Papers by Craig Steinback
Hypertension, 2015
Baseline neurovascular transduction is reduced in normotensive pregnancy; however, little is know... more 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.
Applied Physiology, Nutrition, and Metabolism, 2015
Normal cerebrovascular adaptation during pregnancy is poorly understood. We document a case study... more Normal cerebrovascular adaptation during pregnancy is poorly understood. We document a case study of progressively increased cerebrovascular reactivity to CO2, despite no change in resting blood flow, from prepregnancy to late gestation in a 36-year-old normotensive participant. Increased cerebral reactivity was related to progressive chronic respiratory alkalosis and specifically elevated pH and reduced HCO3(-). These novel data serve as important indicators of normative maternal cerebral adaptation and highlight novel areas of future study.
Frontiers in physiology, 2014
Aging is associated with decreased vascular compliance and diminished neurovascular- and hypercap... more Aging is associated with decreased vascular compliance and diminished neurovascular- and hypercapnia-evoked cerebral blood flow (CBF) responses. However, the interplay between arterial stiffness and reduced CBF responses is poorly understood. It was hypothesized that increased cerebral arterial stiffness is associated with reduced evoked responses to both, a flashing checkerboard visual stimulation (i.e., neurovascular coupling), and hypercapnia. To test this hypothesis, 20 older (64 ± 8 year; mean ± SD) and 10 young (30 ± 5 year) subjects underwent a visual stimulation (VS) and a hypercapnic test. Blood velocity through the posterior (PCA) and middle cerebral (MCA) arteries was measured concurrently using transcranial Doppler ultrasound (TCD). Cerebral and systemic vascular stiffness were calculated from the cerebral blood velocity and systemic blood pressure waveforms, respectively. Cerebrovascular (MCA: young = 76 ± 15%, older = 98 ± 19%, p = 0.004; PCA: young = 80 ± 16%, older =...
Respiratory Physiology & Neurobiology, 2009
The present study is the first to compare the cardiorespiratory responses during progressive weig... more The present study is the first to compare the cardiorespiratory responses during progressive weightbearing 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 ± 0.2 m/s; P < 0.001) compared to NP (33.7 ± 4.9 min; 2.0 ± 0.2 m/s) and were further reduced in PGOB (19.6 ± 2.8 min; 1.4 ± 0.1 m/s; P < 0.001) indicating a performance limitation to exercise. Ventilation in response to exercise was increased in PG (49.4 ± 6.6 L/min) compared to NP (39.8 ± 5.4 L/min, at 100 W; p < 0.05) women, and was further augmented by obesity (56.7 ± 9.3 L/min, at 100 W; p < 0.05 versus PG) secondary to an elevated metabolic cost of exercise as indicated by no further increase inV E /V CO 2 andV 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.
Journal of the Neurological Sciences, 2012
Evidence suggests that the autonomic nervous system may actively regulate the cerebral vasculatur... more Evidence suggests that the autonomic nervous system may actively regulate the cerebral vasculature. In this study, central hemodynamics and brain oxy-hemoglobin, deoxy-hemoglobin and total hemoglobin changes (bO₂Hb, bdHb and bTHb) were monitored during infusion of epinephrine (0.06 μg/kg/min over 6 min, and 0.12 μg/kg/min for 3 min) in 12 men. Epinephrine decreased mean arterial pressure (MAP) and total peripheral resistance (TPR), while heart rate (HR), stroke volume (SV) and cardiac output (CO) increased, but did not affect bO₂Hb, bdHb or bTHb. However, upon the cessation of epinephrine infusion an increase in both Oxy- and Total Hb occurred which peaked at 3 min post infusion (+6.0±4.6 and +4.9±4.8 μmol/L respectively, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) and persisted for 20 min post infusion (+1.5±2.2 and +1.8±2.7 μmol/L respectively, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). No evidence was found for reduction in cerebral oxygenation during a cold-pressor test. The results of the present study demonstrated that clinical doses of epinephrine result in a delayed increase in cortical blood volume due to an increase in Oxy-Hb, consistent with vasodilation.
