Maria Fernanda Frances

Representation of somatosensory inputs within the cortical autonomic network.

Regions of the cortical autonomic network (CAN) are activated during muscle contraction. However, it is not known to what extent CAN activation patterns reflect muscle sensory inputs, top-down signals from the motor cortex, and/or motor drive to cardiovascular structures. The present study explored the functional representation of somatosensory afferent input within the CAN with an a priori interest in the insula and ventral medial prefrontal cortex (vMPFC) (n=12). Heart rate (HR) and functional MRI data were acquired during 1) 30s periods of electrical stimulation of the wrist flexors at sub-motor (SUB; Type I,II afferents) and 2) motor thresholds (MOT; Type I,II,III afferents), 3) volitional wrist flexion at 5% maximal voluntary contraction (MVC) to match the MOT tension (VOL5%), and 4) volitional handgrip at 35% MVC to elicit tachycardia (VOL35%). Compared with rest, HR did not change during SUB, MOT, or VOL5% but increased during VOL35% (p<0.001). High frequency HR variability was 29.42±18.87 ms(2) (mean±S.D.) at rest and 39.85±27.60 ms(2) during SUB (p=0.06). High frequency HR variability was decreased during VOL35% compared to rest (p≤0.005). SUB increased activity in the bilateral posterior insula, vMPFC, subgenual anterior cingulate cortex (ACC), mid-cingulate cortex (MCC), and posterior cingulate cortex. MOT increased activity in the left posterior insula and MCC. During VOL5%, activity increased in the right anterior-mid insula. VOL35% was associated with activity in the bilateral insula as well as vMPFC and subgenual ACC deactivation. These data suggest that the left posterior insula processes sensory input from muscle during passive conditions and specifically that Type I and/or II muscle afferent stimulation during SUB impacts the vMPFC and/or subgenual ACC, regions believed to be involved in brain default mode and parasympathetic activity.

Forebrain organization representing baroreceptor gating of somatosensory afferents within the cortical autonomic network.

Somatosensory afferents are represented within the cortical autonomic network (CAN). However, the representation of somatosensory afferents, and the consequent cardiovascular effects, may be modified by levels of baroreceptor input. Thus, we examined the cortical regions involved with processing somatosensory inputs during baroreceptor unloading. Neuroimaging sessions (functional magnetic resonance imaging [fMRI]) recorded brain activity during 30 mmHg lower-body negative pressure (LBNP) alone and combined with somatosensory stimulation (LBNP+SS) of the forearm (n = 14). Somatosensory processing was also assessed during increased sympathetic outflow via end-expiratory apnea. Heart rate (HR), blood pressure (BP), cardiac output (Q), and muscle sympathetic nerve activity (MSNA) were recorded during the same protocols in a separate laboratory session. SS alone had no effect on any cardiovascular or MSNA variable at rest. Measures of HR, BP, and Q during LBNP were not different compared with LBNP+SS. The rise in MSNA burst frequency was attenuated during LBNP+SS versus LBNP alone (8 vs. 12 bursts/min, respectively, P < 0.05). SS did not affect the change in MSNA during apnea. Activations within the insula and dorsal anterior cingulate cortex (ACC) observed during LBNP were not seen during LBNP+SS. Anterior insula and ACC activations occurring during apnea were not modified by SS. Thus, the absence of insular and dorsal ACC activity during LBNP+SS along with an attenuation of MSNA burst frequency suggest sympathoinhibitory effects of sensory stimulation during decreased baroreceptor input by a mechanism that includes conjoint insula-dorsal ACC regulation. These findings reveal that the level of baroreceptor input influences the forebrain organization of somatosensory afferents.

Ventilatory restraint of sympathetic activity during chemoreflex stress

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 < 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 < 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 < 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.

Splenic constriction during isometric handgrip exercise in humans

During the first minute of a moderate-intensity isometric handgrip (HG) exercise, there is an increase in stroke volume and cardiac output that occurs without any change in systemic vascular conductance. Although the mechanism of increased venous return is not yet known, current focus has been placed on the constriction of visceral organs. The human spleen represents a compliant organ with high perfusion that constricts during the rather severe stresses of maximal exercise, a diving reflex, or prolonged apnea. This study tested the hypothesis that spleen constriction occurs during isometric HG exercise. Eight participants performed a 1 min isometric HG test at 40% maximum voluntary contraction. Splenic length and width were measured (with ultrasound imaging) after 1 min of exercise, and volume was calculated. To investigate the reflex specificity of this response, spleen dimensions were also measured during 4 min of lower-body negative pressure (LBNP; -20 mm Hg). To test the additional impact of altered breathing and intra-abdominal pressures during the HG, measures were also taken during Valsalvas manoeuvre (VM) at 30 mm Hg. Compared with baseline, both length and width of the spleen were reduced by 0.20 to 0.55 cm (or 4.44%-6.09%; p < 0.05) during each test. This resulted in relative reductions in splenic volume of 13 +/- 1% (HG), 9% +/- 7% (LBNP) and 18% +/- 7% (VM) (p < 0.05; all mean +/- SD). It was concluded that the spleen can constrict during the first minute of isometric HG exercise.

