Mechanism of Blood-Heart-Barrier Leakage: Implications for COVID-19 Induced Cardiovascular Injury.

Although blood-heart-barrier (BHB) leakage is the hallmark of congestive (cardio-pulmonary) heart failure (CHF), the primary cause of death in elderly, and during viral myocarditis resulting from the novel coronavirus variants such as the severe acute respiratory syndrome novel corona virus 2 (SARS-CoV-2) known as COVID-19, the mechanism is unclear. The goal of this project is to determine the mechanism of the BHB in CHF. Endocardial endothelium (EE) is the BHB against leakage of blood from endocardium to the interstitium; however, this BHB is broken during CHF. Previous studies from our laboratory, and others have shown a robust activation of matrix metalloproteinase-9 (MMP-9) during CHF. MMP-9 degrades the connexins leading to EE dysfunction. We demonstrated juxtacrine coupling of EE with myocyte and mitochondria (Mito) but how it works still remains at large. To test whether activation of MMP-9 causes EE barrier dysfunction, we hypothesized that if that were the case then treatment with hydroxychloroquine (HCQ) could, in fact, inhibit MMP-9, and thus preserve the EE barrier/juxtacrine signaling, and synchronous endothelial-myocyte coupling. To determine this, CHF was created by aorta-vena cava fistula (AVF) employing the mouse as a model system. The sham, and AVF mice were treated with HCQ. Cardiac hypertrophy, tissue remodeling-induced mitochondrial-myocyte, and endothelial-myocyte contractions were measured. Microvascular leakage was measured using FITC-albumin conjugate. The cardiac function was measured by echocardiography (Echo). Results suggest that MMP-9 activation, endocardial endothelial leakage, endothelial-myocyte (E-M) uncoupling, dyssynchronous mitochondrial fusion-fission (Mfn2/Drp1 ratio), and mito-myocyte uncoupling in the AVF heart failure were found to be rampant; however, treatment with HCQ successfully mitigated some of the deleterious cardiac alterations during CHF. The findings have direct relevance to the gamut of cardiac manifestations, and the resultant phenotypes arising from the ongoing complications of COVID-19 in human subjects.

'White Mars' - nearly two decades of biomedical research at the Antarctic Concordia station.

NEW FINDINGS: What is the topic of this review? Biomedical research at the Antarctic Concordia Station. What advances does it highlight? Overview of findings in psychology, neuroscience, sleep, cardiovascular physiology and immune system, relevant in isolated, confined and extreme environments and spaceflight. ABSTRACT: Extended stays in isolated, confined and extreme (ICE) environments like Antarctica are associated with a whole set of psychological and physiological challenges for the crew. As such, winter-over stays at Antarctica provide an important opportunity to acquire knowledge into the physiological and psychological changes that ICE environments inevitably bring. The European Space Agency (ESA) is particularly interested in conducting research in such an environment, as it is a unique opportunity to translate these results to space crews experiencing very similar issues. In the past two decades, the ESA has supported a total of 36 biomedical research projects at the Concordia station in collaboration with the French and Italian polar institutes. More specifically, studies in the areas of psychology, neuroscience, sleep physiology, cardiovascular physiology and immunology were performed. The outcomes of these studies are directly relevant for people working in ICE environments, but also help to better understand the biomedical challenges of those environments. Consequently, they can help to better prepare for human space exploration and to identify countermeasures to minimize the adverse effects of space environments on astronaut health. The aim of this review is to provide an overview of the biomedical studies that have taken place in the past two decades at the Antarctic Concordia station and to summarize the results and their implication for human spaceflight.

The relationship between the rheological behavior of RBCs and angiogenesis in the morbidly obese.

