RESUMEN

Dronedarone (DRN) is a clinically used drug to mitigate arrhythmias with multichannel block properties, including the sodium channel Nav1.5. Extracellular acidification is known to change the pharmacological properties of several antiarrhythmic drugs. Here, we explore how modification in extracellular pH (pHe) shapes the pharmacological profile of DRN upon Nav1.5 sodium current (INa) and in the ex vivo heart preparation. Embryonic human kidney cells (HEK293T/17) were used to transiently express the human isoform of Nav1.5 α-subunit. Patch-Clamp technique was employed to study INa. Neurotoxin-II (ATX-II) was used to induce the late sodium current (INaLate). Additionally, ex vivo Wistar male rat preparations in the Langendorff system were utilized to study electrocardiogram (ECG) waves. DRN preferentially binds to the closed state inactivation mode of Nav1.5 at pHe 7.0. The recovery from INa inactivation was delayed in the presence of DRN in both pHe 7.0 and 7.4, and the use-dependent properties were distinct at pHe 7.0 and 7.4. However, the potency of DRN upon the peak INa, the voltage dependence for activation, and the steady-state inactivation curves were not altered in both pHe tested. Also, the pHe did not change the ability of DRN to block INaLate. Lastly, DRN in a concentration and pH dependent manner modulated the QRS complex, QT and RR interval in clinically relevant concentration. Thus, the pharmacological properties of DRN upon Nav1.5 and ex vivo heart preparation partially depend on the pHe. The pHe changed the biological effect of DRN in the heart electrical function in relevant clinical concentration.

Asunto(s)

RESUMEN

The proposition of a minimal dose of resistance training (RT) to elicit health benefits, encompassing physiological and psychological aspects, has garnered attention. While empirical investigations have demonstrated the efficacy of low-volume RT protocols in inducing adaptations such as enhanced strength and functional capacity, further exploration of the effects of this paradigm across a broader spectrum of variables is warranted. Thus, this study aimed to investigate the effects of minimal dose RT on strength and functional capacity, cardiac autonomic modulation, and hemodynamic parameters in menopausal women. Twenty-six women were randomly assigned to the training (TG: 63.2 ± 9.3 years) or control group (CG: 59.3 ± 7.6 years). Anthropometric measurements, strength and functional performance tests, cardiac autonomic assessment, and hemodynamic parameters were performed before and after four weeks of intervention. The TG performed the minimum dose RT twice weekly for four weeks (2 sets of 8-12 repetitions in three dynamic exercises, plus three 1-min isometric planks), and the CG had a weekly meeting with lectures and stretching. Two-way ANOVA with repeated measures was applied to each variable. Regarding time comparisons, there was a significant increase for LniRR (F = 4.78; ω2 = 0.046; p = 0.04), one repetition maximum (1RM) bench press (F = 8.06; ω2 = 0,013; p = 0.01), and 1RM leg press (F = 17.3; ω2 = 0,098; p < 0.01). There was a group*time interaction only for the index LnRMSSD (F = 5.11; ω2 = 0.042; p = 0.03), and 1RM bench press (F = 9.52; ω2 = 0,016; p = 0.01). No between-group main effect for any variable was found. The minimal dose RT protocol improved muscle strength, while cardiac autonomic and hemodynamic variables, as well as functional capacity, remained stable over 4 weeks in menopausal women.

Asunto(s)

RESUMEN

Manganese (Mn2+) is an abundant chemical element in the earth's crust and is present in soil, water, and industrial environments, including mining, welding, and battery manufacturing. Manganese (Mn) is an essential metal needed as a cofactor for many enzymes to maintain proper biological functions. Excessive exposure to Mn in high doses can result in a condition known as manganism, which results in disorders of the neurological, cardiac, and pulmonary systems. The aim of this study was to assess cardiac susceptibility to manganese intoxication in Colossoma macropomum subjected to a fixed concentration of 4 mg/mL for a period of up to 96 h. This study used 45 Tambaquis (30.38 ± 3.5 g) divided into five groups of 9 animals/treatment. The treated groups were exposed to the manganese concentration for a period of 24, 48, 72, and 96 h, after which the animals' ECGs were recorded, showing heart rate, R-R interval, P-Q interval, QRS complex duration and S-T interval. The results showed that cardiac activity decreased as the contact time increased, with an increase in the P-Q and S-T intervals. This indicates that the breakdown of circulatory homeostasis in these animals was caused by contact time with manganese.

