alpha-1A Adrenergic Receptor in the Rabbit Heart]]> https://www.researchpad.co/article/5989dad8ab0ee8fa60bb8d8f

The alpha-1A-adrenergic receptor (AR) subtype is associated with cardioprotective signaling in the mouse and human heart. The rabbit is useful for cardiac disease modeling, but data on the alpha-1A in the rabbit heart are limited. Our objective was to test for expression and function of the alpha-1A in rabbit heart. By quantitative real-time reverse transcription PCR (qPCR) on mRNA from ventricular myocardium of adult male New Zealand White rabbits, the alpha-1B was 99% of total alpha-1-AR mRNA, with <1% alpha-1A and alpha-1D, whereas alpha-1A mRNA was over 50% of total in brain and liver. Saturation radioligand binding identified ~4 fmol total alpha-1-ARs per mg myocardial protein, with 17% alpha-1A by competition with the selective antagonist 5-methylurapidil. The alpha-1D was not detected by competition with BMY-7378, indicating that 83% of alpha-1-ARs were alpha-1B. In isolated left ventricle and right ventricle, the selective alpha-1A agonist A61603 stimulated a negative inotropic effect, versus a positive inotropic effect with the nonselective alpha-1-agonist phenylephrine and the beta-agonist isoproterenol. Blood pressure assay in conscious rabbits using an indwelling aortic telemeter showed that A61603 by bolus intravenous dosing increased mean arterial pressure by 20 mm Hg at 0.14 μg/kg, 10-fold lower than norepinephrine, and chronic A61603 infusion by iPRECIO programmable micro Infusion pump did not increase BP at 22 μg/kg/d. A myocardial slice model useful in human myocardium and an anthracycline cardiotoxicity model useful in mouse were both problematic in rabbit. We conclude that alpha-1A mRNA is very low in rabbit heart, but the receptor is present by binding and mediates a negative inotropic response. Expression and function of the alpha-1A in rabbit heart differ from mouse and human, but the vasopressor response is similar to mouse.

]]>
<![CDATA[Differential Effects of E2 on MAPK Activity in the Brain and Heart of Aged Female Rats]]> https://www.researchpad.co/article/5989da87ab0ee8fa60b9c8d8

Aging and the coincident loss of circulating estrogens at menopause lead to increased risks for neurological and cardiovascular pathologies. Clinical studies show that estrogen therapy (ET) can be beneficial in mitigating these negative effects, in both the brain and heart, when it is initiated shortly after the perimenopausal transition. However, this same therapy is detrimental when initiated >10 years postmenopause. Importantly, the molecular mechanisms underlying this age-related switch in ET efficacy are unknown. Estrogen receptors (ERs) mediate the neuroprotective and cardioprotective functions of estrogens by modulating gene transcription or, non-genomically, by activating second messenger signaling pathways, such as mitogen activated protein kinases (MAPK). These kinases are critical regulators of cell signaling pathways and have widespread downstream effects. Our hypothesis is that age and estrogen deprivation following menopause alters the expression and activation of the MAPK family members p38 and ERK in the brain and heart. To test this hypothesis, we used a surgically induced model of menopause in 18 month old rats through bilateral ovariectomy (OVX) followed by an acute dose of 17β-estradiol (E2) administered at varying time points post-OVX (1 week, 4 weeks, 8 weeks, or 12 weeks). Age and E2 treatment differentially regulated kinase activity in both the brain and heart, and the effects were also brain region specific. MAPK signaling plays an integral role in aging, and the aberrant regulation of those signaling pathways might be involved in age-related disorders. Clinical studies show benefits of ET during early menopause but detrimental effects later, which might be reflective of changes in kinase expression and activation status.

