The effect of prolonged physical activity performed during extreme caloric deprivation on cardiac function.
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ABSTRACT:
SUBMITTER: Planer D
PROVIDER: S-EPMC3286482 | biostudies-other | 2012
REPOSITORIES: biostudies-other
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Project description:Human pluripotent stem cells are an important tool for the study of developmental processes, such as cardiomyogenic differentiation. Despite the advances made in this field, the molecular and cellular signals involved in the commitment of embryonic stem cells to the cardiac phenotype are still under investigation. Therefore, this study focuses on identifying the extracellular signals involved in in vitro cardiac differentiation of human embryonic stem cells. Using a three-dimensional cardiomyogenic differentiation protocol, the conditioned medium and the extracellular matrix (ECM) of embryoid body cultures were collected and characterized at four specific time points. Mass spectrometry (MS) and antibody array analysis of the secretome identified a number of secreted proteins related to signaling pathways, such as Wnt and TGFβ, as well as many ECM proteins. When comparing the proteins identified at selected time points, our data pointed out protein interactions and biological process related to cardiac differentiation. Interestingly, the great changes in secretome profile occurred during the cardiac progenitor specification. The secretome results were also compared with our previous RNAseq data, indicating that the secreted proteins undergo some level of gene regulation. During cardiac commitment it was observed an increase in complexity of the ECM, and some proteins as IGFBP7, FN1, HSPG2, as well as other members of the basal lamina could be highlighted. Thus, these findings contribute valuable information about essential microenvironmental signals working on cardiomyogenic differentiation that may be used in future strategies for cardiac differentiation, cardiomyocyte maturation, and in advances for future acellular therapies.
| S-EPMC7025591 | biostudies-literature
Project description:Out-of-hospital cardiac arrest (CA) is a prevalent medical crisis resulting in severe injury to the heart and brain and an overall survival of less than 10%. Mitochondrial dysfunction is predicted to be a key determinant of poor outcomes following prolonged CA. However, the onset and severity of mitochondrial dysfunction during CA and cardiopulmonary resuscitation (CPR) is not fully understood. Ischemic postconditioning (IPC), controlled pauses during the initiation of CPR, has been shown to improve cardiac function and neurologically favorable outcomes after 15min of CA. We tested the hypothesis that mitochondrial dysfunction develops during prolonged CA and can be rescued with IPC during CPR (IPC-CPR).A total of 63 swine were randomized to no ischemia (Naïve), 19min of ventricular fibrillation (VF) CA without CPR (Untreated VF), or 15min of CA with 4min of reperfusion with either standard CPR (S-CPR) or IPC-CPR. Mitochondria were isolated from the heart and brain to quantify respiration, rate of ATP synthesis, and calcium retention capacity (CRC). Reactive oxygen species (ROS) production was quantified from fresh frozen heart and brain tissue.Compared to Naïve, Untreated VF induced cardiac and brain ROS overproduction concurrent with decreased mitochondrial respiratory coupling and CRC, as well as decreased cardiac ATP synthesis. Compared to Untreated VF, S-CPR attenuated brain ROS overproduction but had no other effect on mitochondrial function in the heart or brain. Compared to Untreated VF, IPC-CPR improved cardiac mitochondrial respiratory coupling and rate of ATP synthesis, and decreased ROS overproduction in the heart and brain.Fifteen minutes of VF CA results in diminished mitochondrial respiration, ATP synthesis, CRC, and increased ROS production in the heart and brain. IPC-CPR attenuates cardiac mitochondrial dysfunction caused by prolonged VF CA after only 4min of reperfusion, suggesting that IPC-CPR is an effective intervention to reduce cardiac injury. However, reperfusion with both CPR methods had limited effect on mitochondrial function in the brain, emphasizing an important physiological divergence in post-arrest recovery between those two vital organs.