Asunto(s)

RESUMEN

Mild hyperbaric oxygen therapy (mHBOT) is an adjuvant therapy used in conditions where tissue oxygenation is reduced and is implemented using pressures less than 1.5 ATA and 100% O2 (instead of the classical HBOT at 1.9-3 ATA) which results in cheaper, easier to implement, and equally effective. mHBOT is offered for wellness and beauty and as an anti-aging strategy, in spite of the absence of studies on the cardiovascular system. Consequently, we investigated the impact of mHBOT on the cardiovascular system. Mechanical and energetic parameters of isolated heart submitted to ischemia/reperfusion injury and arterial contractile response from mHBOT-exposed rats were evaluated. In the heart, mHBOT increased pre-ischemic velocity of contraction and ischemic end-diastolic pressure and developed pressure and contractile economy during reperfusion. mHBOT decreased infarct size and increased the plasma nitrite levels. In the artery, mHBOT increased acetylcholine sensitivity. mHBOT protects the heart during ischemia/reperfusion and affects vascular relaxation.

Asunto(s)

Asunto(s)

Asunto(s)

RESUMEN

This study retrospectively examined the hemodynamic effects of passive leg raising (PLR) in mechanically ventilated patients during fluid removal before spontaneous breathing trials. In previous studies, we noticed varying cardiac responses after PLR completion, particularly in positive tests. Using a bioreactance monitor, we recorded and analyzed hemodynamic parameters, including stroke volume and cardiac index (CI), before and after PLR in post-acute ICU patients. We included 27 patients who underwent 60 PLR procedures. In preload-unresponsive patients, no significant CI changes were observed (CI_t-6 = 3.7 [2.6; 4.7] mL/min/m2 vs. CI_t9 = 3.3 [2.5; 3.4] mL/min/m2; p = 0.306), while in preload-responsive patients, two distinct CI response types to PLR were identified: a transient peak with immediate return to baseline (CI_t-6 = 2.7 [2.5; 3.1] mL/min/m2 vs. 3.3 [2.6; 3.8] L/min/m2; p = 0.119) and a sustained CI elevation lasting beyond the PLR maneuver (CI_t-6 = 2.8 [2.3; 2.9] L/min/m2 vs. 3.3 [2.8; 3.9] ml/min/m2; p = 0.034). The latter was particularly noted when ΔCI during PLR exceeded 25%. Our findings suggest that in certain preload-responsive patients, PLR can induce a more sustained increase in CI, indicating a possible persistent hemodynamic effect. This effect could be due to a combination of autotransfusion and sympathetic activation affecting venous return and vascular tone. Further research in larger cohorts and more comprehensive hemodynamic assessments are warranted to validate these observations and elucidate the possible underlying mechanisms.The Fluid unLoading On Weaning (FLOW) study was prospectively registered under the ID NCT04496583 on 2020-07-29 at ClinicalTrials.gov.

Asunto(s)

