Pulsatile blood flow is generally mediated by the compliance of blood vessels whereby they distend locally and momentarily to accommodate the passage of the pressure wave. This freedom of the blood vessels to exercise their compliance may be suppressed within the confines of the rigid skull. The effect of this on the mechanics of pulsatile blood flow within the cerebral circulation is not known, and the situation is compounded by experimental access difficulties. We present an approach which we have developed to overcome these difficulties in a study of the mechanics of pulsatile cerebral blood flow. The main finding is that while the innate compliance of cerebral vessels is indeed suppressed within the confines of the skull, this is compensated somewhat by compliance provided by other “extravascular” elements within the skull. The net result is what we have termed “intracranial compliance,” which we argue is more pertinent to the mechanics of pulsatile cerebral blood flow than is intracranial pressure.

Emission patterns in muscle sympathetic nerve activity stem from differently sized action potential (AP) subpopulations that express varying discharge probabilities. The mechanisms governing these firing behaviours are unclear. This study investigated the hypothesis that the arterial baroreflex exerts varying control over the different AP subpopulations. r During baseline, medium APs expressed the greatest baroreflex slopes, while small and large APs exhibited weaker slopes. On going from baseline to lower body negative pressure (LBNP; simulated orthostatic stress), baroreflex slopes for some clusters of medium APs expressed the greatest increase, while slopes for large APs also increased but to a lesser degree. A subpopulation of previously silent larger APs was recruited with LBNP but these APs expressed weak baroreflex slopes. r The arterial baroreflex heterogeneously regulates sympathetic AP subpopulations, exerting its strongest effect over medium APs. Weak baroreflex mechanisms govern the recruitment of latent larger AP subpopulations during orthostatic stress.

Historically, dynamic cerebral autoregulation has been characterized by adjustments in cerebrovascular resistance following systematic changes in blood pressure. However, with the use of Windkessel modeling approaches, this study revealed rapid and large increases in cerebrovascular compliance that preceded reductions in cerebrovascular resistance following standing-induced blood pressure reductions. Importantly, the rapid cerebrovascular compliance response contributed to preservation of systolic blood velocity during the transient hypotensive phase. These results broaden our understanding of dynamic cerebral autoregulation.

