Effects of Gender and Hypovolemia on Sympathetic Neural Responses to Orthostatic Stress

We tested the hypothesis that women have blunted sympathetic neural responses to orthostatic stress compared with men, which may be elicited under hypovolemic conditions. Muscle sympathetic nerve activity (MSNA) and hemodynamics were measured in eight healthy young women and seven men in supine position and during 6 min of 60° head-up tilt (HUT) under normovolemic and hypovolemic conditions (randomly), with ∼4-wk interval. Acute hypovolemia was produced by diuretic (furosemide) administration ∼2 h before testing. Orthostatic tolerance was determined by progressive lower body negative pressure to presyncope. We found that furosemide produced an ∼13% reduction in plasma volume, causing a similar increase in supine MSNA in men and women (mean ± SD of 5 ± 7 vs. 6 ± 5 bursts/min; P = 0.895). MSNA increased during HUT and was greater in the hypovolemic than in the normovolemic condition (32 ± 6 bursts/min in normovolemia vs. 44 ± 15 bursts/min in hypovolemia in men, P = 0.055; 35 ± 9 vs. 45 ± 8 bursts/min in women, P \u3c 0.001); these responses were not different between the genders (gender effect: P = 0.832 and 0.814 in normovolemia and hypovolemia, respectively). Total peripheral resistance increased proportionately with increases in MSNA during HUT; these responses were similar between the genders. However, systolic blood pressure was lower, whereas diastolic blood pressure was similar in women compared with men during HUT, which was associated with a smaller stroke volume or stroke index. Orthostatic tolerance was lower in women, especially under hypovolemic conditions. These results indicate that men and women have comparable sympathetic neural responses during orthostatic stress under normovolemic and hypovolemic conditions. The lower orthostatic tolerance in women is predominantly because of a smaller stroke volume, presumably due to less cardiac filling during orthostasis, especially under hypovolemic conditions, which may overwhelm the vasomotor reserve available for vasoconstriction or precipitate neurally mediated sympathetic withdrawal and syncope

Debate:Challenges in sports cardiology; US versus European approaches

For practitioners working with elite athletes, the field of sports cardiology provides clinical, academic, administrative and fiscal challenges. These challenges are exemplified and reinforced by the lack of consistency and consensus both in the literature and academic presentations. Through thepresentation of a series of clinical questions, this debate attempts to ‘cut to the chase’ on cardiovascular issues relevant to the clinician dealing with elite athletes. In so doing, we hope to crystallize some of the most important elements of the complex cardiological management of elite athletes, in a concise, readable format. Frequently over the last 10 years, many of the controversies in this field have been (rightly or wrongly) presented in aEurope versus USA paradigm. We have chosen to test whether there really are polarised views across the Atlantic, by deliberately pitting specialists from the USA against those from the UK. Professors Levine and Thompson are both internationally recognised sports cardiologists, with immense academic and clinical credibility, and who will represent the ‘US approach’. Professor Whyte and Doctor Wilson are cardiac physiologists with a wealth of experience in the testing, evaluation and screening of elite athletes, and who have equally impressive academic credibility and for the purposes of this debate, they will be representing the ‘European approach’. To initiate this process, each team was required to provide a concise answer (circa 200–300 words) to a series of fiveclinical conundrums. Subsequently, each team had the opportunity to provide a rebuttal to the opposing team’s answers, and the following reflects the consolidation of those answers

IL-36α Exerts Pro-Inflammatory Effects in the Lungs of Mice

Interleukin (IL-) 36 cytokines (previously designated as novel IL-1 family member cytokines; IL-1F5– IL-1F10) constitute a novel cluster of cytokines structurally and functionally similar to members of the IL-1 cytokine cluster. The effects of IL-36 cytokines in inflammatory lung disorders remains poorly understood. The current study sought to investigate the effects of IL-36α (IL-1F6) and test the hypothesis that IL-36α acts as a pro-inflammatory cytokine in the lung in vivo. Intratracheal instillation of recombinant mouse IL-36α induced neutrophil influx in the lungs of wild-type C57BL/6 mice and IL-1αβ−/− mice in vivo. IL-36α induced neutrophil influx was also associated with increased mRNA expression of neutrophil-specific chemokines CXCL1 and CXCL2 in the lungs of C57BL/6 and IL-1αβ−/− mice in vivo. In addition, intratracheal instillation of IL-36α enhanced mRNA expression of its receptor IL-36R in the lungs of C57BL/6 as well as IL-1αβ−/− mice in vivo. Furthermore, in vitro incubation of CD11c+ cells with IL-36α resulted in the generation of neutrophil-specific chemokines CXCL1, CXCL2 as well as TNFα. IL-36α increased the expression of the co-stimulatory molecule CD40 and enhanced the ability of CD11c+ cells to induce CD4+ T cell proliferation in vitro. Furthermore, stimulation with IL-36α activated NF-κB in a mouse macrophage cell line. These results demonstrate that IL-36α acts as a pro-inflammatory cytokine in the lung without the contribution of IL-1α and IL-1β. The current study describes the pro-inflammatory effects of IL-36α in the lung, demonstrates the functional redundancy of IL-36α with other agonist cytokines in the IL-1 and IL-36 cytokine cluster, and suggests that therapeutic targeting of IL-36 cytokines could be beneficial in inflammatory lung diseases

The ICV Study: Integrated Cardiovascular

This viewgraph presentation describes the effects of long duration manned spaceflight on heart structure and function. Clinical consequences for orthostatic tolerance, cardiac arrhythmias, and countermeasures to prevent clinical problems are also discussed

