Cardiac Baroreflex Variability and Resetting during Sustained Mild Effort

This exploratory study assessed the pattern of closed-loop baroreflex resetting using multi-logistic-curve analysis. Operating point gain and ranges of RR-interval (RRI) and systolic blood pressure (SBP) are derived to examine how these relate to sympathetic activation. Sustained low-intensity isometric handgrip exercise, with a period of post-exercise circulatory occlusion (PECO), provided a model to study baroreflex resetting because the progression toward fatigue at constant tension induces a continuous increase in volitional contribution to neuro-cardiovascular control. Continuous measurements of muscle sympathetic nerve activity (MSNA), blood pressure, and RRI were made simultaneously throughout the experimental session. Spontaneous sequence analysis was used to detect episodes of baroreflex “engagements”, but the results are examined with a view to the fundamental difference between experimental conditions that isolate the carotid sinus (open-loop) and intact physiological conditions (closed-loop). While baroreflex function under open-loop conditions can be described in terms of a single logistic curve, intact physiologic conditions require a family of logistic curves. The results suggest that the baroreflex is in a “floating” state whereby it is continuously resetting during the timeline of the experiment but with minute-by-minute average values that mimic the less complex step-wise resetting pattern reported under open-loop conditions. Furthermore, the results indicate that baroreflex function and resetting of the operating point gain is reflected not in terms of change in the values of blood pressure or RR-interval but in terms of change in the range of values of these variables prevailing under different experimental conditions

Effects of aging and coronary artery disease on sympathetic neural recruitment strategies during end-inspiratory and end-expiratory apnea

In response to acute physiological stress, the sympathetic nervous system modifies neural outflow through increased firing frequency of lower-threshold axons, recruitment of latent subpopulations of higher-threshold axons, and/or acute modifications of synaptic delays. Aging and coronary artery disease (CAD) often modify efferent muscle sympathetic nerve activity (MSNA). Therefore, we investigated whether CAD (n = 14; 61 ± 10 yr) and/or healthy aging without CAD (OH; n = 14; 59 ± 9 yr) modified these recruitment strategies that normally are observed in young healthy (YH; n = 14; 25 ± 3 yr) individuals. MSNA (microneurography) was measured at baseline and during maximal voluntary end-inspiratory (EI) and end-expiratory (EE) apneas. Action potential (AP) patterns were studied using a novel AP analysis technique. AP frequency increased in all groups during both EI- and EE-apnea (all P \u3c 0.05). The mean AP content per integrated burst increased during EI- and EE-apnea in YH (EI: Δ6 ± 4 APs/burst; EE: Δ10 ± 6 APs/burst; both P \u3c 0.01) and OH (EI: Δ3 ± 3 APs/burst; EE: Δ4 ± 5 APs/burst; both P \u3c 0.01), but not in CAD (EI: Δ1 ± 3 APs/burst; EE: Δ2 ± 3 APs/burst; both P = NS). When APs were binned into clusters according to peak-to-peak amplitude, total clusters increased during EI- and EE-apnea in YH (EI: Δ5 ± 2; EE: Δ6 ± 4; both P \u3c 0.01), during EI-apnea only in OH (EI: Δ1 ± 2; P \u3c 0.01; EE: Δ1 ± 2; P = NS), and neither apnea in CAD (EI: Δ -2 ± 2; EE: Δ -1 ± 2; both P = NS). In all groups, the AP cluster size-latency profile was shifted downwards for every corresponding cluster during EI- and EE-apnea (all P \u3c 0.01). As such, inherent dysregulation exists within the central features of apnea-related sympathetic outflow in aging and CAD

Acute changes in forearm vascular compliance during transient sympatho-excitation

The study of vascular regulation often omits important information about the elastic properties of arteries under conditions of pulsatile flow. The purpose of this study was to examine the relationship between muscle sympathetic nerve activity (MSNA), vascular bed compliance, and peripheral blood flow responses in humans. We hypothesized that increases in MSNA would correlate with reductions in vascular compliance, and that changes in compliance would correspond with changes in peripheral blood flow during sympatho-excitation. MSNA (microneurography), blood pressure (Finopres), and brachial artery blood flow (Doppler ultrasound), were monitored in six healthy males at baseline and during the last 15 s of voluntary end-inspiratory, expiratory apneas and 5 min of static handgrip exercise (SHG; 20% maximum voluntary contraction) and 3 min of post-exercise circulatory occlusion (SHG + PECO; measured in the non-exercising arm). A lumped Windkessel model was employed to examine vascular bed compliance. During apnea, indices of MSNA were inversely related with vascular compliance, and reductions in compliance correlated with decreased brachial blood flow rate. During SHG, despite increased MSNA, compliance also increased, but was unrelated to increases in blood flow. Neither during SHG nor PECO did indices of MSNA correlate with forearm vascular compliance nor did vascular compliance correlate with brachial flow. However, during PECO, a linear combination of blood pressure and total MSNA was correlated with vascular compliance. These data indicate the elastic components of the forearm vasculature are regulated by adrenergic and myogenic mechanisms during sympatho-excitation, but in a reflex-dependent manner

