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Results for “HEART FUNCTION”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 253 records · Page 14
All sourcesNASA NTRSDOE OSTI
NASA NTRS2003

Pressor response to intravenous tyramine is a marker of cardiac, but not vascular, adrenergic function

Intravenous injections of the indirect sympathetic amine, tyramine, are used as a test of peripheral adrenergic function. The authors measured the time course of increases in ejection fraction, heart rate, systolic and diastolic pressure, popliteal artery flow, and greater saphenous vein diameter before and after an injection of 4.0 mg/m(2) body surface area of tyramine in normal human subjects. The tyramine caused moderate, significant increases in systolic pressure and significant decreases in total peripheral resistance. The earliest changes were a 30% increase in ejection fraction and a 16% increase in systolic pressure, followed by a 60% increase in popliteal artery flow and a later 11% increase in greater saphenous vein diameter. There were no changes in diastolic pressure or heart rate. These results suggest that pressor responses during tyramine injections are primarily due to an inotropic response that increases cardiac output and pressure and causes a reflex decrease in vascular resistance. Thus, tyramine pressor tests are a measure of cardiac, but not vascular, sympathetic function.

NASA Discipline Cardiopulmonary↗
DOE OSTI2022

Ultrafast Early Warning of Heart Attacks through Plasmon‐Enhanced Raman Spectroscopy using Collapsible Nanofingers and Machine Learning

Abstract As the leading cause of death, heart attacks result in millions of deaths annually, with no end in sight. Early intervention is the only strategy for rescuing lives threatened by heart disease. However, the detection time of the fastest heart‐attack detection system is >15 min, which is too long considering the rapid passage of life. In this study, a machine learning (ML)‐driven system with a simple process, low‐cost, short detection time (only 10 s), and high precision is developed. By utilizing a functionalized nanofinger structure, even a trace amount of biomarker leaked before a heart attack can be captured. Additionally, enhanced Raman profiles are constructed for predictive analytics. Five ML models are developed to harness the useful characteristics of each Raman spectrum and provide early warnings of heart attacks with >98% accuracy. Through the strategic combination of nanofingers and ML algorithms, the proposed warning system accurately provides alerts on silent heart‐attack attempts seconds ahead of actual attacks.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Leukocytic toll-like receptor 2 knockout protects against diabetes-induced cardiac dysfunction

Highlights: • TLR2 KO promotes the functional recovery of myocardium. • TLR2 KO maintains the balance of calcium. • TLR2 KO reduces cell apoptosis induced by oxidative stress. • TLR2 KO decreases the fibrosis of heart tissues in diabetic cardiomyopathy mice. Diabetic cardiomyopathy is characterized by the deterioration of the myocardial function. Emerging evidences have indicated that leukocytic toll-like receptor 2 (TLR2) played an important role in the development of diabetic cardiomyopathy. Our study aimed to investigate whether TLR2 knockout (KO) exerted a cardioprotective effect in vivo. The establishment of diabetes model was set up in mice via intraperitoneal injection of streptozotocin (STZ). Results demonstrated that blocking of TLR2 significantly suppressed the enhanced left ventricular end-diastolic dimension (LVEDD), left ventricular end systolic diameter (LVESD) and the reduced the heart rate in diabetic cardiomyopathy mice. The decreased resting cell length, PS, TPS and + dL/dt while increased TR90 and - dL/dt caused by diabetic cardiomyopathy were remarkably inhibited by TLR2 KO. Besides that, the alleviated ΔFFI (360/380), decreased SERCA2a and p-NFATc3 expressions, extended Ca{sup 2+} decay time and elevated Calcineurin A induced by diabetic cardiomyopathy were vastly repressed by TLR2 KO in cardiocytes. Moreover, TLR2 gene silence could ameliorate oxidative stress-induced apoptosis, evidences were the up-regulated superoxide generation and Bax/Bcl-2 expression while restrained GSH/GSSG ratio caused by diabetic cardiomyopathy were tremendously repressed in TLR2 KO mice. Furthermore, blocking of TLR2 remarkably attenuated the augmented fibrosis areas of heart tissues in mice with diabetic cardiomyopathy. The result of the enhanced α-SMA and collagenⅠ caused by diabetic cardiomyopathy were suppressed in heart tissues of TLR2 KO mice further validate it. All in all, our study demonstrated that diabetes-induced cardiac dysfunction could be attenuated by TLR2 KO.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Unbiased compound screening with a reporter gene assay highlights the role of p13 in the cardiac cellular stress response