Inhibition of Nitric Oxide Inhibition of Nitric Oxide Synthase Does Not Alter Dynamic Cerebral Autoregulation in Humans

The aim of this study was to determine whether inhibition of nitric oxide synthase (NOS) alters dynamic cerebral autoregulation in humans. Beat-to-beat blood pressure (BP) and cerebral blood flow (CBF) velocity (transcranial Doppler) were measured in eight healthy subjects in the supine position and during 60° head-up tilt (HUT). NOS was inhibited by intravenous N G-monomethyl-L-arginine (L-NMMA) infusion. Dynamic cerebral autoregulation was quantified by transfer function analysis of beat-to-beat changes in BP and CBF velocity. Pressor effects of L-NMMA on cerebral hemodynamics were compared with those of phenylephrine infusion. In the supine position, L-NMMA increased mean BP from 83 ± 3 to 94 ± 3 mmHg (P \u3c 0.01). However, CBF velocity remained unchanged. Consequently, cerebrovascular resistance index (CVRI) increased by 15% (P \u3c 0.05). BP and CBF velocity variability and transfer function gain at the low frequencies of 0.07-0.20 Hz did not change with L-NMMA infusion. Similar changes in mean BP, CBF velocity, and CVRI were observed after phenylephrine infusion, suggesting that increase in CVRI after L-NMMA was mediated myogenically by increase in arterial pressure rather than a direct effect of cerebrovascular NOS inhibition. During baseline tilt without L-NMMA, steady-state BP increased and CBF velocity decreased. BP and CBF velocity variability at low frequencies increased in parallel by 277% and 217%, respectively (P \u3c 0.05). However, transfer function gain remained unchanged. During tilt with L-NMMA, changes in steady-state hemodynamics and BP and CBF velocity variability as well as transfer gain and phase were similar to those without L-NMMA. These data suggest that inhibition of tonic production of NO does not appear to alter dynamic cerebral autoregulation in humans

Nitric Oxide Synthase Inhibition Does Not Affect Regulation of Muscle Sympathetic Nerve Activity During Head-Up Tilt

To test the hypothesis that systemic inhibition of nitric oxide (NO) synthase does not alter the regulation of sympathetic outflow during head-up tilt in humans, in eight healthy subjects NO synthase was blocked by intravenous infusion of NG-monomethyl-L-arginine (L-NMMA). Blood pressure, heart rate, cardiac output, total peripheral resistance (TPR), and muscle sympathetic nerve activity (MSNA) were recorded in the supine position and during 60° head-up tilt. In the supine position, infusion of L-NMMA increased blood pressure, via increased TPR, and inhibited MSNA. However, the increase in MSNA evoked by head-up tilt during L-NMMA infusion (change in burst rate: 24 ± 4 bursts/min; change in total activity: 209 ± 36 U/min) was similar to that during head-up tilt without L-NMMA (change in burst rate: 23 ± 4 bursts/min; change in total activity: 251 ± 52 U/min, n = 6, all P \u3e 0.05). Moreover, changes in TPR and heart rate during head-up tilt were virtually identical between the two conditions. These results suggest that systemic inhibition of NO synthase with L-NMMA does not affect the regulation of sympathetic outflow and vascular resistance during head-up tilt in humans

No heartbreak at high altitude; preserved cardiac function in chronic hypoxia

High altitude hypoxia presents a series of challenges to the human heart due to concomitant changes in preload, afterload and contractility. This challenge is characterised by a decrease in blood volume due to plasma volume constriction, an increase in right ventricular afterload via hypoxic pulmonary vasoconstriction, and an increase in sympathetic nerve activity . As such, understanding how the heart adapts to this multifaceted challenge has been a topic of interest to physiologists and clinicians for decades. In the current issue of Experimental Physiology, Maufrais et al. (2019) use modern speckle tracking technology to investigate region-specific cardiac performance in chronic hypoxia

Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac Arrhythmias

Cardiac Atrophy and Diastolic Dysfunction During and After Long Duration Spaceflight: Functional Consequences for Orthostatic Intolerance, Exercise Capability and Risk for Cardiac Arrhythmias (Integrated Cardiovascular) will quantify the extent of long-duration space flightassociated cardiac atrophy (deterioration) on the International Space Station crewmembers

The core symptoms of bulimia nervosa, anxiety, and depression: A network analysis.

Bulimia nervosa (BN) is characterized by symptoms of binge eating and compensatory behavior, and overevaluation of weight and shape, which often co-occur with symptoms of anxiety and depression. However, there is little research identifying which specific BN symptoms maintain BN psychopathology and how they are associated with symptoms of depression and anxiety. Network analyses represent an emerging method in psychopathology research to examine how symptoms interact and may become self-reinforcing. In the current study of adults with a Diagnostic and Statistical Manual for Mental Disorders-Fourth Edition (DSM-IV) diagnosis of BN (N = 196), we used network analysis to identify the central symptoms of BN, as well as symptoms that may bridge the association between BN symptoms and anxiety and depression symptoms. Results showed that fear of weight gain was central to BN psychopathology, whereas binge eating, purging, and restriction were less central in the symptom network. Symptoms related to sensitivity to physical sensations (e.g., changes in appetite, feeling dizzy, and wobbly) were identified as bridge symptoms between BN, and anxiety and depressive symptoms. We discuss our findings with respect to cognitive-behavioral treatment approaches for BN. These findings suggest that treatments for BN should focus on fear of weight gain, perhaps through exposure therapies. Further, interventions focusing on exposure to physical sensations may also address BN psychopathology, as well as co-occurring anxiety and depressive symptoms. (PsycINFO Database Recor