Sympathetic neural activation: An ordered affair

Is there an ordered pattern in the recruitment of postganglionic sympathetic neurones? Using new multi-unit action potential detection and analysis techniques we sought to determine whether the activation of sympathetic vasomotor neurones during stress is governed by the size principle of recruitment. Multi-unit postganglionic sympathetic activity (fibular nerve) was collected from five male subjects at rest and during periods of elevated sympathetic stress (end-inspiratory apnoeas; 178 ± 37 s(mean ± S.D.)). Compared to baseline (0.24 ± 0.04 V), periods of elevated stress resulted in augmented sympathetic burst size (1.34 ± 0.38 V, P \u3c 0.05). Increased burst size was directly related to both the number of action potentials within a multi-unit burst of postganglionic sympathetic activity (r= 0.88 ± 0.04, P \u3c 0.001 in all subjects), and the amplitude of detected action potentials (r= 0.88 ± 0.06, P \u3c 0.001 in all subjects). The recruitment of larger, otherwise silent, neurons accounted for approximately 74% of the increase in detected action potentials across burst sizes. Further, action potential conduction velocities (inverse of latencies) were increased as a function of action potential size (R2= 0.936, P= 0.001). As axon diameter is positively correlated with action potential size and conduction velocity, these data suggest that the principle of ordered recruitment based on neuronal size applies to postganglionic sympathetic vasomotor neurones. This information may be pertinent to our understanding of reflex-specific recruitment strategies in postganglionic sympathetic nerves, patterns of vasomotor control during stress, and the malleability of sympathetic neuronal properties and recruitment in health and disease.The sympathetic nervous system is an important controller of blood pressure and blood flow to critical tissues and organs. In other neural systems (e.g. the skeletal motor system) there is a well understood pattern of neural recruitment during activation. Alternatively, our understanding of how sympathetic neurones are coordinated during stress is limited. We demonstrate that during stress otherwise silent sympathetic neurones are activated in an order based on neuronal size (from smallest to largest). This recruitment pattern is similar to what is known in other neural systems. This information has important implications for how blood pressure and blood flow are controlled, and the malleability of sympathetic activation in health and disease. © 2010 The Authors. Journal compilation © 2010 The Physiological Society

The Effect of Different Training Loads on the Lung Health of Competitive Youth Swimmers

International Journal of Exercise Science 11(6): 999-1018, 2018. Airway hyperresponsiveness (AHR), airway inflammation, and respiratory symptoms are common in competitive swimmers, however it is unclear how volume and intensity of training exacerbate these problems. Thus, our purpose was to measure AHR, inflammation, and respiratory symptoms after low, moderate, and high training loads in swimmers. Competitive youth swimmers (n=8) completed nine weeks of training split into three blocks (Low, Moderate, and High intensity). Spirometry at rest and post-bronchial provocation [Eucapnic Voluntary Hyperpnea (EVH)] and Fractional Exhaled Nitric Oxide (FeNO) were completed at the end of each training block. A weekly self-report questionnaire determined respiratory symptoms. Session Rating of Perceived Exertion (sRPE) quantified internal training loads. Internal load was significantly lower after Moderate training (4840 ± 971 AU) than after High training (5852 ± 737 AU) (p= 0.02, d= 1.17). Pre-EVH FEV1was significantly decreased after Moderate (4.52 ± 0.69 L) compared to Low (4.74 ± 0.63 L) (p= 0.025, d= 0.326), but not different from High load. Post-EVH FeNO after Moderate training was significantly decreased (9.4 ± 4.9 ppb) compared to Low training (15.4 ± 3.6 ppb) (p= 0.012, r= 0.884).Respiratory symptom frequency was significantly correlated with percent decrease in FEV120 minutes post-EVH after Low and Moderate loads (both ρ= -0.71, sig = 0.05), and after High load was significantly correlated with percent decrease in FEV1at 10 (ρ= -0.74, sig = 0.03), 15 (ρ= -0.91, sig = 0.00), and 20 minutes post (ρ= -0.75, sig = 0.03). In conclusion, Moderate load training resulted in the worst lung health results, suggesting there may be factors other than the total amount of stress within training blocks that influence lung health. Further research is needed to determine the effect of manipulating specific acute training load variables on the lung health of swimmers

