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:BackgroundOut-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).MethodsA 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.ResultsCompared 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.ConclusionsFifteen 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.
| S-EPMC5552370 | biostudies-literature
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.
| S-EPMC5851430 | biostudies-literature
Project description:ObjectivesHigh sedentary behaviour is associated with adverse effects on central vascular function and cognitive function. Although interventions to mitigate the adverse effects of workplace sitting are intriguing, evidence of the efficacy of such interventions remains lacking. This randomised cross-over trial was aimed at exploring the effectiveness of prolonged sitting, with or without physical activity breaks, on central, peripheral vascular and cognitive function in adults.MethodsTwenty one healthy adults completed 4 h of simulated work conditions in three experimental visits: (1) uninterrupted sitting (SIT); (2) sitting interrupted by 3 min of walking every hour (LIT); and (3) sitting interrupted by 3 min of stair climbing every hour (MIT). Carotid (CA) and superficial femoral artery (SFA) diameter, velocity, shear rate and blood flow were measured with Duplex ultrasound at 50 MHz at three time points (hours 0, 2 and 4), and executive function was assessed with the computer based Eriksen Flanker task every hour.ResultsThe decreases in reaction time (-30.59%) and accuracy (-10.56%) during SIT conditions were statistically significant, and less of a decrease was observed under LIT and MIT conditions. No significant differences in CA and SFA function were observed with LIT and MIT interventions.ConclusionPhysical activity breaks of varying intensity during prolonged sitting improve reaction time. However, the vascular benefits of physical activity breaks should be confirmed in the future through long term studies in natural environment.
| S-EPMC10040888 | biostudies-literature
Project description:Prolonged cardiac arrest (CA) causes microvascular thrombosis which is a potential barrier to organ reperfusion during extracorporeal cardiopulmonary resuscitation (ECPR). The aim of this study was to test the hypothesis that early intra-arrest anticoagulation during cardiopulmonary resuscitation (CPR) and thrombolytic therapy during ECPR improve recovery of brain and heart function in a porcine model of prolonged out-of-hospital CA.DesignRandomized interventional trial.SettingUniversity laboratory.SubjectsSwine.InterventionsIn a blinded study, 48 swine were subjected to 8 minutes of ventricular fibrillation CA followed by 30 minutes of goal-directed CPR and 8 hours of ECPR. Animals were randomized into four groups (n = 12) and given either placebo (P) or argatroban (ARG; 350 mg/kg) at minute 12 of CA and either placebo (P) or streptokinase (STK, 1.5 MU) at the onset of ECPR.Measurements and main resultsPrimary outcomes included recovery of cardiac function measured by cardiac resuscitability score (CRS: range 0-6) and recovery of brain function measured by the recovery of somatosensory-evoked potential (SSEP) cortical response amplitude. There were no significant differences in recovery of cardiac function as measured by CRS between groups (p = 0.16): P + P 2.3 (1.0); ARG + P = 3.4 (2.1); P + STK = 1.6 (2.0); ARG + STK = 2.9 (2.1). There were no significant differences in the maximum recovery of SSEP cortical response relative to baseline between groups (p = 0.73): P + P = 23% (13%); ARG + P = 20% (13%); P + STK = 25% (14%); ARG + STK = 26% (13%). Histologic analysis demonstrated reduced myocardial necrosis and neurodegeneration in the ARG + STK group relative to the P + P group.ConclusionsIn this swine model of prolonged CA treated with ECPR, early intra-arrest anticoagulation during goal-directed CPR and thrombolytic therapy during ECPR did not improve initial recovery of heart and brain function but did reduce histologic evidence of ischemic injury. The impact of this therapeutic strategy on the long-term recovery of cardiovascular and neurological function requires further investigation.