Sympathetic neural recruitment patterns during the Valsalva maneuver

Sympathetic nerve activity is an important regulator of blood pressure and blood flow in humans. Our understanding about how sympathetic neurons are recruited during baroreflex stress is limited. This paper investigates the sympathetic neural recruitment patterns during the Valsalva maneuver. Using microneurography, muscle sympathetic nerve activity was recorded in seven healthy subjects during baseline and the Valsalva maneuver. A new algorithm for detection and classification of action potentials was employed to study the differences between the recruitment of sympathetic neurons during baseline and the Valsalva maneuver. The data suggests that the Valsalva maneuver increases the number of spikes per sympathetic bursts and also recruits at least one additional new cluster of larger, faster conducting neurons. Also, action potentials latencies (i.e., inverse of conduction velocity) were shifted downward for all action potential clusters during this maneuver.

Dynamic responsiveness of the vascular bed as a regulatory mechanism in vasomotor control

The dynamics of blood supply to a vascular bed depend on lumped mechanical properties of that bed, namely the compliance (C), resistance (R), viscoelasticity (K), and inertance (L). While the study of regulatory mechanisms has so far placed the emphasis largely on R, it is not known how the remaining properties contribute collectively to the play of dynamics in vasomotor control. To examine this question and to establish some benchmark values of these properties, simultaneous measurements of pressure and flow waveforms in the vascular bed of the forearm were obtained from three groups: young healthy individuals, older hypertensives with controlled blood pressure, and older hypertensives with uncontrolled blood pressure. The values of R and C were found to vary within a wide range in each of the three groups to the extent that neither R nor C could be used independently as an indicator of health or age of the subjects tested. However, higher level dynamic properties of the bed, such as the time constants and damping index, which depend on combinations of C,K, and L, and which may reflect measures of the dynamic responsiveness or “sluggishness” of the system, were found to be maintained over a wide range of pulse pressures. These findings support a hypothesis that the pulsatile dynamics of blood supply to a vascular bed are adapted to the individual baseline values of R and C in different subjects with the effect of optimizing the level of dynamic responsiveness to changes in pressure or flow, and that this dynamic property of the vascular bed may be a protected and/or regulated property.

Low-frequency oscillations in R-R interval and blood pressure across the continuum of cardiovascular risk

The purpose of this study was to assess the power and the frequency of low-frequency (LF; 0.04-<0.15 Hz) oscillations in systolic blood pressure (SBP) and R-R interval (RRi) across the continuum of risk of cardiovascular disease, including age. A potential confound in such determinations is low spontaneous breathing frequency in some individuals. We measured beat-to-beat SBP, RRi and respiration in healthy YOUNG (33±3 years) and OLDER subjects (62±5 years) and older patients with hypertension (HT, 61±5 years), coronary artery disease without (CAD, 62±5 years) and with type 2 diabetes (CAD+DM, 62±4 years, n=28 for all groups) during spontaneous breathing at supine rest. Power (Power(LF)) and median frequency (Med(LF)) of LF oscillations were calculated by power spectral analysis after removing respiratory effects by least-mean-square adaptive filtering. OLDER had higher Power(LF-SBP) (5.5±3.0 vs. 3.4±2.5 mmHg(2), p=0.002) and lower Power(LF-RRi) than YOUNG (339±460 vs. 575±422 ms(2), p=0.001) whereas neither variable differed between OLDER and patient groups. Med(LF-SBP) (0.072±0.009 vs. 0.080±0.011 Hz, p=0.005) and Med(LF-RRi) (0.072±0.010 vs. 0.079±0.013 Hz, p=0.027) were lower in OLDER compared with YOUNG. Compared with OLDER, Med(LF-RRi) was lower in CAD (0.065±0.006 Hz, p=0.015) and CAD +DM (0.066±0.008 Hz, p=0.012); whereas CAD+DM had also lower Med(LF-SBP) (0.065±0.006 Hz, p=0.012). No differences were observed between OLDER and HT and between CAD and CAD+DM in these variables. We concluded that age is major determinant of the power of LF oscillations in SBP and RRi at rest, whereas the median frequency of these oscillations is altered also by coronary artery disease.

Non-alpha-adrenergic effects on systemic vascular conductance during lower-body negative pressure, static exercise and muscle metaboreflex activation

This study tested the hypothesis that non‐α‐adrenergic mechanisms contribute to systemic vascular conductance (SVC) in a reflex‐specific manner during the sympathoexcitatory manoeuvres.

Impact of a smoking cessation lifestyle intervention on vascular mechanics in young women

We tested the hypotheses that smoking-induced changes in vascular mechanics would be detected earlier in the lumped properties of peripheral vascular beds, which include the properties of microvasculature, than in the local properties of central conduits, and that such changes are reversible with lifestyle changes that include smoking cessation and exercise. Vascular measures were made in 53 young (18-40 years) female smokers and 25 age-matched non-smokers. Twenty-two of the smokers were tested before and after a 14-week smoking cessation program and, of these, 13 were tested again after 52 weeks of smoking cessation. Compared with non-smokers, lumped forearm vascular bed compliance (C: mL/mm Hg) was lower, while lumped viscoelasticity (K: mm Hg/(mL·min)) and resistance (R: mm Hg/(mL·min)) were higher in the smoker group. Neither the carotid-to-toe pulse wave velocity nor local carotid artery elasticity indices were different between groups. Compared with non-smokers, brachial artery distensibility was less, and other markers of stiffness higher, in the smoker group. At 14 and 52 weeks of smoking cessation, forearm vascular R was reduced and C was increased while K was unchanged. The changes in C and R occurred while maintaining a constant R×C value, which represents a dynamic time constant. Thus, early changes in K were observed in the forearm vascular bed of smokers, which were not reflected in the local properties of central conduit vessels. Forearm C, but not K, was reversed following smoking cessation, a finding that may represent a persistent effect of smoking on the intercellular matrix of the vessel wall.