Effects of anesthesia on conventional and speckle tracking echocardiographic parameters in a mouse model of pressure overload

Genetically‑modified mice are widely applied in cardiovascular studies as model organisms. Echocardiography is a key tool for evaluating cardiac and hemodynamic functions in mice. The present study aimed to examine the effects of isoflurane (ISF) on conventional and speckle tracking echocardiography (STE) parameters under healthy and pathological conditions using a murine model of pressure overload. In addition, the optimal dose of ISF in the process of echocardiographic measurement, with minimum cardiac contraction depression, was investigated. Conventional echocardiographic and STE examinations were performed on 38 adult C57BL/6 male mice. The mice were divided into the following three groups: The sham (n=15); mild thoracic aortic banding (TAB; n=15); and severe TAB (n=8) groups. ISF was administered under deep anesthesia (DA; 1‑2% ISF), light anesthesia (LA; 0.5‑1% ISF) and immediately prior to the mice waking up (awake; 0‑0.5% ISF). Conventional echocardiographic parameters were preserved within the sham and mild TAB groups (P>0.05 for each parameter) under LA and awake conditions. However, under DA conditions, the majority of these parameters were reduced compared with the LA and awake conditions (P<0.05). In the severe TAB group, conventional echocardiographic parameters remained constant under LA, DA and awake conditions. STE parameters in the groups remained similar between the LA and awake conditions, but were significantly reduced under DA conditions. Therefore, conventional echocardiography and STE may be performed using LA induced with low doses of ISF, under various pathological conditions without affecting cardiac function

Myocardial aging as a T-cell–mediated phenomenon

In recent years, the myocardium has been rediscovered under the lenses of immunology, and lymphocytes have been implicated in the pathogenesis of cardiomyopathies with different etiologies. Aging is an important risk factor for heart diseases, and it also has impact on the immune system. Thus, we sought to determine whether immunological activity would influence myocardial structure and function in elderly mice. Morphological, functional, and molecular analyses revealed that the age-related myocardial impairment occurs in parallel with shifts in the composition of tissue-resident leukocytes and with an accumulation of activated CD4+ Foxp3- (forkhead box P3) IFN-γ+ T cells in the heart-draining lymph nodes. A comprehensive characterization of different aged immune-deficient mouse strains revealed that T cells significantly contribute to age-related myocardial inflammation and functional decline. Upon adoptive cell transfer, the T cells isolated from the mediastinal lymph node (med-LN) of aged animals exhibited increased cardiotropism, compared with cells purified from young donors or from other irrelevant sites. Nevertheless, these cells caused rather mild effects on cardiac functionality, indicating that myocardial aging might stem from a combination of intrinsic and extrinsic (immunological) factors. Taken together, the data herein presented indicate that heart-directed immune responses may spontaneously arise in the elderly, even in the absence of a clear tissue damage or concomitant infection. These observations might shed new light on the emerging role of T cells in myocardial diseases, which primarily affect the elderly population.info:eu-repo/semantics/publishedVersio

Automatic segmentation of the left ventricle cavity and myocardium in MRI data

A novel approach for the automatic segmentation has been developed to extract the epi-cardium and endo-cardium boundaries of the left ventricle (lv) of the heart. The developed segmentation scheme takes multi-slice and multi-phase magnetic resonance (MR) images of the heart, transversing the short-axis length from the base to the apex. Each image is taken at one instance in the heart's phase. The images are segmented using a diffusion-based filter followed by an unsupervised clustering technique and the resulting labels are checked to locate the (lv) cavity. From cardiac anatomy, the closest pool of blood to the lv cavity is the right ventricle cavity. The wall between these two blood-pools (interventricular septum) is measured to give an approximate thickness for the myocardium. This value is used when a radial search is performed on a gradient image to find appropriate robust segments of the epi-cardium boundary. The robust edge segments are then joined using a normal spline curve. Experimental results are presented with very encouraging qualitative and quantitative results and a comparison is made against the state-of-the art level-sets method

Therapeutic Effect of Targeting Branched-Chain Amino Acid Catabolic Flux in Pressure-Overload Induced Heart Failure.

Background Branched-chain amino acid (BCAA) catabolic defect is an emerging metabolic hallmark in failing hearts in human and animal models. The therapeutic impact of targeting BCAA catabolic flux under pathological conditions remains understudied. Methods and Results BT2 (3,6-dichlorobenzo[b]thiophene-2-carboxylic acid), a small-molecule inhibitor of branched-chain ketoacid dehydrogenase kinase, was used to enhance BCAA catabolism. After 2 weeks of transaortic constriction, mice with significant cardiac dysfunctions were treated with vehicle or BT2. Serial echocardiograms showed continuing pathological deterioration in left ventricle of the vehicle-treated mice, whereas the BT2-treated mice showed significantly preserved cardiac function and structure. Moreover, BT2 treatment improved systolic contractility and diastolic mechanics. These therapeutic benefits appeared to be independent of impacts on left ventricle hypertrophy but associated with increased gene expression involved in fatty acid utilization. The BT2 administration showed no signs of apparent toxicity. Conclusions Our data provide the first proof-of-concept evidence for the therapeutic efficacy of restoring BCAA catabolic flux in hearts with preexisting dysfunctions. The BCAA catabolic pathway represents a novel and potentially efficacious target for treatment of heart failure

Changes in left atrial deformation in hypertrophic cardiomyopathy: Evaluation by vector velocity imaging.

