Harvey, Ronée E.

Introduction: Menopausal hot flashes are defined as rapid, intense sweating and/or an intense feeling of warmth. Subjective recordings of menopausal hot flashes can be difficult to obtain due to inconvenience to the individual and poor recall. This calls for an improved method to quantify hot flashes that are less dependent on human interaction. The goal of this study was to determine if an ambulatory skin conductance hot flash monitor would detect menopausal hot flash occurrence and frequency to the same degree as those reported by study participants. Methods: Thirty-five peri- and postmenopausal females (age: 53±4 years) participated in this study. An ambulatory, noninvasive sternal skin conductance monitor was placed on each participant for a 24-hour recording period. The monitor recorded a hot flash when an increase of 0.2 micromhos was detected in the participant’s sweat level compared to their baseline (objective). Participants manually recorded perceived hot flash occurrence on the monitor (subjective). For analysis, a monitor recording with ≥20 consecutive hours of intact data was included. Hot flash frequency was defined as the number of hot flashes per recording period. A Mann-Whitney test was conducted to compare subjective and objective hot flash frequencies. Statistical analyses for agreement in hot flash occurrence (yes/no; Cohen’s Kappa) and frequency (Bland-Altman) were completed. Data are reported as mean±SD or median (IQR). Results: The average hot flash monitor recording consisted of 23.8±0.7 hours of data. Twenty-eight females reported at least one hot flash during their recording period (5 [3-9] subjective hot flashes) while 7 females did not report any hot flashes. The monitor detected at least one hot flash in 30 females (10 [5-21] objective hot flashes) and no hot flashes in 5 females. For 3 participants, both the subjective and objective reports showed zero hot flashes. There was a significant difference between the frequency of hot flashes reported by all participants (3 [1-8] subjective hot flashes) and those detected by the hot flash monitor (8 [4-19] objective hot flashes; p=0.006). There was no agreement between the subjective (self-report) and objective (monitor) assessments of hot flash occurrence (k= -0.1734). The Bland-Altman showed a mean bias of 7.1±8.6 towards objective hot flash frequency with limits of agreement of -9.8 to 23.9. Conclusion: The ambulatory sternal skin conductance monitor used in the current study showed no agreement in detecting menopausal hot flashes compared to self-reported hot flashes. Overall, the monitor substantially overestimated the frequency of menopausal hot flashes that participants reported. While further investigation might be needed to improve the monitor’s sensitivity for accurate hot flash detection, it is possible that the monitor may be detecting subclinical menopausal hot flashes that are less recognizable to the individual. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Background: Spontaneous coronary artery dissection (SCAD) is a common type of myocardial infarction in females under the age of 50 years, caused by sudden separation between the coronary arterial wall layers and/or hematoma. The SCAD patient population is mostly females (~80%) with few or no traditional cardiovascular disease risk factors (e.g., obesity, hypertension). Common triggers for SCAD include sympathoexcitatory stimuli, such as intense physical and emotional stress. This implicates the sympathetic nervous system in the pathophysiology of SCAD. Thus, we aimed to investigate sympathetic nervous system responses to mental stress in patients with a history of SCAD. We hypothesized that females with a history of SCAD exhibit a greater increase in muscle sympathetic nerve activity (MSNA) with acute exposure to mental stress compared to healthy females. Methods: Seven females with a history of SCAD (age: 48±9 yrs, BMI: 29±6 kg/m 2 ) and seven age- and BMI-matched