Evaluation of Different Decellularization Protocols for Obtaining and Characterizing Canine Cardiac Extracellular Matrix.

Cardiovascular diseases are considered the leading cause of mortality globally; even with low mortality in dogs, such diseases are described in the same way in companion animals and humans. This study aimed to devise an effective decellularization protocol for the canine myocardium through the association of physical, chemical, and enzymatic methods, assessing resultant alterations in the myocardial extracellular matrix to obtain a suitable scaffold. Two canine hearts were collected; the samples were sectioned into ±1 cm2 fragments, washed in distilled water and 1× PBS solution, and followed by treatment under four distinct decellularization protocols. Sodium Dodecyl Sulfate (SDS) 1% 7 days + Triton X-100 1% for 48 h (Protocol I); Sodium Dodecyl Sulfate (SDS) 1% 5 days + Triton X-100 1% for 48 h (Protocol II); Trypsin 0.05% for 1 h at 36 °C + freezing -80 °C overnight + Sodium Dodecyl Sulfate (SDS) 1% for 3 days, Triton-X-100 for 48 h hours (Protocol III); 0.05% trypsin for 1 h at 36 °C + freezing at -80 °C overnight + 1% Sodium Dodecyl Sulfate (SDS) for 2 days + 1% Triton-X-100 for 24 h (Protocol IV). After analysis, Protocols I and II showed the removal of cellular content and preservation of extracellular matrix (ECM) contents, unlike Protocols III and IV, which retracted the ECM and removed essential elements of the matrix. In theory, although Protocols I and II have similar results, Protocol II stands out for the preservation of the architecture and components of the extracellular matrix, along with reduced exposure time to reagents, making it the recommended protocol for the development of a canine myocardial scaffold.

Myocardial proteome changes in aortic stenosis rats subjected to long-term aerobic exercise.

The effects of exercise training (ET) on the heart of aortic stenosis (AS) rats are controversial and the mechanisms involved in alterations induced by ET have been poorly clarified. In this study, we analyzed the myocardial proteome to identify proteins modulated by moderate-intensity aerobic ET in rats with chronic supravalvular AS. Wistar rats were divided into four groups: sedentary control (C-Sed), exercised control (C-Ex), sedentary aortic stenosis (AS-Sed), and exercised AS (AS-Ex). ET consisted of five treadmill running sessions per week for 16 weeks. Statistical analysis was performed by ANOVA or Kruskal-Wallis and Goodman tests. Results were discussed at a significance level of 5%. At the end of the experiment, AS-Ex rats had higher functional capacity, lower blood lactate concentration, and better cardiac structural and left ventricular (LV) functional parameters than the AS-Sed. Myocardial proteome analysis showed that AS-Sed had higher relative protein abundance related to the glycolytic pathway, oxidative stress, and inflammation, and lower relative protein abundance related to beta-oxidation than C-Sed. AS-Ex had higher abundance of one protein related to mitochondrial biogenesis and lower relative protein abundance associated with oxidative stress and inflammation than AS-Sed. Proteomic data were validated for proteins related to lipid and glycolytic metabolism. Chronic pressure overload changes the abundance of myocardial proteins that are mainly involved in lipid and glycolytic energy metabolism in rats. Moderate-intensity aerobic training attenuates changes in proteins related to oxidative stress and inflammation and increases the COX4I1 protein, related to mitochondrial biogenesis. Protein changes are combined with improved functional capacity, cardiac remodeling, and LV function in AS rats.

Prevalence of myocardial bridges in the Mexican population: A morphometric and histological analysis.

BACKGROUND: Myocardial bridge (MB) is described as an abnormal band of myocardium covering a variable portion of any coronary artery. METHODS: The current study explores the presence of MB throughout the coronary arterial system and provides a morphometric description through instrumented dissection of a sample of 100 human hearts. The study shows a higher prevalence of MB in the Mexican population than in previous reports. RESULTS: In the total sample (n=100), MB was identified in 96% of it. A total of 421 MBs were observed, with a mean of 4.38mm (±0.28) per dissected heart. The most frequently affected vessel is the anterior interventricular artery where a total of 52 MBs were found, of the total sample studied. DISCUSSION: The high prevalence of MB among Mexican patients could be the result of a genetic association for this population or the neoformation of MB after birth due to lifestyle-associated factors. Further studies are required to better understand the high prevalence of MB among Mexican subjects.