Highlights: • Unbiased screening with 2320 known compounds identified 12 chemical probes for p13. • > 80% screened agents increased or decreased p13 mRNA and affected cardiac function. • Four cardiotonic agents decreased p13 levels and induced oxidative stress. • In vivo profile of p13 expression shows its importance in heart pathophysiology. • PGC1-alpha, a mitochondrial master regulator, markedly elevated p13 expression. We recently showed that a 13-kDa protein (p13), the homolog protein of formation of mitochondrial complex V assembly factor 1 in yeast, acts as a potential protective factor in pancreatic islets under diabetes. Here, we aimed to identify known compounds regulating p13 mRNA expression to obtain therapeutic insight into the cellular stress response. A luciferase reporter system was developed using the putative promoter region of the human p13 gene. Overexpression of peroxisome proliferator-activated receptor gamma coactivator 1α, a master player regulating mitochondrial metabolism, increased both reporter activity and p13 expression. Following unbiased screening with 2320 known compounds in HeLa cells, 12 pharmacological agents (including 8 cardiotonics and 2 anthracyclines) that elicited >2-fold changes in p13 mRNA expression were identified. Among them, four cardiac glycosides decreased p13 expression and concomitantly elevated cellular oxidative stress. Additional database analyses showed highest p13 expression in heart, with typically decreased expression in cardiac disease. Accordingly, our results illustrate the usefulness of unbiased compound screening as a method for identifying novel functional roles of unfamiliar genes. Our findings also highlight the importance of p13 in the cellular stress response in heart.

60 APPLIED LIFE SCIENCES↗
NASA NTRSDate not supplied

The Effects of Autogenic Feedback Training Exercise on Heart Rate Variability

INTRODUCTION: The development of Motion Sickness (MS) symptoms is correlated with increased sympathetic influence and irregular patterns of vagal activity. Such autonomic actions can be characterized by indices of heart rate variability (HRV), which reflect autonomic balance through neurocardiac function. Nonpharmacological interventions aimed at attenuating MS symptoms may therefore produce an effect on HRV. One such intervention that has been shown to mitigate MS symptoms is Autogenic Feedback Training Exercise (AFTE), which combines principles of autogenic therapy and biofeedback. AFTE teaches individuals to manipulate various physiological parameters in provocative environments and shows promise as a potential MS intervention in military aviators. The effects of AFTE on HRV have not previously been examined. Understanding HRV changes following AFTE may help to elucidate its indirect effects and inform its implementation for MS mitigation. METHODS: Twenty-four subjects received 2 hours of AFTE over 4 days. Pre- and post-AFTE rotating chair tests, which included stationary periods of baseline data, were conducted to evaluate the effects of AFTE. HRV data were recorded by SOMNOtouch™ NIBP. Post hoc analysis of pre- and post-AFTE short-term HRV (RMSSD, LF, HF, LF/HF) was performed. RESULTS: RMSSD, HF, and LF/HF were not significantly changed following AFTE. However, LF showed a statistically significant (p=0.015) decrease following AFTE. DISCUSSION: AFTE prescribes a respiratory rate of 15 breaths per minute (BPM), which is typically faster than participants’ pre-AFTE BPM (M=12.65). Healthy individuals can increase respiratory sinus arrhythmia (RSA) by slow, deep breathing. However, increasing the respiratory rate to 15 BPM may decrease RSA and subsequently HF. Increasing RSA potentially negates any influence of AFTE on HF, resulting in no significant change. RMSSD is correlated with HF power and was likewise not affected by AFTE. LF power, however, decreased significantly following AFTE, potentially indicating a lower sympathetic response in the post-AFTE measurement.

motion sickness↗
DOE OSTI2013

The LMNA mutation p.Arg321Ter associated with dilated cardiomyopathy leads to reduced expression and a skewed ratio of lamin A and lamin C proteins

