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  • 1
    Online Resource
    Online Resource
    Acute hypoxia elicits lasting reductions in the sympathetic action potential transduction of arterial blood pressure in males
    Wiley ; 2023
    In:  The Journal of Physiology Vol. 601, No. 3 ( 2023-02), p. 669-687
    Details
    In: The Journal of Physiology, Wiley, Vol. 601, No. 3 ( 2023-02), p. 669-687
    Abstract: Post‐hypoxia sympathoexcitation does not elicit corresponding changes in vascular tone, suggesting diminished sympathetic signalling. Blunted sympathetic transduction following acute hypoxia, however, has not been confirmed and the effects of hypoxia on the sympathetic transduction of mean arterial pressure (MAP) as a function of action potential (AP) activity is unknown. We hypothesized that MAP changes would be blunted during acute hypoxia but restored in recovery and asynchronous APs would elicit smaller MAP changes than synchronous APs. Seven healthy males (age: 24 (3) years; BMI: 25 (3) kg/m 2 ) underwent 20 min isocapnic hypoxia (P ET O 2 : 47 (2) mmHg) and 30 min recovery. Multi‐unit microneurography (muscle sympathetic nerve activity; MSNA) and continuous wavelet transform with matched mother wavelet was used to detect sympathetic APs during baseline, hypoxia, early (first 7 min) and late (last 7 min) recovery. AP groups were classified as synchronous APs, asynchronous APs (occurring outside an MSNA burst) and no AP activity. Sympathetic transduction of MAP was quantified using signal‐averaging, with ΔMAP tracked following AP group cardiac cycles. Following synchronous APs, ΔMAP was reduced in hypoxia (+1.8 (0.9) mmHg) and early recovery (+1.5 (0.7) mmHg) compared with baseline (+3.1 (2.2) mmHg). AP group‐by‐condition interactions show that at rest asynchronous APs attenuate MAP reductions compared with no AP activity (−0.4 (1.1) vs . −2.2 (1.2) mmHg, respectively), with no difference between AP groups in hypoxia, early or late recovery. Sympathetic transduction of MAP is blunted in hypoxia and early recovery. At rest, asynchronous sympathetic APs contribute to neural regulation of MAP by attenuating nadir pressure responses. image Key points Acute isocapnic hypoxia elicits lasting sympathoexcitation that does not correspond to parallel changes in vascular tone, suggesting blunted sympathetic transduction. Signal‐averaging techniques track the magnitude and temporal cardiovascular responses following integrated muscle sympathetic nerve activity (MSNA) burst and non‐burst cardiac cycles. However, this does not fully characterize the effects of sympathetic action potential (AP) activity on blood pressure control. We show that hypoxia blunts the sympathetic transduction of mean arterial pressure (MAP) following synchronous APs that form integrated MSNA bursts and that sympathetic transduction of MAP remains attenuated into early recovery. At rest, asynchronous APs attenuate the reduction in MAP compared with cardiac cycles following no AP activity, thus asynchronous sympathetic APs appear to contribute to the neural regulation of blood pressure. The results advance our understanding of sympathetic transduction of arterial pressure during and following exposure to acute isocapnic hypoxia in humans.
    Type of Medium: Online Resource
    ISSN: 0022-3751 , 1469-7793
    URL: Issue
    URL: Article
    DOI: 10.1113/tjp.v601.3
    DOI: 10.1113/JP283979
    RVK:
    WA 15000
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 1475290-6
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Action potential amplitude and baroreflex resetting of action potential clusters mediate hypoxia‐induced sympathetic long‐term facilitation
    Wiley ; 2022
    In:  The Journal of Physiology Vol. 600, No. 13 ( 2022-07), p. 3127-3147
    Details
    In: The Journal of Physiology, Wiley, Vol. 600, No. 13 ( 2022-07), p. 3127-3147
    Abstract: Baroreflex resetting permits sympathetic long‐term facilitation (sLTF) following hypoxia; however, baroreflex control of action potential (AP) clusters and AP recruitment patterns facilitating sLTF is unknown. We hypothesized that baroreflex resetting of arterial pressure operating points (OPs) of AP clusters and recruitment of large‐amplitude APs would mediate sLTF following hypoxia. Eight men (age: 24 (3) years; body mass index: 24 (3) kg/m 2 ) underwent 20 min isocapnic hypoxia (: 47 (2) mmHg) and 30 min recovery. Multi‐unit microneurography (muscle sympathetic nerve activity; MSNA) and a continuous wavelet transform with matched mother wavelet was used to detect sympathetic APs during baseline, hypoxia, early (first 5 min), and late recovery (last 5 min). AP amplitude (normalized to largest baseline AP amplitude), percentage APs occurring outside a MSNA burst (percentage asynchronous APs), and proportion of APs firing in small (1–3), medium (4–6) and large (7–10) normalized cluster sizes was