Impacto Clínico da Avaliação da Reserva de Fluxo Miocárdico na Identificação da Causa do Desconforto Torácico / Clinical Impact of Assessment of Myocardial Flow Reserve in Identifying the Cause of Chest Discomfort

Resumo Fundamento: Gama-câmaras com detectores de telureto-cádmio-zinco (CZT) permitiram a quantificação da reserva de fluxo miocárdico (RFM), podendo aumentar a acurácia da cintilografia miocárdica de perfusão (CMP) para detectar a causa do desconforto torácico. Objetivo: Avaliar o impacto clínico da RFM para detectar a causa do desconforto torácico. Métodos: 171 pacientes com desconforto torácico que foram submetidos a coronariografia ou angiotomografia de coronárias também realizaram CMP e RFM num intervalo de tempo <30 dias. As aquisições das imagens dinâmicas de repouso e estresse foram iniciadas simultaneamente à injeção de 99mTc sestamibi (10 e 30mCi, respectivamente), ambas com duração de onze minutos, seguidas imediatamente pela aquisição das imagens de perfusão durante 5 minutos. O estresse foi realizado com dipiridamol. Uma RFM global ou por território coronariano <2,0 foi classificada como anormal. Resultados: A idade média foi de 65,9±10 anos (60% do sexo feminino). A avaliação anatômica mostrou que 115 (67,3%) pacientes apresentavam obstrução coronariana significativa, sendo que, 69 apresentavam CMP anormal e 91 apresentavam RFM anormal (60,0% vs. 79,1%, p<0,01). Dentre os pacientes sem obstrução (56 - 32,7%), 7 tinham CMP anormais e 23 tinham RFM global reduzida. A realização da RFM identificou a etiologia do desconforto torácico em 114 pacientes enquanto a CMP identificou em 76 (66,7% vs. 44,4%, p<0,001). Conclusão: A RFM é uma medida fisiológica quantificável que aumenta o impacto clínico da CMP na detecção da causa do desconforto torácico através de uma maior acurácia para detecção de DAC obstrutiva e ainda possibilita identificar a presença de doença microvascular.

Abstract Background: Gamma cameras with cadmium-zinc telluride (CZT) detectors allowed the quantification of myocardial flow reserve (MBF), which can increase the accuracy of myocardial perfusion scintigraphy (MPS) to detect the cause of chest discomfort. Objective: To assess the clinical impact of MBF to detect the cause of chest discomfort. Methods: 171 patients with chest discomfort who underwent coronary angiography or coronary CT angiography also underwent MPS and MBF in a time interval of <30 days. The acquisitions of dynamic imaging of rest and stress were initiated simultaneously with the 99mTc injection sestamibi (10 and 30mCi, respectively), both lasting eleven minutes, followed by immediately acquiring perfusion images for 5 minutes. The stress was performed with dipyridamole. A global or per coronary territory MBF <2.0 was classified as abnormal. Results: The average age was 65.9±10 years (60% female). The anatomical evaluation showed that 115 (67.3%) patients had coronary obstruction significant, with 69 having abnormal MPs and 91 having abnormal MBF (60.0% vs 79.1%, p<0.01). Among patients without obstruction (56 - 32.7%), 7 had abnormal MPS, and 23 had reduced global MBF. Performing MBF identified the etiology of the chest discomfort in 114 patients while MPS identified it in 76 (66.7% vs 44.4%, p<0.001). Conclusion: MBF is a quantifiable physiological measure that increases the clinical impact of MPS in detecting the cause of chest discomfort through greater accuracy for detecting obstructive CAD, and it also makes it possible to identify the presence of the microvascular disease.

El fulcro cardíaco y su relación con el nódulo auriculoventricular / Cardiac Fulcrum, its Relationship with the Atrioventricular Node

RESUMEN Introducción. El estudio de la anatomía funcional del miocardio helicoidal continuo permite visualizar su inicio y fin en el nacimiento de los grandes vasos. En nuestras investigaciones siempre hemos considerado que debía tener un punto de unión que permitiera su rotación helicoidal para cumplir los movimientos fundamentales de acortamiento-torsión (sístole) y alargamiento-destorsión (succión). Una vez encontrado, se le llamó fulcro cardíaco. Objetivos. Esta investigación tiene como objeto describir y entender la interrelación entre el fulcro cardíaco y el nódulo auriculoventricular de Aschoff-Tawara Material y métodos. Se utilizaron 31 corazones procedentes de la morgue y del matadero: 17 correspondieron a bóvidos y 14 a seres humanos. Resultados. En nuestras investigaciones hemos demostrado que el soporte del miocardio, denominado fulcro cardíaco, que se localiza en el trayecto del segmento septal del anillo aórtico y se extiende desde el trígono izquierdo hasta el derecho por debajo del origen de la arteria coronaria derecha, es adyacente al nódulo auriculoventricular (AV). Otro aspecto importante de esta posición contigua es que el fulcro está rodeado, e incluso invadido, por un plexo nervioso interconectado con el nódulo. Conclusión. Esta descripción del fulcro cardíaco pondría fin al problema de la falta de apoyo del miocardio para cumplir su función de torsión/destorsión. La proximidad del fulcro al nódulo AV y la penetración de los plexos nerviosos en el apoyo indican la existencia de una unidad electromecánica, que hemos investigado en función de la anatomía helicoidal del corazón. Hemos comprobado una mejor estimulación cardíaca cuando el catéter se coloca en el infundíbulo ventricular derecho.

