Fiber architecture in remodeled myocardium revealed with a quantitative diffusion CMR tractography framework and histological validation

Background: The study of myofiber reorganization in the remote zone after myocardial infarction has been performed in 2D. Microstructural reorganization in remodeled hearts, however, can only be fully appreciated by considering myofibers as continuous 3D entities. The aim of this study was therefore to develop a technique for quantitative 3D diffusion CMR tractography of the heart, and to apply this method to quantify fiber architecture in the remote zone of remodeled hearts. Methods: Diffusion Tensor CMR of normal human, sheep, and rat hearts, as well as infarcted sheep hearts was performed ex vivo. Fiber tracts were generated with a fourth-order Runge-Kutta integration technique and classified statistically by the median, mean, maximum, or minimum helix angle (HA) along the tract. An index of tract coherence was derived from the relationship between these HA statistics. Histological validation was performed using phase-contrast microscopy. Results: In normal hearts, the subendocardial and subepicardial myofibers had a positive and negative HA, respectively, forming a symmetric distribution around the midmyocardium. However, in the remote zone of the infarcted hearts, a significant positive shift in HA was observed. The ratio between negative and positive HA variance was reduced from 0.96 +/- 0.16 in normal hearts to 0.22 +/- 0.08 in the remote zone of the remodeled hearts (p<0.05). This was confirmed histologically by the reduction of HA in the subepicardium from -52.03 degrees +/- 2.94 degrees in normal hearts to -37.48 degrees +/- 4.05 degrees in the remote zone of the remodeled hearts (p < 0.05). Conclusions: A significant reorganization of the 3D fiber continuum is observed in the remote zone of remodeled hearts. The positive (rightward) shift in HA in the remote zone is greatest in the subepicardium, but involves all layers of the myocardium. Tractography-based quantification, performed here for the first time in remodeled hearts, may provide a framework for assessing regional changes in the left ventricle following infarction.

Immunopathology of cardiomyopathy in the experimental Chagas disease

The mechanisms by which Trypanosoma cruzi causes cardiomyopathy and induces neuronal destruction are discussed in this paper. The results suggest that autoimmunity in the chronic phase is the main cause of the progressive cardiac destruction, and that autoreactivity is restricted to the CD4+ T cell compartment. During the acute phase, the neuronal and cardiac fiber destruction occurs when ruptured parasite nests release T. cruzi antigens that bind to the cell surface in the vicinity which become targets for the cellular and humoral immune response against T. cruzi. The various factors involved in the genesis of autoimmunity in chronic T. cruzi infection include molecular mimicry, presentation of self-antigens and imbalance of immune regulation.

Histologia e ultra-estrutura do vaso dorsal de Scaptotrigona postica (Hymenoptera, Apidae) em operárias e rainhas de diferentes idades

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Cardiac-induced localized thoracic motion detected by a fiber optic sensing scheme

The cardiovascular health of the human population is a major concern for medical clinicians, with cardiovascular diseases responsible for 48% of all deaths worldwide, according to the World Health Organization. The development of new diagnostic tools that are practicable and economical to scrutinize the cardiovascular health of humans is a major driver for clinicians. We offer a new technique to obtain seismocardiographic signals up to 54 Hz covering both ballistocardiography (below 20 Hz) and audible heart sounds (20 Hz upward), using a system based on curvature sensors formed from fiber optic long period gratings. This system can visualize the real-time three-dimensional (3-D) mechanical motion of the heart by using the data from the sensing array in conjunction with a bespoke 3-D shape reconstruction algorithm. Visualization is demonstrated by adhering three to four sensors on the outside of the thorax and in close proximity to the apex of the heart; the sensing scheme revealed a complex motion of the heart wall next to the apex region of the heart. The detection scheme is low-cost, portable, easily operated and has the potential for ambulatory applications.

