Our understanding of the impact of long-duration head-down bed rest (HDBR) on sympathetic neurovascular regulation during orthostatic stress remains incomplete. Through retrospective analysis of the WISE-2005 long-duration bed rest trial, this study aimed to investigate the impact of 60 days of -6° HDBR on the transduction of integrated muscle sympathetic nerve activity (MSNA; peroneal microneurography) into total peripheral resistance (TPR; Finometer Modelflow) responses during rest and graded lower body negative pressure (LBNP; -20, -30, and -45 mmHg). Signal averaging quantified sympathetic transduction for 12 cardiac cycles (ECG) following integrated MSNA bursts in healthy females ( n = 12; 25-40 years). Mixed-effects modeling and post-hoct-tests assessed the impact of HDBR on sympathetic transduction during rest (5-min) and graded LBNP (3-min per level). Data are presented as mean ± SD. Long-duration HDBR did not affect resting total MSNA (pre-HDBR: 909 ± 368 AU/min, post-HDBR: 910 ± 254 AU/min; p = 0.999). HDBR did not affect total MSNA responses to -20 mmHg LBNP (pre-HDBR: 1430 ± 599 AU/min, post-HDBR: 1823 ± 433 AU/min), -30 mmHg LBNP (pre-HDBR: 1574 ± 549 AU/min, post-HDBR: 1924 ± 587 AU/min), or -45 mmHg LBNP (pre-HDBR: 1950 ± 819 AU/min, post-HDBR: 2328 ± 880 AU/min; p = 0.191). HDBR did not affect resting sympathetic transduction to TPR (pre-HDBR: 0.002 ± 0.16 mmHg/L/min, post-HDBR: -0.091 ± 0.12 mmHg/L/min; p = 0.296). However, HDBR augmented TPR transduction responses to graded LBNP (HDBR-by-LBNP interaction: p = 0.050). Pre-HDBR, TPR transduction responses were unchanged with graded LBNP (all p > 0.05). In contrast, post-HDBR, TPR transduction responses increased progressively with graded LBNP (rest: -0.09 ± 0.12 mmHg/L/min, -20 mmHg: 0.22 ± 0.31 mmHg/L/min, -30 mmHg: 0.30 ± 0.34 mmHg/L/min, -45 mmHg: 0.44 ± 0.12 mmHg/L/min; all p < 0.005). The same effect of HDBR was observed when sympathetic transduction of mean arterial pressure was analyzed (data not shown). These data suggest that long-duration HDBR augments sympathetic neurovascular responses to integrated MSNA bursts during orthostatic stress among females. This work was supported by the Canadian Space Agency, the French “Centre National d’Etudes Spatiales”, the European Space Agency, and the National Aeronautics and Space Administration of the USA. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Background Adverse childhood experiences (ACEs) have been linked to increased cardiovascular disease (CVD) risk. Previous reports have suggested that accelerated biological aging—indexed by telomere length (TL) and mitochondrial DNA copy number (mtDNAcn)—may contribute to associations between ACEs and cardiovascular health outcomes. Here, we examine the potential mediating effects of TL and mtDNAcn on the association between ACEs and central arterial stiffness—an intermediate cardiovascular health outcome—as a novel pathway linking ACEs to CVD risk among young adults. Methods and Results One hundred and eighty‐five (n=102 women; mean age, 22.5±1.5 years) individuals provided information on ACEs. TL (kb per diploid cell) and mtDNAcn (copies per diploid cell) were quantified using quantitative polymerase chain reaction techniques. Central arterial stiffness was measured as carotid‐femoral pulse wave velocity (cfPWV; m/s). Multiple linear regression analyses were used to examine the associations between ACEs, TL, mtDNAcn, and cfPWV. ACEs were positively associated with cfPWV ( β =0.147, P =0.035). TL ( β =−0.170, P =0.011) and mtDNAcn ( β =−0.159, P =0.019) were inversely associated with cfPWV. Neither TL ( β =−0.027, P =0.726) nor mtDNAcn ( β =0.038, P =0.620) was associated with ACEs. Neither marker mediated the association between ACEs and cfPWV. Conclusions An increasing number of ACEs were associated with a faster cfPWV and thus, a greater degree of central arterial stiffness. ACEs were not associated with either TL or mtDNAcn, suggesting that these markers do not represent a mediating pathway linking ACEs to central arterial stiffness.