ABSTRACT Background. The functional anatomy of the helical, continuous myocardium allows envisioning that it initiates and ends at the origin of the great vessels. In our research, we have always considered that it should have a point of attachment to allow its helical rotation to fulfill the fundamental movements of shortening-torsion (systole) and lengthening-detorsion (suction), which once found, was called the cardiac fulcrum. Objectives. The research aims to describe the important aspect of understanding the interrelationship between the cardiac fulcrum and the Aschoff-Tawara atrioventricular node Material and Methods. A total of 31 hearts, arising from the morgue and slaughterhouse were used: 17 corresponded to bovids and 14 were human. Results. Our investigations have shown that the myocardial support termed cardiac fulcrum, located in the trajectory of the aortic annulus septal segment, extending from the left to the right trigone and below the origin of the right coronary artery, is adjacent to the AV node. Another important aspect of this contiguous position is that the fulcrum is surrounded, and even invaded, by a rich nervous plexus interconnected with the node. Conclusion. This description of the cardiac fulcrum would end the problem of lack of support of the myocardium to fulfill its function of torsion/detorsion. The proximity of the fulcrum to the AV node and the penetration of the nervous plexuses in the support suggest an electromechanical unit, which we have investigated according to the helical anatomy of the heart, establishing an improved cardiac stimulation with a catheter placed in the right ventricular outflow tract.

[Mortality associated with myocardial damage by troponin I in patients with COVID 19]. / Mortalidad asociada a daño miocárdico mediante troponina I en pacientes con COVID-19.

Background: Coronavirus disease 2019 (COVID-19) can cause cardiac injury, probably associated with myocarditis and ischemia induced by the infection. Myocardial damage leads to the liberation of proinflammatory cytokines and to the activation of autoimmune adaptive mechanisms through molecular limitation. Objective: To assess mortality associated with myocardial damage in hospitalized patients with COVID-19 confirmed by troponin I measurement. Material and methods: Case-control study nested in a cohort of patients of a third-level hospital. Descriptive statistics were used to characterize the population. Qualitative variables were expressed as proportions and ranges, quantitative variables as means and standard deviation. Fisher's exact test was used to compare mortality between patients with and without myocardial damage. A p value < 0.05 was considered significant. Results: From June 2020 to August 2020, 28 patients who met the selection criteria were enrolled, out of which 15 had no myocardial damage and 13 had myocardial damage assessed by serum troponin measurement. A strong association was found between mortality and the presence of myocardial damage, since mortality was 20% (3/15) among patients without myocardial damage and 92.3% (12/13) among those with myocardial damage (Fisher's exact test, p < 0.005). Conclusion: Mortality in patients with COVID-19 is associated with myocardial damage assessed by troponin I measurement.

Introducción: la enfermedad por coronavirus del 2019 (COVID-19) puede causar lesión cardiaca, probablemente asociada con miocarditis e isquemias inducidas por la infección. El daño miocárdico conduce a la liberación de citocinas proinflamatorias y a la activación de mecanismos adaptativos de tipo autoinmune por medio de la limitación molecular. Objetivo: evaluar la mortalidad asociada a daño miocárdico en pacientes hospitalizados con COVID-19 confirmado mediante la medición de troponina I. Material y métodos: estudio de casos y controles anidado en una cohorte de los pacientes de un hospital de tercer nivel. Se utilizó estadística descriptiva para caracterizar a la población. Las variables cualitativas se expresaron como proporciones y rangos, las cuantitativas como medias y desviación estándar. Para comparar la mortalidad entre pacientes con y sin daño miocárdico se utilizó la prueba exacta de Fisher. Valores de p < 0.05 fueron significativos. Resultados: de junio del 2020 a agosto del 2020 se enrolaron 28 pacientes que cumplieron los criterios de selección, de los cuales 15 no tuvieron daño miocárdico y 13 tuvieron daño miocárdico evaluado con la medición de troponina sérica. Se encontró fuerte asociación entre la mortalidad y la presencia de daño miocárdico, ya que se registró mortalidad del 20% (3/15) entre los pacientes sin daño miocárdico y de 92.3% (12/13) entre los que tuvieron daño miocárdico (prueba exacta de Fisher: p < 0.005). Conclusiones: la mortalidad en pacientes con COVID-19 se asocia a daño miocárdico evaluado a través de la medición de troponina I.