RESUMEN

The dorsal motor nucleus of the vagus (DMV) contains parasympathetic motoneurons that project to the heart and lungs. These motoneurons control ventricular excitability/contractility and airways secretions/blood flow, respectively. However, their electrophysiological properties, morphology and synaptic input activity remain unknown. One important ionic current described in DMV motoneurons controlling their electrophysiological behaviour is the A-type mediated by voltage-dependent K+ (Kv) channels. Thus, we compared the electrophysiological properties, synaptic activity, morphology, A-type current density, and single cell expression of Kv subunits, that contribute to macroscopic A-type currents, between DMV motoneurons projecting to either the heart or lungs of adult male rats. Using retrograde labelling, we visualized distinct DMV motoneurons projecting to the heart or lungs in acutely prepared medullary slices. Subsequently, whole cell recordings, morphological reconstruction and single motoneuron qRT-PCR studies were performed. DMV pulmonary motoneurons were more depolarized, electrically excitable, presented higher membrane resistance, broader action potentials and received greater excitatory synaptic inputs compared to cardiac DMV motoneurons. These differences were in part due to highly branched dendritic complexity and lower magnitude of A-type K+ currents. By evaluating expression of channels that mediate A-type currents from single motoneurons, we demonstrated a lower level of Kv4.2 in pulmonary versus cardiac motoneurons, whereas Kv4.3 and Kv1.4 levels were similar. Thus, with the distinct electrical, morphological, and molecular properties of DMV cardiac and pulmonary motoneurons, we surmise that these cells offer a new vista of opportunities for genetic manipulation providing improvement of parasympathetic function in cardiorespiratory diseases such heart failure and asthma.

Asunto(s)

Asunto(s)

RESUMEN

A low-power long-term ambulatory ECG monitor was developed for the acquisition, storage and processing of three simultaneous leads DI, aVF and V2 with a beat-to-beat heart rate measurement in real time. It provides long-term continuous ECG recordings until 84 h. The monitor uses a QRS complex detection algorithm based on the continuous wavelet transform with splines, which automatically selects the scale for the analysis of ECG records with different sampling frequencies. It includes a lead-off detection to continuously monitor the electrode connections and a real-time system of visual and acoustic alarms to alert users of abnormal conditions in its operation. The monitor presented is based in an ADS1294 analogue front end with four channels, 24-bit analog-to-digital converters and programmable gain amplifiers, a low-power dual-core ESP32 microcontroller, a microSD memory for data storage in a range of 4 GB to 32 GB and a 1.4 in thin-film transistor liquid crystal display (LCD) variant with a resolution of 128 × 128 pixels. It has programmable sampling rates of 250, 500 and 1000 Hz; a bandwidth of 0 Hz to 50% of the selected sampling rate; a CMRR of -105 dB; an input margin of ±2.4 V; a resolution of 286 nV; and a current consumption of 50 mA for an average battery life of 84 h. The ambulatory ECG monitor was evaluated with the commercial data-acquisition system BIOPAC MP36 and its module for ECG LABEL SS2LB, simultaneously comparing the morphologies of two ECG records and obtaining a correlation of 91.78%. For the QRS detection in real time, the implemented algorithm had an error less than 5%. The developed ambulatory ECG monitor can be used for the analysis of the dynamics of the heart rate variability in long-term ECG records and for the development of one's own databases of ECG recordings of normal subjects and patients with cardiovascular and noncardiovascular diseases.

Asunto(s)

RESUMEN

AIMS: Offspring exposed to an adverse fetal environment, such as gestational diabetes, may manifest increased susceptibility to several chronic diseases later in life. In the present study, the cardiovascular function of three different ages of offspring from diabetic rats was evaluated. METHODS AND RESULTS: Diabetes mellitus was induced in pregnant rats by a single dose of streptozotocin (50 mg/kg). The offspring from diabetic (OD) and control rats (OC) were evaluated at three different ages: 6, 12 or 18 months. In the corresponding OC groups, fasting glycemia, baseline mean arterial pressure, and sympathetic tonus increased in the OD rats at 12 (OD12) and 18 (OD18) months of age, while cardiac hypertrophy was observed in all OD groups. Cardiac function evaluation in vivo showed low left ventricular systolic pressure and+dP/dt in the OD18 rats, suggesting a systolic dysfunction. OD12 and OD18 groups showed high left ventricle end-diastolic pressure, suggesting a diastolic dysfunction. OD groups showed an age-related impairment of both baroreflex-mediated tachycardia and baroreflex-mediated bradycardia in OD12 and OD18 rats. In isolated hearts from OD18 rats, both inotropic and tachycardiac responses to increasing isoproterenol were significantly reduced compared to the corresponding OC group. CONCLUSION: These results suggest that gestational diabetes triggers the onset of hyperglycemia hypertension with impaired baroreflex sensitivity and heart failure in older age of offspring, representing important risk factors for death. Therefore, ensuring optimal glycemic control in diabetic pregnancy is important and serves as a key to preventing cardiovascular disease in the offspring in their older age.

