The Interventricular Septum Is Biomechanically Distinct from the Ventricular Free Walls

The interventricular septum contributes to the pumping function of both ventricles. However, unlike the ventricular wall, its mechanical behavior remains largely unknown. To fill the knowledge gap, this study aims to characterize the biaxial and transmural variation of the mechanical properties of the septum and compare it to the free walls of the left and right ventricles (LV/RV). Fresh hearts were obtained from healthy, adult sheep. The septal wall was sliced along the mid-line into two septal sides and compared to the epicardial layers of the LV- and RV-free walls. Biaxial tensile mechanical tests and constitutive modeling were performed to obtain the passive mechanical properties of the LV- and RV-side of the septum and ventricular walls. We found that both sides of the septum were significantly softer than the respective ventricular walls, and that the septum presented significantly less collagen than the ventricular walls. At low strains, we observed the symmetric distribution of the fiber orientations and a similar anisotropic behavior between the LV-side and RV-side of the septum, with a stiffer material property in the longitudinal direction, rather than the circumferential direction. At high strains, both sides showed isotropic behavior. Both septal sides had similar intrinsic elasticity, as evidenced by experimental data and constitutive modeling. These new findings offer important knowledge of the biomechanics of the septum wall, which may deepen the understanding of heart physiology.

AGE-RELATED FEATURES OF THE CARDIAC OUTPUT IN BASIC POSE CONDITIONS (STANDING/LYING)

The aim of the work was to show the dynamics of cardiac output (CO) in standing and lying positions in postnatal ontogenesis. Material and methods. The data were obtained on the basis of an observational study in 1944 people (1308 men and 636 women). The following age groups were: up to 8 years (n=55), 9-14 years (n=68), 15-21 years (n=226), 22-35 years (n=326), 36-55 years for women and 36-60 years for men (n=658), up to 70 years (n=413) and over 70 years (n=198). The study was performed standing up and after 15-20 minutes in the supine position on the complex of the expert diagnostic system “ANTHROPOS-CAVASCREEN” based on rheography. Results. Our data justify the identification of the type of dynamic organization of blood circulation in humans by the anthropo-physiological ratio of CO in standing/lying positions. The transition to a hyperkinetic state in orthostatics is a manifestation of adaptation to the gravitational (hydrostatic) factor of blood circulation to ensure the circulatory state of the cardiovascular system in the most constant and relevant for human life conditions of upright walking. The obvious direction of such adaptation is the centralization of blood circulation in the standing position and the formation of a hyperkinetic state of the pumping function of the heart. This orientation reflects the strained state of the cardiovascular system in the anti-gravity support mode, which not only limits the functional reserve for cardiac output in the standing position, but also clearly associated with the growth of both problematic circulatory conditions and nosological states formed on this basis.

Start codon disruption with CRISPR/Cas9 prevents murine Fuchs' endothelial corneal dystrophy

A missense mutation of collagen type VIII alpha 2 chain (COL8A2) gene leads to early onset Fuchs' endothelial corneal dystrophy (FECD), which progressively impairs vision through loss of corneal endothelial cells. We demonstrate that CRISPR/Cas9-based postnatal gene editing achieves structural and functional rescue in a mouse model of FECD. A single intraocular injection of an adenovirus encoding both the Cas9 gene and guide RNA (Ad-Cas9-Col8a2gRNA), efficiently knocked down mutant COL8A2 expression in corneal endothelial cells, prevented endothelial cell loss, and rescued corneal endothelium pumping function in adult Col8a2 mutant mice. There were no adverse sequelae on histology or electroretinography. Col8a2 start codon disruption represents a non-surgical strategy to prevent vision loss in early-onset FECD. As this demonstrates the ability of Ad-Cas9-gRNA to restore phenotype in adult post-mitotic cells, this method may be widely applicable to adult-onset diseases, even in tissues affected with disorders of non-reproducing cells.

Emerging Molecular Pathways Involved in Pathophysiology of Cardiac Remodeling

Mammalian heart is a dynamic organ that can adapt morphological changes in response to alteration in workload. Various clinical and experimental findings revealed that in response to physiological stimuli or pathological insults, the heart undergoes cardiac remodeling which can be characterized by molecular, cellular or interstitial changes and can be manifested clinically as changes in size, shape and pumping function of the heart. A Sound understanding of changes in hearts cellular and molecular components and to mediators that derive homeostatic control is necessary before a specific intervention is pursued. Summarized data of this review comprises role of various novel emerging molecular pathways involvement in the pathophysiology of cardiac remodeling. Keywords: Cardiac remodeling, hypertrophy, protein kinase, heart failure, molecular targets, pathological insult.