healthy female controls (CON, age: 49±9 yrs, BMI: 26±6 kg/m 2 ) participated in the study (both p>0.05). MSNA was measured via peroneal microneurography during a 2-minute rest, a 5-minute Stroop Color Word Test aimed at inducing mental stress, and a 2-minute recovery. Heart rate (HR, 3-lead electrocardiography) and BP (finger photoplethysmography) were continuously recorded during each stage. Data are presented as an absolute change from rest (Δmean±SD). Two-way independent t-tests were used for statistical analyses. Results: Resting mean blood pressure (MBP, SCAD: 96±14 vs CON: 89±7 mmHg, p=0.27), heart rate (HR, SCAD: 56±11vs CON: 65±16 bpm, p=0.25), MSNA burst frequency (SCAD: 22±9 vs CON: 18±7 bursts/minute, p=0.40) and total MSNA (SCAD: 1135±471 vs CON: 951±245 au/min, p=0.41) were not different between the groups. During the Stroop Color Word Test, average changes in MBP (SCAD: Δ10±9 vs CON: Δ8±5 mmHg, p=0.67) and HR (SCAD: Δ11±7 vs CON: Δ14±5 bpm, p=0.35) were not different between the groups. Similarly, average changes in MBP (SCAD: Δ3±4 vs CON: Δ-2±5 mmHg, p=0.13) and HR (SCAD: Δ3±4 vs CON: Δ3±2 bpm, p=0.62) were not different during the recovery. Changes in MSNA burst frequency with the Stroop Color Word Test (SCAD: Δ1±7 vs CON: Δ6±7 bursts/minute, p=0.22) and recovery (SCAD: Δ0±5 vs CON: Δ4±4 bursts/minute, p=0.13) were not different between the groups. Total MSNA changes were also not different during the Stroop Color Word Test (SCAD: Δ267±335 vs CON: Δ606±432 au/min, p=0.15) and recovery (SCAD: Δ68±666 vs CON: Δ217±217 au/min, p=0.61) between the two groups. Conclusion: These preliminary data suggest that contrary to our hypothesis, sympathetic nervous system responses to acute mental stress exposure are not different between females with a history of SCAD and healthy females. Further investigation is needed to understand MSNA association with chronic stress exposure in females with a history of SCAD. Funding: NIH K23 HL155506 This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Intravenous dexmedetomidine infusion (selective α 2 -adrenergic receptor agonist) 1) reduced the firing probability and strength of baroreflex control over medium-sized sympathetic action potentials in muscle sympathetic nerve activity (MSNA) and 2) attenuated the transduction of MSNA bursts to changes in blood pressure (BP) by reducing the magnitude of BP responses and increasing the time to peak BP. These data suggest that neural and vascular α 2 -adrenergic mechanisms contribute to sympathetic baroreflex regulation of human BP.

Sympathetic control of human blood pressure is mechanistically regulated by α 2 -adrenergic receptors distributed throughout the nervous system and cardiovascular end-targets. Recently, we discovered the sympathoinhibitory effects of central α 2 -adrenergic mechanisms on human sympathetic neuronal emission patterns. However, our knowledge remains incomplete regarding the impact of α 2 -adrenergic mechanisms on beat-by-beat transduction of muscle sympathetic nerve activity (MSNA) bursts to changes in blood pressure and heart rate (HR). Based on evidence of α 2 -adrenergic receptors within central and peripheral sympathetic neural sites and on the vasculature, this study tested the hypothesis that activation of α 2 -adrenergic receptors with dexmedetomidine (DEX) would reduce sympathetic transduction to blood pressure. In eight healthy participants (5 females; 28 ± 7 years), diastolic blood pressure (DBP; brachial arterial catheter), HR (ECG), and MSNA (peroneal microneurography) were recorded during a 5-minute supine baseline (BSL) and an intravenous DEX infusion consisting of a loading dose (10 minutes at 0.225 μg/kg/hr) and a maintenance dose (~0.15 μg/kg/hr). Signal averaging quantified sympathetic transduction to DBP and HR for 12 cardiac cycles following integrated MSNA bursts. We also quantified sympathetic transduction to DBP using a transduction gain estimate derived from the slope of the linear relationship