APLICABILIDADE DO TESTE DE CAMINHADA DE SEIS MINUTOS PARA QUANTIFICAR O DESEMPENHO CARDIOVASCULAR DO PACIENTE PÓS-INFARTO DO MIOCÁRDIO

O teste de caminhada de seis minutos (TC6) foi usado como ferramenta para quantificar as alterações geradas pela reabilitação. O objetivo desta pesquisa foi estimar as respostas cardíacas após infarto do miocárdio e os benefícios da reabilitação. Utilizou-se um circuito oval, onde foram realizados três testes em dias alternados, foi estabelecida a média dos testes, em que a pressão arterial, frequência cardíaca, frequência respiratória, saturação de oxigênio, escala subjetiva de Borg e a metragem durante a distância percorrida foram verificados. Foram avaliados três participantes com, aproximadamente, 69,3±4,93 anos. O teste ocorreu em duas etapas, a primeira foi a avaliação e, a seguir, a aplicação do protocolo com cargas variando de 40 a 50% da frequência cardíaca (FC) submáxima por idade e, na segunda, ocorreu a repetição do protocolo de avaliação. Os sinais vitais apresentaram alterações fisiologicamente esperadas, a pressão arterial sistólica (PAS) evoluiu 4,54%, a pressão arterial diastólica (PAD)14,28%, após o repouso, a PAS diminuiu para -0,8%, enquanto a PAD sofreu alterações importantes. A FC teve um percentual de evolução de 19,44%, diminuindo para -3,12%. A saturação de oxigênio teve aumento máximo de 2% e -1% de declínio, a maior metragem foi de 515,11 metros e a menor 235,5 metros. O TC6 é um teste confiável para estimar o desempenho cardiovascular de indivíduos após infarto do miocárdio. APPLICABILITY OF THE SIX-MINUTE WALK TEST TO QUANTIFY THE CARDIOVASCULAR PERFORMANCE OF PATIENTS AFTER MYOCARDIAL INFARCTION ABSTRACT The six-minute walk test (6MWT) was used as a tool to quantify the changes generated by rehabilitation. The purpose of this research was to estimate the cardiac responses after myocardial infarction and the benefits of rehabilitation. An oval circuit was used, where three tests were performed on alternate days, the average of the tests was established, in which blood pressure, heart rate, respiratory rate, oxygen saturation, Borg's subjective scale, and the footage over the distance traveled were checked. Three participants with approximately 69.3±4.93 years old were evaluated. The test occurred in two stages, the first was the evaluation and then the application of the protocol with loads varying from 40 to 50% of submaximal heart rate (HR) by age and, in the second, there was the repetition of the evaluation protocol. The vital signs showed physiologically expected changes, the systolic blood pressure (SBP) evolved 4.54%, the diastolic blood pressure (DBP)14.28%, after resting, the SBP decreased to -0.8%, while the DBP suffered important changes. The HR had a percentage of evolution of 19.44%, decreasing to -3.12%. The oxygen saturation had a maximum increase of 2% and -1% decline, the longest distance was 515.11 meters and the shortest 235.5 meters. The 6MWT is a reliable test to estimate the cardiovascular performance of individuals after myocardial infarction. Keywords: Six-minute Walk Test, Elder, Myocardial Infarction.

Expression of Microbial Enzymes in Mammalian Astrocytes to Modulate Lactate Release

Astrocytes support and modulate neuronal activity through the release of L-lactate. The suggested roles of astrocytic lactate in the brain encompass an expanding range of vital functions, including central control of respiration and cardiovascular performance, learning, memory, executive behaviour and regulation of mood. Studying the effects of astrocytic lactate requires tools that limit the release of lactate selectively from astrocytes. Here, we report the validation in vitro of novel molecular constructs derived from enzymes originally found in bacteria, that when expressed in astrocytes, interfere with lactate handling. When lactate 2-monooxygenase derived from M. smegmatis was specifically expressed in astrocytes, it reduced intracellular lactate pools as well as lactate release upon stimulation. D-lactate dehydrogenase derived from L. bulgaricus diverts pyruvate towards D-lactate production and release by astrocytes, which may affect signalling properties of lactate in the brain. Together with lactate oxidase, which we have previously described, this set of transgenic tools can be employed to better understand astrocytic lactate release and its role in the regulation of neuronal activity in different behavioural contexts.

Acute and Sub-Chronic Exposure to Artificial Sweeteners at the Highest Environmentally Relevant Concentration Induce Less Cardiovascular Physiology Alterations in Zebrafish Larvae

Artificial sweeteners are widely used food ingredients in beverages and drinks to lower calorie intake which in turn helps prevent lifestyle diseases such as obesity. However, as their popularity has increased, the release of artificial sweetener to the aquatic environment has also increased at a tremendous rate. Thus, our study aims to systematically explore the potential cardiovascular physiology alterations caused by eight commercial artificial sweeteners, including acesulfame-K, alitame, aspartame, sodium cyclamate, dulcin, neotame, saccharine and sucralose, at the highest environmentally relevant concentration on cardiovascular performance using zebrafish (Danio rerio) as a model system. Embryonic zebrafish were exposed to the eight artificial sweeteners at 100 ppb and their cardiovascular performance (heart rate, ejection fraction, fractional shortening, stroke volume, cardiac output, heartbeat variability, and blood flow velocity) was measured and compared. Overall, our finding supports the safety of artificial sweetener exposure. However, several finding like a significant increase in the heart rate and heart rate variability after incubation in several artificial sweeteners are noteworthy. Biomarker testing also revealed that saccharine significantly increase the dopamine level in zebrafish larvae, which is might be the reason for the cardiac physiology changes observed after saccharine exposure.