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Project description:BACKGROUND/OBJECTIVES:Endocannabinoids (ECs) are associated with obesity and ectopic fat accumulation, both of which play a role in the development of cardiovascular disease (CVD) in type 2 diabetes (T2D). The effect of prolonged caloric restriction on ECs in relation to fat distribution and cardiac function is still unknown. Therefore, our aim was to investigate this relationship in obese T2D patients with coronary artery disease (CAD). SUBJECTS/METHODS:In a prospective intervention study, obese T2D patients with CAD (n?=?27) followed a 16 week very low calorie diet (VLCD; 450-1000?kcal/day). Cardiac function and fat accumulation were assessed with MRI and spectroscopy. Plasma levels of lipid species, including ECs, were measured using liquid chromatography-mass spectrometry. RESULTS:VLCD decreased plasma levels of virtually all measured lipid species of the class of N-acylethanolamines including the EC anandamide (AEA; -15%, p?=?0.016), without decreasing monoacylglycerols including the EC 2-arachidonoylglycerol (2-AG). Baseline plasma AEA levels strongly correlated with the volume of subcutaneous white adipose tissue (SAT; R2?=?0.44, p?<?0.001). VLCD decreased the volume of SAT (-53%, p?<?0.001), visceral white adipose tissue (VAT) (-52%, p?<?0.001), epicardial white adipose tissue (-15%, p?<?0.001) and paracardial white adipose tissue (-28%, p?<?0.001). VLCD also decreased hepatic (-86%, p?<?0.001) and myocardial (-33%, p?<?0.001) fat content. These effects were accompanied by an increased left ventricular ejection fraction (54.8?±?8.7-56.2?±?7.9%, p?=?0.016). CONCLUSIONS:Caloric restriction in T2D patients with CAD decreases AEA levels, but not 2-AG levels, which is paralleled by decreased lipid accumulation in adipose tissue, liver and heart, and improved cardiovascular function. Interestingly, baseline AEA levels strongly correlated with SAT volume. We anticipate that dietary interventions are worthwhile strategies in advanced T2D, and that reduction in AEA may contribute to the improved cardiometabolic phenotype induced by weight loss.
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Project description:Background:Measures of long-term success of total hip arthroplasty (THA) over the past 50 years have focused primarily on implant survival, with less evidence on long-term functional outcomes. Questions/Purposes:We aimed to study 20-to-40-year functional outcomes after primary THA. We investigated the extent to which (1) functional outcomes after THA are maintained long term; (2) patient characteristics such as age, hip disease diagnosis, and comorbidities affect recovery of function and survivorship after THA; and (3) patients' overall function after THA is affected by the need for revision, the aging process, and associated comorbidities. Methods:We retrospectively reviewed outcomes of the senior author's patients between 1968 and 1993. Of 1207 patients, we identified 167 patients (99 female, 68 male; 276 primary THAs) who were at least 65 years old at follow-up and had at least 20 years of follow-up. Mean age at surgery was 55 years; mean follow-up time was 27 years. Bilateral THAs were performed in 109 patients (65%), and revisions in 81 patients (48.5%). Clinical outcomes including pain level, walking ability, range of motion, and overall function were determined by the Hospital for Special Surgery (HSS) hip scoring system. Contralateral and revision surgery, as well as patient age, sex, and body mass index, were included as covariates. To account for unequally spaced follow-up time points and competing causes of functional decline (e.g., age, contralateral hip disease, and need for revision THA), a latent class mixed model approach was used to identify unobserved classes of patients who had similar outcomes. Linear, quadratic, and piecewise-polynomial growth models were considered for class identification. The best fitting model was determined based on Bayesian information criterion. Results:A four-class model of this patient population was identified: (1) the Elderly Class, who had a mean age of 62 years at the time of primary THA; (2) the Bilateral Class, who underwent simultaneous or staged bilateral THA; (3) the Revision Class, who required at least one revision; and (4) the Youngest Class, who had a mean age of 49 years. After an initial period of improvement in all groups, the functional trajectory diverged according to classifications. Age was the strongest determinant of long-term outcome, with HSS hip scores in the Elderly Class declining after about 20 years. The Youngest Class maintained good-to-excellent hip function for over 30 years. Revision THA and contralateral THA accounted for a temporary decline in function, after which overall good function was regained for the long term. Conclusions:All classes in the study population enjoyed good-to-excellent outcomes after THA for about 20 years. Thereafter, functional decline was attributed more to aging than to the need for revision. One or more revision THA did not negatively influence long-term clinical outcomes, suggesting that, even for younger patients, symptoms, rather than the avoidance of possible revision, should be the primary determining factor when indicating THA.