IMPROVEMENT OF THE PREOPERATIVE ECHOCARDIOGRAPHIC SCREENING METHODS IN DWARF BREEDS DOGS

The article presents the results of assessing the informativeness of the improved technique of preoperative echocardiographic screening study in dwarf dog breeds. Evaluation of the ratio of the sizes of the left atrium to the root of the aorta, the pulmonary vein to the right branch of the pulmo-nary artery, normalized to the body weight of the end-systolic and end-diastolic dimensions, the fraction of the shortening of the left ventricle, the velocity of the peak E of the transmitral blood flow and the time of isovolumic relaxation makes it possible to carry out an effective preoperative assessment functional state of the cardiovascular system in dwarf dogs. These indicators do not de-pend on the body weight of dogs and characterize the state of remodeling, systolic and diastolic functions of the left chambers of the heart. Determination of the complex of these echocardiograph-ic parameters within 8-11 minutes makes it possible to assess the pumping function of the heart, to predict and reduce the risk of developing cardiogenic pulmonary edema.

О молекулярной природе различий в реакции сенсорных нейронов и фибробластов на уабаин

Atomic force microscopy was used to study under physiologically adequate conditions the effect of ouabain on the mechanical characteristics of sensory neurons and fibroblasts of 10–12-day old chick embryos. Fibroblasts express only the α1-isoform of Na,K-ATPase, and sensory neurons the α1- and α3-isoforms. It was found that the action of ouabain at a concentration corresponding to the endogenous value leads to an increase in the membrane rigidity of sensory neurons, which is apparently due to the activation of the transducer function of Na,K-ATPase, rather than the pumping function. The endogenous concentration of ouabain did not change the mechanical characteristics of fibroblasts. The results obtained suggest that endogenous ouabain modulates the transducer function of the α3-isoform of Na,K-ATPase of the sensory neuron membrane. Thus, the method of atomic force microscopy allows a comparative study of intracellular signaling cascades in living cells.

Abstract 13732: Evaluation of the Mechanical Effect of Thickened IPS Derived Cardiomyocyte Patch on the Distressed Left Ventricle Using Cardiac Simulator “Ut-heart”

Introduction: iPS cell-derived cardiac cell sheet (iPS sheet) transplantation is expected to have both cytokine paracrine effect and mechanical effect on the failed heart. In order to clarify the latter effect, we utilized the cardiac simulator “UT-Heart” to quantitatively evaluate the improvement of pumping function of the left ventricle with myocardial infarction covered by the thickened iPS sheet in silico. The direct mechanical impact of iPS sheet with various thicknesses was calculated first, and then the remodeling effect of fiber orientation was investigated. Patient and Method: An infarcted heart model based on the actual patient’s data was created on the computer and an iPS sheet was virtually implanted under the following assumptions: (1) electrophysiologically synchronized with the underlying cardiac muscle, (2) covered the infarct area entirely, (3) the fiber orientation of sheet was parallel to that of the epicardial tissue when attached, (4) if remodeling occurs, the fiber orientations of myocardial tissue and the attached sheet change such that the contraction force and the fiber strains are homogenized in the heart. The UT-Heart simulation was performed while changing iPS sheet thickness from 1mm to 5mm. Results: The LVEF of 18.0 % at pre-implantation was improved to 18.5 % with 1 mm thickness, and 19.6 % with 5 mm thickness without remodeling assumption as shown in the left of the figure. If LV remodeling occurs, the LVEF was improved to 20.9 % with 1mm thickness and 22.8 % with 5mm thickness. The LVESP was 10 mmHg higher than that of pre-implantation even when 1mm thickness was implanted. Conclusion: The direct mechanical effect of the thickened iPS sheet on the distressed LV was quantitatively evaluated in silico. Because changes in fiber orientation have a significant impact on pumping function, the remodeling assumption used herein should be experimentally verified in the future.

Determination of efficacy of the cellular cardiomyoplasty, using navigation system NOGA XP

Objective. Improvement of the treatment results in patients with refractory angina, complicated by the heart insufficiency, using new methods of correction of the heart pumping function elaborated. Materials and methods. Clinical investigation was performed, basing on retro- and prospective analysis of the treatment results in 156 patients: efficacy of myocardial remodeling was studied, using mesenchymal stem cells in patients, suffering refractory angina. For determination of the cellular therapy efficacy a navigation system NOGA XP was applied. Results. There were presented the results of investigation of efficacy of intravenous injections of autologous mesenchymal stem cells to patients, suffering refractory angina, complicated by lowering of the heart pumping function, and immediate results of cardiomyoplasty using stem cells as well. For the first time a navigation system NOGA XP for determination of myocardial hibernation zones was applied in patients, suffering refractory angina. Also, using navigation system NOGA XP, the results of cellular cardiomyoplasty were obtained, while comparing electro-mechanical schemes before and after cellular therapy. Conclusion. There was established the improvement of indices of the heart pumping function and the patients’ quality of life.