between the peak DBP response and the number of cardiac cycles until peak DBP response. Data (mean ± SD) are reported for the 5-minute BSL and the last 5-minute period during the DEX infusion. Mixed-effects modeling and t -tests were performed. Non-parametric tests were performed for non-normally distributed data. DEX reduced resting MAP (BSL: 92 ± 7, DEX: 82 ± 6 mmHg: p < 0.001) but did not affect resting HR (BSL: 62 ± 14, DEX: 61 ± 14 bpm; p = 0.853). DEX reduced resting integrated MSNA burst frequency (BSL: 14 ± 6, DEX: 4 ± 3 bursts/min; p = 0.001) and total integrated MSNA (BSL: 663 ± 252, DEX: 188 ± 142 AU/min; p < 0.001). DEX attenuated the DBP transduction response, particularly for the cardiac cycle associated with peak DBP during BSL (cardiac cycle 6: BSL: 4.3 ± 3.2, DEX: 3.3 ± 2.0 mmHg; p = 0.025) and prolonged the time to peak DBP transduction (BSL: 6 ±1, DEX: 10 ± 3 cardiac cycles; p = 0.014). Also, DEX reduced DBP transduction gain (BSL: 1.6 ± 2.4, DEX: 0.9 ± 1.3 mmHg/cardiac cycle; p = 0.029). By contrast, DEX did not affect the mean transduction of MSNA bursts to changes in HR (BSL: 3.2 ± 3.1, DEX: 3.9 ± 4.6 mmHg; p = 0.668). These data suggest that α 2 -adrenergic mechanisms distributed among central and peripheral sympathetic neural regions and the cardiovascular system influence moment-to-moment sympathetic regulation of blood pressure homeostasis, but not HR, in humans. This work was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) and the National Institutes of Health (NIH). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Background: Spontaneous coronary artery dissection (SCAD) is an acute separation of coronary artery wall layers that blocks blood flow to the heart and leads to acute coronary syndrome. Patients with SCAD are relatively young females (~40-50 years) who have few cardiovascular risk factors. Sympathoexcitatory stress often precedes SCAD events (i.e. intense physical and/or emotional stress), suggesting that patients with SCAD may have augmented hemodynamic responses to sympathoexcitatory stressors. As such, we aimed to evaluate hemodynamic responses to cold stress in females with a history of SCAD and females without a history of SCAD. We hypothesized that females with a history of SCAD would have augmented hemodynamic responses to cold stress relative to females without a history of SCAD. Methods: Females with a history of SCAD were matched to females without a history of SCAD for age and body mass index. Heart rate (electrocardiogram) and beat-to-beat blood pressure (finger photoplethysmography) were recorded and averaged during two minutes of resting baseline and the minute during the cold pressor test that produced the peak hemodynamic response. Delta (Δ) values of the hemodynamic parameters were calculated. Data are reported as mean ± SD. Unpaired t-tests were used to analyze demographics, anthropometrics, resting hemodynamics, and hemodynamic responses between females with a history of SCAD and females without a history of SCAD. Results: Age (50±9 vs 56±8 years) and body mass index (27±6 vs 24±3 kg/m 2 ) did not differ between females with a history of SCAD (n=20) and females without a history of SCAD (n=12, both p>0.05), respectively. Resting heart rate ([HR], 57±10 vs 59±11 bpm), systolic blood pressure ([SBP], 112±14 vs 110±13 mmHg), diastolic blood pressure ([DBP], 72±10 vs 72±9 mmHg), and mean arterial pressure ([MAP], 86±11 vs 85±9 mmHg) were not different between females with a history of SCAD and females without a history of SCAD, respectively (all p>0.05). Hemodynamic responses to cold stress (ΔHR, 6±5 vs 7±5 bpm; ΔSBP, 20±16 vs 18±7 mmHg; ΔDBP, 7±11 vs 11±6 mmHg; ΔMAP, 10±14 vs 13±5 mmHg; all p>0.05) were not different between females with a history of SCAD and females without a history of SCAD, respectively. Conclusion: Hemodynamic responses to cold stress were not different between females with a history of SCAD and females without a history of SCAD, indicating that