calculated. Normalized clusters were used to assess baroreflex OPs and sensitivity. Hypoxia increased total MSNA activity, which remained elevated during recovery ( P   〈  0.0001). Baroreflex OPs were shifted rightward for all clusters in recovery, with no effect on slope. Compared to baseline, AP amplitude was elevated by 3 (2)% and 4 (2)% while asynchronous APs were reduced by 9 (5)% and 7 (6)% in early and late recovery, respectively. In early recovery, the proportion of APs firing in large clusters was increased compared to baseline. Hypoxia‐induced sLTF is mediated by baroreflex resetting of AP clusters to higher OPs, reduced asynchronous AP firing, and increased contribution from large‐amplitude APs. image Key points Acute isocapnic hypoxia resets the arterial baroreflex and permits long‐lasting sympathoexcitation, termed sympathetic long‐term facilitation. Our understanding of sympathetic long‐term facilitation following hypoxia in humans is based on multiunit muscle sympathetic nerve activity and does not fully characterize the underlying baroreflex control of sympathetic neuronal subpopulations or their discharge/recruitment strategies. We show that sympathetic long‐term facilitation is mediated by baroreflex resetting of sympathetic action potential clusters to higher arterial pressure operating points, a reduction in the percentage of action potentials firing asynchronously, and a shift toward larger amplitude action potential activity. The results advance our fundamental understanding of how the sympathetic nervous system mediates sympathetic long‐term facilitation following exposure to acute isocapnic hypoxia in humans.
    Type of Medium: Online Resource
    ISSN: 0022-3751 , 1469-7793
    URL: Issue
    URL: Article
    DOI: 10.1113/tjp.v600.13
    DOI: 10.1113/JP282933
    RVK:
    WA 15000
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 1475290-6
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Within-breath sympathetic baroreflex sensitivity is modulated by lung volume but unaffected by acute intermittent hypercapnic hypoxia in men
    American Physiological Society ; 2020
    In:  American Journal of Physiology-Heart and Circulatory Physiology Vol. 319, No. 1 ( 2020-07-01), p. H213-H221
    Details
    In: American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 319, No. 1 ( 2020-07-01), p. H213-H221
    Abstract: Muscle sympathetic nerve activity (MSNA) exhibits well-described within-breath respiratory modulation, but the interactive contributions of the arterial baroreflex remain unclear. The present study assessed 1) within-breath modulation of sympathetic baroreflex sensitivity (BRS) and 2) the effect of acute intermittent hypercapnic hypoxia (IHH) on within-breath sympathetic BRS and respiratory-sympathetic entrainment. Seventeen men (24 ± 4 yr) underwent an 8- to 10-min spontaneously breathing baseline while continuous measures of blood pressure (BP), heart rate, MSNA, ventilation, and end-tidal gases were collected. A subset of 12 participants subsequently underwent a 40-min IHH exposure composed of 40 consecutive 1-min breathing cycles: 40 s of hypercapnic hypoxia and 20 s of normoxia. Data were compared between inspiration and expiration and low and high lung volume (calculated from the integral of spirometry-derived flow). Sympathetic BRS was determined by the slope of the weighted linear regression between diastolic BP and MSNA burst incidence. Respiratory-sympathetic entrainment was quantified as percentage of MSNA bursts during each respiratory epoch relative to the total burst count. Sympathetic BRS was similar between inspiration and expiration (−3.9 ± 2.0 vs. −3.6 ± 1.8 bursts·100 heartbeats −1 ·mmHg −1 ; P = 0.61) but greater during low versus high lung volumes (−4.6 ± 2.3 vs. −2.1 ± 1.6 bursts·100 heartbeats −1 ·mmHg −1 ; P 〈 0.01). High ( r = −0.64; P 〈 0.01)- but not low ( r = −0.24; P = 0.35)-lung volume sympathetic BRS was associated with resting MSNA. IHH increased resting MSNA burst frequency (15 ± 7 vs. 20 ± 7 bursts/min; P 〈 0.01) and diastolic BP (68 ± 5 vs. 77 ± 9 mmHg; P = 0.02), without altering resting or within-breath sympathetic BRS or respiratory-sympathetic entrainment (all P 〉 0.05). These findings provide novel insight into the mechanisms controlling within-breath modulation of sympathetic outflow in humans. NEW & NOTEWORTHY In resting spontaneously breathing men, the present study observed that sympathetic baroreflex sensitivity (BRS) was higher during low versus high lung volumes but not different between inspiration and expiration. High- but not low-lung volume BRS was negatively associated with resting muscle sympathetic nerve activity (MSNA). Acute intermittent hypercapnic hypoxia increased resting MSNA and diastolic blood pressure, without altering within-breath BRS. These findings provide novel insight into mechanisms controlling within-breath modulation of MSNA in humans.