Cardiac Neural Crest Cells and Their Role in Murine Purkinje Fiber Development

The heart beat is regulated by the cardiac conduction system (CCS), a specialized group of cells that transmit electrical impulses around the heart chambers. During development, ventricular CCS cells originate from embryonic cardiomyocytes and not from the neural crest. Nonetheless, discoveries in chick implied that the cardiac neural crest (CNC) cells contribute to proper development of the ventricular CCS. In this report, the Splotch mouse mutant (Pax3sp), in which the CNC cells do not migrate to the heart, was used to investigate whether these cells also affect proper CCS development in mammals. Homozygote mutants (Pax3Sp!Sp) are lethal on 111 Embryonic Day 13 (E13), and can be phenotyped by spina bifida and exencephaly. Pax3Spi+ mice were crossed to obtain wild type, Pax3 Spi+ and Pax3 Sp!Sp embryos. Comparison of hematoxylin and eosin stained histological sections showed less trabeculation in El2.5 cardiac ventricles of Pax3Sp!Sp. Furthermore, immunofluorescence analysis with the Purkinje fiber marker Cx40 showed a qualitative difference between wild type and mutant hearts. Quantitative analysis indicated that Pax3 Sp!Sp ventricles had fewer Cx40 expressing cells, as well as less Cx40 being expressed per cell when compared to wild type ventricles. Immunofluorescence with the H3 histome mitosis antibody showed fewer proliferating cells in the ventricles of mutant embryos when compared to controls. These results suggest that CNCC affect the morphogenesis of cardiac ventricles and the development of the ventricular CCS by contributing cellular proliferation.

Fat and fiber consumption are associated with peripheral arterial disease in a cross-sectional study of a Japanese-Brazilian population

Background The Western diet plays a role for the epidemics of obesity and related diseases. This study examined a possible association between peripheral arterial disease (PAD) and the dietary components of Japanese immigrants living in Brazil. Methods and Results In this cross-sectional study, 1,267 subjects (aged 30 years) with complete dietary, clinical and laboratory data were studied according to a standardized protocol. Ankle-to-brachial index was used to identify subjects with PAD. The overall prevalence of PAD was 14.6%. Subjects with PAD were older, had lower education and higher mean values of blood pressure, triglycerides, and fasting and 2-h plasma glucose levels compared with those without the disease. Among the subjects with PAD, the consumption of fiber from whole grains (3.0 vs 3.4g, p=0.001) and linoleic acids (11.0 vs 11.7g, p=0.017) were lower and intake of total (72.8 vs 69.1 a, p=0.016) and saturated fatty acids (17.4 vs 16.3g, p=0.012) were higher than those without PAD. Results of multiple logistic regression analysis showed a significant association between PAD with high total fat intake, low intake of fiber from fruit and oleic acid, independently of other variables. Conclusions Despite limitations in examining the cause-effect relationship, the data support the notion that diet could be important in reducing the occurrence of PAD.

Impact of the Advisa MRI pacing system on the diagnostic quality of cardiac MR images and contraction patterns of cardiac muscle during scans: Advisa MRI randomized clinical multicenter study results.

BACKGROUND: The Advisa MRI system is designed to safely undergo magnetic resonance imaging (MRI). Its influence on image quality is not well known. OBJECTIVE: To evaluate cardiac magnetic resonance (CMR) image quality and to characterize myocardial contraction patterns by using the Advisa MRI system. METHODS: In this international trial with 35 participating centers, an Advisa MRI system was implanted in 263 patients. Of those, 177 were randomized to the MRI group and 150 underwent MRI scans at the 9-12-week visit. Left ventricular (LV) and right ventricular (RV) cine long-axis steady-state free precession MR images were graded for quality. Signal loss along the implantable pulse generator and leads was measured. The tagging CMR data quality was assessed as the percentage of trackable tagging points on complementary spatial modulation of magnetization acquisitions (n=16) and segmental circumferential fiber shortening was quantified. RESULTS: Of all cine long-axis steady-state free precession acquisitions, 95% of LV and 98% of RV acquisitions were of diagnostic quality, with 84% and 93%, respectively, being of good or excellent quality. Tagging points were trackable from systole into early diastole (360-648 ms after the R-wave) in all segments. During RV pacing, tagging demonstrated a dyssynchronous contraction pattern, which was not observed in nonpaced (n = 4) and right atrial-paced (n = 8) patients. CONCLUSIONS: In the Advisa MRI study, high-quality CMR images for the assessment of cardiac anatomy and function were obtained in most patients with an implantable pacing system. In addition, this study demonstrated the feasibility of acquiring tagging data to study the LV function during pacing.

