Craig D. Steinback

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 < 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 < 0.001 in all subjects), and the amplitude of detected action potentials (r= 0.88 ± 0.06, P < 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.

Recruitment pattern of sympathetic neurons during breath-holding at different lung volumes in apnea divers and controls

We tested the hypothesis that breath-hold divers (BHD) attain higher level of sympathetic activation than controls due to the duration of breath-hold rather than a different recruitment strategy. In 6 control subjects and 8 BHD we measured muscle sympathetic neural activity (MSNA) prior to and during functional residual capacity (FRC) and total lung capacity (TLC) breath-holding. On a subset of subjects we applied a new technique for the detection of action potentials (APs) in multiunit MSNA. Compared with controls, BHD group had lower burst AP content (13±7 vs. 6±3AP/burst; P=0.05) and number of active clusters (5±1 vs. 3±1clusters/burst; P=0.05) at baseline. However, the overall sympathetic AP/unit-time was comparable between the groups (131±105 vs. 173±152AP/min; P=0.62) due to increased burst frequency in BHD group (20±4bursts/min) vs. controls (13±3bursts/min) (P=0.039). The achieved level in total MSNA during FRC breath-holds was higher in divers (2298±780 vs. 1484±575a.u./min; P=0.039). Total MSNA at the end of TLC breath-hold was comparable between the groups (157±50 (controls) vs. 214±41s (BHD); P=0.61). FRC and TLC breath-holds increased AP frequency, burst AP content and active clusters/bursts in both groups but the response magnitude was determined by the type of the breath-hold. The divers used fewer number of APs/burst and active clusters/burst. In both groups breath-holds resulted in similar increases in MSNA which were reached both by an increase in firing frequency and by recruitment of previously silent, larger (faster conducting) sympathetic neurons, and possibly by repeated firing within the same burst.

Impact of pregnancy and obesity on cardiorespiratory responses during weight-bearing exercise.

The present study is the first to compare the cardiorespiratory responses during progressive weight-bearing treadmill exercise in normal-weight non-pregnant (NP, n=14), normal-weight pregnant (PG, n=20) and obese pregnant (PGOB, n=20) women. Exercise duration and peak treadmill speed were lower in PG (23.9+/-4.9 min; 1.6+/-0.2m/s; P<0.001) compared to NP (33.7+/-4.9 min; 2.0+/-0.2m/s) and were further reduced in PGOB (19.6+/-2.8 min; 1.4+/-0.1m/s; P<0.001) indicating a performance limitation to exercise. Ventilation in response to exercise was increased in PG (49.4+/-6.6L/min) compared to NP (39.8+/-5.4 L/min, at 100W; p<0.05) women, and was further augmented by obesity (56.7+/-9.3 L/min, at 100W; p<0.05 versus PG) secondary to an elevated metabolic cost of exercise as indicated by no further increase in .V(E)/.V(CO2) and .V(E)/.V(O2) in PGOB compared to PG women. The normal augmentation of heart rate observed in PG during exercise was not further increased by obesity at standardized sub-maximal work rates.

Regulation of Sympathetic Nerve Activity During the Cold Pressor Test in Normotensive Pregnant and Nonpregnant Women

Baseline neurovascular transduction is reduced in normotensive pregnancy; however, little is known about changes to neurovascular transduction during periods of heightened sympathetic activation. We tested the hypothesis that, despite an exacerbated muscle sympathetic nerve activity (microneurography) response to cold pressor stimulation, the blunting of neurovascular transduction in normotensive pregnant women would result in similar changes in vascular resistance and mean arterial pressure (Finometer) relative to nonpregnant controls. Baseline neurovascular transduction was reduced in pregnant women relative to controls when expressed as the quotient of both total resistance and mean arterial pressure and sympathetic burst frequency (0.32±0.07 versus 0.58±0.16 mm Hg/L/min/bursts/min, P<0.001 and 2.4±0.7 versus 3.6±0.8 mm Hg/bursts/min, P=0.001). Sympathetic activation was greater across all 3 minutes of cold pressor stimulation in the pregnant women relative to the nonpregnant controls. Peak sympathoexcitation was also greater in pregnant than in nonpregnant women, whether expressed as sympathetic burst frequency (+17±13 versus +7±8 bursts/min, P=0.049), burst incidence (+17±9 versus +6±11 bursts/100 hb, P=0.03), or total activity (+950±660 versus +363±414 arbitrary units, P=0.04). However, neurovascular transduction during peak cold pressor–induced sympathoexcitation remained blunted in pregnant women (0.25±0.11 versus 0.45±0.08 mm Hg/L/min/bursts/min, P<0.001 and 1.9±1.0 versus 3.2±0.9 mm Hg/bursts/min, P=0.006). Therefore, mean arterial pressure (93±21 versus 99±6 mm Hg, P=0.4) and total peripheral resistance (12±3 versus 14±3 mm Hg/L/min) were not different between pregnant and nonpregnant women during peak sympathoexcitation. These data indicate that the third trimester of normotensive pregnancy is associated with reductions in neurovascular transduction, which result in the dissociation of sympathetic outflow from hemodynamic outcomes, even during cold pressor–induced sympathoexcitation.

