Peripheral physiological mechanisms of cardiovascular stress reactivity

This thesis aimed to increase understanding of the underlying physiological sources of the substantial inter-individual variability in heart rate (HR) and blood pressure (BP) reactions to acute psychological stress. This aim was achieved using a multi-method approach that included meta-analysis, laboratory studies, and prospective secondary analysis of epidemiological data. Chapter 2 implicated beta-adrenergic sympathetic activation and parasympathetic withdrawal in the cardiovascular stress response and showed that autonomic changes vary as a function of stress task, age, and sex. Chapter 3 demonstrated that individual differences in a unique HR complexity marker accounted for a significant amount of the observed variance in HR reactivity and that this effect was independent of task performance and changes in autonomic activity and respiration. Chapter 4 revealed that individual differences in resting physiological allostatic load related to HR reactivity such that higher allostatic load indicated lower reactivity. Finally, in Chapter 5, multivariate cluster analysis of HR, systolic and diastolic BP reactivity resolved a large sample into four homogenous clusters, each displaying significantly different reactivity patterns and risk of hypertension at 5-year follow-up. The research reported in this thesis confirms already suspected physiological sources of individual difference but also reveals novel sources that deserve further inquiry

Blunted cardiac stress reactors exhibit relatively high levels of behavioural impulsivity

Blunted physiological reactions to acute psychological stress are associated with a range of adverse health and behavioural outcomes. This study examined whether extreme stress reactors differ in their behavioural impulsivity. Individuals showing blunted (N = 23) and exaggerated (N = 23) cardiovascular reactions to stress were selected by screening a healthy student population (N = 276). Behavioural impulsivity was measured via inhibitory control and motor impulsivity tasks. Blunted reactors exhibited greater impulsivity than exaggerated reactors on both stop-signal, F(1,41) = 4.99, p = 0.03, ηp2 = 0.108, and circle drawing, F(1,43) = 4.00, p = 0.05, η p 2 = 0.085, tasks. Individuals showing blunted cardiovascular stress reactions are characterized by greater impulsivity which may contribute to their increased susceptibility to outcomes such as obesity and addiction

A tale of two mechanisms: A meta-analytic approach toward understanding the autonomic basis of cardiovascular reactivity to acute psychological stress: Autonomic basis of cardiovascular reactivity

A series of meta‐analyses was undertaken to determine the contributions of sympathetic and parasympathetic activation to cardiovascular stress reactivity. A literature search yielded 186 studies of sufficient quality that measured indices of sympathetic (n = 113) and/or parasympathetic activity (n = 73). A range of psychological stressors perturbed blood pressure and heart rate. There were comparable aggregate effects for sympathetic activation, as indexed by increased plasma epinephrine and norepinephrine, and shortened pre‐ejection period and parasympathetic deactivation, as indexed by heart rate variability measures. Effect sizes varied with stress task, sex, and age. In contrast to alpha‐adrenergic blockade, beta‐blockade attenuated cardiovascular reactivity. Cardiovascular reactivity to acute psychological stress would appear to reflect both beta‐adrenergic activation and vagal withdrawal to a largely equal extent

Physical activity and sleep relate to antibody maintenance following naturalistic infection and/or vaccination in older adults

Health behaviours such as being physically active and having good quality sleep have been associated with decreased susceptibility to infection and stronger antibody responses to vaccination. Less is known about how such factors might influence the maintenance of immunity following naturalistic infection and/or prior vaccination, particularly among older adults who may have formed initial antibodies some time ago. This analysis explored antibody levels against a range of common infectious diseases in 104 older adults (60 women) aged 65+ years, and whether these relate to self-reported physical activity (PA) and sleep. PA and sleep were measured subjectively through standardized questions. Antibody levels to a range of common pathogens, including pneumococcal (Pn) and meningococcal (Men) serotypes, Haemophilus influenza type b, diphtheria, and tetanus were assayed using Multiplex technology. Higher PA at baseline related to higher antibody levels against three Pn serotypes and MenY, and higher PA at one month with higher levels against six Pn serotypes. Longer time in bed related to higher antibody levels against Pn4, and longer sleep related to higher levels against Pn19f. More difficulty staying awake in the day related to lower antibodies against Pn19a, Pn19f, MenA and MenY, and more frequent daytime napping related to lower levels against three Pn serotypes and MenY. Using clinically protective antibody thresholds as an outcome showed similar results for PA, but effects for sleep became non-significant, with the exception of time in bed. This extends beyond existing literature demonstrating associations between PA and sleep and peak antibody response to vaccination to antibody maintenance. Longitudinal research with objective measures of health behaviours is warranted