MDM2 Regulation of HIF Signaling Causes Microvascular Dysfunction in Hypertrophic Cardiomyopathy.

BACKGROUND: Microvasculature dysfunction is a common finding in pathologic remodeling of the heart and is thought to play an important role in the pathogenesis of hypertrophic cardiomyopathy (HCM), a disease caused by sarcomere gene mutations. We hypothesized that microvascular dysfunction in HCM was secondary to abnormal microvascular growth and could occur independent of ventricular hypertrophy. METHODS: We used multimodality imaging methods to track the temporality of microvascular dysfunction in HCM mouse models harboring mutations in the sarcomere genes Mybpc3 (cardiac myosin binding protein C3) or Myh6 (myosin heavy chain 6). We performed complementary molecular methods to assess protein quantity, interactions, and post-translational modifications to identify mechanisms regulating this response. We manipulated select molecular pathways in vivo using both genetic and pharmacological methods to validate these mechanisms. RESULTS: We found that microvascular dysfunction in our HCM models occurred secondary to reduced myocardial capillary growth during the early postnatal time period and could occur before the onset of myocardial hypertrophy. We discovered that the E3 ubiquitin protein ligase MDM2 (murine double minute 2) dynamically regulates the protein stability of both HIF1α (hypoxia-inducible factor 1 alpha) and HIF2α (hypoxia-inducible factor 2 alpha)/EPAS1 (endothelial PAS domain protein 1) through canonical and noncanonical mechanisms. The resulting HIF imbalance leads to reduced proangiogenic gene expression during a key period of myocardial capillary growth. Reducing MDM2 protein levels by genetic or pharmacological methods normalized HIF protein levels and prevented the development of microvascular dysfunction in both HCM models. CONCLUSIONS: Our results show that sarcomere mutations induce cardiomyocyte MDM2 signaling during the earliest stages of disease, and this leads to long-term changes in the myocardial microenvironment.

Resveratrol Attenuates Degeneration and Apoptosis of Cardiomyocytes Induced by Aortic Clamping.

INTRODUCTION: Objective: To investigate the potential beneficial effects of resveratrol (RVT) against ischemia-reperfusion injury of myocardial tissue during surgical treatment of ruptured abdominal aortic aneurysm. METHODS: Four groups were established - control, ischemia/reperfusion (I/R), sham (I/R+solvent/dimethyl sulfoxide [DMSO]), and I/R+RVT. Ruptured abdominal aortic aneurysm model was used as the experimental protocol. RESULTS: In the I/R and I/R+DMSO groups, malondialdehyde (MDA) levels in myocardial tissue were found to be significantly increased compared to the control group. The MDA level in myocardial tissue was significantly decreased in the I/ R+RVT group compared to the I/R group. In I/R and I/R+DMSO groups, glutathione peroxidase (GSH) levels in myocardial tissue were found to be significantly decreased compared to the control group. The GSH level in the myocardial tissue was significantly increased in the I/R+RVT group compared to the I/R group. In the light microscope, isotropic and anisotropic band disorganized atypical cardiomyocytes in the I/R group and degenerative cardiomyocytes and edematous areas in the I/R+DMSO group were observed. Degenerative cardiomyocytes and edematous areas were decreased in the I/R+RVT group. When heart tissue sections incubated with cleaved caspase-3 primary antibodies were examined under the light microscope, apoptotic cardiomyocytes were present in I/R and I/R+DMSO groups. A decrease in the number of apoptotic cardiomyocytes was observed in the I/R+RVT group. CONCLUSION: The findings of the present study indicate that RVT exhibits protective effects against ischemia-reperfusion injury occurring in the myocardium as a distant organ as a result of abdominal aorta clamping.

Cardiac Corpuscles: A "New" Morphofunctional Entity? / Corpúsculos Cardíacos: ¿Una "Nueva" Entidad Morfofuncional?