Dietary restriction and fibre supplementation: Oxidative stress and metabolic shifting for cardiac health

Dietary modification ought to be the first line of strategy in prevention of the development of cardiac disease. The purpose of this study was to investigate whether dietary restriction, dietary-fibre-enriched diet, and their interactions might affect antioxidant capacity and oxidative stress in cardiac tissue. Male Wistar rats (180-200 g; n = 10) were divided into four groups: control ad libitum diet (C), 50% restricted diet (DR), fed with fibre-enriched diet (F), and 50% restricted fibre-enriched diet (DR-F). After 35 days of the treatments, F, DR, and DR-F rats showed low cholesterol, LDL-cholesterol, and triacylglycerol, and high HDL-cholesterol in serum. The DR, DR-F, and F groups had decreased myocardial lipoperoxide and lipid hydroperoxide. The DR-F and F treatments increased superoxide dismutase and glutatione peroxidase (GSH-Px). The DR treatment increased GSH-Px and catalase activities. Dietary fibre beneficial effects were related to metabolic alterations. The F and DR-F groups showed high cardiac glycogen and low lactate dehydrogenase/citrate synthase ratios, indicating diminished anaerobic and elevated aerobic myocardial metabolism in these animals. There was no synergistic effect between dietary restriction and dietary fibre addition, since no differences were observed in markers of oxidative stress in the F and DR-F groups. Dietary fibre supplementation, rather than energy intake and dietary restriction, appears to be the main process retarding oxidative stress in cardiac tissue.

Hypertrophied myocardium is more dependent on extracellular calcium than the normal cardiac muscle

Background: The aim of this study was to analyze stable hypertrophied myocardial function and its response to inotropic maneuvers in rats submitted to renovascular hypertension for a 10-week period (RHT group, n=10). Material/Methods: Myocardial performance was studied in isolated left ventricle papillary muscles in isometric contraction under the following conditions: at postrest contraction of 30 seconds (PRC), at extracellular calcium (ECa 2+) chloride concentration of 1.25 and 5.20 mM, and after beta-adrenergic stimulation with 10 -6 M isoproterenol (ISOP). Results: The results were compared with normotensive Wistar controls rats (C group, n=10). In basal condition, resting tension, and contraction time (TPT) were greater, while relaxation time (RT 50) tended to be longer in RHT than C group. PRC and ISOP promoted a similar change in muscle function response intensity (Δ) in both groups. ECa 2+ shift did not change TPT in the C group and decreased TPT in the RHT animals; Δ was different between these groups. RT 50 increased in C and decreased in RHT, both without statistical significance; however, Δ was different. Conclusions: These results suggest that hypertrophied myocardial dysfunction may be attibuted to changes in intracellular calcium cycling. © Med Sci Monit, 2010.