]]>
<![CDATA[Activation of Chymotrypsin-Like Activity of the Proteasome during Ischemia Induces Myocardial Dysfunction and Death]]> https://www.researchpad.co/article/5989dacdab0ee8fa60bb50fe

Inhibitors of the ubiquitin-proteasome system improve hemodynamic parameters and decrease the infarct size after ischemia reperfusion. The molecular basis of this protection is not fully understood since most available data report inhibition of the 26 proteasome after ischemia reperfusion. The decrease in cellular ATP levels during ischemia leads to the dissociation of the 26S proteasome into the 19S regulatory complex and the 20S catalytic core, which results in protein degradation independently of ubiquitination. There is scarce information on the activity of the 20S proteasome during cardiac ischemia. Accordingly, the aim of this work was to determine the effects of 30 minutes of ischemia, or 30 min of ischemia followed by 60 minutes of reperfusion on the three main peptidase activities of the 20S proteasome in Langendorff perfused rat hearts. We found that 30 min of ischemia produced a significant increase in the chymotrypsin-like activity of the proteasome, without changes in its caspase-like or trypsin-like activities. In contrast, all three activities were decreased upon reperfusion. Ixazomib, perfused before ischemia at a concentration that reduced the chymotrypsin-like activity to 50% of the control values, without affecting the other proteasomal activities, improved the hemodynamic parameters upon reperfusion and decreased the infarct size. Ixazomib also prevented the 50% reduction in RyR2 content observed after ischemia. The protection was lost, however, when simultaneous inhibition of chymotrypsin-like and caspase-like activities of the proteasome was achieved at higher concentration of ixazomib. Our results suggest that selective inhibition of chymotrypsin-like activity of the proteasome during ischemia preserves key proteins for cardiomyocyte function and exerts a positive impact on cardiac performance after reperfusion.

]]>
<![CDATA[The Effect of Haemodialysis Access Types on Cardiac Performance and Morbidities in Patients with Symptomatic Heart Disease]]> https://www.researchpad.co/article/5989dad8ab0ee8fa60bb8c30

Background

Little is known about whether the arteriovenous type haemodialysis access affects cardiac function and whether it is still advantageous to the uremic patient with symptomatic heart disease.

Methods

We conducted a retrospective comparative study. Patients with heart disease and end-stage renal disease that had a new chronic access created between January 2007 and December 2008 and met the inclusion criteria were assessed. The endpoint was major adverse event (MAE)-free survivals of arteriovenous access (AVA) and tunneled cuffed double-lumen central venous catheter (CVC) groups. Whether accesses worsened heart failure was also evaluated.

Results

There were 43 CVC patients and 60 AVA patients. The median follow-up time from access creation was 27.6 months (IQR 34.7, 10.9~45.6). Although CVC patients were older than AVA patients (median age 78.0, IQR 14.0 vs. 67.5, IQR 16.0, respectively, p = .009), they manifested non-inferior MAE-free survival (mean 17.1, 95% CI 10.3~24.0 vs. 12.9, 95% CI 8.5~17.4 months in CVC and AVA patients, respectively, p = .290). During follow-up, more patients in the AVA group than in the CVC group deteriorated in heart failure status (35 of 57 vs. 10 of 42, respectively, odds ratio 5.1, p < .001). Preoperative-postoperative pairwise comparison of echocardiographic scans revealed an increased number of abnormal findings in the AVA group (Z = 3.91, p < .001), but not in the CVC group.

Conclusions

In patients with both symptomatic heart disease and end stage renal disease (ESRD), CVC patients showed non-inferior MAE-free survival in comparison to those in the AVA group. AV type access could deteriorate heart failure. Accordingly, uremic patients with symptomatic heart disease are not ideal candidates for AV type access creation.

]]>
<![CDATA[Effects of Malnutrition on Left Ventricular Mass in a North-Malagasy Children Population]]> https://www.researchpad.co/article/5989da8bab0ee8fa60b9e1f0

Background

Malnutrition among children population of less developed countries is a major health problem. Inadequate food intake and infectious diseases are combined to increase further the prevalence. Malnourishment brings to muscle cells loss with development of cardiac complications, like arrhythmias, cardiomyopathy and sudden death. In developed countries, malnutrition has generally a different etiology, like chronic diseases. The aim of our study was to investigate the correlation between malnutrition and left ventricular mass in an African children population.