Pulse‐rhythmic bursts formed by synchronous action potential (AP) discharge characterises the firing behaviour of muscle sympathetic nerve activity (MSNA). However, complex AP discharge patterns related to multiple sites of control warrant an investigation of synchronicity in the human sympathetic system. Therefore, this study quantified the synchronicity of muscle sympathetic AP discharge in eight healthy individuals (4 females, 23 – 31 years, 170 ± 7 cm, 69 ± 13 kg, 60 ± 7 bpm, 89 ± 6 mmHg). MSNA (microneurography) was measured during baseline (BSL), −10 mmHg lower body negative pressure (LBNP), −40 mmHg LBNP, and an end‐expiratory apnea (APN; 30 ± 7 s). MSNA APs were detected from the filtered raw signal using a wavelet deconstruction approach and binned in clusters based on peak‐to‐peak amplitude (normalized within‐participant). An AP was considered to fire synchronously: 1) if its occurrence corresponded with a burst in the integrated MSNA signal (i.e., within ± 0.4 s of the burst peak), or 2) if it was one of ≥ 2 visible APs in the filtered microneurographic signal firing within ± 0.4 s of an ECG R‐wave, after adjusting for the conduction delay. All other APs were considered to fire asynchronously. At BSL, 33 ± 12 % of total AP activity was asynchronous (99 ± 48 asynchronous APs/100beats) and a pattern emerged whereby the probability of asynchronous AP firing decreased logarithmically (R2 = 0.80, P < 0.01) as AP cluster size increased. Compared to BSL (20 ± 6 bursts/min, 42 ± 7 AU), MSNA burst frequency increased on going to −10 mmHg LBNP (24 ± 6 bursts/min), −40 mmHg LBNP (35 ± 8 bursts/min), and APN (35 ± 9 bursts/min), while burst amplitude increased only with −40 mmHg LBNP (57 ± 8 AU) and APN (64 ± 14 AU) (both repeated measures analysis of variance [RM ANOVA]: P < 0.05, all Ppost‐hoc < 0.05). Compared with BSL, within‐burst AP discharge increased across all conditions (BSL: 144 ± 69 AP/min, 7 ± 2 AP/burst; −10 mmHg LBNP: 211 ± 87 AP/min, 8 ± 3 AP/burst; −40 mmHg LBNP: 410 ± 207 AP/min, 11 ± 4 AP/burst; APN: 397 ± 160 AP/min, 11 ± 3 AP/burst) (both RM ANOVA: P < 0.05, all Ppost‐hoc < 0.05). Compared to BSL, increased burst amplitude with −40 mmHg LBNP and APN was attributed to an increase in the within‐burst firing of previously active APs (BSL: 4 ± 1 clusters/burst, −40 mmHg LBNP: 5 ± 2 clusters/burst, APN: 5 ± 1 clusters/burst; RM ANOVA: P < 0.05, both Ppost‐hoc < 0.05) more so than the recruitment of new AP clusters (BSL: 14 ± 4 total clusters; −40 mmHg LBNP: 18 ± 7 total clusters; APN: 16 ± 6 total clusters; RM ANOVA: P > 0.05). However, compared to BSL (33 ± 12 %), the probability of asynchronous AP firing was reduced with −10 mmHg LBNP (26 ± 10 %), −40 mmHg LBNP (16 ± 7 %), and APN (14 ± 7 %; RM ANOVA: P < 0.05, all Ppost‐hoc < 0.05). The probability of asynchronous AP discharge was inversely and linearly related to burst frequency (β = −0.98, r2 = 0.67) and amplitude (β = −0.41, r2 = 0.20; both P < 0.01). This study suggests that: 1) integrated bursts of MSNA formed by synchronous AP firing are not separated by ‘neural silence’ but rather, by asynchronous AP discharge, and 2) smaller sympathetic APs are more likely to exhibit asynchronous discharge.Support or Funding InformationThis work was funded by a Natural Sciences and Engineering Research Council of Canada Discovery Grant.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Pulse‐rhythmic bursts formed by synchronous action potential (AP) discharge characterises the firing behaviour of muscle sympathetic nerve activity (MSNA). However, complex AP discharge patterns related to multiple sites of control warrant an investigation of synchronicity in the human sympathetic system. Therefore, this study quantified the synchronicity of muscle sympathetic AP discharge in eight healthy individuals (4 females, 23 – 31 years, 170 ± 7 cm, 69 ± 13 kg, 60 ± 7 bpm, 89 ± 6 mmHg). MSNA (microneurography) was measured during baseline (BSL), −10 mmHg lower body negative pressure (LBNP), −40 mmHg LBNP, and an end‐expiratory apnea (APN; 30 ± 7 s). MSNA APs were detected from the filtered raw signal using a wavelet deconstruction approach and binned in clusters based on peak‐to‐peak amplitude (normalized within‐participant). An AP was considered to fire synchronously: 1) if its occurrence corresponded with a burst in the integrated MSNA signal (i.e., within ± 0.4 s of the burst peak), or 2) if it was one of ≥ 2 visible APs in the filtered microneurographic signal firing within ± 0.4 s of an ECG R‐wave, after adjusting for the conduction delay. All other APs were considered to fire asynchronously. At BSL, 33 ± 12 % of total AP activity was asynchronous (99 ± 48 asynchronous APs/100beats) and a pattern emerged whereby the probability of asynchronous AP firing decreased logarithmically (R2 = 0.80, P < 0.01) as AP cluster size increased. Compared to BSL (20 ± 6 bursts/min, 42 ± 7 AU), MSNA burst frequency increased on going to −10 mmHg LBNP (24 ± 6 bursts/min), −40 mmHg LBNP (35 ± 8 bursts/min), and APN (35 ± 9 bursts/min), while burst amplitude increased only with −40 mmHg LBNP (57 ± 8 AU) and APN (64 ± 14 AU) (both repeated measures analysis of variance [RM ANOVA]: P < 0.05, all Ppost‐hoc < 0.05). Compared with BSL, within‐burst AP discharge increased across all conditions (BSL: 144 ± 69 AP/min, 7 ± 2 AP/burst; −10 mmHg LBNP: 211 ± 87 AP/min, 8 ± 3 AP/burst; −40 mmHg LBNP: 410 ± 207 AP/min, 11 ± 4 AP/burst; APN: 397 ± 160 AP/min, 11 ± 3 AP/burst) (both RM ANOVA: P < 0.05, all Ppost‐hoc < 0.05). Compared to BSL, increased burst amplitude with −40 mmHg LBNP and APN was attributed to an increase in the within‐burst firing of previously active APs (BSL: 4 ± 1 clusters/burst, −40 mmHg LBNP: 5 ± 2 clusters/burst, APN: 5 ± 1 clusters/burst; RM ANOVA: P < 0.05, both Ppost‐hoc < 0.05) more so than the recruitment of new AP clusters (BSL: 14 ± 4 total clusters; −40 mmHg LBNP: 18 ± 7 total clusters; APN: 16 ± 6 total clusters; RM ANOVA: P > 0.05). However, compared to BSL (33 ± 12 %), the probability of asynchronous AP firing was reduced with −10 mmHg LBNP (26 ± 10 %), −40 mmHg LBNP (16 ± 7 %), and APN (14 ± 7 %; RM ANOVA: P < 0.05, all Ppost‐hoc < 0.05). The probability of asynchronous AP discharge was inversely and linearly related to burst frequency (β = −0.98, r2 = 0.67) and amplitude (β = −0.41, r2 = 0.20; both P < 0.01). This study suggests that: 1) integrated bursts of MSNA formed by synchronous AP firing are n...