an augmented pressor response to this stress is likely not a primary predisposing factor to a SCAD. However, it remains important to assess other forms of stress to inform future care and counseling of patients with history of SCAD. Funding: K23HL155506 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Introduction: Spontaneous coronary artery dissection (SCAD) is one of the most common causes of myocardial infarction in females under the age of 50 and peripartum females. Furthermore, approximately 10% of patients with a history of SCAD have recurrent SCAD within 5 years. In a subset of patients, SCAD events are preceded by sympathoexcitatory stimuli, such as emotional or physical stress. This implicates the sympathetic nervous system in the pathophysiology of SCAD. Thus, we aimed to investigate this relationship through measuring muscle sympathetic nerve activity (MSNA) and quantifying MSNA transduction into diastolic blood pressure (BP) in females with a history of SCAD compared to healthy female controls. We hypothesized that females with a history of SCAD would have both augmented MSNA and MSNA transduction at rest compared to their healthy counterparts. Methods: Females with a history of SCAD and healthy controls (HC) were recruited for the study. MSNA was continuously recorded using microneurography at the peroneal nerve during 10-minute supine rest. Heart rate (HR, 3-lead electrocardiography) and BP (finger photoplethysmography) were continuously recorded during this period. We plotted binned MSNA burst areas against diastolic BP, using linear regression analysis in MATLAB R2023a to quantify the transduction slope. We compared peak bins of transduction slopes between the two groups. Data are presented as mean±SD. Independent samples t-tests were performed for statistical analyses. Results: Seven females with a history of SCAD (49±11 years; BMI: 28.5±7 kg/m 2 ) and six controls (51±8 years; BMI: 26.2±6.3 kg/m 2 ) participated in the study (both p>0.05). Resting systolic BP (SCAD: 121±8 vs. HC: 122±15 mmHg), diastolic BP (SCAD: 78±9 vs. HC: 75±7 mmHg) and HR (SCAD: 59±13 vs. HC: 67±18 bpm) were not different between groups (all p >0.05). MSNA burst frequency (SCAD: 25±12 vs. HC: 27±7 bursts/minute), burst incidence (SCAD: 42±18 vs. HC: 46±15 bursts/100 heartbeats), and total MSNA (SCAD: 820±286 vs. HC: 1050±119 au/minute) did not differ between groups (all p >0.05). MSNA transduction at rest was not different between females with a history of SCAD and healthy controls (0.02±0.03 vs. 0.05±0.05 mmHg(%·s) -1 , p>0.05). Conclusions: These preliminary data suggest that resting MSNA and transduction do not differ between females with a history of SCAD and healthy controls, contrary to our hypothesis. Further investigation is needed to determine if this observation is preserved with exposure to sympathoexcitatory stimuli. Funding: NIH K23 HL155506, T32 DK07352, K01 HL148144, UL1 TR0022377, and AHA 898649 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Biological sex impacts baroreflex control of integrated muscle sympathetic nerve activity (MSNA), yet our knowledge remains incomplete regarding sex differences in baroreflex regulation of the differently sized APs contributing to variations in MSNA burst frequency and size. We hypothesized that sex differences in baroreflex control of sympathetic action potential (AP) discharge contribute to higher resting AP activity in males compared to females. We measured diastolic blood pressure (DBP; Finometer or brachial arterial catheter) and MSNA (peroneal microneurography and continuous wavelet transform, APs normalized to 10 clusters) in 24 healthy individuals (aged 18-30, 12 females) during a 5-minute supine baseline. Sympathetic AP baroreflex threshold gain was measured as the slope of the linear relationship between AP discharge probability and DBP. Sympathetic AP baroreflex sensitivity gain was measured as the slope of the linear relationship between AP clusters per burst and