Sympathetic arterial baroreflex hysteresis in humans: different patterns during low- and high-pressure levels.

Fluctuations in diastolic pressure modulate muscle sympathetic nerve activity (MSNA) through the arterial baroreflex. A higher sympathetic baroreflex sensitivity (sBRS) to pressure falls compared with rises has been reported; however, the underlying mechanisms are unclear. We assessed whether beat-to-beat falling and rising diastolic pressures operate on two distinct baroreflex response curves. Twenty-two men (32 ± 8 yr) underwent sequential bolus injections of nitroprusside and phenylephrine (modified Oxford test) with continuous recording of heart rate, blood pressure, and MSNA. The weighted negative linear regression slope between falling or rising diastolic pressure and MSNA burst incidence quantified sBRSfall and sBRSrise, respectively. The diastolic pressure evoking a MSNA burst incidence of 50 (T50) was calculated. sBRSfall was greater than sBRSrise (-6.24 ± 2.80 vs. -4.34 ± 2.16 bursts·100 heartbeats-1·mmHg-1, P = 0.01) and had a narrower operating range (14 ± 8 vs. 20 ± 10 mmHg, P = 0.01) that was shifted rightward (T50, 75 ± 9 and 70 ± 11 mmHg, P < 0.001). At diastolic pressures below baseline, sBRSfall was less than sBRSrise (-1.81 ± 1.31 vs. -3.59 ± 1.70 bursts·100 heartbeats-1·mmHg-1, P = 0.003) as low absolute pressures operated closer to the saturation plateau on the falling, compared with the rising pressure curve. At pressures above baseline, sBRSfall was greater than sBRSrise (-5.23 ± 1.94 and -3.79 ± 1.67 bursts·100 heartbeats-1·mmHg-1, P = 0.03). These findings demonstrate that the sympathetic arterial baroreflex possesses two response curves for processing beat-to-beat diastolic pressure falls and rises. The falling pressure curve is rightward shifted, which reduces sensitivity to falling pressure at low absolute pressures. This demonstrates that the direction of the hysteresis is influenced by the prevailing pressure level relative to each baroreflex response curve.NEW & NOTEWORTHY The findings show that the arterial baroreflex processes diastolic pressure dependent on the direction of pressure change from the previous beat, yielding two distinct baroreflex response curves to falling and rising pressure. Overall, the falling pressure curve is rightward shifted and more sensitive. The rightward shift caused a hysteresis reversal at hypotensive pressures as the falling pressure saturation plateau of the sigmoid response curve occurred at higher pressures than the rising pressure curve.

Arterial baroreflex regulation of muscle sympathetic single-unit activity in men: influence of resting blood pressure.

The arterial baroreflex has dominant control over multiunit muscle sympathetic nerve activity (MSNA) burst occurrence, but whether this extends to all single units or is influenced by resting blood pressure status is unclear. In 22 men (32 ± 8 yr), we assessed 68 MSNA single units during sequential bolus injections of nitroprusside and phenylephrine (modified Oxford). Sympathetic baroreflex sensitivity (sBRS) was quantified as the weighted negative linear regression slope between diastolic blood pressure (DBP) and single-unit spike firing probability and multiple spike firing. Strong negative linear relationships (r ≥ -0.50) between DBP and spike firing probability were observed in 63/68 (93%) single units (-2.27 ± 1.27%·cardiac cycle-1·mmHg-1 [operating range, 18 ± 8 mmHg]). In contrast, only 45/68 (66%) single units had strong DBP-multiple spike firing relationships (-0.13 ± 0.18 spikes·cardiac cycle-1·mmHg-1 [operating range, 14 ± 7 mmHg]). Participants with higher resting DBP (65 ± 3 vs. 77 ± 3 mmHg, P < 0.001) had similar spike firing probability sBRS (low vs. high, -2.08 ± 1.08 vs. -2.46 ± 1.42%·cardiac cycle-1·mmHg-1, P = 0.33), but a smaller sBRS operating range (20 ± 6 vs. 16 ± 9 mmHg, P = 0.01; 86 ± 24 vs. 52 ± 25% of total range, P < 0.001) and a higher proportion of single units without arterial baroreflex control outside this range [6/31 (19%) vs. 21/32 (66%), P < 0.001]. Participants with higher resting DBP also had fewer single units with arterial baroreflex control of multiple spike firing (79 vs. 53%, P = 0.04). The majority of MSNA single units demonstrate strong arterial baroreflex control over spike firing probability during pharmacological manipulation of blood pressure. Changes in single-unit sBRS operating range and control of multiple spike firing may represent altered sympathetic recruitment patterns associated with the early development of hypertension.NEW & NOTEWORTHY Muscle sympathetic single units can be differentially controlled during stress. In contrast, we demonstrate that 93% of single units maintain strong arterial baroreflex control during pharmacological manipulation of blood pressure. Interestingly, the operating range and proportion of single units that lose arterial baroreflex control outside of this range are influenced by resting blood pressure levels. Altered single unit, but not multiunit, arterial baroreflex control may represent changes in sympathetic recruitment patterns in early stage development of hypertension.