OBJECTIVE: The aim of this study was to investigate the relationship between red blood cell (RBC) aggregation and deformability and angiogenesis parameters in obese patients. METHODS: We studied 35 obese subjects and 20 non-obese people as a control group. Angiogenesis was detected using Bio-Plex Pro Human Angiogenesis Multiplex Assays. The RBC aggregation and deformability of the red blood cell aggregation were performed by the Laser-assisted Optical Rotational Cell Analyser - LORCA. RESULTS: The aggregation index and the syllectogram's amplitude were significantly higher in the obese patients, whereas the aggregation half-time (t1/2) was lower compared with the control group. The deformability of RBC expressed as EI was significantly lower in the obese group than it was in the control group. All angiogenesis parameters were higher in obese individuals than they were in the control group. Significant differences were observed in angiopoietin 2 (p = 0.048), folistin (p = 0.0017), G-CSF (p = 0.042), HGF (p = 0.016), and PECAM-1 (p = 0.014). The VEGF tended to be higher in the obese patients than in the control group (p = 0.09); nevertheless, the concentration of PDGF-BB was similar in both groups. EI at shear stresses of 18.49 Pa and 30.2 Pa was strongly correlated with all angiogenesis parameters. No correlations were found between the studied RBC aggregation indices and angiogenesis parameters. Multivariate analyses indicated that only HGF was an independent predictor of RBC deformability at 18.49 Pa (ß-0.83, P < 0.000005) and at 30.2 Pa (ß-0.83, P < 0.00005). CONCLUSIONS: The study found that there are relationships between enhanced RBC rigidity and angiogenesis status in obese subjects. Because this correlation between angiogenesis and RBC deformability is presented for the first time, the physiological importance of the relationship requires further research.

Negative Cardiovascular Consequences of Small Molecule Immunosuppressants.

Immunosuppressants are critical after transplantation and prescribed as immune-modulators for autoimmune disorders and glomerulonephritides. Immunosuppressants include large (e.g., thymoglobulin, alemtuzumab, and rituximab) and small molecules (e.g., corticosteroids, calcineurin inhibitors, antimetabolites, and mammalian target of rapamycin (mTOR) inhibitors). The majority of the small molecules worsen traditional cardiovascular risks. This review describes cardiovascular risks of small molecule immunosuppressants: corticosteroids, calcineurin inhibitors (tacrolimus and cyclosporine), and mTOR inhibitors (rapamycin), by categorizing these risks into two categories: ischemic heart disease and nonischemic cardiac effects.

Relevancia actual de la capacidad aeróbica máxima en la práctica clínica / Current relevance of maximal aerobic capacity in clinical practice

La capacidad aeróbica máxima (CAM) o capacidad funcional, refleja la capacidad de funcionamiento del sistema cardiorrespiratorio, y es uno de los indicadores pronósticos más potentes de mortalidad y enfermedad cardiovascular, igual o por encima de los factores de riesgo tradicionales. Aunque no tiene un poder diagnóstico de isquemia, una alta CAM, disminuye las probabilidades de una cardiopatía isqué- mica. Asimismo, la CAM forma parte de los pilares que afectan el rendimiento de resistencia, y su evaluación es frecuente en los deportistas. La determinación de la CAM se realiza mediante una prueba de esfuerzo, y junto con otros parámetros electrocardiográficos y hemodinámicos, se puede obtener un perfil diagnóstico, pronóstico o funcional del paciente. En esta revisión, se pretende mostrar las potentes relaciones comprobadas de la CAM con el pronóstico de morbimortalidad cardiovascular y por todas las causas. La solicitud de una prueba de esfuerzo es una práctica poco extendida, quizás por desconocimiento de la utilidad por parte de los propios médicos, y debería ser incluida en la práctica clínica diaria, dentro de los servicios ofrecidos al paciente (AU)

The maximum aerobic capacity (MAC) or functional capacity, reflects functional capacity of the cardiorespiratory system, and is one of the most powerful prognostic indicators of cardiovascular mortality, equal to, or above, the traditional risk factors. Although it has not a diagnostic power of ischemia, a high MAC decreases the probabilities of ischemic heart disease. Also, the CAM is part of the pillars that affect endurance performance, and evaluation of this is common in athletes. Determining the MAC is done through a stress test, and along with other electrocardiographic and hemodynamic parameters, a functional diagnostic or prognostic profile can be obtained. In this review, we intend to show the powerful proven MAC relations with prognosis of cardiovascular morbidity and mortality from all causes. The request for a exercise testing is not in widespead use, perhaps for lack of knowledge of this technique by the doctors themselves, and should be included in the daily clinical practice, amongst the services offered to the patient (AU)

Integrated Immune and Cardiovascular Function in Pancrustacea: Lessons from the Insects.