Large artery stiffness is an independent predictor of cardiovascular disease (CVD) and all‐cause mortality. Stiffening of the large arteries (e.g., the aorta) is characterized by a marked reduction in the elastin‐collagen ratio in the extracellular matrix (ECM) of the arterial wall, and is largely the result of fatigue and fragmentation of ECM components due to cyclic stress. Matrix metalloproteinases (MMPs), a family of zinc‐dependent endopeptidases, may be important in the progression of arterial stiffness due to their involvement in ECM homeostasis and arterial wall remodeling. MMP‐3 may be of particular importance in arterial wall remodeling due to its ability to degrade numerous constituents of the arterial ECM, such as elastin and collagen. Previous studies have examined the effects of MMP‐3 genotype and expression on arterial wall stiffness in different disease populations; however, none have examined the association between MMP‐3 expression and large artery stiffness in a population of healthy young adults. Thus, the purpose of this study was to examine the association between serum MMP‐3 and carotid‐femoral pulse wave velocity (cfPWV), a non‐invasive measure of large artery stiffness, in a sample of healthy young adults. It is expected that individuals with higher serum MMP‐3 levels will present with larger cfPWVs. 156 participants ( n = 68 males) aged 20–25 years were recruited as part of the Niagara Longitudinal Heart Study (NLHS), and all participants were free of any clinically diagnosed CVD. cfPWV (m/s) was determined using applanation tonometry as a non‐invasive surrogate of large artery stiffness. Serum MMP‐3 concentrations (pg/mL) were measured using standard ELISA techniques. Linear regression analyses were used to investigate the cross‐sectional association between serum MMP‐3 and cfPWV. Analyses were adjusted for age, sex, mean arterial pressure (MAP), body mass index (BMI), and smoking status. Data on cfPWV and MMP‐3 were available on 139 participants ( n = 63 males), and were subsequently used in analysis. After adjustment for age, sex, MAP, BMI, and smoking status, serum MMP‐3 was significantly and positively associated with cfPWV ( p = 0.038). cfPWV was also significantly and positively associated with MAP and smoking status (both p < 0.001), but not age ( p = 0.336). The association between cfPWV and both sex and BMI showed a positive trend, but only reached borderline significance ( p = 0.059 and p = 0.054, respectively). Together, MAP, smoking status and serum MMP‐3 predicted 22% of the variation in cfPWV (adjusted R 2 = 0.220, p < 0.001). These data suggest that greater serum MMP‐3 levels are associated with larger cfPWVs and thus, greater large artery stiffness. Physiologic MMP‐3 levels function to maintain ECM homeostasis; however, greater MMP‐3 levels may exacerbate ECM degradation and contribute to stiffening of the large arteries. Future research should examine the potential functional role of MMP‐3 in CVD progression. Support or Funding Information The NLHS is funded by the Canadian Institute of Health Research (CIHR #363774 and #399332). KSD is funded by CIHR Doctoral Research Award—Frederick Banting and Charles Best Canada Graduate scholarship (RFN #167014). ARRM is supported by the Ontario Graduate Scholarship program
Objective Iron deficiency anemia (IDA) in patients with heart disease is correlated with decreased exercise capacity and poor health-related quality of life, and predicts worse cardiovascular outcomes, especially for elderly patients. IDA can worsen cardiac function that can be monitored with Heart Rate Variability (HRV) analysis, providing important information about cardiac health. In a recent study we explored the effect and the tolerability of the administration of Ferric Sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel Forte®) in frailty patients with secondary anemia and low kidney failure, by analysing the HRV frequency domain. The aim of the present study is the further confirmation of the safety of the already evaluated intervention, by analysing non-linear domain of HRV. Patients and methods In this pilot study we enrolled 52 frailty elderly