Arterial baroreflex regulation of muscle sympathetic nerve activity at rest and during stress.

KEY POINTS: The arterial baroreflex controls vasoconstrictor muscle sympathetic nerve activity (MSNA) in a negative feedback manner by increasing or decreasing activity during spontaneous blood pressure falls or elevations, respectively. Spontaneous sympathetic baroreflex sensitivity is commonly quantified as the slope of the relationship between MSNA burst incidence or strength and beat-to-beat variations in absolute diastolic blood pressure. We assessed the relationships between blood pressure inputs related to beat-to-beat blood pressure change or blood pressure rate-of-change (variables largely independent of absolute pressure) and MSNA at rest and during exercise and mental stress. The number of participants with strong linear relationships between MSNA and beat-to-beat diastolic blood pressure change variables or absolute diastolic blood pressure were similar at rest, although during stress the beat-to-beat diastolic blood pressure change variables were superior. Current methods may not fully characterize the capacity of the arterial baroreflex to regulate MSNA. ABSTRACT: Spontaneous sympathetic baroreflex sensitivity (sBRS) is commonly quantified as the slope of the relationship between variations in absolute diastolic blood pressure (DBP) and muscle sympathetic nerve activity (MSNA) burst incidence or strength. This relationship is well maintained at rest but not during stress. We assessed whether sBRS could be calculated at rest and during stress (static handgrip, rhythmic handgrip, mental stress) using blood pressure variables that quantify relative change: beat-to-beat DBP change (ΔDBP), ΔDBP rate-of-change (ΔDBP rate), pulse pressure (PP) and PP rate-of-change (PP rate). Sixty-six healthy participants underwent continuous measures of blood pressure (finger photoplethysmography) and multi-unit MSNA (microneurography). At rest, absolute DBP (91%), ΔDBP (97%) and ΔDBP rate (97%) each yielded higher proportions of participants with strong linear relationships (r ≥ 0.6) with MSNA burst incidence compared to PP (57%) and PP rate (56%) and produced similar sBRS slopes (DBP: -4.5 ± 2.0 bursts 100 heartbeats-1 /mmHg; ΔDBP: -5.0 ± 2.1 bursts 100 heartbeats-1 /ΔmmHg; ΔDBP rate: -4.9 ± 2.2 bursts 100 heartbeats-1 /ΔmmHg s-1 ; P > 0.05). During stress, ΔDBP (74%) and ΔDBP rate (74%) yielded higher proportions of strong linear relationships with MSNA burst incidence than absolute DBP (43%), PP (46%) and PP rate (49%) (all P < 0.05). The absolute DBP associated with a 50% chance of a MSNA burst (T50 ) was shifted rightward during static handgrip (Δ+15 ± 11 mmHg, P < 0.001) and mental stress (Δ+11 ± 7 mmHg, P < 0.001); however, the ΔDBP T50 was shifted rightward during static handgrip (Δ+2.5 ± 3.7 mmHg, P = 0.009) but not mental stress (Δ0.0 ± 4.4 mmHg, P = 0.99). These findings suggest that calculating sBRS using absolute DBP alone may not adequately characterize arterial baroreflex regulation of MSNA, particularly during stress.