The Effect of Different Training Loads on the Lung Health of Competitive Youth Swimmers

International Journal of Exercise Science 11(6): 999-1018, 2018. Airway hyperresponsiveness (AHR), airway inflammation, and respiratory symptoms are common in competitive swimmers, however it is unclear how volume and intensity of training exacerbate these problems. Thus, our purpose was to measure AHR, inflammation, and respiratory symptoms after low, moderate, and high training loads in swimmers. Competitive youth swimmers (n=8) completed nine weeks of training split into three blocks (Low, Moderate, and High intensity). Spirometry at rest and post-bronchial provocation [Eucapnic Voluntary Hyperpnea (EVH)] and Fractional Exhaled Nitric Oxide (FeNO) were completed at the end of each training block. A weekly self-report questionnaire determined respiratory symptoms. Session Rating of Perceived Exertion (sRPE) quantified internal training loads. Internal load was significantly lower after Moderate training (4840 ± 971 AU) than after High training (5852 ± 737 AU) (p= 0.02, d= 1.17). Pre-EVH FEV1was significantly decreased after Moderate (4.52 ± 0.69 L) compared to Low (4.74 ± 0.63 L) (p= 0.025, d= 0.326), but not different from High load. Post-EVH FeNO after Moderate training was significantly decreased (9.4 ± 4.9 ppb) compared to Low training (15.4 ± 3.6 ppb) (p= 0.012, r= 0.884).Respiratory symptom frequency was significantly correlated with percent decrease in FEV120 minutes post-EVH after Low and Moderate loads (both ρ= -0.71, sig = 0.05), and after High load was significantly correlated with percent decrease in FEV1at 10 (ρ= -0.74, sig = 0.03), 15 (ρ= -0.91, sig = 0.00), and 20 minutes post (ρ= -0.75, sig = 0.03). In conclusion, Moderate load training resulted in the worst lung health results, suggesting there may be factors other than the total amount of stress within training blocks that influence lung health. Further research is needed to determine the effect of manipulating specific acute training load variables on the lung health of swimmers

A sympathetic view of blood pressure control at high altitude: new insights from microneurographic studies

High altitude (HA) hypoxia is a potent activator of the sympathetic nervous system, eliciting increases in sympathetic vasomotor activity. Microneurographic evidence of HA sympathoexcitation dates back to the late 20thcentury, yet only recently have the characteristics and underpinning mechanisms been explored in detail. This review summarises recent findings and highlightstheimportance of HA sympathoexcitation for theregulation of blood pressure in lowlanders and indigenous highlanders. In addition, this review will identify gaps in our knowledge and corresponding avenues for future study

Chemoreflex Mediated Arrhythmia during Apnea at 5050m in Low but not High Altitude Natives