SUMMARY: The existence of "transitional muscular structures" between subendocardial branches (Purkinje fibers) and ventricular working muscle fibers (WF) was first described by the German anatomist, Kurt Goerttler, in 1964. He designated them as "subendocardial nucleus organs." He supposed such fibers functioned as mechanoreceptors, controlling of the intensity of contraction of the ventricular musculature. Brazilian anatomist Ferraz de Carvalho described similar structures in 1993. A thorough literature search failed to identify any other research articles confirming or denying their existence. The objective of this work was to find such structures in subendocardial ventricular walls in human hearts. We collected fifteen formalin-preserved hearts from the Anatomy Department of São Paulo University and sectioned the apical portions on the right and left ventricles according to method used by Goerttler. We utilized conventional histology (light microscopy- LM), scanning electron microscopy (SEM), and a new preservation method called micro- plastination (MP). At the anterior wall of the right ventricle in the subendocardial region between the interventricular septum and moderator band, we found several bundles of fusiform and helicoidal fibers of similar histology to the WF. The bundles measured between 400 and 1150 µm in length and were separated from adjacent muscular fibers by thin collagen fiber, thus acting as a "pseudo capsule." Some structures seemed to be linked to PF and were appeared to be lymphatic and blood vessels and nerves. We called those structures "cardiac corpuscles" (CC). The observation of the previously "unknown" CC in this initial study confirmed the previous descriptions and its discovery may contribute to new perspectives in the study of cardiac muscle structure and function.

La existencia de "estructuras musculares de transición" entre los ramos subendocárdicos (fibras de Purkinje) y las fibras musculares ventriculares activas(FMV) fue descrita por primera vez por el anatomista alemán Kurt Goerttler en 1964, quien las denominó "órganos del núcleo subendocárdico". Supuso que tales fibras funcionaban como mecanoreceptores, controlando la intensidad de la contracción de la musculatura ventricular. El anatomista brasileño Ferraz de Carvalho describió estructuras similares en 1993. Una búsqueda bibliográfica exhaustiva no logró identificar ningún otro artículo de investigación que confirmara o negara su existencia. El objetivo de este trabajo fue encontrar dichas estructuras en las paredes ventriculares subendocárdicas de corazones humanos. Recolectamos 15 corazones conservados en formalina del Departamento de Anatomía de la Universidad de São Paulo y seccionamos las porciones apicales de los ventrículos derecho e izquierdo según el método utilizado por Goerttler. Utilizamos histología convencional (microscopía de luz-LM), microscopía electrónica de barrido (SEM) y un nuevo método de conservación llamado microplastinación (MP). En la pared anterior del ventrículo derecho en la región subendocárdica entre el tabique interventricular y la banda moderadora, encontramos varios haces de fibras fusiformes y helicoidales de histología similar a la FMV. Los haces medían entre 400 y 1150 µm de longitud y estaban separados de las fibras musculares adyacentes por una fina fibra de colágeno, actuando así como una "pseudocápsula". Algunas estructuras parecían estar vinculadas a la fibras de purkinje y parecían ser vasos linfáticos, sanguíneos y nerviosos. Llamamos a esas estructuras "corpúsculos cardíacos" (CC). La observación del CC previamente "desconocido" en este estudio inicial confirmó las descripciones anteriores y su descubrimiento puede contribuir a nuevas perspectivas en el estudio de la estructura y función del músculo cardíaco.

The role of acid sensing ion channels in the cardiovascular function.

Acid Sensing Ion Channels (ASIC) are proton sensors involved in several physiological and pathophysiological functions including synaptic plasticity, sensory systems and nociception. ASIC channels have been ubiquitously localized in neurons and play a role in their excitability. Information about ASIC channels in cardiomyocyte function is limited. Evidence indicates that ASIC subunits are expressed in both, plasma membrane and intracellular compartments of mammalian cardiomyocytes, suggesting unrevealing functions in the cardiomyocyte physiology. ASIC channels are expressed in neurons of the peripheral nervous system including the nodose and dorsal root ganglia (DRG), both innervating the heart, where they play a dual role as mechanosensors and chemosensors. In baroreceptor neurons from nodose ganglia, mechanosensation is directly associated with ASIC2a channels for detection of changes in arterial pressure. ASIC channels expressed in DRG neurons have several roles in the cardiovascular function. First, ASIC2a/3 channel has been proposed as the molecular sensor of cardiac ischemic pain for its pH range activation, kinetics and the sustained current. Second, ASIC1a seems to have a critical role in ischemia-induced injury. And third, ASIC1a, 2 and 3 are part of the metabolic component of the exercise pressure reflex (EPR). This review consists of a summary of several reports about the role of ASIC channels in the cardiovascular system and its innervation.

Morphogeometric Evaluation of the Left Ventricle and Left Atrioventricular Ring in Dogs: A Computerized Anatomical Study.