Effects of acute and chronic interval sprint exercise performed on a manually propelled treadmill on upper limb vascular mechanics in healthy young men

© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society. Interval sprint exercise performed on a manually propelled treadmill, where the hands grip the handle bars, engages lower and upper limb skeletal muscle, but little is known regarding the effects of this exercise modality on the upper limb vasculature. We tested the hypotheses that an acute bout of sprint exercise and 6 weeks of training induces brachial artery (BA) and forearm vascular remodeling, favoring a more compliant system. Before and following a single bout of exercise as well as 6 weeks of training three types of vascular properties/methodologies were examined in healthy men: (1) stiffness of the entire upper limb vascular system (pulse wave velocity (PWV); (2) local stiffness of the BA; and (3) properties of the entire forearm vascular bed (determined by a modified lumped parameter Windkessel model). Following sprint exercise, PWV declined (P \u3c 0.01), indices of BA stiffness did not change (P ≥ 0.10), and forearm vascular bed compliance increased and inertance and viscoelasticity decreased (P ≤ 0.03). Following manually propelled treadmill training, PWV remained unchanged (P = 0.31), indices of BA stiffness increased (P ≤ 0.05) and forearm vascular bed viscoelasticity declined (P = 0.02), but resistance, compliance, and inertance remained unchanged (P ≥ 0.10) compared with pretraining values. Sprint exercise induced a more compliant forearm vascular bed, without altering indices of BA stiffness. These effects were transient, as following training the forearm vascular bed was not more compliant and indices of BA stiffness increased. On the basis of these data, we conclude that adaptations to acute and chronic sprint exercise on a manually propelled treadmill are not uniform along the arterial tree in upper limb

Determining sources of reactive mercury compounds in Reno, Nevada, United States

There is much uncertainty regarding the sources of reactive mercury (RM) compounds and atmospheric chemistry driving their formation. This work focused on assessing the chemistry and potential sources of reactive mercury measured in Reno, Nevada, United States, using 1 year of data collected using Reactive Mercury Active System. In addition, ancillary meteorology and criteria air pollutant data, Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) analyses, and a generalized linear model were applied to better understand reactive mercury observations. During the year of sampling, a fire event impacted the sampling site, and gaseous elemental Hg and particulate-bound mercury concentrations increased, as did HgII-S compounds. Data collected on a peak above Reno showed that reactive mercury concentrations were higher at higher elevation, and compounds found in Reno were the same as those measured on the peak. HYSPLIT results demonstrated RM compounds were generated inside and outside of the basin housing Reno. Compounds were sourced from San Francisco, Sacramento, and Reno in the fall and winter, and from long-range transport and the marine boundary layer during the spring and summer. The generalized linear model produced correlations that could be explained; however, when applying the model to similar data collected at two other locations, the Reno model did not predict the observations, suggesting that sampling location chemistry and concentration cannot be generalized

Pharmacological assessment of the contribution of the arterial baroreflex to sympathetic discharge patterns in healthy humans

To study how changes in baroreceptor afferent activity affect patterns of sympathetic neural activation, we manipulated arterial blood pressure with intravenous nitroprusside (NTP) and phenylephrine (PE) and measured action potential (AP) patterns with wavelet-based methodology. We hypothesized that 1) baroreflex unloading (NTP) would increase firing of low-threshold axons and recruitment of latent axons and 2) baroreflex loading (PE) would decrease firing of low-threshold axons. Heart rate (HR, ECG), arterial blood pressure (BP, brachial catheter), and muscle sympathetic nerve activity (MSNA, microneurography of peroneal nerve) were measured at baseline and during steady-state systemic, intravenous NTP (0.5-1.2 µg·kg -1 ·min -1 , n = 13) or PE (0.2-1.0 µg·kg -1 ·min -1 , n = 9) infusion. BP decreased and HR and integrated MSNA increased with NTP (P \u3c 0.01). AP incidence (326 ± 66 to 579 ± 129 APs/100 heartbeats) and AP content per integrated burst (8 ± 1 to 11 ± 2 APs/burst) increased with NTP (P \u3c 0.05). The firing probability of low-threshold axons increased with NTP, and recruitment of high-threshold axons was observed (22 ± 3 to 24 ± 3 max cluster number, 9 ± 1 to 11 ± 1 clusters/burst; P \u3c 0.05). BP increased and HR and integrated MSNA decreased with PE (P \u3c 0.05). PE decreased AP incidence (406 ± 128 to 166 ± 42 APs/100 heartbeats) and resulted in fewer unique clusters (15 ± 2 to 9 ± 1 max cluster number, P \u3c 0.05); components of an integrated burst (APs or clusters per burst) were not altered (P \u3e 0.05). These data support a hierarchical pattern of sympathetic neural activation during manipulation of baroreceptor afferent activity, with rate coding of active neurons playing the predominant role and recruitment/derecruitment of higher-threshold units occurring with steady-state hypotensive stress. NEW & NOTEWORTHY To study how changes in baroreceptor afferent activity affect patterns of sympathetic neural activation, we manipulated arterial blood pressure with intravenous nitroprusside and phenylephrine and measured sympathetic outflow with wavelet-based methodology. Baroreflex unloading increased sympathetic activity by increasing firing probability of low-threshold axons (rate coding) and recruiting new populations of high-threshold axons. Baroreflex loading decreased sympathetic activity by decreasing the firing probability of larger axons (derecruitment); however, the components of an integrated burst were unaffected