Dilated cardiomyopathy (DCM) is a disease of the heart muscle characterized by cardiac chamber enlargement and reduced systolic function of the left ventricle. Mutations in the LMNA gene represent the most frequent known genetic cause of DCM associated with disease of the conduction systems. The LMNA gene generates two major transcripts encoding the nuclear lamina major components lamin A and lamin C by alternative splicing. Both haploinsuffiency and dominant negative effects have been proposed as disease mechanism for premature termination codon (PTC) mutations in LMNA. These mechanisms however are still not clearly established. In this study, we used a representative LMNA nonsense mutation, p.Arg321Ter, to shed light on the molecular disease mechanisms. Cultured fibroblasts from three DCM patients carrying this mutation were analyzed. Quantitative reverse transcriptase PCR and sequencing of these PCR products indicated that transcripts from the mutant allele were degraded by the nonsense-mediated mRNA decay (NMD) mechanism. The fact that no truncated mutant protein was detectable in western blot (WB) analysis strengthens the notion that the mutant transcript is efficiently degraded. Furthermore, WB analysis showed that the expression of lamin C protein was reduced by the expected approximately 50%. Clearly decreased lamin A and lamin C levels were also observed by immunofluorescence microscopy analysis. However, results from both WB and nano-liquid chromatography/mass spectrometry demonstrated that the levels of lamin A protein were more reduced suggesting an effect on expression of lamin A from the wild type allele. PCR analysis of the ratio of lamin A to lamin C transcripts showed unchanged relative amounts of lamin A transcript suggesting that the effect on the wild type allele was operative at the protein level. Immunofluorescence microscopy analysis showed no abnormal nuclear morphology of patient fibroblast cells. Based on these data, we propose that heterozygosity for the nonsense mutation causes NMD degradation of the mutant transcripts blocking expression of the truncated mutant protein and an additional trans effect on lamin A protein levels expressed from the wild type allele. We discuss the possibility that skewing of the lamin A to lamin C ratio may contribute to ensuing processes that destabilize cardiomyocytes and trigger cardiomyopathy - Highlights: • We study disease mechanisms in DCM patients carrying PTC mutations in the LMNA gene. • The mutant transcript is degraded by the nonsense mediated mRNA decay system. • Skewed lamin A to lamin C protein ratio expressed from the wild type allele. • We suggest a combined pathomechanism: haploinsuffiency plus lamin A/C imbalance.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

DUSP14 knockout accelerates cardiac ischemia reperfusion (IR) injury through activating NF-κB and MAPKs signaling pathways modulated by ROS generation

Highlights: • DUSP14 expression is decreased in the infarcted area following myocardial I/R. • DUSP14 knockout aggregates cardiac function following myocardial I/R. • DUSP14 ablation intensifies inflammation in murine hearts with IR injury. • DUSP14 deficiency exacerbates MAPKs pathway and oxidative stress in murine hearts. Inflammation and oxidative stress are significantly involved in the progression of a variety of diseases, including myocardial ischemia/reperfusion (IR). In the present study, we hypothesized a protective role of dual-specificity phosphatase 14 (DUSP14) in myocardial IR, as well as the underlying molecular mechanism. The results indicated that DUSP14 was down-regulated following cardiac IR injury. Subsequently, the wild type (WT) and DUSP14-knockout (KO) mice were included to further reveal the potential role of DUSP14 in cardiac IR injury progression. DUSP14-KO mice exhibited increased infarction area and elevated apoptosis, as evidenced by the increased TUNEL-positive cells in ischemia heart following reperfusion compared to WT mice. Further, DUSP14-KO significantly aggregated cardiac dysfunction of mice after IR injury. Cardiac IR injury to DUSP14-KO mice led to markedly increased expression of pro-inflammatory cytokines and activated nuclear factor-κB (NF-κB) pathway in the heart in comparison to WT mice. Meanwhile, mitogen-activated protein kinases (MAPKs), including p38, ERK1/2 and JNK, were significantly activated by DUSO14-KO in mice after IR injury. Compared to WT mice, DUSP14-KO mice showed markedly increased oxidative stress markers in cardiac tissues, including malondialdehyde (MDA), NADPH oxidase-4 (NOX4) and p47, while decreased activities or expressions of anti-oxidants, such as glutathione (GSH), glutathione peroxidase (GPx), glutathion reductases (GR), superoxide dismutase (SOD) and hemeoxygenase-1 (HO-1). DUSP14-knockdown (KD) in primary cardiomyocytes using its specific siRNA sequence elevated hypoxia and reoxygenation (HR)-induced activation of NF-κB and MAPKs signaling pathways, and reactive oxygen species (ROS) generation. Intriguingly, pre-treatment of ROS scavenger, N-acetylcysteine (NAC), markedly abolished DUSP14-KD-augmented NF-κB and MAPKs activation in HR-stimulated primary cardiomyocytes. Together, the results above indicated that DUSP14 might be served as a positive regulator to attenuate cardiac IR injury. Suppressing DUSP14 exacerbated cardiac injury through activating NF-κB and MAPKs signaling pathways regulated by ROS production. Thus, DUSP14 could be a valuable target for developing treatments for myocardial IR injury.