In veterinary, there is scarce availability of morphogeometric studies in normal and remodeled hearts; furthermore, ventricular geometry acts as an indicator of cardiac function. It is a highly necessary field of knowledge for the development of therapeutic protocols, especially surgical ones. The objectives of this study were: to obtain measurements of the left atrioventricular valve ring and left ventricle, to analyze the proportionality between the segments of the left cardiac chamber of normal hearts and to describe reference values for morphogeometric analysis of the left ventricle. For this, 50 hearts from small (Group 1-G1) and medium to large (Group 2-G2) dogs were laminated in the apical, basal and equatorial segments, and submitted to computer analysis to identify the perimeter of each segment and the left atrioventricular ring, wall thickness and distance from the atrioventricular sulcus to the apex. The largest internal perimeter was that of the equatorial. The basal segment had the highest mean for ventral parietal wall thickness, suggesting greater contractile reserve at that location. Considering the proportionality relationships, there was no statistical difference between the intersegmental perimeter indices for the two groups. This suggests that despite the animals' weight variations, the proportions between the left ventricular segments are maintained. Therefore, it is concluded that the data can be used as a standard of comparison for cardiac geometric assessments, as well as a basis for the development of therapeutic measures in the context of adverse cardiac remodeling.

Enhanced Mitochondria-SR Tethering Triggers Adaptive Cardiac Muscle Remodeling.

BACKGROUND: Cardiac contractile function requires high energy from mitochondria, and Ca2+ from the sarcoplasmic reticulum (SR). Via local Ca2+ transfer at close mitochondria-SR contacts, cardiac excitation feedforward regulates mitochondrial ATP production to match surges in demand (excitation-bioenergetics coupling). However, pathological stresses may cause mitochondrial Ca2+ overload, excessive reactive oxygen species production and permeability transition, risking homeostatic collapse and myocyte loss. Excitation-bioenergetics coupling involves mitochondria-SR tethers but the role of tethering in cardiac physiology/pathology is debated. Endogenous tether proteins are multifunctional; therefore, nonselective targets to scrutinize interorganelle linkage. Here, we assessed the physiological/pathological relevance of selective chronic enhancement of cardiac mitochondria-SR tethering. METHODS: We introduced to mice a cardiac muscle-specific engineered tether (linker) transgene with a fluorescent protein core and deployed 2D/3D electron microscopy, biochemical approaches, fluorescence imaging, in vivo and ex vivo cardiac performance monitoring and stress challenges to characterize the linker phenotype. RESULTS: Expressed in the mature cardiomyocytes, the linker expanded and tightened individual mitochondria-junctional SR contacts; but also evoked a marked remodeling with large dense mitochondrial clusters that excluded dyads. Yet, excitation-bioenergetics coupling remained well-preserved, likely due to more longitudinal mitochondria-dyad contacts and nanotunnelling between mitochondria exposed to junctional SR and those sealed away from junctional SR. Remarkably, the linker decreased female vulnerability to acute massive ß-adrenergic stress. It also reduced myocyte death and mitochondrial calcium-overload-associated myocardial impairment in ex vivo ischemia/reperfusion injury. CONCLUSIONS: We propose that mitochondria-SR/endoplasmic reticulum contacts operate at a structural optimum. Although acute changes in tethering may cause dysfunction, upon chronic enhancement of contacts from early life, adaptive remodeling of the organelles shifts the system to a new, stable structural optimum. This remodeling balances the individually enhanced mitochondrion-junctional SR crosstalk and excitation-bioenergetics coupling, by increasing the connected mitochondrial pool and, presumably, Ca2+/reactive oxygen species capacity, which then improves the resilience to stresses associated with dysregulated hyperactive Ca2+ signaling.

Microcirculatory changes as a hallmark of aging in the heart and kidney / Cambios microcirculatorios como sello distintivo del envejecimiento en el corazón y riñón

SUMMARY: Changes in the microcirculation of multiple tissues and organs have been implicated as a possible mechanism in physiological aging. In particular, vascular endothelial growth factor is a secretory protein responsible for regulating angiogenesis via altering endothelial proliferation, survival, migration, extracellular matrix degradation and cell permeability. The aim of the present study was to evaluate the role of vascular endothelial growth factor in the progression of morphological alterations caused by physiological aging in the heart and kidney and to examine its relation to changes in capillary density. We used two age groups of healthy Wistar rats - 6- and 12-month- old. The expression of vascular endothelial growth factor was examined through immunohistochemistry and immunofluorescence and assessed semi-quantitatively. Changes in capillary density were evaluated statistically and correlated with the expression of vascular endothelial growth factor. We reported stronger immunoreactivity for vascular endothelial growth factor in the left compared to the right ventricle and also observed an increase in its expression in both ventricles in older animals. Contrasting results were reported for the renal cortex and medulla. Capillary density decreased statistically in all examined structures as aging progressed. The studied correlations were statistically significant in the two ventricles in 12-month-old animals and in the renal cortex of both age groups. Our results shed light on some changes in the microcirculation that take place as aging advances and likely contribute to impairment in the function of the examined organs.