Swimming Training in Rats Increases Cardiac MicroRNA-126 Expression and Angiogenesis

DA SILVA, N. D. JR, T. FERNANDES, U. P. R. SOCI, A. W. A. MONTEIRO, M. I. PHILLIPS, and E. M. DE OLIVEIRA. Swimming Training in Rats Increases Cardiac MicroRNA-126 Expression and Angiogenesis. Med. Sci. Sports Exerc., Vol. 44, No. 8, pp. 1453-1462, 2012. Purpose: MicroRNA (miRNA)-126 is angiogenic and has two validated targets: Sprouty-related protein 1 (Spred-1) and phosphoinositol-3 kinase regulatory subunit 2 (PI3KR2), negative regulators of angiogenesis by VEGF pathway inhibition. We investigated the role of swimming training on cardiac miRNA-126 expression related to angiogenesis. Methods: Female Wistar rats were assigned to three groups: sedentary (S), training 1 (T1, moderate volume), and training 2 (T2, high volume). T1 consisted of 60 min.d(-1) of swimming, five times per week for 10 wk with 5% body overload. T2 consisted of the same protocol of T1 until the eighth week; in the ninth week, rats trained for two times a day, and in the 10th week, rats trained for three times a day. MiRNA and PI3KR2 gene expression analysis was performed by real-time polymerase chain reaction in heart muscle. We assessed markers of training, the cardiac capillary-fiber ratio, cardiac protein expression of VEGF, Spred-1, Raf-1/ERK 1/2, and PI3K/Akt/eNOS. Results: The cardiac capillary-fiber ratio increased in T1 (58%) and T2 (101%) compared with S. VEGF protein expression was increased 42% in T1 and 108% in T2. Cardiac miRNA-126 expression increased 26% (T1) and 42% (T2) compared with S, correlated with angiogenesis. The miRNA-126 target Spred-1 protein level decreased 41% (T1) and 39% (T2), which consequently favored an increase in angiogenic signaling pathway Raf-1/ERK 1/2. On the other hand, the gene expression of PI3KR2, the other miRNA-126 target, was reduced 39% (T1) and 78% (T2), and there was an increase in protein expression of components of the PI3K/Akt/eNOS signaling pathway in the trained groups. Conclusions: This study showed that aerobic training promotes an increase in the expression of miRNA-126 and that this may be related to exercise-induced cardiac angiogenesis, by indirect regulation of the VEGF pathway and direct regulation of its targets that converged in an increase in angiogenic pathways, such as MAPK and PI3K/Akt/eNOS.

Noninvasive and invasive evaluation of cardiac dysfunction in experimental diabetes in rodents

Abstract Background Because cardiomyopathy is the leading cause of death in diabetic patients, the determination of myocardial function in diabetes mellitus is essential. In the present study, we provide an integrated approach, using noninvasive echocardiography and invasive hemodynamics to assess early changes in myocardial function of diabetic rats. Methods Diabetes was induced by streptozotocin injection (STZ, 50 mg/kg). After 30 days, echocardiography (noninvasive) at rest and invasive left ventricular (LV) cannulation at rest, during and after volume overload, were performed in diabetic (D, N = 7) and control rats (C, N = 7). The Student t test was performed to compare metabolic and echocardiographic differences between groups at 30 days. ANOVA was used to compare LV invasive measurements, followed by the Student-Newman-Keuls test. Differences were considered significant at P < 0.05 for all tests. Results Diabetes impaired LV systolic function expressed by reduced fractional shortening, ejection fraction, and velocity of circumferential fiber shortening compared with that in the control group. The diabetic LV diastolic dysfunction was evidenced by diminished E-waves and increased A-waves and isovolumic relaxation time. The myocardial performance index was greater in diabetic compared with control rats, indicating impairment in diastolic and systolic function. The LV systolic pressure was reduced and the LV end-diastolic pressure was increased at rest in diabetic rats. The volume overload increased LVEDP in both groups, while LVEDP remained increased after volume overload only in diabetic rats. Conclusion These results suggest that STZ-diabetes induces systolic and diastolic dysfunction at rest, and reduces the capacity for cardiac adjustment to volume overload. In addition, it was also demonstrated that rodent echocardiography can be a useful, clinically relevant tool for the study of initial diabetic cardiomyopathy manifestations in asymptomatic patients.