| S-EPMC6609668 | biostudies-literature
Project description:Inflammation is increasingly recognized as a contributor to the pathophysiology of neuropsychiatric disorders, including depression, anxiety disorders and autism, though the factors leading to contextually inappropriate or sustained inflammation in pathological conditions are yet to be elucidated. Microglia, as the key mediators of inflammation in the CNS, serve as likely candidates in initiating pathological inflammation and as an ideal point of therapeutic intervention. Glucose deprivation, as a component of the pathophysiology of ischemia or occurring transiently in diabetes, may serve to modify microglial function contributing to inflammatory injury. To this end, primary microglia were cultured from postnatal rat brain and subject to glucose deprivation in vitro. Microglia were characterized for their proliferation, phagocytic function and secretion of inflammatory factors, and tested for their capacity to respond to a potent inflammatory stimulus. In the absence of glucose, microglia remained capable of proliferation, phagocytosis and inflammatory activation and showed increased release of inflammatory factors after presentation of an inflammatory stimulus. Glucose-deprived microglia demonstrated increased phagocytic activity and decreased accumulation of lipids in lipid droplets over a 48-h timecourse, suggesting they may use scavenged lipids as a key alternate energy source during metabolic stress. In the present manuscript, we present novel findings that glucose deprivation may sensitize microglial release of inflammatory mediators and prime microglial functions for both survival and inflammatory roles, which may contribute to psychiatric comorbidities of ischemia, diabetes and/or metabolic disorder.
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Project description:Accurate recording of large, earthquake-induced ground shaking is critical for our understanding of earthquake physics as well as seismic hazard assessment. Extremely large accelerations with the peak value of 3.2 times the gravity acceleration were recorded at seismic station WTMC located in northern South Island of New Zealand during the recent magnitude 7.8 Kaikoura earthquake. However, the mechanisms responsible for the generation of such large accelerations are not well understood. Here we use numerical simulations to examine a range of physical models that can reproduce the observed characteristics of the acceleration record. We find that the record of the asymmetric, vertical accelerations, also observed during a magnitude 6.3 earthquake, can be explained by a flapping effect, that is, the local, elastic bouncing of a foundation slab on which the sensor is installed. Our results suggest that the extremely large accelerations recorded at seismic station WTMC do not reflect the actual ground shaking, but were caused by a local, system response around the sensor. Our finding has important implications for both the evaluation of future seismic hazard based on the waveform records of the Kaikoura earthquake and the installation methodology of strong-motion seismometers in all earthquake prone countries.
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Project description:BackgroundObservational studies suggest that regular physical activity may reduce cardiovascular morbidity and cancer recurrence in survivors of breast cancer. The association between physical activity and cardiac function with breast cancer therapy is unknown.MethodsSelf-reported physical activity was assessed using the Godin Leisure-Time Exercise Questionnaire at repeated intervals in a longitudinal cohort study of 603 breast cancer participants treated with doxorubicin and/or trastuzumab. Multivariable regression models estimated associations between clinical variables and physical activity. Generalized estimating equations adjusted for prespecified variables estimated associations between baseline physical activity and longitudinal echocardiographic measures of systolic and diastolic function.ResultsPhysical activity was low at baseline, prior to cancer therapy initiation. More than half of participants reported no moderate-strenuous physical activity, and only 12.1% met guideline recommended levels of physical activity. Physical activity increased after chemotherapy completion; however, only 26.0% of individuals were sufficiently active 3 years after cancer diagnosis. Body mass index, hyperlipidemia and higher cancer stage were significantly associated with lower total physical activity at baseline. Higher baseline physical activity was very modestly associated with an attenuation in the absolute decline in left ventricular ejection fraction over time (β 0.4%, 95% CI 0.1, 0.7, P = .02 for each 10-unit increase in total activity). There tended to be a cardioprotective association with cardiotoxicity risk, although this was not statistically significant (HR 0.83, 95% CI 0.66, 1.04, P = .097).ConclusionsA small proportion of breast cancer patients and survivors are engaged in regular moderate-strenuous physical activity. While only modest associations between self-reported physical activity and left ventricular systolic function were observed, our findings do not exclude a cardioprotective benefit of exercise.