| S-EPMC10174369 | biostudies-literature
Project description:Clinical trials conventionally test aggregate mean differences and assume homogeneous variances across treatment groups. However, significant response heterogeneity may exist. The purpose of this study was to model treatment response variability using gait speed change among older adults participating in caloric restriction (CR) trials. Eight randomized controlled trials (RCTs) with five- or six-month assessments were pooled, including 749 participants randomized to CR and 594 participants randomized to non-CR (NoCR). Statistical models compared means and variances by CR assignment and exercise assignment or select subgroups, testing for treatment differences and interactions for mean changes and standard deviations. Continuous equivalents of dichotomized variables were also fit. Models used a Bayesian framework, and posterior estimates were presented as means and 95% Bayesian credible intervals (BCI). At baseline, participants were 67.7 (SD = 5.4) years, 69.8% female, and 79.2% white, with a BMI of 33.9 (4.4) kg/m2. CR participants reduced body mass [CR: -7.7 (5.8) kg vs. NoCR: -0.9 (3.5) kg] and increased gait speed [CR: +0.10 (0.16) m/s vs. NoCR: +0.07 (0.15) m/s] more than NoCR participants. There were no treatment differences in gait speed change standard deviations [CR-NoCR: -0.002 m/s (95% BCI: -0.013, 0.009)]. Significant mean interactions between CR and exercise assignment [0.037 m/s (95% BCI: 0.004, 0.070)], BMI [0.034 m/s (95% BCI: 0.003, 0.066)], and IL-6 [0.041 m/s (95% BCI: 0.009, 0.073)] were observed, while variance interactions were observed between CR and exercise assignment [-0.458 m/s (95% BCI: -0.783, -0.138)], age [-0.557 m/s (95% BCI: -0.900, -0.221)], and gait speed [-0.530 m/s (95% BCI: -1.018, -0.062)] subgroups. Caloric restriction plus exercise yielded the greatest gait speed benefit among older adults with obesity. High BMI and IL-6 subgroups also improved gait speed in response to CR. Results provide a novel statistical framework for identifying treatment heterogeneity in RCTs.
| S-EPMC9070937 | biostudies-literature
Project description:BackgroundMeasures 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/purposesWe 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.MethodsWe 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.ResultsA 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.ConclusionsAll 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.
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Project description:Cancer treatment increases cardiovascular disease risk, but physical activity (PA) may prevent cardiovascular disease. This study examined whether greater PA was associated with better submaximal exercise capacity and cardiac function during cancer therapy. Participants included 223 women with stage I to III breast cancer (BC) before and 3 months after undergoing treatment and 126 control participants. Leisure-time PA (LTPA) was reported using the Godin-Shephard LTPA questionnaire. Cardiac function was assessed by cardiac magnetic resonance. Submaximal exercise capacity was determined by 6-minute walk distance. BC participants reported similar baseline LTPA scores (24.7; 95% CI: 21.7-28.0) as control participants (29.4; 95% CI: 25.0-34.2). The BC group declined to 16.9 (95% CI: 14.4-19.6) at 3 months relative to 30.8 (95% CI: 26.2-35.8) in control participants. Among BC participants, more LTPA was related to better exercise capacity (β ± SE: 7.1 ± 1.6; 95% CI: 4.0-10.1) and left ventricular (LV) circumferential strain (-0.16 ± 0.07; 95% CI: -0.29 to -0.02). Increased LTPA over the 3 months was associated with decreased likelihood of treatment-induced cardiac dysfunction according to LV circumferential strain classifications (OR: 0.98; 95% CI: 0.97-0.998). BC participants reporting insufficient LTPA according to PA guidelines exhibited deteriorations in exercise capacity (adjusted mean difference ± SE: -29 ± 10 m; P = 0.029), LV end-systolic volume (5.8 ± 1.3 mL; P < 0.001), LV ejection fraction (-3.2% ± 0.8%; P = 0.002), and LV circumferential strain (2.5% ± 0.5%; P < 0.001), but BC participants meeting LTPA guidelines did not exhibit these adverse changes. PA declined during BC therapy; however, PA participation was associated with attenuated declines in exercise capacity and cardiac function that are often observed in this population. (Understanding and Predicting Breast Cancer Events After Treatment [WF97415 UPBEAT]; NCT02791581).
| S-EPMC10635881 | 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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