Induction of Purkinje fiber differentiation by coronary arterialization

A synchronized heart beat is controlled by pacemaking impulses conducted through Purkinje fibers. In chicks, these impulse-conducting cells are recruited during embryogenesis from myocytes in direct association with developing coronary arteries. In culture, the vascular cytokine endothelin converts embryonic myocytes to Purkinje cells, implying that selection of conduction phenotype may be mediated by an instructive cue from arteries. To investigate this hypothesis, coronary arterial development in the chicken embryo was either inhibited by neural crest ablation or activated by ectopic expression of fibroblast growth factor (FGF). Ablation of cardiac neural crest resulted in ≈70% reductions (P < 0.01) in the density of intramural coronary arteries and associated Purkinje fibers. Activation of coronary arterial branching was induced by retrovirus-mediated overexpression of FGF. At sites of FGF-induced hypervascularization, ectopic Purkinje fibers differentiated adjacent to newly induced coronary arteries. Our data indicate the necessity and sufficiency of developing arterial bed for converting a juxtaposed myocyte into a Purkinje fiber cell and provide evidence for an inductive function for arteriogenesis in heart development distinct from its role in establishing coronary blood circulation.

Optical in-fiber Bragg grating sensor systems for medical applications

Two in-fiber Bragg grating (FBG) temperature sensor systems for medical applications are demonstrated: (1) an FBG flow-directed thermodilution catheter based on interferometric detection of wavelength shift that is used for cardiac monitoring; and (2) an FBG sensor system with a tunable Fabry-Perot filter for in vivo temperature profiling in nuclear magnetic resonance (NMR) machines. Preliminary results show that the FBG sensor is in good agreement with electrical sensors that are widely used in practice. A field test shows that the FBG sensor system is suitable for in situ temperature profiling in NMR machines for medical applications.

Optical in-fiber Bragg grating sensor systems for medical applications

Two in-fiber Bragg grating (FBG) temperature sensor systems for medical applications are demonstrated: (1) an FBG flow-directed thermodilution catheter based on interferometric detection of wavelength shift that is used for cardiac monitoring; and (2) an FBG sensor system with a tunable Fabry-Perot filter for in vivo temperature profiling in nuclear magnetic resonance (NMR) machines. Preliminary results show that the FBG sensor is in good agreement with electrical sensors that are widely used in practice. A field test shows that the FBG sensor system is suitable for in situ temperature profiling in NMR machines for medical applications.

Expression of the Myod and T-Box Families of Transcription Factors in the Developing Purkinje Fiber

The coordinated beating of the heart depends on a group ofhighly specialized cells that constitute the cardiac conduction system. Among these cells, the Purkinje fibers are responsible for propagation of the electric impulse into the ventricles. In early stages of development, Purkinje fibers and skeletal muscle fibers originate from similar but separate populations of myocytes. The role of the MyoD family of transcription factors in the development of the myotube is well known, but the role of these factors in the development of the Purkinje fiber is not. Members of the T-Box family of transcription.The coordinated beating of the heart depends on a group ofhighly specialized cells that constitute the cardiac conduction system. Among these cells, the Purkinje fibers are responsible for propagation of the electric impulse into the ventricles. In early stages of development, Purkinje fibers and skeletal muscle fibers originate from similar but separate populations of myocytes. The role of the MyoD family of transcription factors in the development of the myotube is well known, but the role of these factors in the development of the Purkinje fiber is not. Members of the T-Box family of transcription factors are also involved in the development of various cardiac tissues, including the conduction system but little is known about their role in the development of the Purkinje fiber. We explored the expression of members of the MyoD and T-Box families in the developing cardiac conduction system in vivo and in vitro. We showed that the expression of these factors changes as the myocyte differentiates into the Purkinje fiber. We also showed that NRG-1, a secreted protein involved in the development of the Purkinje fiber, features a dose-dependent response in the differentiation of cultured ventricular myocytes.