patients, with a recent diagnosis of secondary anemia due to iron deficiency, with Class II New York Heart Association (NYHA) hypertensive heart disease, low kidney failure, and atherosclerosis. The patients were divided in 2 groups: Group A (N=23 patients) received oral administration of Ferric Sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel Forte®) 2 tabs/day, containing 60 mg of Fe3+, for 24 days; Group B (N=29 patients) received intravenous administration of ferrous gluconate 63 mg/day added to saline solution, while they were hospitalized (15±5 days). We evaluated laboratory values of hemoglobin (Hb) and sideremia levels. Furthermore, we measured ECG signals before and after treatment, using non-linear analysis techniques. Results Both intravenous and oral treatments evaluated in this study, were effective and safe about the cardiovascular risk in frailty elderly patients, as resulted from non-linear HRV analysis. Efficacy results showed that hemoglobin and sideremia levels after treatments are significantly increased. The HRV non-linear analysis showed that all parameters evaluated, except for the SD1 values in the Group A, were not affected by treatments, confirming the absence of cardiovascular risk of the therapy. Conclusions Non-linear HRV evaluation confirmed that oral administration of Ferric Sodium EDTA, in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel forte®) did not impact the cardiovascular risk, without causing adverse events typically reported with other iron supplementation therapies, both oral and intravenous.
The central neural mechanisms affecting sympathetic neuronal discharge strategies supporting homeostatic adjustments in human muscle sympathetic nerve activity (MSNA) remain unclear. This study investigated the hypothesis that central alpha-2 adrenergic mechanisms affect sympathetic action potential (AP) discharge, recruitment, and latency patterns within human MSNA (peroneal nerve microneurography and continuous wavelet transform). An alpha-2 adrenergic agonist (dexmedetomidine) was infused in eight healthy male and female participants (5 females; 28 ± 7years). Data were recorded during a 5-minute resting control condition, a 10-minute intravenous dexmedetomidine loading dose (0.225 μg/kg), and a dexmedetomidine maintenance dose (~0.1 μg/kg/hr). Data are reported as mean (SD) for the 5-minute control condition and 2-minutes of the dexmedetomidine infusion when MSNA bursting activity was demonstrably reduced. Two-tailed paired t-tests were performed. Dexmedetomidine reduced mean pressure (92 ± 7 to 80 ± 8 mmHg; P < 0.01) but did not affect heart rate (61 ± 13 to 60 ± 14 bpm; P = 0.75). Dexmedetomidine reduced integrated MSNA burst frequency (14 ± 6 to 4 ± 3 bursts/min; P < 0.01), sympathetic AP frequency (75 ± 46 to 16 ± 14 AP/min; P < 0.01), APs per burst (5 ± 1 to 4 ± 1 AP/burst; P = 0.01), AP clusters per burst (3.5 ± 0.7 to 3.0 ± 0.7 clusters/burst; P = 0.03), and de-recruited the largest AP clusters (12 ± 3 to 7 ± 2 AP clusters; P < 0.01). Despite de-recruiting large AP clusters with short conduction times, dexmedetomidine elicited shorter sympathetic AP conduction times (1.18 ± 0.12 to 1.14 ± 0.13 s; P = 0.03). Six participants performed a Valsalva Maneuver (20 s, 40 mmHg mouth pressure) during the control condition and during the dexmedetomidine maintenance dose. Data are reported as mean (SD) change (Δ) from the 2-minute period preceding the Valsalva Maneuver to the Valsalva Maneuver for each condition. During the control condition, Valsalva Maneuver increased AP frequency (Δ 311 ± 317 AP/min; P = 0.048), recruited larger previously silent AP clusters (Δ 2 ± 1 AP clusters; P < 0.01), and elicited shorter AP conduction times (Δ ‑0.09 ± 0.07 s; P = 0.02). Compared to the control condition, Valsalva Maneuver performed during the dexmedetomidine maintenance dose condition elicited lesser increases in AP frequency (Δ 116 ± 189 AP/min; P vs. control = 0.02) and lesser recruitment of larger previously silent AP clusters (Δ 0 ± 1 AP clusters; P vs. control = 0.02). Dexmedetomidine did not affect the latency reduction elicited by Valsalva Maneuver (Δ ‑0.07 ± 0.14 s; P vs. control = 0.61). These data suggest that human central alpha-2 adrenergic mechanisms affect: i) sympathetic postganglionic neuronal discharge and recruitment patterns, and ii) synaptic delays within the sympathetic neurocircuitry influencing AP latency. This work was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) and the National Institutes of Health (NIH). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
