UBC-Nepal Expedition: Acute alterations in sympathetic nervous activity do not influence brachial artery endothelial function at sea-level and high-altitude.

Evidence indicates that increases in sympathetic nervous activity (SNA), and acclimatization to high-altitude (HA), may reduce endothelial function as assessed by brachial artery flow-mediated dilatation (FMD); however, it is unclear whether such changes in FMD are due to direct vascular constraint, or consequential altered hemodynamics (e.g. shear stress) associated with increased SNA as a consequence of exposure to HA. We hypothesized that: 1) at rest, SNA would be elevated and FMD would be reduced at HA compared to sea-level (SL); and 2) at SL and HA, FMD would be reduced when SNA was acutely increased, and elevated when SNA was acutely decreased. Using a novel, randomized experimental design, brachial artery FMD was assessed at SL (344m) and HA (5050m) in 14 participants during mild lower-body negative pressure (LBNP; -10 mmHg) and lower-body positive pressure (LBPP; +10 mmHg). Blood pressure (finger photoplethysmography), heart rate (electrodcardiogram), oxygen saturation (pulse oximetry), and brachial artery blood flow and shear rate (Duplex ultrasound) were recorded during LBNP, control, and LBPP trials. Muscle SNA was recorded (via microneurography) in a subset of participants (n=5). Our findings were: 1) at rest, SNA was elevated (P<0.01), and absolute FMD was reduced (P=0.024), but relative FMD remained unaltered (P=0.061), at HA compared to SL, and 2) despite significantly altering SNA with LBNP (+60.3±25.5%) and LBPP (-37.2±12.7%) (P<0.01), FMD was unaltered at SL (P=0.448), and HA (P=0.537). These data indicate that acute and mild changes in SNA do not directly influence brachial artery FMD at SL or HA

UBC-Nepal Expedition: Acute alterations in sympathetic nervous activity do not influence brachial artery endothelial function at sea-level and high-altitude.

Evidence indicates that increases in sympathetic nervous activity (SNA), and acclimatization to high-altitude (HA), may reduce endothelial function as assessed by brachial artery flow-mediated dilatation (FMD); however, it is unclear whether such changes in FMD are due to direct vascular constraint, or consequential altered hemodynamics (e.g. shear stress) associated with increased SNA as a consequence of exposure to HA. We hypothesized that: 1) at rest, SNA would be elevated and FMD would be reduced at HA compared to sea-level (SL); and 2) at SL and HA, FMD would be reduced when SNA was acutely increased, and elevated when SNA was acutely decreased. Using a novel, randomized experimental design, brachial artery FMD was assessed at SL (344m) and HA (5050m) in 14 participants during mild lower-body negative pressure (LBNP; -10 mmHg) and lower-body positive pressure (LBPP; +10 mmHg). Blood pressure (finger photoplethysmography), heart rate (electrodcardiogram), oxygen saturation (pulse oximetry), and brachial artery blood flow and shear rate (Duplex ultrasound) were recorded during LBNP, control, and LBPP trials. Muscle SNA was recorded (via microneurography) in a subset of participants (n=5). Our findings were: 1) at rest, SNA was elevated (P<0.01), and absolute FMD was reduced (P=0.024), but relative FMD remained unaltered (P=0.061), at HA compared to SL, and 2) despite significantly altering SNA with LBNP (+60.3±25.5%) and LBPP (-37.2±12.7%) (P<0.01), FMD was unaltered at SL (P=0.448), and HA (P=0.537). These data indicate that acute and mild changes in SNA do not directly influence brachial artery FMD at SL or HA

Positive End-Expiratory Pressure may alter breathing cardiovascular variability and baroreflex gain in mechanically ventilated patients

<p>Abstract</p> <p>Background</p> <p>Baroreflex allows to reduce sudden rises or falls of arterial pressure through parallel RR interval fluctuations induced by autonomic nervous system. During spontaneous breathing, the application of positive end-expiratory pressure (PEEP) may affect the autonomic nervous system, as suggested by changes in baroreflex efficiency and RR variability. During mechanical ventilation, some patients have stable cardiorespiratory phase difference and high-frequency amplitude of RR variability (HF-RR amplitude) over time and others do not. Our first hypothesis was that a steady pattern could be associated with reduced baroreflex sensitivity and HF-RR amplitude, reflecting a blunted autonomic nervous function. Our second hypothesis was that PEEP, widely used in critical care patients, could affect their autonomic function, promoting both steady pattern and reduced baroreflex sensitivity.</p> <p>Methods</p> <p>We tested the effect of increasing PEEP from 5 to 10 cm H2O on the breathing variability of arterial pressure and RR intervals, and on the baroreflex. Invasive arterial pressure, ECG and ventilatory flow were recorded in 23 mechanically ventilated patients during 15 minutes for both PEEP levels. HF amplitude of RR and systolic blood pressure (SBP) time series and HF phase differences between RR, SBP and ventilatory signals were continuously computed by complex demodulation. Cross-spectral analysis was used to assess the coherence and gain functions between RR and SBP, yielding baroreflex-sensitivity indices.</p> <p>Results</p> <p>At PEEP 10, the 12 patients with a stable pattern had lower baroreflex gain and HF-RR amplitude of variability than the 11 other patients. Increasing PEEP was generally associated with a decreased baroreflex gain and a greater stability of HF-RR amplitude and cardiorespiratory phase difference. Four patients who exhibited a variable pattern at PEEP 5 became stable at PEEP 10. At PEEP 10, a stable pattern was associated with higher organ failure score and catecholamine dosage.</p> <p>Conclusions</p> <p>During mechanical ventilation, stable HF-RR amplitude and cardiorespiratory phase difference over time reflect a blunted autonomic nervous function which might worsen as PEEP increases.</p