Methods

313 children were studied, in the region of Antsiranana, Madagascar, with age ranging from 4 to 16 years old (mean 7,8 ± 3 years). A clinical and echocardiographic evaluation was performed with annotation of anthropometric and left ventricle parameters. Malnutrition was defined as a body mass index (BMI) value age- and sex-specific of 16, 17 and 18,5 at the age of 18, or under the 15th percentile. Left ventricle mass was indexed by height2.7 (LVMI).

Results

We identified a very high prevalence of children malnutrition: 124 children, according to BMI values, and 100 children under the 15th percentile. LVMI values have shown to be increased in proportion to BMI percentiles ranging from 29,8 ± 10,8 g/m2.7 in the malnutrition group to 45 ± 15,1 g/m2.7 in >95th percentile group. LVMI values in children < 15th BMI percentile were significantly lower compared to normal nutritional status (29,8 ± 10,8 g/m2,7 vs. 32,9 ± 12,1 g/m2,7, p = 0.02). Also with BMI values evaluation, malnourished children showed statistically lower values of LVMI (29,3 ± 10,1 g/m2,7 vs. 33,6 ± 12,5 g/m2,7, p = 0.001).

Conclusion

In African children population, the malnourishment status is correlated with cardiac muscle mass decrease, which appears to be reduced in proportion to the decrease in body size.

]]>
<![CDATA[Relations between Cardiac and Visual Phenotypes in Diabetes: A Multivariate Approach]]> https://www.researchpad.co/article/5989d9e4ab0ee8fa60b6a815

Cardiovascular disease and diabetes represent a major public health concern. The former is the most frequent cause of death and disability in patients with type 2 diabetes, where left ventricular dysfunction is highly prevalent. Moreover, diabetic retinopathy is becoming a dominant cause of visual impairment and blindness. The complex relation between cardiovascular disease and diabetic retinopathy as a function of ageing, obesity and hypertension remains to be clarified. Here, we investigated such relations in patients with diabetes type 2, in subjects with neither overt heart disease nor advanced proliferative diabetic retinopathy. We studied 47 patients and 50 controls, aged between 45 and 65 years, equally distributed according to gender. From the 36 measures regarding visual structure and function, and the 11 measures concerning left ventricle function, we performed data reduction to obtain eight new derived variables, seven of which related to the eye, adjusted for age, gender, body mass index and high blood pressure using both discriminant analysis (DA) and logistic regression (LR). We found moderate to strong correlation between left ventricle function and the eye constructs: minimum correlation was found for psychophysical motion thresholds (DA: 0.734; LR: 0.666), while the maximum correlation was achieved with structural volume density in the neural retina (DA: 0.786; LR: 0.788). Controlling the effect of pairwise correlated visual constructs, the parameters that were most correlated to left ventricle function were volume density in retina and thickness of the retinal nerve fiber layers (adjusted multiple R2 is 0.819 and 0.730 for DA and LR), with additional contribution of psychophysical loss in achromatic contrast discrimination. We conclude that visual structural and functional changes in type 2 diabetes are related to heart dysfunction, when the effects of clinical, demographic and associated risk factors are taken into account, revealing a genuine relation between cardiac and retinal diabetic phenotypes.

]]>
<![CDATA[Altered Diastolic Flow Patterns and Kinetic Energy in Subtle Left Ventricular Remodeling and Dysfunction Detected by 4D Flow MRI]]> https://www.researchpad.co/article/5989da30ab0ee8fa60b84103

Aims

4D flow magnetic resonance imaging (MRI) allows quantitative assessment of left ventricular (LV) function according to characteristics of the dynamic flow in the chamber. Marked abnormalities in flow components’ volume and kinetic energy (KE) have previously been demonstrated in moderately dilated and depressed LV’s compared to healthy subjects. We hypothesized that these 4D flow-based measures would detect even subtle LV dysfunction and remodeling.