    Type of Medium: Online Resource
    ISSN: 0363-6135 , 1522-1539
    URL: Article
    DOI: 10.1152/ajpheart.00296.2020
    RVK:
    WA 15000
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2020
    detail.hit.zdb_id: 1477308-9
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Functional optical coherence tomography at altitude: retinal microvascular perfusion and retinal thickness at 3,800 meters
    American Physiological Society ; 2022
    In:  Journal of Applied Physiology Vol. 133, No. 3 ( 2022-09-01), p. 534-545
    Details
    In: Journal of Applied Physiology, American Physiological Society, Vol. 133, No. 3 ( 2022-09-01), p. 534-545
    Abstract: Cerebral hypoxia is a serious consequence of several cardiorespiratory illnesses. Measuring the retinal microvasculature at high altitude provides a surrogate for cerebral microvasculature, offering potential insight into cerebral hypoxia in critical illness. In addition, although sex-specific differences in cardiovascular diseases are strongly supported, few have focused on differences in ocular blood flow. We evaluated the retinal microvasculature in males ( n = 11) and females ( n = 7) using functional optical coherence tomography at baseline (1,130 m) ( day 0), following rapid ascent ( day 2), and prolonged exposure ( day 9) to high altitude (3,800 m). Retinal vascular perfusion density (rVPD; an index of total blood supply), retinal thickness (RT; reflecting vascular and neural tissue volume), and arterial blood were acquired. As a group, rVPD increased on day 2 versus day 0 ( P 〈 0.001) and was inversely related to [Formula: see text] ( R 2  = 0.45; P = 0.006). By day 9, rVPD recovered to baseline but was significantly lower in males than in females ( P = 0.007). RT was not different on day 2 versus day 0 ( P 〉 0.99) but was reduced by day 9 relative to day 0 and day 2 ( P 〈 0.001). RT changes relative to day 0 were inversely related to changes in [Formula: see text] on day 2 ( R 2  = 0.6; P = 0.001) and day 9 ( R 2  = 0.4; P = 0.02). RT did not differ between sexes. These data suggest differential time course and regulation of the retina during rapid ascent and prolonged exposure to high altitude and are the first to demonstrate sex-specific differences in rVPD at high altitude. The ability to assess intact microvasculature contiguous with the brain has widespread research and clinical applications. NEW & NOTEWORTHY Measuring the retinal microvasculature at high altitude provides a surrogate for cerebral microvasculature, offering potential insight into consequence of cerebral hypoxia in critical illness. This study demonstrates dynamic regulation of the retina during rapid ascent and prolonged exposure to high altitude and is the first to demonstrate sex-specific differences in retinal microvasculature at high altitude. The ability to dynamically assess intact microvasculature contiguous with the brain has widespread research and clinical applications.
    Type of Medium: Online Resource
    ISSN: 8750-7587 , 1522-1601
    URL: Article
    DOI: 10.1152/japplphysiol.00132.2022
    RVK:
    WA 15000
    RVK:
    XA 52094
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2022
    detail.hit.zdb_id: 1404365-8
    SSG: 12
    SSG: 31
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  • 5
    Online Resource
    Online Resource
    Muscle sympathetic single-unit responses during rhythmic handgrip exercise and isocapnic hypoxia in males: the role of sympathoexcitation magnitude
    American Physiological Society ; 2021
    In:  Journal of Neurophysiology Vol. 126, No. 1 ( 2021-07-01), p. 170-180
    Details
    In: Journal of Neurophysiology, American Physiological Society, Vol. 126, No. 1 ( 2021-07-01), p. 170-180
    Abstract: A small proportion of postganglionic muscle sympathetic single units can be inhibited during sympathoexcitatory stressors in humans. However, whether these responses are dependent on the specific stressor or the level of sympathoexcitation remains unclear. We hypothesize that, when matched by sympathoexcitatory magnitude, different stressors can evoke similar proportions of inhibited single units. Multiunit and single-unit muscle sympathetic nerve activity (MSNA) were recorded in seven healthy young males at baseline and during 1) rhythmic handgrip exercise (40% of maximum voluntary contraction) and 2) acute isocapnic hypoxia (partial pressure of end-tidal O 2 47 ± 3 mmHg). Single units were classified as activated, nonresponsive, or inhibited if the spike frequency was above, within, or below the baseline variability, respectively. By design, rhythmic handgrip and isocapnic hypoxia similarly increased multiunit total MSNA [Δ273 ± 208 vs. Δ254 ± 193 