60 APPLIED LIFE SCIENCES↗
NASA NTRS1994

Development of the NASA/Baylor VAD

A cooperative effort between the NASA/Johnson Space Center (JSC) and the Baylor College of Medicine (BCM) has been underway since 1988 to develop a long-term implantable Ventricular Assist Device (VAD). The VAD is intended to boost the cardiac output of patients with deteriorated cardiac function. For many of these patients, the best alternative is heart transplantation. Heart transplantation is a complex and expensive procedure and usually requires a long waiting period for a donor heart. The condition of the patient often deteriorates during this waiting period which complicates the pre and post-operative care. Because of these factors, the need for a long-term implantable VAD for use as a bridge-to-transplant device or as a permanent assist device has become the focus of much research. The need for a VAD has been estimated at 50,000 to 60,000 patients per year in the United States alone. A device which satisfies all the system performance and reliability requirements has yet to be achieved. However, the development of the NASA/Baylor VAD has progressed to a state in which commercial viability can being to be considered. The device is small, simple, efficient and reliable which meets all requirements for a totally implantable VAD.

Aber, G. S.↗
NASA NTRS2001

Mechanisms of blood pressure regulation that differ in men repeatedly exposed to high-G acceleration

The purpose of this study was to test the hypothesis that repeated exposure to high acceleration (G) would be associated with enhanced functions of specific mechanisms of blood pressure regulation. We measured heart rate (HR), stroke volume (SV), cardiac output (), mean arterial blood pressure, central venous pressure, forearm and leg vascular resistance, catecholamines, and changes in leg volume (%DeltaLV) during various protocols of lower body negative pressure (LBNP), carotid stimulation, and infusions of adrenoreceptor agonists in 10 males after three training sessions on different days over a period of 5-7 days using a human centrifuge (G trained). These responses were compared with the same measurements in 10 males who were matched for height, weight, and fitness but did not undergo G training (controls). Compared with the control group, G-trained subjects demonstrated greater R-R interval response to equal carotid baroreceptor stimulation (7.3 +/- 1.2 vs. 3.9 +/- 0.4 ms/mmHg, P = 0.02), less vasoconstriction to equal low-pressure baroreceptor stimulation (-1.4 +/- 0.2 vs. -2.6 +/- 0.3 U/mmHg, P = 0.01), and higher HR (-1.2 +/- 0.2 vs. -0.5 +/- 0.1 beats. min(-1). mmHg(-1), P = 0.01) and alpha-adrenoreceptor response (32.8 +/- 3.4 vs. 19.5 +/- 4.7 U/mmHg, P = 0.04) to equal dose of phenylephrine. During graded LBNP, G-trained subjects had less decline in and SV, %DeltaLV, and elevation in thoracic impedance. G-trained subjects also had greater total blood (6,497 +/- 496 vs. 5,438 +/- 228 ml, P = 0.07) and erythrocyte (3,110 +/- 364 vs. 2,310 +/- 96 ml, P = 0.06) volumes. These results support the hypothesis that exposure to repeated high G is associated with increased capacities of mechanisms that underlie blood pressure regulation.

Non-NASA Center↗
NASA NTRS2010

Aerobic Capacity Following Long Duration International Spaces Station (ISS) Missions: Preliminary Results