Methods and Results

We acquired 4D flow and morphological MRI data from 26 patients with chronic ischemic heart disease with New York Heart Association (NYHA) class I and II and with no to mild LV systolic dysfunction and remodeling, and from 10 healthy controls. A previously validated method was used to separate the LV end-diastolic volume (LVEDV) into functional components: direct flow, which passes directly to ejection, and non-ejecting flow, which remains in the LV for at least 1 cycle. The direct flow and non-ejecting flow proportions of end-diastolic volume and KE were assessed. The proportions of direct flow volume and KE fell with increasing LVEDV-index (LVEDVI) and LVESV-index (LVESVI) (direct flow volume r = -0.64 and r = -0.74, both P<0.001; direct flow KE r = -0.48, P = 0.013, and r = -0.56, P = 0.003). The proportions of non-ejecting flow volume and KE rose with increasing LVEDVI and LVESVI (non-ejecting flow volume: r = 0.67 and r = 0.76, both P<0.001; non-ejecting flow KE: r = 0.53, P = 0.005 and r = 0.52, P = 0.006). The proportion of direct flow volume correlated moderately to LVEF (r = 0.68, P < 0.001) and was higher in a sub-group of patients with LVEDVI >74 ml/m2 compared to patients with LVEDVI <74 ml/m2 and controls (both P<0.05).

Conclusion

Direct flow volume and KE proportions diminish with increased LV volumes, while non-ejecting flow proportions increase. A decrease in direct flow volume and KE at end-diastole proposes that alterations in these novel 4D flow-specific markers may detect LV dysfunction even in subtle or subclinical LV remodeling.

]]>
<![CDATA[Acute exhaustive aerobic exercise training impair cardiomyocyte function and calcium handling in Sprague-Dawley rats]]> https://www.researchpad.co/article/5989db50ab0ee8fa60bdbdb8

Introduction

Recent data from long-distance endurance participants suggest that cardiac function is impaired after completion. Existing data further indicate that right ventricular function is more affected than left ventricular function. The cellular mechanisms underpinning cardiac deterioration are limited and therefore the aim of this study was to examine cardiomyocyte and molecular responses of the right and left ventricle to an acute bout of exhaustive endurance exercise.

Materials and methods

Male Sprague-Dawley rats were assigned to sedentary controls or acute exhaustive endurance exercise consisting of a 120 minutes long forced treadmill run. The contractile function and Ca2+ handling properties in isolated cardiomyocytes, protein expression levels of sarcoplasmic reticulum Ca2+-ATPase and phospholamban including two of its phosphorylated states (serine 16 and threonine 17), and the mitochondrial respiration in permeabilized cardiac muscle fibers were analyzed.

Results

The exercise group showed a significant reduction in cardiomyocyte fractional shortening (right ventricle 1 Hz and 3 Hz p<0.001; left ventricle 1 Hz p<0.05), intracellular Ca2+ amplitude (right ventricle 1 and 3 Hz p<0.001; left ventricle 1 Hz p<0.01 and 3 Hz p<0.05) and rate of diastolic Ca2+ decay (right ventricle 1 Hz p<0.001 and 3 Hz p<0.01; left ventricle 1 and 3 Hz p<0.01). Cardiomyocyte relaxation during diastole was only significantly prolonged at 3 Hz in the right ventricle (p<0.05) compared to sedentary controls. We found an increase in phosphorylation of phospholamban at serine 16 and threonine 17 in the left (p<0.05), but not the right, ventricle from exhaustively exercised animals. The protein expression levels of sarcoplasmic reticulum Ca2+-ATPase and phospholamban was not changed. Furthermore, we found a reduction in maximal oxidative phosphorylation and electron transport system capacities of mitochondrial respiration in the right (p<0.01 and p<0.05, respectively), but not the left ventricle from rats subjected to acute exhaustive treadmill exercise.

Conclusion

Acute exhaustive treadmill exercise is associated with impairment of cardiomyocyte Ca2+ handling and mitochondrial respiration that causes depression in both contraction and diastolic relaxation of cardiomyocytes.