Effects of dynamic arm and leg exercise on muscle sympathetic nerve activity and vascular conductance in the inactive leg.

The influence of muscle sympathetic nerve activity (MSNA) responses on local vascular conductance during exercise are not well established. Variations in exercise mode and active muscle mass can produce divergent MSNA responses. Therefore, we sought to examine the effects of small- versus large-muscle mass dynamic exercise on vascular conductance and MSNA responses in the inactive limb. Thirty-five participants completed two study visits in a randomized order. During visit 1, superficial femoral artery (SFA) blood flow (Doppler ultrasound) was assessed at rest and during steady-state rhythmic handgrip (RHG; 1:1 duty cycle, 40% maximal voluntary contraction), one-leg cycling (17 ± 3% peak power output), and concurrent exercise at the same intensities. During visit 2, MSNA (contralateral fibular nerve microneurography) was acquired successfully in 12/35 participants during the same exercise modes. SFA blood flow increased during RHG (P < 0.0001) and concurrent exercise (P = 0.03) but not cycling (P = 0.91). SFA vascular conductance was unchanged during RHG (P = 0.88) but reduced similarly during concurrent and cycling exercise (both P < 0.003). RHG increased MSNA burst frequency (P = 0.04) without altering burst amplitude (P = 0.69) or total MSNA (P = 0.26). In contrast, cycling and concurrent exercise had no effects on MSNA burst frequency (both P ≥ 0.10) but increased burst amplitude (both P ≤ 0.001) and total MSNA (both P ≤ 0.007). Across all exercise modes, the changes in MSNA burst amplitude and SFA vascular conductance were correlated negatively (r = -0.43, P = 0.02). In summary, the functional vascular consequences of alterations in sympathetic outflow to skeletal muscle are most closely associated with changes in MSNA burst amplitude, but not frequency, during low-intensity dynamic exercise.NEW & NOTEWORTHY Low-intensity small- versus large-muscle mass exercise can elicit divergent effects on muscle sympathetic nerve activity (MSNA). We examined the relationships between changes in MSNA (burst frequency and amplitude) and superficial femoral artery (SFA) vascular conductance during rhythmic handgrip, one-leg cycling, and concurrent exercise in the inactive leg. Only changes in MSNA burst amplitude were inversely associated with SFA vascular conductance responses. This result highlights the functional importance of measuring MSNA burst amplitude during exercise.

An investigation of pilot fatigue in helicopter emergency medical services.

Pilot error has caused the majority of helicopter emergency medical services (HEMS) accidents in the United States for almost 2 decades. Pilot fatigue may have contributed to some of these accidents. This nonexperimental quantitative study investigated the relationships between fatigue reported by on-duty HEMS pilots (the criterion variable) and consecutive HEMS pilot day shifts, consecutive HEMS pilot night shifts, age, and experience as an HEMS pilot (the predictor variables). Surveys completed by 395 on-duty HEMS pilots in the US were examined to quantify respondent fatigue with the Brief Fatigue Inventory (BFI). This study found some evidence of a statistically significant positive relationship between HEMS pilot night shift respondent BFI scores and experience as an HEMS pilot, while controlling for consecutive HEMS pilot night shifts and age. A 1-way analysis of variance suggested that the effect of experience as an HEMS pilot on HEMS pilot night shift respondent BFI scores was statistically significant. Multivariate regression analysis suggested that experience as an HEMS pilot predicted HEMS pilot night shift respondent BFI scores. Additional quantitative research is recommended to confirm the results of this study and to investigate relationships between fatigue experienced by HEMS pilots and other variables that were not considered in this investigation. Qualitative research to identify and document fatigue management strategies that are used by experience HEMS pilots is also recommended.