Asunto(s)

RESUMEN

SUMMARY: Magnolia bark extract supplementation has an anti-oxidative role in mammalians. However, its role in physiological aged-associated heart insufficiency is not known yet. Therefore, we investigated the effects of a magnolia bark complex, including magnolol and honokiol components (MAHOC), in elderly rat hearts (24-month-old aged group). One group of aged rats was supplemented with MAHOC (400 mg/kg/d, for 12 weeks) besides the standard rat diet while the second group of elderly rats and adult rats (to 6-month- old adult-group) were only fed with the standard rat diet. The morphological analysis using light microscopy has shown marked myofibrillar losses, densely localized fibroblasts, vacuolizations, infiltrated cell accumulations, and collagen fibers in the myocardium of the elderly rats compared to the adults. We also detected a markedly increased amount of degenerated cardiomyocytes including the euchromatic nucleus. The MAHOC supplementation of the elderly rats provided marked ameliorations in these abnormal morphological changes in the heart tissue. Furthermore, electrophysiological analysis of electrocardiograms (ECGs) in the supplemented group showed significant attenuations in the prolonged durations of P-waves, QRS-complexes, QT-intervals, and low heart rates compared to the unsupplemented elderly group. The biochemical analysis also showed significant attenuations in the activity of arylesterase and total antioxidant status in the myocardium of the supplemented group. We further determined significant attenuations in the activity of a mitochondrial enzyme succinate dehydrogenase, known as a source of reactive oxygen species (ROS), and the decreased level of ATP/ADP in the heart homogenates of the supplemented group. Moreover, under in vitro conditions by using an aging-mimicked cardiac cell line induced by D-galactose, we demonstrated that MAHOC treatment could provide prevention of depolarization in mitochondria membrane potential and high-level ROS production. Overall, our data presented significant myocardial ameliorations in physiological aging-associated morphological alterations parallel to the function and biochemical attenuations with MAHOC supplementation, at most, through recoveries in mitochondria.

La suplementación con extracto de corteza de magnolia tiene un papel antioxidante en los mamíferos, sin embargo, su rol en la insuficiencia cardíaca asociada al envejecimiento fisiológico aún no se conoce. Por lo anterior, investigamos los efectos de un complejo de corteza de magnolia, incluidos los componentes magnolol y honokiol (MAHOC), en corazones de ratas seniles (grupo de edad de 24 meses). La alimentación de grupo de ratas seniles se complementó con MAHOC (400 mg/kg/d, durante 12 semanas) además de la dieta estándar, mientras que el segundo grupo de ratas seniles y ratas adultas (hasta el grupo de adultos de 6 meses) solo recibió la dieta estándar para ratas. El análisis morfológico mediante microscopía óptica ha mostrado marcadas pérdidas miofibrilares, fibroblastos densamente localizados, vacuolizaciones, acumulaciones de células infiltradas y fibras de colágeno en el miocardio de las ratas seniles en comparación con las adultas. También detectamos una cantidad notablemente mayor de cardiomiocitos degradados, incluido el núcleo eucromático. La suplementación con MAHOC de las ratas seniles proporcionó mejoras marcadas en estos cambios morfológicos anormales en el tejido cardiaco. Por otra parte, el análisis de los electrocardiogramas (ECG) en el grupo suplementado mostró atenuaciones significativas en las duraciones prolongadas de las ondas P, los complejos QRS, los intervalos QT y las frecuencias cardíacas bajas, en comparación con el grupo de ratas seniles sin suplementación alimenticia. El análisis bioquímico también mostró atenuaciones significativas en la actividad de la arilesterasa y el estado antioxidante total en el miocardio del grupo suplementado. Determinamos además atenuaciones significativas en la actividad de la enzima mitocondrial succinato deshidrogenasa, conocida como fuente de especies reactivas de oxígeno (ROS), y la disminución del nivel de ATP/ADP en los homogeneizados de corazón del grupo suplementado. Además, en condiciones in vitro mediante el uso de una línea de células cardíacas, imitando el envejecimiento inducido por D- galactosa, demostramos que el tratamiento con MAHOC podría prevenir la despolarización en el potencial de membrana de las mitocondrias y la producción de ROS de alto nivel. En general, nuestros datos presentaron mejoras miocárdicas significativas en alteraciones morfológicas asociadas con el envejecimiento fisiológico paralelas a la función y atenuaciones bioquímicas con la suplementación con MAHOC, como máximo, a través de recuperaciones en las mitocondrias.