When pathogens invade the insect hemocoel (body cavity) they immediately confront two major forces: immune-responses and circulatory currents. The immune response is mediated by circulating and sessile hemocytes, the fat body, the midgut, and the salivary glands. These tissues drive cellular and humoral immune processes that kill pathogens via phagocytosis, melanization, lysis, encapsulation, and nodulation. Moreover, immune-responses take place within a three-dimensional and dynamic space that is governed by the forces of the circulatory system. The circulation of hemolymph (insect blood) is primarily controlled by the wave-like contraction of a dorsal vessel, which is a muscular tube that extends the length of the insect and is divided into a thoracic aorta and an abdominal heart. Distributed along the heart are valves, called ostia, that allow hemolymph to enter the vessel. Once inside the heart, hemolymph is sequentially propelled to the anterior and to the posterior of the body. During an infection, circulatory currents sweep small pathogens to all regions of the body. As they circulate, pathogens encounter immune factors of the insect that range from soluble cytotoxic peptides to phagocytic hemocytes. A prominent location for these encounters is the surface of the heart. Specifically, periostial hemocytes aggregate in the extracardiac regions that flank the heart's ostia (the periostial regions) and phagocytoze pathogens in areas of high flow of hemolymph. This review summarizes the biology of the immune and circulatory systems of insects, including how these two systems have co-adapted to fight infection. This review also compares the immune and circulatory systems of insects to that of crustaceans, and details how attachment of hemocytes to cardiac tissues and the biology of the lymphoid organ demonstrate that dynamic interactions between the immune and circulatory systems also occur in lineages of crustaceans.

Aptitud física cardiorrespiratoria y riesgo cardiometabólico en personas adultas jóvenes / Cardiorespiratory fitness and cardiometabolic risk in young adults

Fundamentos: La evaluación del VO2max permite clasificar a los sujetos según el riesgo para la salud. Sin embargo los factores que pueden afectar a las clasificaciones han sido poco estudiados. El objetivo de esta investigación fue determinar si el tipo de ecuación predictiva del VO2max y los criterios de referencia del Fitnessgram® modifican la proporción de adultos jóvenes clasificados con un nivel de capacidad aeróbica indicativo de riesgo cardiometabólico. Métodos: El diseño del estudio fue observacional, relacional y de corte transversal. Participaron voluntariamente 240 adultos jóvenes. El VO2max fue estimado mediante el test de Course Navette aplicando 9 ecuaciones predictivas. Las diferencias en las clasificaciones fueron analizadas con la prueba Q de Cochran y la de MacNemar. Resultados: El nivel de capacidad aeróbica indicativo de riesgo cardiometabólico osciló entre 7,1% y 70,4% según el tipo de ecuación predictiva y el criterio de referencia utilizado (p<0,001). Independientemente del la ecuación predictiva del VO2max y el criterio de referencia aplicado; una mayor proporción de mujeres, del 29,4% al 85,3%, fueron clasificadas con un nivel no saludable de capacidad aeróbica frente al 4,8% a 51% en varones (p<0,001). En ambos sexos, los viejos criterios de referencia clasificaron a una menor proporción de hombres (del 4,8% al 48,1%) y mujeres (del 39,4% al 68,4%) con capacidad aeróbica no saludable, independientemente de la ecuación aplicada (p<0,001). Conclusiones: El tipo de ecuación predictiva del VO2max y los criterios de referencia del Fitnessgram® modifican las clasificaciones de adultos jóvenes con un nivel de capacidad aeróbica saludable o de riesgo cardiometabólico(AU)