Peripheral pulse pressure responses to postural stress do not reflect those at the carotid artery.

Objective:  Interpretation of baroreflex cardiovascular control requires accurate assessment of pulse pressure (PP) in central arteries under conditions of varying systemic or hydrostatic pressure. The objective of this study was to examine whether changes in PP during postural stress were similar in the peripheral versus carotid arteries.

Sympathetic baroreflex gain in normotensive pregnant women

Muscle sympathetic nerve activity is increased during normotensive pregnancy while mean arterial pressure is maintained or reduced, suggesting baroreflex resetting. We hypothesized spontaneous sympathetic baroreflex gain would be reduced in normotensive pregnant women relative to nonpregnant matched controls. Integrated muscle sympathetic burst incidence and total sympathetic activity (microneurography), blood pressure (Finometer), and R-R interval (ECG) were assessed at rest in 11 pregnant women (33 ± 1 wk gestation, 31 ± 1 yr, prepregnancy BMI: 23.5 ± 0.9 kg/m(2)) and 11 nonpregnant controls (29 ± 1 yr; BMI: 25.2 ± 1.7 kg/m(2)). Pregnant women had elevated baseline sympathetic burst incidence (43 ± 2 vs. 33 ± 2 bursts/100 heart beats, P = 0.01) and total sympathetic activity (1,811 ± 148 vs. 1,140 ± 55 au, P < 0.01) relative to controls. Both mean (88 ± 3 vs. 91 ± 2 mmHg, P = 0.4) and diastolic (DBP) (72 ± 3 vs. 73 ± 2 mmHg, P = 0.7) pressures were similar between pregnant and nonpregnant women, respectively, indicating an upward resetting of the baroreflex set point with pregnancy. Baroreflex gain, calculated as the linear relationship between sympathetic burst incidence and DBP, was reduced in pregnant women relative to controls (-3.7 ± 0.5 vs. -5.4 ± 0.5 bursts·100 heart beats(-1)·mmHg(-1), P = 0.03), as was baroreflex gain calculated with total sympathetic activity (-294 ± 24 vs. -210 ± 24 au·100 heart beats(-1)·mmHg(-1); P = 0.03). Cardiovagal baroreflex gain (sequence method) was not different between nonpregnant controls and pregnant women (49 ± 8 vs. 36 ± 8 ms/mmHg; P = 0.2). However, sympathetic (burst incidence) and cardiovagal gains were negatively correlated in pregnant women (R = -0.7; P = 0.02). Together, these data indicate that the influence of the sympathetic nervous system over arterial blood pressure is reduced in normotensive pregnancy, in terms of both long-term and beat-to-beat regulation of arterial pressure, likely through a baroreceptor-dependent mechanism.