Maximum oxygen uptake (VO2max) is reduced immediately following space flights lasting <15 d, but has not been measured following long-duration missions. The purpose of this study is to measure VO2max and maximum work rate (WRmax) data from astronauts following ISS flights (91 to 188 d). Methods: Five astronauts [3 M, 2 F: 47+/-6 yr, 174+/-6 cm, 71.9+/-10.9 kg (mean +/- SD)] have participated in the study. Subjects performed upright cycle exercise tests to symptom-limited maximum. An initial test was done approx.270 d before flight to establish work rates for subsequent tests. Subsequent tests, conducted approx.45 d before flight and repeated on the first or second day (R+1/2) and at approx.10 d (R+10) following landing, consisted of 3 5 min stages designed to elicit 25%, 50%, and 75% of preflight VO2max, followed by 25 W(dot)/min increases. VO2, WR, and heart rate (HR) were measured using the ISS Portable Pulmonary Function System [Damec, Odense, DK]. Descriptive statistics are reported. Results: On R+1/2 mean VO2max decreased compared to preflight (Pre: 2.98+/-0.99, R+1/2: 2.63+/-0.56 L(dot)/min); 4 of 5 subjects demonstrated a loss of > 6%. WRmax also decreased on R+1/2 compared to preflight (Pre: 245+/-69, R+1/2: 210+/-45 W). On R+10, VO2max was 2.86+/-0.62 L(dot)/min, with 2 subjects still demonstrating a loss of > 6% from preflight. WRmax on R+10 was 240+/-49 W. HRmax did not change from pre to post-flight. Conclusions: These preliminary results, from the first 5 of 12 planned subjects of an ongoing ISS study, suggest that the majority of astronauts will experience a decrease in VO2max after long-duration space-flight. Interestingly, the two astronauts with the highest preflight VO2max had the greatest loss on R+1/2, and the astronaut with the lowest preflight VO2max increased by 13%. Thus, maintenance of VO2max may be more difficult in astronauts who have a high aerobic capacity, perhaps requiring more intense in-flight exercise countermeasure prescriptions.

Moore, Alan D.↗
NASA NTRS2010

Maximum Oxygen Uptake During Long-Duration Space Flight: Preliminary Results

INTRODUCTION: Maximum oxygen uptake (VO2max) is maintained during space flight lasting <15 d, but has not been measured during long-duration missions. This abstract describes pre-flight and in-flight preliminary findings from the International Space Station (ISS) VO2max experiment. METHODS: Seven astronauts (4 M, 3 F: 47 +/- 5 yr, 174 +/- 7 cm, 74.1 +/- 14.7 kg [mean +/- SD]) performed cycle exercise tests to volitional maximum approx.45 d before flight and tests were scheduled every 30 d during flight beginning on flight day (FD) 14. Tests consisted of three 5-min stages designed to elicit 25%, 50%, and 75% of preflight VO2max, followed by 25 W/min increases. VO2 and heart rate (HR) were measured using the ISS Portable Pulmonary Function System (PPFS) (Damec, Odense, DK). Unfortunately the PPFS did not arrive at the ISS in time to support early test sessions for 3 crewmembers. Descriptive statistics are presented for pre-flight vs. late-flight (FD 147 +/- 33 d) comparisons for all subjects (n=7); and pre-flight, early (FD 18 +/- 3) and late-flight (FD 156 +/- 5) data are presented for subjects (n=4) who completed all of these test sessions. RESULTS: When all subjects are considered, average VO2max decreased from pre- to late in-flight (2.98 +/- 0.85 vs. 2.57 +/- 0.50 L/min) while maximum HR late-flight seemed unchanged (178 +/- 9 vs. 175 +/- 8 beats/min). Similarly, for subjects who completed pre-, early, and late flight measurements (n=4), mean VO2max declined from 3.19 +/- 0.75 L/min preflight to 2.43 +/- 0.43 and 2.62 +/- 0.38 L/min early and late-flight, respectively. Maximum HR was 183 +/- 8, 174 +/- 8, and 179 +/- 6 beats/min pre-, early- and late-flight. DISCUSSION: Average VO2max declined during flight and did not appreciably recover as flight duration increased; however much inter-subject variation occurred in these changes.

Moore, A. D., Jr.↗
NASA NTRS1997

Deviations from uniform power law scaling in nonstationary time series

A classic problem in physics is the analysis of highly nonstationary time series that typically exhibit long-range correlations. Here we test the hypothesis that the scaling properties of the dynamics of healthy physiological systems are more stable than those of pathological systems by studying beat-to-beat fluctuations in the human heart rate. We develop techniques based on the Fano factor and Allan factor functions, as well as on detrended fluctuation analysis, for quantifying deviations from uniform power-law scaling in nonstationary time series. By analyzing extremely long data sets of up to N = 10(5) beats for 11 healthy subjects, we find that the fluctuations in the heart rate scale approximately uniformly over several temporal orders of magnitude. By contrast, we find that in data sets of comparable length for 14 subjects with heart disease, the fluctuations grow erratically, indicating a loss of scaling stability.