Sympatho-renal axis in chronic disease

Essential hypertension, insulin resistance, heart failure, congestion, diuretic resistance, and functional renal disease are all characterized by excessive central sympathetic drive. The contribution of the kidney’s somatic afferent nerves, as an underlying cause of elevated central sympathetic drive, and the consequences of excessive efferent sympathetic signals to the kidney itself, as well as other organs, identify the renal sympathetic nerves as a uniquely logical therapeutic target for diseases linked by excessive central sympathetic drive. Clinical studies of renal denervation in patients with resistant hypertension using an endovascular radiofrequency ablation methodology have exposed the sympathetic link between these conditions. Renal denervation could be expected to simultaneously affect blood pressure, insulin resistance, sleep disorders, congestion in heart failure, cardiorenal syndrome and diuretic resistance. The striking epidemiologic evidence for coexistence of these disorders suggests common causal pathways. Chronic activation of the sympathetic nervous system has been associated with components of the metabolic syndrome, such as blood pressure elevation, obesity, dyslipidemia, and impaired fasting glucose with hyperinsulinemia. Over 50% of patients with essential hypertension are hyperinsulinemic, regardless of whether they are untreated or in a stable program of treatment. Insulin resistance is related to sympathetic drive via a bidirectional mechanism. In this manuscript, we review the data that suggests that selective impairment of renal somatic afferent and sympathetic efferent nerves in patients with resistant hypertension both reduces markers of central sympathetic drive and favorably impacts diseases linked through central sympathetics—insulin resistance, heart failure, congestion, diuretic resistance, and cardiorenal disorders

The 2018 Lake Louise Acute Mountain Sickness Score.

Roach, Robert C., Peter H. Hackett, Oswald Oelz, Peter Bärtsch, Andrew M. Luks, Martin J. MacInnis, J. Kenneth Baillie, and The Lake Louise AMS Score Consensus Committee. The 2018 Lake Louise Acute Mountain Sickness Score. High Alt Med Biol 19:1-4, 2018.- The Lake Louise Acute Mountain Sickness (AMS) scoring system has been a useful research tool since first published in 1991. Recent studies have shown that disturbed sleep at altitude, one of the five symptoms scored for AMS, is more likely due to altitude hypoxia per se, and is not closely related to AMS. To address this issue, and also to evaluate the Lake Louise AMS score in light of decades of experience, experts in high altitude research undertook to revise the score. We here present an international consensus statement resulting from online discussions and meetings at the International Society of Mountain Medicine World Congress in Bolzano, Italy, in May 2014 and at the International Hypoxia Symposium in Lake Louise, Canada, in February 2015. The consensus group has revised the score to eliminate disturbed sleep as a questionnaire item, and has updated instructions for use of the score

Acute Hyperglycemia Decreases Neurovascular Coupling Magnitude in Healthy Females and Males

Neurovascular coupling (NVC) is the link between neural activity and the corresponding changes to regional cerebral blood flow. Chronic hyperglycemia associated with diabetes has deleterious effects on vascular function. However, the potential effects of acute hyperglycemia on NVC in healthy humans is unknown. We aimed to characterize the effects of acute hyperglycemia on NVC response magnitude in females and males, and hypothesized that acute hyperglycemia would reduce NVC response magnitude. 40 healthy participants (21.6±1.7 yrs; BMI 24.1±4.1 kg/m2; 20 females) were instrumented with electrocardiogram (ECG) to measure heart rate (HR), Finometer to measure mean arterial pressure (MAP), transcranial Doppler ultrasound (TCD) for measurement of posterior cerebral artery velocity (PCAv). Blood glucose was tested using a glucometer and capillary draw via sterile lancet. NVC responses were elicited using &nbsp;a standardized strobe light visual stimulus (VS; 6Hz, 360rpm; 5x30sec on/60sec off) before (fasted) and 30-min after an acute hyperglycemic load (75g glucose, 300ml; 4.8±0.4 vs. 7.5±1.2 mg/dl; P&lt;0.0001). NVC magnitude was quantified as the difference (delta) and percent (%)-change between the mean baseline (2-min average) and the mean of five responses over the 30- sec VS. Acute hyperglycemia reduced delta NVC responses (4.8±3.9 vs. 3.3±3.4 cm/s; P=0.004) and %-change NVC responses (12.5±9.6 vs. 8.1±7.9%; P=0.002). Neither delta nor %-change NVC responses were different between women and men while fasted (P=0.98; P=0.74), nor when hyperglycemic (P=0.42; P=0.34). Our data suggest that acute hyperglycemia decreases NVC response magnitude in healthy adults equally in females and males. Funding Sources: NSERC Discovery, MRU Faculty of Science and Technology *Indicates presente