DBP. Analyses were performed during DBP rises and falls to explore baroreflex hysteresis. Mixed-effects analyses and t-tests were performed. Data are reported as mean ± SD. In the aggregate cohort, baroreflex control of medium-sized APs exhibited hysteresis. Compared to rises in DBP, DBP falls were associated with greater AP firing probabilities (cluster 3; DBP rise: 20 ± 11, DBP fall: 26 ± 12%; p < 0.01) and greater AP baroreflex gains (cluster 3; DBP rise: -4.36 ± 2.43, DBP fall: -5.32 ± 3.09 %/mmHg; p < 0.01). In the aggregate cohort, baroreflex hysteresis was not detected for small- or large-sized AP clusters (both p ≥ 0.56). Similar observations were detected for medium-sized APs in male (M) and female (F) cohorts when analyses were stratified by sex. Compared to females, males exhibited greater medium-sized AP firing probabilities during DBP rises (cluster 3; M: 23 ± 12, F: 16 ± 8%; p < 0.01) and falls (cluster 3; M: 32 ± 13, F: 20 ± 8%; p < 0.01). However, AP baroreflex gains were not different between sexes during DBP rises (cluster 3; M: -4.87 ± 2.05, F: -3.84 ± 2.75%/mmHg; p = 0.13) and falls (cluster 3; M: -5.87 ± 2.25, F: -4.76 ± 3.77 %/mmHg; p = 0.15). In the aggregate cohort, the number of AP clusters per burst and the AP baroreflex sensitivity gain were not different between rises and falls in DBP. However, compared to females, males demonstrated a greater number of AP clusters per burst during DBP rises (M: 4 ± 0.9, F: 3 ± 0.6 clusters/burst; p < 0.01) and falls (M: 4 ± 0.8, F: 3 ± 0.7 clusters/burst; p < 0.01). No sex differences in AP baroreflex sensitivity gain were detected during DBP rises (M: -0.08 ± 0.09, F: -0.30 ± 0.07 clusters/burst/mmHg; p = 0.14) or falls (M: -0.08 ± 0.08, F: -0.02 ± 0.08 clusters/burst/mmHg; p = 0.09). These data suggest that 1) hysteresis exists in baroreflex regulation of medium-sized but not small or large sympathetic APs firing under baseline conditions and 2) in line with earlier integrated MSNA studies, compared to females, males demonstrate greater resting sympathetic outflow from greater sympathetic AP discharge and more AP clusters firing per burst in periods of rising and falling DBPs. This work was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) and the National Institutes of Health (NIH). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

AbstractMenopause is associated with vascular dysfunction. During the menopausal transition, endogenous oestradiol concentrations diminish. Oestradiol is vasoprotective because it has direct and indirect effects on the vasculature. The present study aimed to determine the effect of acute exogenous oestradiol on endothelium‐dependent, endothelium independent and β2‐adrenergic receptor‐induced vasodilatation in females. Forearm blood flow (venous occlusion plethysmography) was measured during brachial intraarterial infusions of ACh (endothelium‐dependent agonist), sodium nitroprusside (endothelium independent agonist) and terbutaline (β2‐adrenergic receptor agonist) with and without concurrent infusion of 17β‐oestradiol. Nine young premenopausal (age: 26 ± 4 years) and nine postmenopausal (PM, age: 58 ± 4 years, 8 ± 1 years post‐menopause) females completed the study. Concurrent oestradiol infusion augmented the vasodilatory response to ACh, sodium nitroprusside and terbutaline in young premenopausal (all P < 0.05) but not older postmenopausal (all P > 0.05), females. Local infusion of exogenous 17β‐oestradiol augmented endothelial and smooth muscle microvascular vasodilatation in premenopausal but not postmenopausal, females. imageKey points Menopause is associated with vascular dysfunction. Because oestradiol has vasoprotective effects, the menopause‐associated drop in oestradiol concentrations is hypothesized to contribute to vascular dysfunction during the menopause transition. The present study shows that local infusion of exogenous oestradiol augmented microvascular vasodilatation in premenopausal but not postmenopausal females.