Journal of Applied Physiology, 2005
In this study, we tested the hypothesis that carotid arteries undergo rapid changes in distensibi... more In this study, we tested the hypothesis that carotid arteries undergo rapid changes in distensibility on moving from the supine to head-up tilt (HUT) postures and, subsequently, that this change in carotid distensibility (cDa) might be associated with concurrent reductions in cardiovagal baroreflex sensitivity (BRS). Thus the effect of posture on carotid vascular mechanics and cardiovagal BRS with consideration for altered central hemodynamics (i.e., stroke volume; Doppler ultrasound) was examined. Carotid pulse pressure (cPP; Millar transducer) and contralateral B-mode ultrasound images were assessed at the carotid artery during supine and 60 degrees HUT postures. From these measures, cDa was calculated at 5-mmHg pressure increments experienced during the cardiac cycle (n = 6). cPP (n = 9) was not different in the two postures. A smaller stroke volume being ejected into a smaller carotid artery in HUT explained the maintenance of cPP in HUT. Also, compared with supine, cDa was reset to a lower level in HUT (main effect of posture; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). Cardiovagal BRS (sequence method) was diminished in HUT vs. supine (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). A positive correlation was observed between the tilt-induced changes in maximal cDa (in early systole) and cardiovagal BRS (r2 = 0.75; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05), but there was little predictive relationship between changes in cPP, systolic vessel dimensions, or average cDa and the corresponding change in BRS. The present results indicate that HUT elicits rapid changes in carotid artery mechanics and further suggest that reductions in the maximal cDa measured in early systole contribute to reduced cardiovagal BRS with HUT.
Free Radical Biology and Medicine, 2009
Clinical Physiology and Functional Imaging, 2004
Interpretation of baroreflex cardiovascular control requires accurate assessment of pulse pressur... more 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. Protocol A: Pulse pressure was measured in both the left (Millar tonometer) and right (Colin Pilot) radial arteries, and in the finger (Finapres) in seated subjects (n = 7) who performed Valsalva&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s manoeuvre. Protocol B: PP was measured from the carotid (Millar tonometer), and from the finger and wrist kept at the level of the carotid artery, during supine and 60 degrees head-up postures. Protocol A: Pulse pressures during Valsalva&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s manoeuvre were highly correlated between all devices (r = 0.6-0.8). Protocol B: compared with supine, PP was reduced in both the finger and wrist during head-up-tilt (HUT) (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05), but not in the carotid artery. During Valsalva manoeuvers the Millar and Colin tonometers similarly tracked PP over a wide range of rapidly changing pressures. This observation provided confidence for the further use of the hand-held device for central measurements during changes in posture. The results from Protocol B indicate that peripheral PP measurements are not suitable surrogates for carotid pulse pressures during HUT.
Canadian Journal of Physiology and Pharmacology, 2005
Previous evidence indicates that sensitivity of the baroreflex cardiovagal and sympathetic arms i... more Previous evidence indicates that sensitivity of the baroreflex cardiovagal and sympathetic arms is dissociated. In addition, pharmacologic assessment of baroreflex sensitivity (BRS) has revealed that cardiovagal, but not sympathetic, BRS is greater when blood pressure is increasing versus falling. The origin of this hysteresis is unknown. In this study, carotid artery distensibility and absolute distension (diameter) were assessed to test the hypothesis that vessel mechanics in barosensitive regions affect the BRS of cardiovagal, but not sympathetic, outflow. R-R interval (i.e. time between successive R waves), finger arterial blood pressure, muscle sympathetic nerve activity, and carotid artery dimensions (B-mode imaging) were measured during sequential infusions of sodium nitroprusside (SNP) and phenylephrine (PHE). Systolic and diastolic common carotid artery diameters and pulse pressure were recorded to calculate distensibility of this vessel under each drug condition. Cardiovagal BRS was greater when blood pressure was increasing versus decreasing (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01). Sympathetic BRS was not affected by direction of pressure change. Distensibility did not differ between SNP and PHE injections. However, compared with SNP, infusion of PHE resulted in larger absolute systolic and diastolic carotid diameters (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Therefore, cardiovagal reflex hysteresis was related to drug-induced changes in common carotid artery diameter but not distensibility. The lack of sympathetic hysteresis in this model suggests a relative insensitivity of this baroreflex component to carotid artery dimensions and provides a possible mechanism for the dissociation between cardiovagal and sympathetic BRS.