Objective: To study autonomic responses to postural changes in concussed adolescents. The influence of sex was also studied. Design: Longitudinal cohort observational study. Participants: Concussed adolescents (CONC; n = 65; 26 male adolescents; age 15 ± 1 years, range = 12-18 years) and a control (CTRL) group of nonconcussed adolescents of similar age and sport (CTRL; n = 54; 29 male adolescents; age 14 ± 1 years, range = 12-18 years). Interventions: Concussed participants were monitored through 6 weekly visits throughout usual physician care. Control participants underwent 2 visits separated by at least 1 week to account for intrapersonal variation in testing measures. Main Outcome Measures: Heart rate variability as the root mean square of successive differences in R–R intervals (RMSSD), heart rate (HR), and blood pressure [mean arterial pressure (MAP) and diastolic blood pressure (DBP)] were measured in supine, sitting, and standing postures. Results: A mixed analysis of variance revealed a group × sex × posture interaction ( P = 0.04) where seated values of RMSSD were less in concussed female participants versus control female participants (42 ± 4 vs 61 ± 7 ms; P = 0.01; Mann–Whitney rank test). Compared with CTRL, CONC exhibited increased pretesting seated DBP (69 ± 1 vs 74 ± 1 mm Hg; P < 0.01), MAP (83 ± 1 vs 86 ± 1 mm Hg; P = 0.02), and baseline seated HR (72 ± 1 vs 77 ± 2 bpm; P = 0.03). Values of DBP ( P = 0.03) and MAP ( P < 0.01) improved at clinical discharge, whereas the RMSSD in female participants did not ( P > 0.5). Data are mean ± SEM. Conclusions: A modest reduction in female cardiac autonomic regulation was observed during seated postures. Alterations in seated concussed DBP and MAP, but not RMSSD, resolved at clinical discharge (median = 37 days). The results indicate that, in adolescents, concussion may impair cardiovagal function in a sex- and posture-dependent manner. The findings also suggest that BP metrics, but not RMSSD, are associated with clinical concussion recovery.

The IHG test could aid concussion diagnosis and support return-to-play decisions.

Breath-hold divers (BHD) experience repeated bouts of severe hypoxia and hypercapnia with large increases in blood pressure. However, the impact of long-term breath-hold diving on cerebrovascular control remains poorly understood. The ability of cerebral blood vessels to respond rapidly to changes in blood pressure represents the property of dynamic autoregulation. The current investigation tested the hypothesis that breath-hold diving impairs dynamic autoregulation to a transient hypotensive stimulus. Seventeen BHD (3 women, 11 ± 9 yr of diving) and 15 healthy controls (2 women) completed two or three repeated sit-to-stand trials during spontaneous breathing and poikilocapnic conditions. Heart rate (HR), finger arterial blood pressure (BP), and cerebral blood flow velocity (BFV) from the right middle cerebral artery were measured continuously with three-lead electrocardiography, finger photoplethysmography, and transcranial Doppler ultrasonography, respectively. End-tidal carbon dioxide partial pressure was measured with a gas analyzer. Offline, an index of cerebrovascular resistance (CVRi) was calculated as the quotient of mean BP and BFV. The rate of the drop in CVRi relative to the change in BP provided the rate of regulation [RoR; (∆CVRi/∆T)/∆BP]. The BHD demonstrated slower RoR than controls ( P ≤ 0.001, d = 1.4). Underlying the reduced RoR in BHD was a longer time to reach nadir CVRi compared with controls ( P = 0.004, d = 1.1). In concert with the longer CVRi response, the time to reach peak BFV following standing was longer in BHD than controls ( P = 0.01, d = 0.9). The data suggest impaired dynamic autoregulatory mechanisms to hypotension in BHD. NEW & NOTEWORTHY Impairments in dynamic cerebral autoregulation to hypotension are associated with breath-hold diving. Although weakened autoregulation was observed acutely in this group during apneic stress, we are the first to report on chronic adaptations in cerebral autoregulation. Impaired vasomotor responses underlie the reduced rate of regulation, wherein breath-hold divers demonstrate a prolonged dilatory response to transient hypotension. The slower cerebral vasodilation produces a longer perturbation in cerebral blood flow velocity, increasing the risk of cerebral ischemia.