The purpose of sympathetic neuronal discharge and the recruitment of neuronal subpopulations for human circulatory homeostasis remains unknown. This study tested the hypothesis that sympathetic neuronal discharge and recruitment patterns regulate neuropeptide Y (NPY) bioavailability. Across baseline and an intravenous dexmedetomidine infusion (α2-adrenergic agonist) sympathetic action potential (AP) frequency and total sympathetic AP clusters were associated with NPY bioavailability. This is the first study to report that sympathetic neuronal discharge and recruitment patterns regulate NPY bioavailability to support circulatory homeostasis in humans.

AbstractThe present study investigated the impact of central α2‐adrenergic mechanisms on sympathetic action potential (AP) discharge, recruitment and latency strategies. We used the microneurographic technique to record muscle sympathetic nerve activity and a continuous wavelet transform to investigate postganglionic sympathetic AP firing during a baseline condition and an infusion of a α2‐adrenergic receptor agonist, dexmedetomidine (10 min loading infusion of 0.225 µg kg−1; maintenance infusion of 0.1–0.5 µg kg h−1) in eight healthy individuals (28 ± 7 years, five females). Dexmedetomidine reduced mean pressure (92 ± 7 to 80 ± 8 mmHg, P < 0.001) but did not alter heart rate (61 ± 13 to 60 ± 14 bpm; P = 0.748). Dexmedetomidine reduced sympathetic AP discharge (126 ± 73 to 27 ± 24 AP 100 beats−1, P = 0.003) most strongly for medium‐sized APs (normalized cluster 2: 21 ± 10 to 5 ± 5 AP 100 beats−1; P < 0.001). Dexmedetomidine progressively de‐recruited sympathetic APs beginning with the largest AP clusters (12 ± 3 to 7 ± 2 clusters, P = 0.002). Despite de‐recruiting large AP clusters with shorter latencies, dexmedetomidine reduced AP latency across remaining clusters (1.18 ± 0.12 to 1.13 ± 0.13 s, P = 0.002). A subset of six participants performed a Valsalva manoeuvre (20 s, 40 mmHg) during baseline and the dexmedetomidine infusion. Compared to baseline, AP discharge (Δ 361 ± 292 to Δ 113 ± 155 AP 100 beats−1, P = 0.011) and AP cluster recruitment elicited by the Valsalva manoeuvre were lower during dexmedetomidine (Δ 2 ± 1 to Δ 0 ± 2 AP clusters, P = 0.041). The reduction in sympathetic AP latency elicited by the Valsalva manoeuvre was not affected by dexmedetomidine (Δ –0.09 ± 0.07 to Δ –0.07 ± 0.14 s, P = 0.606). Dexmedetomidine reduced baroreflex gain, most strongly for medium‐sized APs (normalized cluster 2: –6.0 ± 5 to –1.6 ± 2 % mmHg−1; P = 0.008). These data suggest that α2‐adrenergic mechanisms within the central nervous system modulate sympathetic postganglionic neuronal discharge, recruitment and latency strategies in humans. imageKey points Sympathetic postganglionic neuronal subpopulations innervating the human circulation exhibit complex patterns of discharge, recruitment and latency. However, the central neural mechanisms governing sympathetic postganglionic discharge remain unclear. This microneurographic study investigated the impact of a dexmedetomidine infusion (α2‐adrenergic receptor agonist) on muscle sympathetic postganglionic action potential (AP) discharge, recruitment and latency patterns. Dexmedetomidine infusion inhibited the recruitment of large and fast conducting sympathetic APs and attenuated the discharge of medium sized sympathetic APs that fired during resting conditions and the Valsalva manoeuvre. Dexmedetomidine infusion elicited shorter sympathetic AP latencies during resting conditions but did not affect the reductions in latency that occurred during the Valsalva manoeuvre. These data suggest that α2‐adrenergic mechanisms within the central nervous system modulate sympathetic postganglionic neuronal discharge, recruitment and latency strategies in humans.