Autonomic Neuroscience, 2009
Autonomic Neuroscience, 2011
We tested the hypothesis that breath-hold divers (BHD) attain higher level of sympathetic activat... more 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 ± 3 AP/burst; P = 0.05) and number of active clusters (5 ± 1 vs. 3 ± 1 clusters/burst; P = 0.05) at baseline. However, the overall sympathetic AP/unit-time was comparable between the groups (131 ± 105 vs. 173 ± 152 AP/min; P = 0.62) due to increased burst frequency in BHD group (20 ± 4 bursts/min) vs. controls (13 ± 3 bursts/min) (P = 0.039). The achieved level in total MSNA during FRC breath-holds was higher in divers (2298 ± 780 vs. 1484 ± 575 a.u./min; P = 0.039). Total MSNA at the end of TLC breath-hold was comparable between the groups (157 ± 50 (controls) vs. 214 ± 41 s (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.
American Journal of Respiratory and Critical Care Medicine, 2007
Rationale: Acute mountain sickness (AMS) may affect individuals who (rapidly) ascend to altitudes... more Rationale: Acute mountain sickness (AMS) may affect individuals who (rapidly) ascend to altitudes higher than 2,000-3,000 m. A more serious consequence of rapid ascent may be high-altitude pulmonary edema, a hydrostatic edema associated with increased pulmonary capillary pressures. Acetazolamide is effective against AMS, possibly by increasing ventilation and cerebral blood flow (CBF). In animals, it inhibits hypoxic pulmonary vasoconstriction. Objectives: We examined the influence of acetazolamide on the response to hypoxia of ventilation, CBF, and pulmonary vascular resistance (PVR).
AJP: Regulatory, Integrative and Comparative Physiology, 2012
Current evidence suggests that the persistent sympathetic nerve activity (SNA), commonly observed... more Current evidence suggests that the persistent sympathetic nerve activity (SNA), commonly observed after exposure to hypoxia (HX), is mediated by chemoreceptor sensitization and or baroreflex resetting. Evidence in humans and animals suggests that these reflexes may independently regulate the frequency (gating) and amplitude (neuronal recruitment) of SNA bursts. In humans (n = 7), we examined the regulation of SNA following acute isocapnic HX (5 min; end-tidal P(O2) = 45 Torr) and euoxic hypercapnia (HC; 5 min; end-tidal P(CO2) = +10 from baseline). HX increased SNA burst frequency (21 ± 7 to 28 ± 8 bursts/min, P &amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) and amplitude (99 ± 10 to 125 ± 19 au, P &amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) as did HC (14 ± 6 to 22 ± 10 bursts/min, P &amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05 and 100 ± 12 to 133 ± 29 au, P &amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05, respectively). Burst frequency (26 ± 7 bursts/min, P &amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05), but not amplitude (97 ± 12 au), remained elevated 10 min post-HX. The change in burst amplitude (but not frequency) was significantly related to the measured change in ventilation (r(2) = 0.527, P &amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Both frequency and amplitude decreased during recovery following HC. These data indicate the differential regulation of pattern and magnitude of sympathetic outflow in humans with sympathetic persistence following HX being specific to burst frequency and not amplitude.