Non-NASA Center↗
NASA NTRS1992

Fractal mechanisms in the electrophysiology of the heart

The mathematical concept of fractals provides insights into complex anatomic branching structures that lack a characteristic (single) length scale, and certain complex physiologic processes, such as heart rate regulation, that lack a single time scale. Heart rate control is perturbed by alterations in neuro-autonomic function in a number of important clinical syndromes, including sudden cardiac death, congestive failure, cocaine intoxication, fetal distress, space sickness and physiologic aging. These conditions are associated with a loss of the normal fractal complexity of interbeat interval dynamics. Such changes, which may not be detectable using conventional statistics, can be quantified using new methods derived from "chaos theory.".

NASA Discipline Cardiopulmonary↗
DOE OSTI2020

The sodium channel Na X : Possible player in excitation–contraction coupling

Abstract The sodium channel Na X (encoded by the SCN7A gene) was originally identified in the heart and skeletal muscle and is structurally similar to the other voltage‐gated sodium channels but does not appear to be voltage gated. Although Na X is expressed at high levels in cardiac and skeletal muscle, little information exists on the function of Na X in these tissues. Transcriptional profiling of ion channels in the heart in a subset of patients with Brugada syndrome revealed an inverse relationship between the expression of Na X and Na V 1.5 suggesting that, in cardiac myocytes, the expression of these channels may be linked. We propose that Na X plays a role in excitation–contraction coupling based on our experimental observations. Here we show that in cardiac myocytes, Na X is expressed in a striated pattern on the sarcolemma in regions corresponding to the sarcomeric M‐line. Knocking down Na X expression decreased Na V 1.5 mRNA and protein and reduced the inward sodium current ( I Na+ ) following cell depolarization. When the expression of Na V 1.5 was knocked down, ~85% of the I Na+ was reduced consistent with the observations that Na V 1.5 is the main voltage‐gated sodium channel in cardiac muscle and that Na X likely does not directly participate in mediating the I Na+ following depolarization. Silencing Na V 1.5 expression led to significant upregulation of Na X mRNA. Similar to Na V 1.5, Na X protein levels were rapidly downregulated when the intracellular [Ca 2+ ] was increased either by CaCl 2 or caffeine. These data suggest that a relationship exists between Na X and Na V 1.5 and that Na X may play a role in excitation–contraction coupling.

Bogdanovic, Elena↗
DOE OSTI2016

Halofuginone alleviates acute viral myocarditis in suckling BALB/c mice by inhibiting TGF-β1

Viral myocarditis (VMC) is an inflammation of heart muscle in infants and young adolescents. This study explored the function of halofuginone (HF) in Coxsackievirus B3 (CVB3) -treated suckling mice. HF-treated animal exhibited higher survival rate, lower heart/body weight, and more decreased blood sugar concentration than CVB3 group. HF also reduced the expressions of interleukin(IL)-17 and IL-23 and the numbers of Th17 cells. Moreover, HF downregulated pro-inflammatory cytokine levels and increased anti-inflammatory cytokine levels. The expressions of transforming growth factor(TGF-β1) and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) p65/ tumor necrosis factor-α (TNF-α) proteins were decreased by HF as well. Finally, the overexpression of TGF-β1 counteracted the protection effect of HF in CVB3-treated suckling mice. In summary, our study suggests HF increases the survival of CVB3 suckling mice, reduces the Th17 cells and pro-inflammatory cytokine levels, and may through downregulation of the TGF-β1-mediated expression of NF-κB p65/TNF-α pathway proteins. These results offer a potential therapeutic strategy for the treatment of VMC. - Highlights: • Halofuginone (HF) increases the survival of suckling BALB/c mice infected with acute CVB3. • HF reduces the expression of Th17 cell markers (IL-17 and IL-23) and the number of CD4{sup +} IL17{sup +} cells. • Pro-inflammatory cytokines levels associated with myocarditis were reduced by HF in CVB3-treated suckling mice. • HF alleviates VMC via inhibition of TGF-β1-mediated NF-κB p65/TNF-α pathway.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Early Cardiac Mitochondrial Molecular and Functional Responses to Acute Anthracycline Treatment in Wistar Rats