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Depression symptomology is linked with incident cardiovascular disease (CVD). Increased central arterial stiffness represents a potential mechanism connecting depression and increased cardiovascular risk. Therefore, the objective of this study was to examine the association between depressive symptomology and central arterial stiffness in healthy young adults without cardiovascular disease. The study tested the hypothesis that higher depressive symptomology is associated with greater central arterial stiffness. Using existing data from the Niagara Longitudinal Heart Study (NLHS), a sample of 293 young adults (22.5±1.71 years; 55% female) was included. Depressive symptomology (Centre for Epidemiological Studies Depression Scale; CESD), central arterial stiffness (carotid-femoral pulse wave velocity; cfPWV), beat-by-beat mean arterial pressure (MAP; finger photoplethysmography), and heart rate (HR; electrocardiogram) were measured. Multiple linear regression analyses were used to examine the association between depressive symptomology and cfPWV, adjusting for age, sex, body mass index, physical activity, smoking status, MAP, and HR. Depressive symptomology was categorized as low (CESD score < 16), moderate (CESD score ≥16 and < 26), and high (CESD score ≥ 26), where low symptomology was used as the reference group. After adjusting for covariates, high depressive symptomology was predictive of a faster cfPWV (β = 0.134, p = 0.026), whereas moderate depressive symptomology was not (β = 0.053, p = 0.365). These findings suggest that high depressive symptomatology is associated with a faster cfPWV, signifying elevated central arterial stiffness. Therefore, central arterial stiffness may act as a mechanism connecting depression to CVD. Future research should aim to decipher the causal direction between depression and cfPWV. This work was supported by the Canadian Institute of Health Research (CIHR) and Brock University. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Central arterial stiffness is an independent predictor of cardiovascular disease. It is characterized by a marked reduction in the elastin-collagen ratio of the arterial wall extracellular matrix (ECM), and is largely the result of degradation of various ECM components. Matrix metalloproteinase-3 (MMP-3) may contribute to central arterial stiffness via its involvement in ECM homeostasis and remodeling. This study examined the association between serum MMP-3 concentrations and central arterial stiffness and potential interactions of MMP-3 and traditional cardiovascular risk factors in a population of healthy young adults. A total of 206 participants (n = 109 females) aged 19–25 years were included in the current study. Central arterial stiffness was measured non-invasively as carotid-femoral pulse wave velocity (cfPWV) (m/s). MMP-3 concentrations (ng/ml) were measured using ELISA techniques. Regression analyses were used to examine the association between cfPWV and MMP-3, adjusting for age, sex, smoking status, body mass index (BMI), instantaneous mean arterial pressure (MAP) and heart rate, and serum C-reactive protein. Interactions between MMP-3 with smoking, BMI, sex, and MAP were analyzed in subsequent regression models. MMP-3 was an independent predictor of cfPWV (β = 0.187, p = 0.007), and significant interactions between MMP-3 and regular smoking (β = 0.291, p = 0.022), and MMP-3 and BMI (β = 0.210, p = 0.013) were observed. Higher serum MMP-3 concentrations were associated with a faster cfPWV and thus, greater central arterial stiffness. Interactions between MMP-3 and smoking, and MMP-3 and BMI may, in part, drive the association between MMP-3 and central arterial stiffness.