Los cambios en la microcirculación de múltiples tejidos y órganos se han implicado como un posible mecanismo en el envejecimiento fisiológico. En particular, el factor de crecimiento endotelial vascular es una proteína secretora responsable de regular la angiogénesis mediante la alteración de la proliferación endotelial, la supervivencia, la migración, la degradación de la matriz extracelular y la permeabilidad celular. El objetivo del presente estudio fue evaluar el papel del factor de crecimiento del endotelio vascular en la progresión de las alteraciones morfológicas causadas por el envejecimiento fisiológico en el corazón y riñón y examinar su relación con los cambios en la densidad capilar. Utilizamos dos grupos de ratas Wistar sanas: 6 y 12 meses de edad. La expresión del factor de crecimiento del endotelio vascular se examinó mediante inmunohistoquímica e inmunofluorescencia y se evaluó semicuantitativamente. Los cambios en la densidad capilar se evaluaron estadísticamente y se correlacionaron con la expresión del factor de crecimiento del endotelio vascular. Informamos una inmunorreactividad más fuerte para el factor de crecimiento endotelial vascular en el ventrículo izquierdo en comparación con el derecho y también observamos un aumento en su expresión en ambos ventrículos en animales mayores. Se informaron resultados contrastantes para la corteza renal y la médula. La densidad capilar disminuyó estadísticamente en todas las estructuras examinadas a medida que avanzaba el envejecimiento. Las correlaciones estudiadas fueron estadísticamente significativas en los dos ventrículos en animales de 12 meses y en la corteza renal de ambos grupos de edad. Nuestros resultados arrojan luz sobre algunos cambios en la microcirculación que tienen lugar a medida que avanza el envejecimiento y probablemente contribuyan a un deterioro en la función de los órganos examinados.

Como eu faço o strain longitudinal do ventrículo direito com softwares automatizados 2D e 3D / My approach to right ventricular longitudinal strain with automated 2D and 3D software

A análise da deformação miocárdica ventricular direita tem surgido como uma ferramenta diagnóstica importante na detecção de disfunção sistólica ventricular direita inicial não detectada pelas técnicas ecocardiográficas convencionais. Além disso, é capaz de trazer informações diagnósticas e prognósticas adicionais aos parâmetros tradicionais de avaliação da função sistólica ventricular direita em diversas patologias. O método ecocardiográfico de escolha para sua avaliação é o strain longitudinal derivado do speckletracking. Ele tem se mostrado mais sensível para pequenas mudanças na função sistólica quando comparado à excursão sistólica do plano do anel tricúspide, estudo da onda s´ ao Doppler tecidual do anel tricúspide e variação da área fracional do ventrículo direito. O avanço da inteligência artificial e a presença de softwares com análise automatizada entram neste cenário visando tornar a aplicabilidade do método mais simples, rápida e com menor variabilidade inter e intraobservador. O objetivo deste artigo de revisão é demonstrar o passo a passo da técnica, desde a otimização e aquisição de imagens até a interpretação dos resultados, com figuras ilustrativas de casos selecionados.(AU)

Right ventricular strain analysis has emerged as an important diagnostic tool in the detection of early right ventricular systolic dysfunction not detected by conventional echocardiography techniques. Furthermore, it is capable of providing additional diagnostic and prognostic information to the traditional parameters for evaluating right ventricular systolic function in various pathologies. The echocardiography method of choice for its assessment is longitudinal strain derived from speckletracking. This method has been shown to be more sensitive for small changes in systolic function when compared to tricuspid annular plane systolic excursion, tissue Doppler imaging of the tricuspid annular s' wave, and right ventricular fractional area change. Advances in artificial intelligence and software with automated analysis have been introduced to this scenario with the aim of making the method simpler and quicker to apply, with lower inter- and intra-observer variability. The objective of this review article is to demonstrate the technique step by step, from image optimization and acquisition to interpretation of results, with illustrative figures of selected cases.(AU)

Postoperative myocardial fibrosis assessment in aortic valvular heart diseases-a cardiovascular magnetic resonance study.