High intensity aerobic exercise training improves deficits of cardiovascular autonomic function in a rat model of type 1 diabetes mellitus with moderate hyperglycemia

© 2016 Kenneth N. Grisé et al. Indices of cardiovascular autonomic neuropathy (CAN) in experimental models of Type 1 diabetes mellitus (T1DM) are often contrary to clinical data. Here, we investigated whether a relatable insulin-treated model of T1DM would induce deficits in cardiovascular (CV) autonomic function more reflective of clinical results and if exercise training could prevent those deficits. Sixty-four rats were divided into four groups: sedentary control (C), sedentary T1DM (D), control exercise (CX), or T1DM exercise (DX). Diabetes was induced via multiple low-dose injections of streptozotocin and blood glucose was maintained at moderate hyperglycemia (9-17 mM) through insulin supplementation. Exercise training consisted of daily treadmill running for 10 weeks. Compared to C, D had blunted baroreflex sensitivity, increased vascular sympathetic tone, increased serum neuropeptide Y (NPY), and decreased intrinsic heart rate. In contrast, DX differed from D in all measures of CAN (except NPY), including heart rate variability. These findings demonstrate that this T1DM model elicits deficits and exercise-mediated improvements to CV autonomic function which are reflective of clinical T1DM

Pan-Antarctic analysis aggregating spatial estimates of Adélie penguin abundance reveals robust dynamics despite stochastic noise

© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nature Communications 8 (2017): 832, doi:10.1038/s41467-017-00890-0.Colonially-breeding seabirds have long served as indicator species for the health of the oceans on which they depend. Abundance and breeding data are repeatedly collected at fixed study sites in the hopes that changes in abundance and productivity may be useful for adaptive management of marine resources, but their suitability for this purpose is often unknown. To address this, we fit a Bayesian population dynamics model that includes process and observation error to all known Adélie penguin abundance data (1982–2015) in the Antarctic, covering >95% of their population globally. We find that process error exceeds observation error in this system, and that continent-wide “year effects” strongly influence population growth rates. Our findings have important implications for the use of Adélie penguins in Southern Ocean feedback management, and suggest that aggregating abundance across space provides the fastest reliable signal of true population change for species whose dynamics are driven by stochastic processes.H.J.L., C.C.-C., G.H., C.Y., and K.T.S. gratefully acknowledge funding provided by US National Aeronautics and Space Administration Award No. NNX14AC32G and U.S. National Science Foundation Office of Polar Programs Award No. NSF/OPP-1255058. S.J., L.L., M.M.H., Y.L., and R.J. gratefully acknowledge funding provided by US National Aeronautics and Space Administration Award No. NNX14AH74G. H.J.L., C.Y., S.J., Y.L., and R.J. gratefully acknowledge funding provided by U.S. National Science Foundation Office of Polar Programs Award No. NSF/PLR-1341548. S.J. gratefully acknowledges support from the Dalio Explore Fund

Developing population models with data from marked individuals

Population viability analysis (PVA) is a powerful tool for biodiversity assessments, but its use has been limited because of the requirements for fully specified population models such as demographic structure, densitydependence, environmental stochasticity, and specification of uncertainties. Developing a fully specified population model from commonly available data sources -notably, mark-recapture studies -remains complicated due to lack of practical methods for estimating fecundity, true survival (as opposed to apparent survival), natural temporal variability in both survival and fecundity, density-dependence in the demographic parameters, and uncertainty in model parameters. We present a general method that estimates all the key parameters required to specify a stochastic, matrix-based population model, constructed using a long-term mark-recapture dataset. Unlike standard mark-recapture analyses, our approach provides estimates of true survival rates and fecundities, their respective natural temporal variabilities, and density-dependence functions, making it possible to construct a population model for long-term projection of population dynamics. Furthermore, our method includes a formal quantification of parameter uncertainty for global (multivariate) sensitivity analysis. We apply this approach to 9 bird species and demonstrate the feasibility of using data from the Monitoring Avian Productivity and Survivorship (MAPS) program. Bias-correction factors for raw estimates of survival and fecundity derived from markrecapture data (apparent survival and juvenile:adult ratio, respectively) were non-negligible, and corrected parameters were generally more biologically reasonable than their uncorrected counterparts. Our method allows the development of fully specified stochastic population models using a single, widely available data source, substantially reducing the barriers that have until now limited the widespread application of PVA. This method is expected to greatly enhance our understanding of the processes underlying population dynamics and our ability to analyze viability and project trends for species of conservation concern