Peripheral chemoreflex mediated increases in both parasympathetic and sympathetic drive under chronic hypoxia may evoke bradyarrhythmias during apneic periods. We determined whether 1) voluntary apnea unmasks arrhythmia at low (344 m) and high (5,050 m) altitude, 2) high-altitude natives (Nepalese Sherpa) exhibit similar cardiovagal responses at altitude, and 3) bradyarrhythmias at altitude are partially chemoreflex mediated. Participants were grouped as Lowlanders ( n = 14; age = 27 ± 6 yr) and Nepalese Sherpa ( n = 8; age = 32 ± 11 yr). Lowlanders were assessed at 344 and 5,050 m, whereas Sherpa were assessed at 5,050 m. Heart rate (HR) and rhythm (lead II ECG) were recorded during rest and voluntary end-expiratory apnea. Peripheral chemoreflex contributions were assessed in Lowlanders ( n = 7) at altitude after 100% oxygen. Lowlanders had higher resting HR at altitude (70 ± 15 vs. 61 ± 15 beats/min; P &lt; 0.01) that was similar to Sherpa (71 ± 5 beats/min; P = 0.94). High-altitude apnea caused arrhythmias in 11 of 14 Lowlanders [junctional rhythm ( n = 4), 3° atrioventricular block ( n = 3), sinus pause ( n = 4)] not present at low altitude and larger marked bradycardia (nadir −39 ± 18 beats/min; P &lt; 0.001). Sherpa exhibited a reduced bradycardia response during apnea compared with Lowlanders ( P &lt; 0.001) and did not develop arrhythmias. Hyperoxia blunted bradycardia (nadir −10 ± 14 beats/min; P &lt; 0.001 compared with hypoxic state) and reduced arrhythmia incidence (3 of 7 Lowlanders). Degree of bradycardia was significantly related to hypoxic ventilatory response (HVR) at altitude and predictive of arrhythmias ( P &lt; 0.05). Our data demonstrate apnea-induced bradyarrhythmias in Lowlanders at altitude but not in Sherpa (potentially through cardioprotective phenotypes). The chemoreflex is an important mechanism in genesis of bradyarrhythmias, and the HVR may be predictive for identifying individual susceptibility to events at altitude. NEW &amp; NOTEWORTHY The peripheral chemoreflex increases both parasympathetic and sympathetic drive under chronic hypoxia. We found that this evoked bradyarrhythmias when combined with apneic periods in Lowlanders at altitude, which become relieved through supplemental oxygen. In contrast, high-altitude residents (Nepalese Sherpa) do not exhibit bradyarrhythmias during apnea at altitude through potential cardioprotective adaptations. The degree of bradycardia and bradyarrhythmias was related to the hypoxic ventilatory response, demonstrating that the chemoreflex plays an important role in these findings. </jats:p

Muscle sympathetic reactivity to apneic and exercise stress in high-altitude Sherpa

Lowland-dwelling populations exhibit persistent sympathetic hyperactivity at altitude that may alter vascular function. High altitude populations, such as Sherpa, exhibit greater peripheral blood flow in response to acute stress, suggesting Sherpas may exhibit lower sympathetic activity and reactivity to stress than Lowlanders. Muscle sympathetic activity (MSNA; microneurography) including frequency (bursts/min), incidence (bursts/100HB), amplitude (% of max burst), was measured at rest in Lowlanders (n=14; age=27±6yrs) at 344m and following a 8- 9 days of graded ascent to 5050m. Sherpa (age=32±11yrs) were tested at 5050m (n=8). Neurovascular reactivity (i.e., change in MSNA patterns) was measured during maximal end expiratory apnea, isometric hand-grip (IHG; 30% maximal voluntary contraction for 2 minutes) and post exercise circulatory occlusion (PECO; 3 minutes). Total normalized SNA (au/min) was calculated over 10 cardiac cycles during baseline and pre-volitional apnea breakpoint. Lowlander burst frequency (11±5 bursts/min to 30±7 bursts/min; Mean±SD; p<0.001) and burst incidence (25±13 bursts/100HB to 53±15 bursts/100HB; p<0.001) increased at 5050m. In contrast, Sherpas had lower burst frequency (23±11 bursts/min; p<0.05) and incidence (30±13 bursts/100HB; p<0.05) at 5050m. MSNA increases in Lowlanders and Sherpa during apnea at 5050m were significantly lower than Lowlanders at 344m (both P<0.05), with a possible sympathetic ceiling reached in Lowlanders at 5050m. MSNA increased similarly during the IHG/PECO in Lowlanders at 334m and 5050m altitude and Sherpa at 5050m. Sherpa demonstrate overall lower sympathetic activity and reactivity during severe stress. This may be a result of improved systemic hemodynamic function associated with evolutionary adaptations to permanent residency at altitude

Global REACH: Assessment of brady-arrhythmias in Andeans and Lowlanders during apnea at 4330m