AIMS: Left ventricular remodelling occurs during the chronic course of aortic regurgitation (AR) and aortic stenosis (AS), leading to myocardial hypertrophy and fibrosis. Several studies have shown that extracellular volume fraction (ECV) and indexed extracellular volume (iECV) are important surrogate markers of diffuse myocardial fibrosis (MF). Postoperative data on these cardiovascular magnetic resonance (CMR) extracellular expansion parameters for either AS or AR are scarce. This study aimed to demonstrate the postoperative changes that occur in diffuse MF, and the influence of preoperative MF on the reversal of LV remodelling, in patients with AR or AS. METHODS AND RESULTS: Patients with severe AR or AS and indications for surgery were prospectively enrolled. Patients underwent pre- and postoperative CMR, and ECV and iECV were quantified. Data from 99 patients were analysed (32 with AR and 67 with AS). After surgery, the left ventricle mass index decreased in both groups (AR: 110 vs. 91 g/m2; AS: 86 vs. 68 g/m2, both P < 0.001). The late gadolinium enhancement fraction (AR: preoperative 1.9% vs. postoperative 1.7%, P = 0.575; AS: preoperative 2.4% vs. postoperative 2.4%, P = 0.615) and late gadolinium enhancement mass (AR: preoperative 3.8 g vs. postoperative 2.5 g, P = 0.635; AS: preoperative 3.4 g vs. postoperative 3.5 g, P = 0.575) remained stable in both groups. Preoperative iECV and ECV were greater in the AR group (iECV: 30 mL/m2 vs. 22 mL/m2, P = 0.001; ECV: 28.4% vs. 27.2%, P = 0.048). Indexed extracellular volume decreased after surgery in both groups (AR: 30-26.5 mL/m2, AS: 22-18.2 mL/m2, both P < 0.001); it was still greater in the AR group (AR: 26.5 mL/m2 vs. AS: 18.2 mL/m2, P < 0.001). Postoperative ECV remained stable in the AR group (preoperative 28.4% vs. postoperative 29.9%; P = 0.617) and increased in the AS group (preoperative 27.2% vs. postoperative 28.6%; P = 0.033). CONCLUSION: Patients with both AR or AS presented reduction in iECV after surgery, unfolding the reversible nature of diffuse MF. In contrast to patients with AS, those with AR developed postoperative iECV regression with stable ECV, suggesting a balanced reduction in both intracellular and extracellular myocardial components.

Impact of Prenatal Alcohol Exposure on the Development and Myocardium of Adult Mice: Morphometric Changes, Transcriptional Modulation of Genes Related to Cardiac Dysfunction, and Antioxidant Cardioprotection.

The impact of prenatal alcohol exposure (PAE) varies considerably between individuals, leading to morphological and genetic changes. However, minor changes usually go undetected in PAE children. We investigated PAE's effects on gene transcription of genes related to cardiac dysfunction signaling in mouse myocardium and morphological changes. C57Bl/6 mice were subjected to a 10% PAE protocol. In postnatal days 2 and 60 (PN2 and PN60), morphometric measurements in the offspring were performed. Ventricular samples of the heart were collected in PN60 from male offspring for quantification of mRNA expression of 47 genes of nine myocardial signal transduction pathways related to cardiovascular dysfunction. Animals from the PAE group presented low birth weight than the Control group, but the differences were abolished in adult mice. In contrast, the mice's size was similar in PN2; however, PAE mice were oversized at PN60 compared with the Control group. Cardiac and ventricular indexes were increased in PAE mice. PAE modulated the mRNA expression of 43 genes, especially increasing the expressions of genes essential for maladaptive tissue remodeling. PAE animals presented increased antioxidant enzyme activities in the myocardium. In summary, PAE animals presented morphometric changes, transcription of cardiac dysfunction-related genes, and increased antioxidant protection in the myocardium.

Successful Correction of Postinfarction Interventricular Septum Rupture Diagnosed Online During the COVID-19 Pandemic (Clinical Case)

ABSTRACT Postinfarction interventricular septum defect is a rare, but very serious and sometimes fatal, complication of acute myocardial infarction. This article describes a clinical case of online diagnosis of a late-stage myocardial infarction and the subsequent successful endovascular repair of a postinfarction ventricular septum defect with a Myval™ occluder.

Successful Correction of Postinfarction Interventricular Septum Rupture Diagnosed Online During the COVID-19 Pandemic (Clinical Case).

Postinfarction interventricular septum defect is a rare, but very serious and sometimes fatal, complication of acute myocardial infarction. This article describes a clinical case of online diagnosis of a late-stage myocardial infarction and the subsequent successful endovascular repair of a postinfarction ventricular septum defect with a Myval™ occluder.