]]>
<![CDATA[Determinants of Indices of Cerebral Volume in Former Very Premature Infants at Term Equivalent Age]]> https://www.researchpad.co/article/5989db4fab0ee8fa60bdb9f2

Conventional magnetic resonance imaging (MRI) at term equivalent age (TEA) is suggested to be a reliable tool to predict the outcome of very premature infants. The objective of this study was to determine simple reproducible MRI indices, in premature infants and to analyze their neonatal determinants at TEA. A cohort of infants born before 32 weeks gestational age (GA) underwent a MRI at TEA in our center. Two axial images (T2 weighted), were chosen to realize nine measures. We defined 4 linear indices (MAfhlv: thickness of lateral ventricle; CSI: cortex-skull index; VCI: ventricular-cortex index; BOI: bi occipital index) and 1 surface index (VS.A: volume slice area). Perinatal data were recorded. Sixty-nine infants had a GA (median (interquartile range)) of 30.0 weeks GA (27.0; 30.0) and a birth weight of 1240 grams (986; 1477). MRI was done at 41.0 (40.0; 42.0) weeks post menstrual age (PMA). The inter-investigator reproducibility was good. Twenty one MRI (30.5%) were quoted abnormal. We observed an association with retinopathy of prematurity (OR [95CI] = 4.205 [1.231–14.368]; p = 0.017), surgery for patent ductus arteriosus (OR = 4.688 [1.01–21.89]; p = 0.036), early onset infection (OR = 4.688 [1.004–21.889]; p = 0.036) and neonatal treatment by cefotaxime (OR = 3.222 [1.093–9.497]; p = 0.03). There was a difference for VCI between normal and abnormal MRI (0.412 (0.388; 0.429) vs. 0.432 (0.418; 0.449); p = 0,019); BOI was higher when fossa posterior lesions were observed; VS.A seems to be the best surrogate for cerebral volume, 80% of VS.As’ variance being explained by a multiple linear regression model including 7 variables (head circumference at birth and at TEA, PMA, dopamine, ibuprofen treatment, blood and platelets transfusions). These indices, easily and rapidly achievable, seem to be useful but need to be validated in a large population to allow generalization for diagnosis and follow-up of former premature infants.

]]>
<![CDATA[Extracorporeal life support prior to left ventricular assist device implantation leads to improvement of the patients INTERMACS levels and outcome]]> https://www.researchpad.co/article/5989db52ab0ee8fa60bdc62b

Background

The objective of this study was to evaluate the outcome of left ventricular assist device (LVAD) implantation after initial extracorporeal life support (ECLS) in patients with cardiogenic shock and the incidence of post implantation right ventricular failure.

Methods & results

All patients on ECLS therapy for cardiogenic shock prior to LVAD implantation (n = 15) between October 2011 and January 2014 were analyzed. Baseline patient characteristics, as well as detailed pre-operative treatment and postoperative outcome data were collected retrospectively. At time of admission to our unit all patients were classified INTERMACS II or higher (12 [80%] INTERMACS I). Improvement to INTERMACS III temporary cardiac support (TCS) at time of LVAD implantation was successful in 14 patients (93.3%). End-organ function recovered during ECLS support. No patient needed ongoing ECLS or additional right ventricular support after LVAD implantation. Both in-hospital and 30-day mortality was 6.7% (n = 1). The median duration of LVAD support was 687.9 ± 374.5 days. At the end of the study (follow-up 810.7 +/- 338.9 days), 13 (86.7%) patients were alive. The majority of patients (10 [66.7%]) remained on LVAD support. Transplantation could be performed in 1 (6.7%) patient, 2 (13.3%) patients could be successfully weaned.

Conclusion

LVAD implantation in ECLS patients leads to improvement of INTERMACS level to INTERMACS III TCS status. Excellent mid-term survival comparable to true INTERMACS III-IV patients could be shown. ECLS prior to LVAD as a bridge-to-bridge therapy may help to lower mortality in primarily unstable patients.