AJP: Regulatory, Integrative and Comparative Physiology, 2010
The within-breath modulation of muscle sympathetic nerve activity (MSNA) is well established, wit... more The within-breath modulation of muscle sympathetic nerve activity (MSNA) is well established, with greater activity occurring during expiration and less during inspiration. Whether ventilation per se affects the longer-term (i.e., minute-to-minute) regulation of MSNA has not been determined. We sought to define the specific role of ventilation in regulating sympathetic activation during chemoreflex activation, where both ventilation and MSNA are increased. Ten young healthy subjects performed both asphyxic rebreathing and repeated, rebreathing apneas to cause the same magnitude of chemoreflex stress in the presence or absence of ventilation. Both protocols caused increases in sympathetic burst frequency, burst amplitude, and burst incidence. However, burst frequency was increased more during repeated apneas (12 ± 6 to 25 ± 7 bursts/min) compared with rebreathing (12 ± 5 to 17 ± 7 bursts/min; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) due to a greater burst incidence during apneas (36 ± 11 bursts/100 heart beats) vs. rebreathing (26 ± 8 bursts/100 heart beats, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). The sympathetic gain to chemoreflex stress was also larger during repeated apneas (2.29 ± 1.29 au/% desaturation) compared with rebreathing (1.44 ± 0.53 au/% desaturation, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). The augmented sympathetic response during apneas was associated with a larger pressor response and total peripheral resistance compared with rebreathing. These data demonstrate that ventilation per se restrains sympathetic activation during chemoreflex activation. Further, the augmented sympathetic response during apneas was associated with greater cardiovascular stress and may be relevant to the cardiovascular pathology associated with sleep-disordered breathing.
AJP: Regulatory, Integrative and Comparative Physiology, 2008
We compared the integrated cardiovascular and autonomic responses to hypercapnia and hypoxia to t... more We compared the integrated cardiovascular and autonomic responses to hypercapnia and hypoxia to test the hypothesis that these stimuli differentially affect muscle sympathetic nerve activity (MSNA) discharge patterns and cardiovagal and sympathetic baroreflex function in a manner related to ventilatory chemoreflex sensitivity. Six males and six females underwent 5 min of hypoxia (end-tidal Po2 = 45 Torr) and 5 min of hypercapnia (end-tidal Pco2 = +8 Torr from baseline), causing similar ventilatory responses. A downward right shift in cardiovagal set point was observed during both conditions, which was strongly related to the change in inspiratory time (Ti) from baseline to hypercapnia (r2 = 0.67, P = 0.007) and hypoxia (r2 = 0.79, P &amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Cardiovagal baroreflex gain was decreased during hypoxia (20.1 +/- 6.9 vs. 8.9 +/- 5.1 ms/mmHg, P &amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) but not hypercapnia (26.7 +/- 12.7 vs. 23.0 +/- 9.1 ms/mmHg). Both hypoxia and hypercapnia increased MSNA burst amplitude, whereas hypoxia, but not hypercapnia, also increased in MSNA burst frequency (21 +/- 9 vs. 28 +/- 7 bursts/min, P = 0.03) and total MSNA (4.56 +/- 3.07 vs. 7.37 +/- 3.26 mV/min, P = 0.002). However, neither hypercapnia nor hypoxia affected sympathetic burst probability or baroreflex gain. Hypoxia also caused a greater reduction in total peripheral resistance (P = 0.04), a greater increase in heart rate (P = 0.002), and a trend for a greater cardiac output response (P = 0.06) compared with hypercapnia. Nonetheless, central venous pressure remained unchanged during either condition. These results suggest that hypercapnia and hypoxia exert differential effects on cardiovagal, but not sympathetic, baroreflex gain and set point in a manner not related to ventilatory chemoreflex sensitivity. Furthermore, the data suggest that the individual&amp;amp;amp;amp;amp;amp;amp;amp;#39;s respiratory pattern to hypoxia or hypercapnia, as reflected in the inspiratory time, was a strong determinant of cardiovagal baroreflex set- point rather than the total ventilatory chemoreflex gain per se.
Sleep apnoea, with repeated periods of hypoxia, results in cardiovascular morbidity and concomita... more 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.
Is there an ordered pattern in the recruitment of postganglionic sympathetic neurones? Using new ... more 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001 in all subjects), and the amplitude of detected action potentials (r = 0.88 ± 0.06, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 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.
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Papers by Craig Steinback