What is the purpose of sympathetic neuronal action potential (AP) discharge and recruitment patterns for human vascular regulation? This study tested the hypothesis that sympathetic neuronal discharge and recruitment patterns regulate neuropeptide Y (NPY) bioavailability. We used microneurography to record muscle sympathetic nerve activity (MSNA) and a continuous wavelet transform to detect sympathetic APs during a baseline condition and intravenous dexmedetomidine infusion (α 2 -adrenergic agonist, 10 min loading infusion of 0.225 µg kg −1 ; maintenance infusion of 0.1-0.5 µg kg h −1 ) in six healthy individuals (5 females, 27 ± 6 years). Arterial blood samples provided NPY (enzyme-linked immunosorbent assay) and norepinephrine (Liquid Chromatography Tandem Mass Spectrometry) levels during baseline and the dexmedetomidine maintenance infusion. Linear mixed model regressions assessed the relationships between AP discharge, recruitment, and neurotransmitter levels. Across baseline and the dexmedetomidine condition, NPY levels were positively related to mean arterial pressure (β = 1.63 [0.34], P = 0.002), total AP clusters (β = 0.90 [0.22], P = 0.005), and AP frequency (β = 0.11 [0.03], P = 0.003). Norepinephrine levels were not related to mean arterial pressure (β = 0.03 [0.02], P = 0.133) but were positively related to total AP clusters (β = 19.50 [7.07], P = 0.030) and AP frequency (β = 2.66 [0.81], P = 0.014). These data suggest that sympathetic neuronal discharge and recruitment patterns regulate NPY and norepinephrine bioavailability in healthy adults. As such, sympathetic neuronal firing strategies are important for human vascular regulation.
BACKGROUND Pulse interval is a biomarker of psychological and physiological health. Pulse interval can now be assessed using mobile phone apps, which expands researchers’ ability to assess pulse interval in the real world. Prior to implementation, measurement accuracy should be established. OBJECTIVE This investigation evaluated the validity of the Light Heart mobile app to measure pulse interval and pulse rate variability in healthy young adults. METHODS Validity was assessed by comparing the pulse interval and SD of normal pulse intervals obtained by Light Heart to the gold standard, electrocardiogram (ECG), in 14 young healthy individuals (mean age 24, SD 5 years; n=9, 64% female) in a seated posture. RESULTS Mean pulse interval (Light Heart: 859, SD 113 ms; ECG: 857, SD 112 ms) demonstrated a strong positive linear correlation (<i>r</i>=0.99; <i>P</i><.001) and strong agreement (intraclass correlation coefficient=1.00, 95% CI 0.99-1.00) between techniques. The Bland-Altman plot demonstrated good agreement for the mean pulse interval measured with Light Heart and ECG with evidence of fixed bias (–1.56, SD 1.86; 95% CI –5.2 to 2.1 ms), suggesting that Light Heart overestimates pulse interval by a small margin. When Bland-Altman plots were constructed for each participant’s beat-by-beat pulse interval data, all participants demonstrated strong agreement between Light Heart and ECG with no evidence of fixed bias between measures. Heart rate variability, assessed by SD of normal pulse intervals, demonstrated strong agreement between techniques (Light Heart: mean 73, SD 23 ms; ECG: mean 73, SD 22 ms; <i>r=</i>0.99; <i>P</i><.001; intraclass correlation coefficient=0.99, 95% CI 0.97-1.00). CONCLUSIONS This study provides evidence to suggest that the Light Heart mobile app provides valid measures of pulse interval and heart rate variability in healthy young adults.
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