arbitrary units (AU), P = 0.84] and single-unit spike frequency (Δ8 ± 10 vs. Δ12 ± 13 spikes/min, P = 0.12). Among 19 identified single units, the proportions of activated (47% vs. 68%), nonresponsive (32% vs. 16%), and inhibited (21% vs. 16%) single units were not different between rhythmic handgrip and isocapnic hypoxia ( P = 0.42). However, only 9 (47%) single units behaved with concordant response patterns across both stressors (7 activated, 1 nonresponsive, and 1 inhibited during both stressors). During the 1-min epoch with the highest increase in total MSNA during hypoxia (Δ595 ± 282 AU, P 〈 0.01) only one single unit was inhibited. These findings suggest that the proportions of muscle sympathetic single units inhibited during stress are associated with the level of sympathoexcitation and not the stressor per se in healthy young males. NEW & NOTEWORTHY Subpopulations of muscle sympathetic single units can be inhibited during mild sympathoexcitatory stress. We demonstrate that rhythmic handgrip exercise and isocapnic hypoxia, when matched by multiunit sympathoexcitation, induce similar proportions of single-unit inhibition, highlighting that heterogeneous single-unit response patterns are related to the level of sympathoexcitation independent of the stressor type. Interestingly, only 47% of single units behaved with concordant response patterns between stressors, suggesting the potential for functional specificity within the postganglionic neuronal pool.
    Type of Medium: Online Resource
    ISSN: 0022-3077 , 1522-1598
    URL: Article
    DOI: 10.1152/jn.00678.2020
    RVK:
    XA 10000 ; XA 552555
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2021
    detail.hit.zdb_id: 80161-6
    detail.hit.zdb_id: 1467889-5
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  • 6
    Online Resource
    Online Resource
    Case Studies in Physiology: Sympathetic neural discharge patterns in a healthy young male during end-expiratory breath hold-induced sinus pause
    American Physiological Society ; 2020
    In:  Journal of Applied Physiology Vol. 129, No. 2 ( 2020-08-01), p. 230-237
    Details
    In: Journal of Applied Physiology, American Physiological Society, Vol. 129, No. 2 ( 2020-08-01), p. 230-237
    Abstract: This case study reports the efferent muscle sympathetic nerve activity (MSNA) discharge patterns during a sinus pause observed during a maximal end-expiratory apnea in a young healthy male (age = 26 yr). During a 15.3-s end-expiratory apnea following a bout of intermittent hypercapnic hypoxia, we observed a 5.2-s (R-R interval) sinus pause and integrated MSNA recording, demonstrating a square-wave discharge pattern atypical of sharp MSNA burst peaks entrained to cardiac cycles or during preventricular contractions. This abnormal MSNA discharge pattern was observed again during a follow-up experiment, where an end-expiratory apnea at baseline resulted in pronounced bradycardia (R-R intervals 〉 2.5-s) but failed to reproduce the 5.2-s sinus pause. Action potential (AP) discharge patterns during MSNA bursts were detected using a continuous wavelet transform approach. AP discharge increased by 300% during the end-expiratory apnea with 5.2-s sinus pause compared with baseline and involved increased firing (i.e., rate-coding) of AP clusters (bins of AP with similar morphology) already present during baseline and pronounced recruitment of larger-amplitude AP clusters not present at baseline. Large-amplitude AP clusters continued to discharge during sinus pause. In summary, we show MSNA discharge during sinus pause and pronounced bradycardia during end-expiratory apnea, which demonstrates a square-wave discharge with recruitment of latent larger-amplitude AP clusters. The MSNA discharge was terminated before systole following sinus pause potentially through an inhibitory influence of inspiration, or cardiac mechanoreceptor feedback causing burst termination. NEW & NOTEWORTHY We characterize the occurrence of a square-wave discharge pattern of efferent muscle sympathetic nerve activity during a sinus pause in a young healthy male. This discharge pattern comprised large recruited action potential clusters undetected at baseline that continuously discharged during the sinus pause. Notably, this discharge pattern was still contained within a single cardiac cycle.
    Type of Medium: Online Resource
    ISSN: 8750-7587 , 1522-1601
    URL: Article
    DOI: 10.1152/japplphysiol.00307.2020
    RVK:
    WA 15000
    RVK:
    XA 52094
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2020
    detail.hit.zdb_id: 1404365-8
    SSG: 12
    SSG: 31
    Location Call Number Limitation Availability
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