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Project description:Background: Sleep loss contributes to obesity through a variety of mechanisms, including neuroendocrine functioning, increased hunger, and increased food intake. Additionally, sleep loss alters functional activation within brain regions associated with reward and behavioral control. However, it remains unknown whether individual differences in baseline neural functioning can predict eating behaviors during total sleep deprivation (TSD). We used functional magnetic resonance imaging (fMRI) to test the hypothesis that individuals with increased baseline responsiveness within reward regions are more vulnerable to TSD-induced overeating. Methods: N = 45 subjects completed several fMRI scans during a single pre-TSD session that included performance on the Multi-Source Interference Task (MSIT) and the n-back task. Subjects returned to the laboratory for an overnight TSD session, during which they were given ad libitum access to 10,900 kcal of food. Leftover food and packaging were collected every 6 h (00:00, 06:00, and 12:00) to measure total food consumption. Subjects reported sleepiness every hour and performed a food rating task every 3 h. Results: Functional activation within the ventral striatum during the MSIT and n-back positively correlated with total caloric and carbohydrate intake during the final 6 h (06:00-12:00) of TSD. Activation within the middle and superior temporal gyri during the MSIT also correlated with total carbohydrates consumed. Food consumption did not correlate with subjective sleepiness, hunger, or food desire. Conclusions: Individual differences in neural activity of reward processing areas (i.e., nucleus accumbens) prior to sleep deprivation are associated with an individual's propensity to overeat during subsequent sleep deprivation. This suggests that individual differences within reward processing pathways are potential key factors in sleep loss related overeating. Sleep loss and obesity are tightly linked. Both phenomena have been associated with increased neural activation in regions associated with reward, inhibitory control, and disrupted dopamine signaling. Elevated baseline reward sensitivity in the ventral striatum appears to be further compounded by sleep deprivation induced dysfunction in the reward neurocircuitry, increasing the likelihood of overeating. Our findings suggest that large individual differences in baseline responsiveness of hedonic reward pathways may modulate the association between sleep loss and obesity.
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Project description:During cardiac arrest (CA), myocardial perfusion is solely dependent on cardiopulmonary resuscitation (CPR) although closed-chest compressions only provide about 10-20% of normal myocardial perfusion. The study was conducted in a whole animal CPR model to determine whether CPR-generated oxygen delivery preserves or worsens mitochondrial function. Male Sprague-Dawley rats (400-450 g) were randomly divided into four groups: (1) BL (instrumentation only, no cardiac arrest), (2) CA(15) (15 min cardiac arrest without CPR), (3) CA(25) (25 min cardiac arrest without CPR) and (4) CPR (15 min cardiac arrest, followed by 10 min CPR). The differences between groups were evaluated by measuring mitochondrial respiration, electron transport chain (ETC) complex activities and mitochondrial ultrastructure by transmission electron microscopy (TEM). The CA(25) group had the greatest impairment of mitochondrial respiration and ETC complex activities (I-III). In contrast, the CPR group was not different from the CA(15) group regarding all measures of mitochondrial function. Complex I was more susceptible to ischemic injury than the other complexes and was the major determinant of mitochondrial dysfunction. Observations of mitochondrial ultrastructure by TEM were compatible with the biochemical results. The findings suggest that, despite low blood flow and oxygen delivery, CPR is able to preserve heart mitochondrial function and viability during ongoing global ischemia. Preservation of complex I activity and mitochondrial function during cardiac arrest may be an important mechanism underlying the beneficial effects of CPR which have been shown in clinical studies.
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Project description:Variations in the availability of nutritional resources in animals can trigger reversible adjustments, which in the short term are manifested as behavioral and physiological changes. Several of these responses are mediated by Sirt1, which acts as an energy status sensor governing a global genetic program to cope with changes in nutritional status. Growing evidence suggests a key role of the response of the perinatal environment to caloric restriction in the setup of physiological responses in adulthood. The existence of adaptive predictive responses has been proposed, which suggests that early nutrition could establish metabolic capacities suitable for future food-scarce environments. We evaluated how perinatal food deprivation and maternal gestational weight gain impact the transcriptional, physiological, and behavioral responses in mice, when acclimated to caloric restriction in adulthood. Our results show a strong predictive capacity of maternal weight and gestational weight gain, in the expression of Sirt1 and its downstream targets in the brain and liver, mitochondrial enzymatic activity in skeletal muscle, and exploratory behavior in offspring. We also observed differential responses of both lactation and gestational food restriction on gene expression, thermogenesis, organ masses, and behavior, in response to adult caloric restriction. We conclude that the early nutritional state could determine the magnitude of responses to food scarcity later in adulthood, mediated by the pivotal metabolic sensor Sirt1. Our results suggest that maternal gestational weight gain could be an important life history trait and could be used to predict features that improve the invasive capacity or adjustment to seasonal food scarcity of the offspring.
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