]]>
<![CDATA[Embryonic Ethanol Exposure Dysregulates BMP and Notch Signaling, Leading to Persistent Atrio-Ventricular Valve Defects in Zebrafish]]> https://www.researchpad.co/article/5989da24ab0ee8fa60b7ff8a

Fetal alcohol spectrum disorder (FASD), birth defects associated with ethanol exposure in utero, includes a wide spectrum of congenital heart defects (CHDs), the most prevalent of which are septal and conotruncal defects. Zebrafish FASD model was used to dissect the mechanisms underlying FASD-associated CHDs. Embryonic ethanol exposure (3–24 hours post fertilization) led to defects in atrio-ventricular (AV) valvulogenesis beginning around 37 hpf, a morphogenetic event that arises long after ethanol withdrawal. Valve leaflets of the control embryos comprised two layers of cells confined at the compact atrio-ventricular canal (AVC). Ethanol treated embryos had extended AVC and valve forming cells were found either as rows of cells spanning the AVC or as unorganized clusters near the AV boundary. Ethanol exposure reduced valve precursors at the AVC, but some ventricular cells in ethanol treated embryos exhibited few characteristics of valve precursors. Late staged larvae and juvenile fish exposed to ethanol during embryonic development had faulty AV valves. Examination of AVC morphogenesis regulatory networks revealed that early ethanol exposure disrupted the Bmp signaling gradient in the heart during valve formation. Bmp signaling was prominent at the AVC in controls, but ethanol-exposed embryos displayed active Bmp signaling throughout the ventricle. Ethanol exposure also led to mislocalization of Notch signaling cells in endocardium during AV valve formation. Normally, highly active Notch signaling cells were organized at the AVC. In ethanol-exposed embryos, highly active Notch signaling cells were dispersed throughout the ventricle. At later stages, ethanol-exposed embryos exhibited reduced Wnt/β-catenin activity at the AVC. We conclude that early embryonic ethanol exposure alters Bmp, Notch and other signaling activities during AVC differentiation leading to faulty valve morphogenesis and valve defects persist in juvenile fish.

]]>
<![CDATA[Comparative Quantitative Studies on the Microvasculature of the Heart of a Highly Selected Meat-Type and a Wild-Type Turkey Line]]> https://www.researchpad.co/article/5989db53ab0ee8fa60bdcc56

In this study the macroscopic and microscopic structure of the heart of a fast growing, meat-type turkey line (British United turkeys BUT Big 6) and a wild-type turkey line (Canadian Wild turkey) were compared. At 8 and 16 weeks of age, 10 birds of each genotype and sex were sampled. The body mass and heart mass of the meat-type turkey both increased at a faster rate than those of the wild-type turkey. However in both turkey lines, the relative heart mass decreased slightly with age, the decrease was statistically significant only in the male turkeys. Furthermore meat-type turkeys had a significantly (p < 0.01) lower relative heart mass and relative thickness of the left ventricle compared to the wild-type turkeys of the same age. The wild-type turkeys showed no significant change in the size of cardiomyocytes (cross sectional area and diameter) from 8 weeks to 16 weeks. In contrast, the size of cardiomyocytes increased significantly (p < 0.001) with age in the meat-type turkeys. The number of capillaries in the left ventricular wall increased significantly (p < 0.001) in wild-type turkeys from 2351 per mm2 at the age of 8 weeks to 2843 per mm2 at 16 weeks. However, in the meat-type turkeys there were no significant changes, capillary numbers being 2989 per mm2 at age 8 weeks and 2915 per mm2 at age 16 weeks. Correspondingly the area occupied by capillaries in the myocardium increased in wild-type turkeys from 8.59% at the age of 8 weeks to 9.15% at 16 weeks, whereas in meat-type turkeys this area decreased from 10.4% at 8 weeks to 9.95% at 16 weeks. Our results indicate a mismatch in development between body mass and heart mass and a compromised cardiac capillary density and architecture in the meat-type turkeys in comparison to the wild-type turkeys.