Abstract Doxorubicin (DOX) is an anticancer drug widely used to treat human and nonhuman tumors but the late and persistent cardio-toxicity reduces the therapeutic utility of the drug. The full mechanism(s) of DOX-induced acute, subchronic and delayed toxicity, which has a preponderant mitochondrial component, remains unclear; therefore, it is clinically relevant to identify early markers to identify patients who are predisposed to DOX-related cardiovascular toxicity. To address this, Wistar rats (16 weeks old) were treated with a single DOX dose (20 mg/kg, i.p.); then, mRNA, protein levels and functional analysis of mitochondrial endpoints were assessed 24 h later in the heart, liver, and kidney. Using an exploratory data analysis, we observed cardiac-specific alterations after DOX treatment for mitochondrial complexes III, IV, and preferentially for complex I. Conversely, the same analysis revealed complex II alterations are associated with DOX response in the liver and kidney. Interestingly, H2O2 production by the mitochondrial respiratory chain as well as loss of calcium-loading capacity, markers of subchronic toxicity, were not reliable indicators of acute DOX cardiotoxicity in this animal model. By using sequential principal component analysis and feature correlation analysis, we demonstrated for the first time alterations in sets of transcripts and proteins, but not functional measurements, that might serve as potential early acute markers of cardiac-specific mitochondrial toxicity, contributing to explain the trajectory of DOX cardiac toxicity and to develop novel interventions to minimize DOX cardiac liabilities.

Pereira, Gonçalo C.↗
NASA NTRS2010

Spaceflight-Induced Cardiovascular Changes and Recovery During NASA's Functional Task Test

Microgravity-induced physiological changes could impair a crewmember s performance upon return to a gravity environment. The Functional Task Test (FTT) is designed to correlate these physiological changes to performance in mission-critical tasks. The Recovery from Fall/Stand Test (RFST) simulates one such task, measuring the ability to recover from a prone position and the cardiovascular response to orthostasis. The purpose of this study was to evaluate spaceflight-induced cardiovascular changes during the FTT. METHODS: Five astronauts participated in the FTT before 10-15 day missions, on landing day (R+0), and one (R+1), six (R+6) and thirty (R+30) days after landing. The RFST consisted of a 2-minute prone rest followed by a 3-minute stand during which heart rate (HR, Holter) and continuous blood pressure (BP, Finometer) were measured. Spectral heart rate variability (HRV) was calculated during the RFST to approximate autonomic function. Statistical analysis was performed with two-factor repeated measures ANOVA. RESULTS: During RFST, HR was higher on R+0 than preflight (p<0.004). This increase in HR persisted on R+1 and R+6 during the stand portion of RFST (p<0.026). BP was well-regulated on all test days. Parasympathetic activity was diminished on R+0 (p=0.035). Sympathovagal balance tended to be affected by spaceflight (main effect, p=0.072), appearing to be slightly elevated during postflight RFST except on R+30. Additionally, analysis of HR during the functional tasks yielded a higher HR on R+0 than preflight during 8 of 11 tasks analyzed, where all tasks had HR return to preflight values by R+30 (p<0.05). CONCLUSION: Spaceflight causes an increase in HR, decrease in parasympathetic activity, and increase in sympathovagal balance, which we confirmed during RFST. These spaceflight-induced changes seen in the RFST, along with the increased postflight HR in most functional tasks, can be used to assess functional performance after short-duration spaceflight.

Arzeno, N. M.↗
NASA NTRS1997

Adaptive responses of the cardiovascular system to prolonged spaceflight conditions: assessment with Holter monitoring

This article presents selected findings obtained with Holter monitoring from two crew members of the expedition, performed during a 175-day space mission on board orbital space station "MIR." Using mathematical processing of daily cardiointervals files, 5-minute sections of records were analyzed consecutively. Then, the average daily values of indices, the average-per-every-eight-hours values (morning, evening, night) and mean values per hour were computed. The results of analysis showed that prolonged exposure of man to microgravity conditions leads to important functional alteration in human neuroautonomic regulatory mechanisms. Both crew members had significant increase of heart rate, the rise of stress index, the decrease in power of the spectrum in the range of respiratory sinus arrhythmia. These marked signs of activation of the sympathetic section of the vegetative nervous system showed individual variations. The analysis of the daily collection of cardiointervals with Holter monitoring allows us to understand and forecast the functional feasibilities of the human organism under a variety of stress conditions associated with acute and chronic microgravity exposure.

manned↗