BACKGROUND: Ascent to altitude increases the prevalence of arrhythmogenesis in low-altitude dwelling populations (Lowlanders). High altitude populations (ie. Nepalese Sherpa) may have arrhythmias resistant adaptations that prevent arrhythmogenesis at altitude, though this has not been documented in other High altitude groups, including those diagnosed with chronic mountain sickness (CMS). We investigated whether healthy (CMS-) and CMS afflicted (CMS+) Andeans exhibit cardiac arrhythmias under acute apneic stress at altitude. METHODS AND RESULTS: Electrocardiograms (lead II) were collected in CMS- (N=9), CMS+ (N=8), and Lowlanders (N= 13) following several days at 4330m (Cerro de Pasco, Peru). ECG rhythm and HR were assessed at both rest and during maximal volitional apnea (End-Expiratory [EXP]). Both CMS- and CMS+ had similar basal HR (69 ± 8 beats/min vs. 62 ± 11 beats/min), while basal HR was higher in Lowlanders (77 ± 18 beats/min; P<0.05 versus CMS+). Apnea elicited significant bradycardia (nadir -32 ± 15 beats/min; P<0.01) and the development of arrhythmias in 8/13 Lowlanders (junctional rhythm, 3° atrio-venticular block, sinus pause). HR was preserved was prior to volitional breakpoint in both CMS- (nadir -6 ± 1 beat/min) and CMS+ (1 ±12 beats/min), with 2/17 Andeans developing arrhythmias ( 1 CMS+ and 1 CMS-; both Premature Atrial Contraction) prior to breakpoint. CONCLUSIONS: Andeans showed an absence of arrhythmias and preserved HR response to volitional apnea at altitude, demonstrating that potential cardio-resistant adaptations to arrhythmogenesis exist across permanent HA populations. Acclimatized Lowlanders have further demonstrated an increased prevalence of arrhythmias at altitude

Acute intermittent hypercapnic hypoxia and sympathetic neurovascular transduction in men

Acute intermittent hypercapnic hypoxia (IH) induces long‐lasting elevations in sympathetic vasomotor outflow and blood pressure in healthy humans. It is unknown whether IH alters sympathetic neurovascular transduction (sNVT), measured as the relationship between sympathetic vasomotor outflow and either forearm vascular conductance (FVC; regional sNVT) or diastolic blood pressure (systemic sNVT). We tested the hypothesis that IH augments sNVT by exposing healthy males to 40 consecutive 1 min breathing cycles, each comprising 40 s of hypercapnic hypoxia (urn:x-wiley:00223751:media:tjp13923:tjp13923-math-0001: +4 ± 3 mmHg above baseline; urn:x-wiley:00223751:media:tjp13923:tjp13923-math-0002: 48 ± 3 mmHg) and 20 s of normoxia (n = 9), or a 40 min air‐breathing control (n = 7). Before and after the intervention, lower body negative pressure (LBNP; 3 min at –15, –30 and –45 mmHg) was applied to elicit reflex increases in muscle sympathetic nerve activity (MSNA, fibular microneurography) when clamping end‐tidal gases at baseline levels. Ventilation, arterial pressure [systolic blood pressure, diastolic blood pressure, mean arterial pressure (MAP)], brachial artery blood flow (urn:x-wiley:00223751:media:tjp13923:tjp13923-math-0003BA), FVC (urn:x-wiley:00223751:media:tjp13923:tjp13923-math-0004BA/MAP) and MSNA burst frequency were measured continuously. Following IH, but not control, ventilation [5 L min–1; 95% confidence interval (CI) = 1–9] and MAP (5 mmHg; 95% CI = 1–9) were increased, whereas FVC (–0.2 mL min–1 mmHg–1; 95% CI = –0.0 to –0.4) and mean shear rate (–21.9 s–1; 95% CI = –5.8 to –38.0; all P < 0.05) were reduced. Systemic sNVT was increased following IH (0.25 mmHg burst–1 min–1; 95% CI = 0.01–0.49; P < 0.05), whereas changes in regional forearm sNVT were similar between IH and sham. Reductions in vessel wall shear stress and, consequently, nitric oxide production may contribute to heightened systemic sNVT and provide a potential neurovascular mechanism for elevated blood pressure in obstructive sleep apnoea