]]>
<![CDATA[T-wave loop area from a pre-implant 12-lead ECG is associated with appropriate ICD shocks]]> https://www.researchpad.co/article/5989db50ab0ee8fa60bdbf0f

Aims

In implantable cardioverter-defibrillator (ICD) patients, predictors of ICD shocks and mortality are needed to improve patient selection. Electrocardiographic (ECG) markers are simple to obtain and have been demonstrated to predict mortality. We aimed to assess the association of T-wave loop area and circularity with ICD shocks.

Methods

The study investigated patients with ICDs implanted between 1998 and 2010 for whom digital 12-lead ECGs (Schiller CS200 ECG-Network) of sufficient quality were obtained within 1 month prior to the implantation. T-wave loop area and circularity were calculated. Follow-up data of appropriate shocks were obtained during ICD clinic visits that included reviews of device stored electrograms.

Results

A total of 605 patients (82% males) were included; 68% had ischemic cardiomyopathy and 72% were treated for primary prevention. Over 3.8±1.4 years of follow-up, 114 patients (19%) experienced appropriate shock(s). Those with smaller T-wave loop area received fewer shocks (TLA, hazard ratio, HR, per increase of 1 technical unit, 0.71; [95% confidence interval, 0.53–0.94]; P = 0.02) and those with larger T-wave loop circularity (TLC) representing rounder T wave loop received more shocks (HR per 1% TLC increase 2.96; [0.85–10.36]; P = 0.09). When the quartile containing the largest TLA and TLC values, respectively, were compared to the remaining cases, TLA remained significantly associated with fewer and TLC with more frequent shocks also after multivariate adjustment for clinical variables (HR, 0.59 [0.35–0.99], P = 0.044; and 1.64 [1.08–2.49], P = 0.021, respectively).

Conclusions

The size and shape of the T-wave loop calculated from pre-implantation 12-lead ECGs are associated with appropriate ICD shocks.

]]>
<![CDATA[Estrogen Protects the Female Heart from Ischemia/Reperfusion Injury through Manganese Superoxide Dismutase Phosphorylation by Mitochondrial p38β at Threonine 79 and Serine 106]]> https://www.researchpad.co/article/5989d9f3ab0ee8fa60b6f446

A collective body of evidence indicates that estrogen protects the heart from myocardial ischemia/reperfusion (I/R) injury, but the underlying mechanism remains incompletely understood. We have previously delineated a novel mechanism of how 17β-estradiol (E2) protects cultured neonatal rat cardiomyocytes from hypoxia/reoxygenation (H/R) by identifying a functionally active mitochondrial pool of p38β and E2-driven upregulation of manganese superoxide dismutase (MnSOD) activity via p38β, leading to the suppression of reactive oxygen species (ROS) and apoptosis. Here we investigate these cytoprotective actions of E2 in vivo. Left coronary artery ligation and reperfusion was used to produce I/R injury in ovariectomized (OVX) female mice and in estrogen receptor (ER) null female mice. E2 treatment in OVX mice reduced the left ventricular infarct size accompanied by increased activity of mitochondrial p38β and MnSOD. I/R-induced infarct size in ERα knockout (ERKO), ERβ knockout (BERKO) and ERα and β double knockout (DERKO) female mice was larger than that in wild type (WT) mice, with little difference among ERKO, BERKO, and DERKO. Loss of both ERα and ERβ led to reduced activity of mitochondrial p38β and MnSOD at baseline and after I/R. The physical interaction between mitochondrial p38β and MnSOD in the heart was detected by co-immunoprecipitation (co-IP). Threonine 79 (T79) and serine 106 (S106) of MnSOD were identified to be phosphorylated by p38β in kinase assays. Overexpression of WT MnSOD in cardiomyocytes reduced ROS generation during H/R, while point mutation of T79 and S106 of MnSOD to alanine abolished its antioxidative function. We conclude that the protective effects of E2 and ER against cardiac I/R injury involve the regulation of MnSOD via posttranslational modification of the dismutase by p38β.

]]>