Exercise, programmed cell death and exhaustion of cardiomyocyte proliferation in aging zebrafish

As the human heart ages, the myocardium undergoes fibrotic remodelling, there is declining cardiovascular performance and eventual heart failure. It is suggested that exercise is an important intervention to ameliorate these changes. In this study we establish zebrafish as a laboratory model to understand how aging and exercise affect cardiomyocyte turnover. We show the zebrafish heart does not exhibit indeterminate growth but follows the pattern seen in human aging. In zebrafish, cardiomyocyte proliferation remains constant, but a late increase cell death underlies the pattern of initial cardiac growth and later fibrosis. These anatomical findings are corelated with the human like decline in cardiovascular performance reflected in voluntary swimming activity, critical swimming speed (Ucrit) and biomarkers of cardiac insufficiency. Whilst the vertebrate heart can respond to injury through cardiomyocyte proliferation, it is not known if a proliferative response occurs when the cardiovascular system is exposed to prolonged severe physiological stress, or if this changes with age. To investigate this, young and old adult zebrafish were challenged by 72 hours of enforced swimming in a purpose-built flume at levels close to maximal Ucrit. Whilst young adult fish produced a significant proliferative response older fish had a dramatically impaired response, provided by a smaller proliferative cardiomyocyte population. Finally, we asked if these aging responses could be improved by increased activity throughout adulthood. Whilst there was some improvement in the aged proliferative response the size of the reduced proliferative cardiomyocyte pool remained unchanged and importantly, there was increased myocardial fibrosis. The zebrafish heart thus provides a laboratory model to study cardiomyocyte turnover during aging and physiological stresses, revealing the important trade-off between preserving cardiovascular fitness through exercise and accelerated fibrotic change, whilst the available proliferative pool of cardiomyocytes continues to diminish.

Non-invasive MRI Studies of Ventilatory and Cardiovascular Performance in Edible Crabs Cancer pagurus During Warming Under Elevated CO2 Levels

The thermal tolerance of marine decapod crustacea is defined through their capacities for oxygen uptake and distribution. High ambient CO2 levels were previously shown to reduce hemolymph oxygen levels at enhanced cardiac performance during warming. This study investigated the impacts of warming under two CO2 levels on ventilation and hemolymph circulation in edible crabs Cancer pagurus. It also highlights changes in the ventilatory and cardiac pauses displayed by Decapoda under routine metabolism. Animals were exposed to step-wise, sub-critical warming (12–20°C over 5 days) under control (470 μatm) and high (1,350 μatm) water PCO2. Flow-through respirometry was combined with magnetic resonance imaging and infra-red photoplethysmography to allow for simultaneous, non-invasive measurements of metabolic rates (M˙O2), ventilation and cardiovascular performance. Crabs spent significantly more time in a low M˙O2 state (metabolic pause), when experiencing high CO2 conditions above 16°C, compared to normocapnic warming. Heart rates leveled off beyond 18°C at any CO2 level. Cardiac output continued to increase with high-CO2-warming, due to elevated cardiac stroke volumes. Consequently, temperature-dependent branchial hemolymph flow remained unaffected by CO2. Instead, a suppressing effect of CO2 on ventilation was found beyond 16°C. These results indicate constrained oxygen uptake at stable cardiovascular performance in a decapod crustacean.Cancer pagurus: urn:lsid:zoobank.org:act:B750F89A-84B5-448B-8D80-EBD724A1C9D4

Abstract 452: Role of CD38 in Cardiovascular Performance and Its Use as a Therapeutic Target in Obesity-Induced Diastolic Dysfunction

Background: Cardiac tissue possesses high energetic requirements. During development of heart failure there is a shift from fatty acid oxidation to the utilization of other substrates. This transition leads to the decline in NAD/NADH ratio, which increases susceptibility to stress. CD38 is the main NAD + -consuming enzyme responsible for NAD + levels regulation in tissue and therefore represents a possible therapeutic target in such conditions. Objective: To investigate the role of CD38 in cardiovascular performance and its potential use as a therapeutic target in obesity-induced heart failure. Results: When comparing adult Wild-Type (WT) and CD38 Knock-out (KO) mice we observed that the latter had higher exercise performance, increased heart rate variability (HRV) and decreased heart rate (HR). When comparing WT and CD38 catalytically inactive (CI) mice we observed the same results, showing its relation with CD38 catalytic activity. WT mice treated with an antibody which blocks CD38 activity showed improved exercise capacity and HRV. In both genetically modified or antibody treated groups, NAD+ levels were significantly increased in heart. In order to explore the NAD + role in these findings, we compared WT control and CD38KO treated with FK866 (Nampt inhibitor) and observed that NAD+ levels in heart decreased as well as exercise capacity. We then aimed to demonstrate CD38 role as a target for therapeutic intervention in a model of cardiac strain induced by obesity in aged mice. We compared WT and CD38 CI aged mice, placed in normal diet (ND) or high fat diet (HFD). WT animals fed HFD showed decreased exercise capacity and this effect is reversed in CD38 CI fed HFD. Similarly, WT placed in HFD developed diastolic dysfunction seen as a significant increase in E/e’ ratio, and CD38 CI placed in HFD were protect against the development of this dysfunction. Mechanistically, we observed that blockage of CD38 resulted in decreased protein acetylation and increased SERCA expression. Conclusion: CD38 plays a role in cardiovascular performance by regulation of NAD + homeostasis. In a model of obesity-induced diastolic dysfunction NAD+-boosting by blocking CD38 activity led to protection by up-regulating SERCA expression.