Background: The assessment of VO2max allow classify subjects according to the health risk. However the factors that may affect the classifications have been little studied. The main purpose was to determine whether the type of VO2max prediction equation and the Fitnessgram® criterion- referenced standards modified the proportion of young adults classified with a level of aerobic capacity cardiometabolic risk indicative. Methods: The study design was observational, cross-sectional and relational. Young adults (n= 240) participated voluntarily. The VO2max was estimated by 20-m shuttle run test applying 9 predictive equations. The differences in the classifications were analyzed with the Cochran Q and McNemar tests. Results: The level of aerobic capacity indicative of cardiometabolic risk ranged between 7.1% and 70.4% depending on the criterion-referenced standards and predictive equation used (p<0.001). A higher percentage of women were classified with an unhealthy level in all equations (women: 29.4% to 85.3% vs 4.8% to 51% in men), regardless of the criterion-referenced standards (p<0.001). Both sexes and irrespective of the equation applied the old criterion-referenced standards classified a lower proportion of subjects (men: 4.8% to 48.1% and women: 39.4% a 68.4%) with unhealthy aerobic capacity (p≤ 0.004). Conclusions: The type ofVO2max prediction equation and Fitnessgram ® criterion-referenced standards changed classifications young adults with a level of aerobic capacity of cardiometabolic risk indicative(AU)

Physical activity: do patients infected with HIV practice? How much? A systematic review.

Several studies have suggested that aerobic physical activity is safe and beneficial for HIV-infected adults. However, there is information lacking regarding whether HIV-infected patients practice physical activity and to what extent. Therefore, the aim of this systematic review was to determine the prevalence of physical activity, sedentary lifestyle or lack of physical activity in non-experimental conditions performed by HIV-infected subjects. The electronic search was conducted using Medline and EMBASE bibliographic databases and the platforms of Bireme, Ovid, Science Direct, High Wire and SCIELO from January 1990 to July 2011. Original observational studies were included. Of the 2,838 articles found, 48 met the inclusion criteria. Following data extraction and after reading the manuscripts, 24 were selected for systematic review. Of the 24 studies, most were cross-sectional studies. The average quality score using the modified Newcastle-Ottawa scale was 2.8±1.5. The diversity of methods used to assess physical activity precluded the calculated summary estimate of prevalence. The percentage of sedentary lifestyle was determined in 13 articles which conducted studies on HIV-infected individuals. The percentage of sedentary lifestyle or physical inactivity ranged from 19%to 73%, with the level determined by different methods. In conclusion, there are few well-designed studies with adequate sample size to represent the population of HIV-infected individuals. A pooled estimate could not be calculated due to the differences in physical activity measurements and definitions of physically active and non-active HIV-infected individuals.

Cardiac function and circulating cytokines after endotoxin exposure in neonatal mice.

Complications after cardiac surgery in neonates can occur because of activation of the inflammatory system. This study used lipopolysaccharide (LPS) endotoxin exposure to cause cytokine activation in neonatal mice and examine left ventricular (LV) function and the effects of antioxidant treatment on cytokine levels. Neonatal mice (6 d old) were injected with either 25 mg/kg LPS (n = 13) or PBS (n = 14), and LV function (echocardiography) was measured at 4 h. Plasma levels of TNF-α, IL-4, IL-6, and IL-10 were measured at 30 min, 1, 2, and 4 h after injection (n = 5 mice per group). Effects of pretreatment with N-acetylcysteine (NAC, 50 mg/kg) on cytokine levels were examined at 2 and 4 h after PBS or LPS (n = 5 mice per group). Four hours after LPS, heart rate was increased (434 ± 14 versus 405 ± 14 bpm, p < 0.05). LV end-diastolic dimension and ejection time were reduced with LPS (both p < 0.05). LPS exposure increased plasma TNF-α, IL-6, and IL-10 levels. NAC pretreatment attenuated the increases in TNF-α and IL-6 levels, but augmented IL-10 levels at 2 h post-LPS. LPS exposure altered cardiac performance and activated cytokines in neonatal mice, which may be ameliorated using antioxidants.