Cardiovascular reactivity patterns and pathways to hypertension: a multivariate cluster analysis

Substantial evidence links exaggerated mental stress induced blood pressure reactivity to future hypertension, but the results for heart rate reactivity are less clear. For this reason multivariate cluster analysis was carried out to examine the relationship between heart rate and blood pressure reactivity patterns and hypertension in a large prospective cohort (age range 55–60 years). Four clusters emerged with statistically different systolic and diastolic blood pressure and heart rate reactivity patterns. Cluster 1 was characterised by a relatively exaggerated blood pressure and heart rate response while the blood pressure and heart rate responses of cluster 2 were relatively modest and in line with the sample mean. Cluster 3 was characterised by blunted cardiovascular stress reactivity across all variables and cluster 4, by an exaggerated blood pressure response and modest heart rate response. Membership to cluster 4 conferred an increased risk of hypertension at 5-year follow-up (hazard ratio=2.98 (95% CI: 1.50–5.90),

Exploring the possible mechanisms of blunted cardiac reactivity to acute psychological stress

Blunted cardiovascular reactivity to acute psychological stress has been linked to a range of adverse health and behavioral outcomes. However, the origins of blunted reactivity remain unclear. The current study aimed to explore the following possibilities: different appraisals of task stressfulness and/or difficulty, diminished task effort, or reduced physiological capacity to respond. Individuals characterized, via pre-screening, as blunted (n = 17) or exaggerated (n = 16) heart rate (HR) reactors to acute psychological stress (socially evaluative mental arithmetic) were exposed to a psychological stress, cold pressor and exercise tasks during a follow-up testing session while HR and blood pressure (BP) were measured. At follow-up, groups again mounted significantly different HR reactions to psychological stress, despite reporting similar levels of subjective stress and difficulty, and achieving similar tasks scores (measure of task effort) at both testing sessions. In response to the cold pressor and exercise blunted and exaggerated reactors displayed similar HR and BP responses. Results indicated that blunted reactors do not differ from exaggerated reactors on appraisals of task stressfulness or difficulty, or objective task effort, and do possess the physiological capacity to respond to other laboratory challenges. Other sources of blunted stress reactivity remain to be explored

Interstellar Polarization and the Position Angle Orientations of Seyfert 1 Galaxies

We comment on recent spectropolarimetric studies that compare the observed polarization position angles (PAs) of Seyfert 1 galaxies near H alpha with the observed orientations of their radio source axes on the sky. For a Seyfert galaxy in which scattering occurs mainly in an equatorial scattering region, one expects the polarization PA to be parallel to the radio axis, while in a case in which light scatters predominantly in the polar regions, the H alpha polarization PA should be perpendicular to the radio axis. In practice, these correlations are difficult to establish because a Galactic interstellar polarization contribution can introduce a significant uncertainty into the polarization PA determination, even when the magnitude of interstellar polarization is small. We show how such uncertainties may affect the analysis of PA alignments and present spectropolarimetric observations of a probe star along the line of sight to the Seyfert 1 galaxy Mrk 871 that allow us to assess the intrinsic H alpha polarization and PA of Mrk 871. These results suggest that spectropolarimetric observations of such probe stars should form an integral part of future Seyfert galaxy polarization studies.Comment: 15 pages, 3 figures, accepted by MNRAS; made small corrections to the derived ISP of Mrk 871 and other minor revisions in response to the referee's recommendation

Systematic NMR Analysis of Stable Isotope Labeled Metabolite Mixtures in Plant and Animal Systems: Coarse Grained Views of Metabolic Pathways