OBJECTIVES: Hypertrophic cardiomyopathy (HCM) represents a generalized myopathic process affecting both ventricular and atrial myocardium. We assessed the global and regional left atrial (LA) function and its relation to left ventricular (LV) mechanics and clinical status in patients with HCM using Vector Velocity Imaging (VVI). METHODS: VVI of the LA and LV was acquired from apical four- and two-chamber views of 108 HCM patients (age 40 ± 19years, 56.5% men) and 33 healthy subjects, all had normal LV systolic function. The LA subendocardium was traced to obtain atrial volumes, ejection fraction, velocities, and strain (ϵ)/strain rate (SR) measurements. RESULTS: Left atrial reservoir (ϵsys,SRsys) and conduit (early diastolic SRe) function were significantly reduced in HCM compared to controls (P  - 1.8s(- 1) was 81% sensitive and 30% specific, SRa> - 1.5s(- 1) was 73% sensitive and 40% specific. By multivariate analysis global LVϵsys and LV septal thickness are independent predictors for LAϵsys, while end systolic diameter is the only independent predictor for SRsys, P < .001. CONCLUSION: Left atrial reservoir and conduit function as measured by VVI were significantly impaired while contractile function was preserved among HCM patients. Left atrial deformation was greatly influenced by LV mechanics and correlated to severity of phenotype

Early diagnosis of cardiovascular diseases in workers: role of standard and advanced echocardiography

Cardiovascular disease (CVD) still remains the main cause of morbidity and mortality and consequently early diagnosis is of paramount importance. Working conditions can be regarded as an additional risk factor for CVD. Since different aspects of the job may affect vascular health differently, it is important to consider occupation from multiple perspectives to better assess occupational impacts on health. Standard echocardiography has several targets in the cardiac population, as the assessment of myocardial performance, valvular and/or congenital heart disease, and hemodynamics. Three-dimensional echocardiography gained attention recently as a viable clinical tool in assessing left ventricular (LV) and right ventricular (RV), volume, and shape. Two-dimensional (2DSTE) and, more recently, three-dimensional speckle tracking echocardiography (3DSTE) have also emerged as methods for detection of global and regional myocardial dysfunction in various cardiovascular diseases, and applied to the diagnosis of subtle LV and RV dysfunction. Although these novel echocardiographic imaging modalities have advanced our understanding of LV and RV mechanics, overlapping patterns often show challenges that limit their clinical utility. This review will describe the current state of standard and advanced echocardiography in early detection (secondary prevention) of CVD and address future directions for this potentially important diagnostic strategy

Left-ventricle myocardium segmentation using a coupled level-set with a priori knowledge

This paper presents a coupled level-set segmentation of the myocardium of the left ventricle of the heart using a priori information. From a fast marching initialisation, two fronts representing the endocardium and epicardium boundaries of the left ventricle are evolved as the zero level-set of a higher dimension function. We introduce a novel and robust stopping term using both gradient and region-based information. The segmentation is supervised both with a coupling function and using a probabilistic model built from training instances. The robustness of the segmentation scheme is evaluated by performing a segmentation on four unseen data-sets containing high variation and the performance of the segmentation is quantitatively assessed

Myocarditis, disseminated infection, and early viral persistence following experimental coxsackievirus B infection of cynomolgus monkeys.

Coxsackievirus B (CVB) infection is a common cause of acute viral myocarditis. The clinical presentation of myocarditis caused by this enterovirus is highly variable, ranging from mildly symptoms to complete hemodynamic collapse. These variations in initial symptoms and in the immediate and long term outcomes of this disease have impeded development of effective treatment strategies. Nine cynomolgus monkeys were inoculated with myocarditic strains of CVB. Virological studies performed up to 28 days post-inoculation demonstrated the development of neutralizing antibody in all animals, and the presence of CVB in plasma. High dose intravenous inoculation (n = 2) resulted in severe disseminated disease, while low dose intravenous (n = 6) or oral infection (1 animal) resulted in clinically unapparent infection. Transient, minor, echocardiographic abnormalities were noted in several animals, but no animals displayed signs of significant acute cardiac failure. Although viremia rapidly resolved, signs of myocardial inflammation and injury were observed in all animals at the time of necropsy, and CVB was detected in postmortem myocardial specimens up to 28 days PI. This non-human primate system replicates many features of illness in acute coxsackievirus myocarditis and demonstrates that myocardial involvement may be common in enteroviral infection; it may provide a model system for testing of treatment strategies for enteroviral infections and acute coxsackievirus myocarditis

The Relationship of Left Ventricular Trabeculation to Ventricular Function and Structure Over a 9.5-Year Follow-Up The MESA Study

Left ventricular (LV) trabeculation is highly variable among individuals and is increased in some diseases (e.g., congenital heart disease or cardiomyopathies), but its significance in population-representative individuals is unknown

Toward three-dimensional echocardiographic determination of regional myofiber structure

As a step toward the goal of relating changes in underlying myocardial structure to observed altered cardiac function in the hearts of individual patients, this study addresses the feasibility of creating echocardiography-derived maps of regional myocardial fiber structure for entire, intact, excised sheep hearts. Backscatter data were obtained from apical echocardiographic images acquired with a clinical ultrasonic imaging system and used to determine local fiber orientations in each of seven hearts. Systematic acquisition across the entire heart volume provided information sufficient to give a complete map for each heart. Results from the echocardiography-derived fiber maps compare favorably with corresponding results derived from diffusion tensor magnetic resonance imaging. The results of this study provide evidence of the feasibility of using echocardiographic methods to generate individualized whole heart fiber maps for patients