Asunto(s)

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

To date, the ventricular myocardial band is the anatomical-functional model that best explains cardiac mechanics during systolic-diastolic phenomena in the cardiac cycle. The implications of the model fundamentally affect the anatomical interpretation of the ventricular myocardium, giving meaning to the direction that muscle fibers take, turning them into an object of study with potential clinical, imaging, and surgical applications. Re-interpreting the anatomy of the ventricular muscle justifies changes in the physiological interpretation, from its functional focus as a fiber unraveling the mechanical phenomena carried out during systole and diastole. We identify the functioning of the heart from the electrical and hemodynamic point of view, but it is necessary to delve into the mechanics that originate the hemodynamic changes observed flowmetrically, and that manifested during the pathology. In this review, the mechanical phenomena that the myocardium performs in each phase of the cardiac cycle are broken down in detail, emphasizing the physical displacements that each of the muscle segments presents, as well as a vision of their alteration and in which pathologies they are mainly identified. Visually, an anatomical correlation to the echocardiogram is provided, pointing out the direction of the segmental myocardial displacement by the strain velocity vector technique.

Asunto(s)

RESUMEN

BACKGROUND: High-intensity interval training (HIIT) has been suggested as an alternative for continuous training (CT) in people with diabetes mellitus (DM) due to its short duration and potential to improve adherence to exercise. However, data on its impact on heart rate variability (HRV) are scarce. OBJECTIVES: To assess and compare the effects of HIIT and CT on exercise capacity, HRV and isolated hearts in diabetic rats. METHODS: DM (intravenous streptozotocin, 45 mg.kg -1 ) and control (C) animals performed 20 sessions (5 days/week, 50 min, for 4 weeks) of CT on a treadmill (70% of maximal exercise capacity) or HIIT (cycles of 1:1min at 50% and 90% of maximal exercise capacity). HRV was assessed by continuous electrocardiogram, and cardiac function assessed in isolated perfused hearts. For data analysis, we used the framework of the multivariate covariance generalized linear model or one-way ANOVA followed by Tukey's test, considering p<0.05 as significant. RESULTS: Higher exercise capacity (m/min) was achieved in HIIT (DM-HIIT: 36.5 [IQR 30.0-41.3]; C-HIIT: 41.5 [37.8-44.5], both n=10) compared to CT (DM-CT: 29.0 [23.8-33.0]; C-CT: 32.0 [29.5-37.0], both n=10) (p<0.001). Heart rate (bpm) was lower in DM compared to controls (p<0.001) both in vivo (DM-HIIT:348±51, C-HIIT:441±66, DM-CT:361±70, C-CT:437±38) and in isolated hearts. There were no differences in HRV between the groups. Maximum and minimal dP/dt were reduced in DM, except +dP/dt in DM-HIIT vs. C-HIIT (mean difference: 595.5±250.3, p=0.190). CONCLUSION: Short-term HIIT promotes greater improvement in exercise performance compared to CT, including in DM, without causing significant changes in HRV.