Autonomic and cardiovascular responses to chemoreflex stress in apnoea divers

Sleep apnoea, with repeated periods of hypoxia, results in cardiovascular morbidity and concomitant autonomic dysregulation. Trained apnoea divers also perform prolonged apnoeas accompanied by large lung volumes, large reductions in cardiac output and severe hypoxia and hypercapnia. We tested the hypothesis that apnoea training would be associated with decreased cardiovagal and sympathetic baroreflex gains and reduced respiratory modulation of muscle sympathetic nerve activity (MSNA; microneurography). Six trained divers and six controls were studied at rest and during asphyxic rebreathing. Despite an elevated resting heart rate (70+/-14 vs. 56+/-10 bpm; p=0.038), divers had a similar cardiovagal baroreflex gain (-1.22+/-0.47 beats/mmHg) as controls (-1.29+/-0.61; NS). Similarly, though MSNA burst frequency was slightly higher in divers at rest (16+/-4 bursts/min vs. 10+/-5 bursts/min, p=0.03) there was no difference in baseline burst incidence, sympathetic baroreflex gain (-3.8+/-2.1%/mmHg vs. -4.7+/-1.7%/mmHg) or respiratory modulation of MSNA between groups. Resting total peripheral resistance (11.9+/-2.6 vs. 12.3+/-2.2 mmHg/L/min) and pulse wave velocity (5.82+/-0.55 vs. 6.10+/-0.51 m/s) also were similar between divers and controls, respectively. Further, the sympathetic response to asphyxic rebreathing was not different between controls and divers (-1.70+/-1.07 vs. -1.74+/-0.84 a.u./% desaturation). Thus, these data suggest that, unlike patients with sleep apnoea, apnoea training in otherwise healthy individuals does not produce detectable autonomic dysregulation or maladaption.

Comparing and characterizing transient and steady‐state tests of the peripheral chemoreflex in humans

What is the central question of this study? We aimed to characterize the cardiorespiratory and cerebrovascular responses to transient and steady‐state tests of the peripheral chemoreflex and to compare the hypoxic ventilatory responses (HVRs) between these tests. What is the main finding and its importance? The cardiovascular and cerebrovascular responses to transient tests were small in magnitude and short in duration. The steady‐state isocapnic hypoxia test elicited a larger HVR than the transient 100% N2 test, but the response magnitudes were correlated within individuals. The transient test of the HVR elicits fewer systemic effects than steady‐state techniques and may have greater experimental utility than previously appreciated.

The effects of head-up and head-down tilt on central respiratory chemoreflex loop gain tested by hyperoxic rebreathing.

Central respiratory chemosensitivity is mediated via chemoreceptor neurons located throughout brain stem tissue. These receptors detect proximal CO2/[H(+)] (i.e., controller gain) and modulate breathing in a classic negative feedback loop. Loop gain (responsiveness) is the theoretical product of controller (chemoreceptors), mixing/feedback (cardiovascular and cerebrovascular systems), and plant (pulmonary system) gains. The level of chemoreceptor stimulation is determined by interactions between mixing and plant gains. The extent to which steady-state changes in body position may affect central chemoreflex loop gain in response to CO2 is unclear. Because of the potential effects of tilt on pulmonary mechanics, we hypothesized that plant gain would be altered by head-up and head-down tilt (HUT, HDT) during hyperoxic rebreathing, which theoretically isolates plant gain by eliminating systemic arterial-tissue gradients. Sixteen subjects (eight females) underwent hyperoxic rebreathing tests on a tilt table to quantify central chemoreflex loop gain in five steady-state positions: 90° HUT, 45° HUT, supine, 45° HDT, and 90° HDT. Respiratory responses (tidal volume, VT; frequency, fR; minute ventilation, VE) were quantified during steady-state and increases in CO2 during rebreathing by linear regression above the ventilatory recruitment threshold (VRT). Using one-factor analysis of variance, we found that there were no differences in the respiratory responses between the five positions (VRT, P=0.711; VT, P=0.290; fR, P=0.748; VE, P=0.325). Our findings suggest that during steady-state orthostatic stress, the ability of subjects to mount a normal ventilatory response to increased CO2 was unaffected, despite any potential changes in pulmonary mechanics associated with positional challenges.

Maternal Responses to Aerobic Exercise in Pregnancy.

Exercise is one of the most physiologically challenging stressors requiring the coordination of metabolic, respiratory, and cardiovascular responses to meet increased energy requirements of the working muscle. During pregnancy, all women without contraindication are encouraged to exercise as part of a healthy lifestyle. Pregnancy itself is associated with profound physiological adaptations to the maternal cardiovascular, respiratory, and metabolic systems, which serve to support the needs of the growing fetus. Therefore the physiological adaptations to exercise during pregnancy are more pronounced and critically important. This review provides an overview of our current understanding of the physiological adaptations to acute prenatal exercise.