BACKGROUND: Metabolic phenotyping has become an important 'bird's-eye-view' technology which can be applied to higher organisms, such as model plant and animal systems in the post-genomics and proteomics era. Although genotyping technology has expanded greatly over the past decade, metabolic phenotyping has languished due to the difficulty of 'top-down' chemical analyses. Here, we describe a systematic NMR methodology for stable isotope-labeling and analysis of metabolite mixtures in plant and animal systems. METHODOLOGY/PRINCIPAL FINDINGS: The analysis method includes a stable isotope labeling technique for use in living organisms; a systematic method for simultaneously identifying a large number of metabolites by using a newly developed HSQC-based metabolite chemical shift database combined with heteronuclear multidimensional NMR spectroscopy; Principal Components Analysis; and a visualization method using a coarse-grained overview of the metabolic system. The database contains more than 1000 (1)H and (13)C chemical shifts corresponding to 142 metabolites measured under identical physicochemical conditions. Using the stable isotope labeling technique in Arabidopsis T87 cultured cells and Bombyx mori, we systematically detected >450 HSQC peaks in each (13)C-HSQC spectrum derived from model plant, Arabidopsis T87 cultured cells and the invertebrate animal model Bombyx mori. Furthermore, for the first time, efficient (13)C labeling has allowed reliable signal assignment using analytical separation techniques such as 3D HCCH-COSY spectra in higher organism extracts. CONCLUSIONS/SIGNIFICANCE: Overall physiological changes could be detected and categorized in relation to a critical developmental phase change in B. mori by coarse-grained representations in which the organization of metabolic pathways related to a specific developmental phase was visualized on the basis of constituent changes of 56 identified metabolites. Based on the observed intensities of (13)C atoms of given metabolites on development-dependent changes in the 56 identified (13)C-HSQC signals, we have determined the changes in metabolic networks that are associated with energy and nitrogen metabolism

Do guidelines influence breathlessness management in advanced lung diseases? A multinational survey of respiratory medicine and palliative care physicians

Background Respiratory medicine (RM) and palliative care (PC) physicians’ management of chronic breathlessness in advanced chronic obstructive pulmonary disease (COPD), fibrotic interstitial lung disease (fILD) and lung cancer (LC), and the influence of practice guidelines was explored via an online survey. Methods A voluntary, online survey was distributed to RM and PC physicians via society newsletter mailing lists. Results 450 evaluable questionnaires (348 (77%) RM and 102 (23%) PC) were analysed. Significantly more PC physicians indicated routine use (often/always) of opioids across conditions (COPD: 92% vs. 39%, fILD: 83% vs. 36%, LC: 95% vs. 76%; all p < 0.001) and significantly more PC physicians indicated routine use of benzodiazepines for COPD (33% vs. 10%) and fILD (25% vs. 12%) (both p < 0.001). Significantly more RM physicians reported routine use of a breathlessness score (62% vs. 13%, p < 0.001) and prioritised exercise training/rehabilitation for COPD (49% vs. 7%) and fILD (30% vs. 18%) (both p < 0.001). Overall, 40% of all respondents reported reading non-cancer palliative care guidelines (either carefully or looked at them briefly). Respondents who reported reading these guidelines were more likely to: routinely use a breathlessness score (χ2 = 13.8; p < 0.001), use opioids (χ2 = 12.58, p < 0.001) and refer to pulmonary rehabilitation (χ2 = 6.41, p = 0.011) in COPD; use antidepressants (χ2 = 6.25; p = 0.044) and refer to PC (χ2 = 5.83; p = 0.016) in fILD; and use a handheld fan in COPD (χ2 = 8.75, p = 0.003), fILD (χ2 = 4.85, p = 0.028) and LC (χ2 = 5.63; p = 0.018). Conclusions These findings suggest a need for improved dissemination and uptake of jointly developed breathlessness management guidelines in order to encourage appropriate use of existing, evidence-based therapies. The lack of opioid use by RM, and continued benzodiazepine use in PC, suggest that a wider range of acceptable therapies need to be developed and trialled