FUNDAMENTO: O treinamento intervalado de alta intensidade (HIIT) tem sido sugerido como alternativa ao treinamento contínuo (TC) em indivíduos com diabetes mellitus (DM) devido à sua curta duração e potencial para melhorar a adesão ao exercício. No entanto, dados sobre seu impacto sobre a variabilidade da frequência cardíaca (VFC) são escassos. OBJETIVOS: Avaliar e comparar os efeitos do HIIT e TC sobre a capacidade no exercício, VFC e corações isolados em ratos diabéticos. MÉTODOS: Animais diabéticos (estreptozotocina intravenosa, 45 mg.kg -1 ) e controles (C) realizaram 20 sessões de TC (5 dias/semana, 50 min, por quatro semanas) em esteira (70% da capacidade máxima de exercício) ou HIIT (ciclos de 1:1min a 50% e 90% da capacidade máxima de exercício). A VFC foi avaliada por eletrocardiograma contínuo, e a função cardíaca foi avaliada em corações isolados perfundidos. Para a análise dos dados, utilizamos a matriz do modelo linear generalizado de covariância multivariada ou o teste one-way ANOVA seguido pelo teste de Tukey, considerando um valor de p<0,05 como significativo. RESULTADOS: A capacidade de exercício (m/min) foi maior no grupo submetido ao HIIT [DM-HIIT: 36,5 (IIQ 30,0-41,3); C-HIIT: 41,5 (37,8-44,5), ambos n=10) em comparação ao grupo submetido ao TC [DM-TC: 29,0 (23,8-33,0); C-TC: 32,0 (29,5-37,0), ambos n=10) (p<0,001). A frequência cardíaca (bpm) foi mais baixa no grupo DM em comparação aos controles (p<0,001) tanto in vivo (DM-HIIT: 348±51, C-HIIT:441±66, DM-TC:361±70, C-TC:437±38) como nos corações isolados. Não houve diferenças na VFC entre os grupos. Os valores máximos e mínimos de dP/dt foram reduzidos no DM, com exceção da +dP/dt no grupo DM-HIIT vs. C-HIIT (diferença média: 595,5±250,3, p=0,190). CONCLUSÃO: O HIIT de curto prazo promoveu melhora superior no desempenho no exercício em comparação ao TC, sem causar mudanças significativas na variabilidade da frequência cardíaca.

Asunto(s)

Asunto(s)

RESUMEN

Objective.To conduct a systematic review of the possible effects of passive heating protocols on cardiovascular autonomic control in healthy individuals.Approach.The studies were obtained from MEDLINE (PubMed), LILACS (BVS), EUROPE PMC (PMC), and SCOPUS databases, simultaneously. Studies were considered eligible if they employed passive heating protocols and investigated cardiovascular autonomic control by spontaneous methods, such as heart rate variability (HRV), systolic blood pressure variability (SBPV), and baroreflex sensitivity (BRS), in healthy adults. The revised Cochrane risk-of-bias tool (RoB-2) was used to assess the risk of bias in each study.Main results.Twenty-seven studies were included in the qualitative synthesis. Whole-body heating protocols caused a reduction in cardiac vagal modulation in 14 studies, and two studies reported both increased sympathetic modulation and vagal withdrawal. Contrariwise, local-heating protocols and sauna bathing seem to increase cardiac vagal modulation. A reduction of BRS was reported in most of the studies that used whole-body heating protocols. However, heating effects on BRS remain controversial due to methodological differences among baroreflex analysis and heating protocols.Significance.Whole-body heat stress may increase sympathetic and reduce vagal modulation to the heart in healthy adults. On the other hand, local-heating therapy and sauna bathing seem to increase cardiac vagal modulation, opposing sympathetic modulation. Nonetheless, further studies should investigate acute and chronic effects of thermal therapy on cardiovascular autonomic control.

Asunto(s)

RESUMEN

BACKGROUND: Developmental cardiac tissue holds remarkable capacity to regenerate after injury and consists of regenerative mononuclear diploid cardiomyocytes. On maturation, mononuclear diploid cardiomyocytes become binucleated or polyploid and exit the cell cycle. Cardiomyocyte metabolism undergoes a profound shift that coincides with cessation of regeneration in the postnatal heart. However, whether reprogramming metabolism promotes persistence of regenerative mononuclear diploid cardiomyocytes enhancing cardiac function and repair after injury is unknown. Here, we identify a novel role for RNA-binding protein LIN28a, a master regulator of cellular metabolism in cardiac repair after injury. METHODS: LIN28a overexpression was tested using mouse transgenesis on postnatal cardiomyocyte numbers, cell cycle, and response to apical resection injury. With the use of neonatal and adult cell culture systems and adult and Mosaic Analysis with Double Markers myocardial injury models in mice, the effect of LIN28a overexpression on cardiomyocyte cell cycle and metabolism was tested. Last, isolated adult cardiomyocytes from LIN28a and wild-type mice 4 days after myocardial injury were used for RNA-immunoprecipitation sequencing. RESULTS: LIN28a was found to be active primarily during cardiac development and rapidly decreases after birth. LIN28a reintroduction at postnatal day (P) 1, P3, P5, and P7 decreased maturation-associated polyploidization, nucleation, and cell size, enhancing cardiomyocyte cell cycle activity in LIN28a transgenic pups compared with wild-type littermates. Moreover, LIN28a overexpression extended cardiomyocyte cell cycle activity beyond P7 concurrent with increased cardiac function 30 days after apical resection. In the adult heart, LIN28a overexpression attenuated cardiomyocyte apoptosis, enhanced cell cycle activity, cardiac function, and survival in mice 12 weeks after myocardial infarction compared with wild-type littermate controls. Instead, LIN28a small molecule inhibitor attenuated the proreparative effects of LIN28a on the heart. Neonatal rat ventricular myocytes overexpressing LIN28a mechanistically showed increased glycolysis, ATP production, and levels of metabolic enzymes compared with control. LIN28a immunoprecipitation followed by RNA-immunoprecipitation sequencing in cardiomyocytes isolated from LIN28a-overexpressing hearts after injury identified long noncoding RNA-H19 as its most significantly altered target. Ablation of long noncoding RNA-H19 blunted LIN28a-induced enhancement on cardiomyocyte metabolism and cell cycle activity. CONCLUSIONS: Collectively, LIN28a reprograms cardiomyocyte metabolism and promotes persistence of mononuclear diploid cardiomyocytes in the injured heart, enhancing proreparative processes, thereby linking cardiomyocyte metabolism to regulation of ploidy/nucleation and repair in the heart.

Asunto(s)

RESUMEN

OBJECTIVE: Patients with COPD are prone to cardiac remodeling; however, little is known about cardiac function in patients recovering from an acute exacerbation of COPD (AECOPD) and its association with exercise capacity. The aim of this study was to evaluate the cardiac function and structure and to compare their relationship with exercise capacity in patients with a recent AECOPD and patients with clinically stable COPD. METHODS: This was a cross-sectional study including 40 COPD patients equally divided into two groups: recent AECOPD group (AEG) and clinically stable COPD group (STG). Echocardiography was performed to assess cardiac function and chamber structure. The six-minute walk distance (6MWD) and the Duke Activity Status Index (estimated Vo2) were used in order to assess exercise capacity. RESULTS: No significant differences in cardiac function and structure were found between the groups. The 6MWD was associated with early/late diastolic mitral filling velocity ratio (r = 0.50; p < 0.01), left ventricular posterior wall thickness (r = -0.33; p = 0.03), and right atrium volume index (r = -0.34; p = 0.04), whereas Vo2 was associated with right atrium volume index (r = -0.40; p = 0.02). CONCLUSIONS: Regardless of the clinical condition (recent AECOPD vs. stable COPD), the cardiac function and structure were similar between the groups, and exercise capacity (determined by the 6MWD and Vo2) was associated with cardiac features.

Asunto(s)