J.K. Shoemaker

Differential effect of head-up tilt on cardiovagal and sympathetic baroreflex sensitivity in humans

The purpose of this study was to determine the effect of baroreceptor unloading on the sensitivity of the cardiovagal and sympathetic arms of the baroreflex during upright posture. Beat‐by‐beat R‐R interval, arterial blood pressure and cardiac output (Doppler ultrasound), as well as muscle sympathetic nerve activity (MSNA) were recorded during periods in supine (Supine) and 60 deg head‐up tilt (HUT) positions (n = 8 volunteers). Cardiovagal baroreflex sensitivity (BRS) was measured by the spontaneous sequence analysis method using systolic blood pressure and R‐R interval, while sympathetic BRS was determined using the slope of the linear relationship between decreasing segments of diastolic blood pressure (DBP) and corresponding increases in MSNA. On changing to HUT, mean R‐R interval and cardiac output decreased, while mean measures of MSNA, DBP and total peripheral resistance increased (P < 0.05). Cardiovagal BRS decreased from Supine to 60 deg HUT (19 ± 2 ms mmHg−1 versus 7.6 ± 1.2 ms mmHg−1; P < 0.01). In contrast, sympathetic BRS increased from ‐6.1 ± 1.4 a.u. mmHg−1 in Supine to ‐14 ± 2 a.u. mmHg−1 in HUT (P < 0.01). Thus, HUT produced differential effects on cardiac versus sympathetic BRS. The data suggest that dynamic baroreflex‐mediated cardiovascular control is dominated by sympathetic control during baroreceptor unloading.

Test–retest repeatability of muscle sympathetic nerve activity: influence of data analysis and head-up tilt

Total integrated muscle sympathetic nerve activity (MSNA) is composed of bursts that vary in both frequency and amplitude. Various quantifiable indices are currently used to characterize MSNA and its reflex-mediated responses. However, a comprehensive and systematic analysis on the test-retest repeatability of these measures has not been conducted. Therefore, the purpose of this study was to compare the consistency of supine and passive head-up tilt-mediated sympathetic nerve activity using different descriptors of MSNA and a statistical paradigm that included Model II ordinary least products (OLP) regression, Bland-Altman method of differences, and analysis of variance. MSNA (microneurography), stroke volume (SV, Doppler), and arterial blood pressure (ABP, Finapres) were measured during repeated supine and 60 degrees head-up tilt (HUT) conditions separated by a minimum of 3 weeks. MSNA was quantified using; burst frequency (and incidence), burst amplitudes (and total integrated activity) normalized to the largest absolute amplitude within each posture, and calculated percent changes (from supine) in absolute burst amplitude and total integrated activity. Most indices of MSNA showed excellent test-retest repeatability during both postures with neither fixed nor proportional bias. However, MSNA expressed as burst incidence demonstrated both fixed and proportional bias in the supine position, but not during HUT. In addition, HUT-induced percent changes in absolute burst amplitude and total activity displayed a fixed bias with greater increases during the second test (P<0.05). The hemodynamic variables associated with the reflex responses were quite similar between tests (i.e., no bias). It was concluded that, with the exception of burst incidence, the majority of MSNA indices provided reliable markers of sympathetic activity on repeated tests. However, care must be taken when using percent changes in MSNA that incorporate absolute amplitudes.

Circulating norepinephrine and cerebrovascular control in conscious humans

Background:  Cerebral vasoconstriction without concurrent changes in systemic arterial blood pressure has been observed in both normal individuals and those with idiopathic orthostatic intolerance following several minutes of postural stress when circulating catecholamines are elevated. Therefore, we tested the hypothesis that α‐adrenergic activation with and without elevated circulating norepinephrine (NE) directly affects cerebrovascular tone in healthy individuals.

Cerebral vasoconstriction precedes orthostatic intolerance after parabolic flight

The effects of brief but repeated bouts of micro- and hypergravity on cerebrovascular responses to head-up tilt (HUT) were examined in 13 individuals after (compared to before) parabolic flight. Middle cerebral artery mean flow velocity (MCA MFV; transcranial Doppler ultrasound), eye level blood pressure (BP) and end tidal CO(2) (P(ET)CO(2)) were measured while supine and during 80 degrees HUT for 30 min or until presyncope. In the postflight tests subjects were classified as being orthostatically tolerant (OT) (n = 7) or intolerant (OI) (n = 6). BP was diminished with HUT in the OT group in both tests (p < 0.05) whereas postflight BP was not different from supine in the OI group. Postflight compared to preflight, the reduction in P(ET)CO(2) with HUT (p < 0.05) increased in both groups, although significantly so only in the OI group (p < 0.05). The OI group also had a significant decrease in supine MCA MFV postflight (p < 0.05) that was unaccompanied by a change in supine P(ET)CO(2). The decrease in MCA MFV that occurred during HUT in both groups preflight (p < 0.05) was accentuated only in the OI group postflight, particularly during the final 30 s of HUT (p < 0.05). However, this accentuated decrease in MCA MFV was not correlated to the greater decrease in P(ET)CO(2) during the same period (R = 0.20, p = 0.42). Although cerebral vascular resistance (CVR) also increased in the OI group during the last 30 s of HUT postflight (p < 0.05), the dynamic autoregulatory gain was not simultaneously changed. Therefore, we conclude that in the OI individuals, parabolic flight was associated with cerebral hypoperfusion following a paradoxical augmentation of CVR by a mechanism that was not related to changes in autoregulation nor strictly to changes in P(ET)CO(2).

Myogenic activity in autoregulation during low frequency oscillations

Lower body negative pressure (LBNP) was applied in eight human subjects to trigger low frequency oscillations in order to study the nature of functional coupling between the hemodynamic and autonomic nervous systems, with particular focus on how the myogenic response fits within this coupling. To this end muscle sympathetic nerve activity (MSNA), mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), and total peripheral resistance (TPR) were measured at baseline and during LBNP and were then examined in both the time and frequency domains. At the height of low frequency oscillations (~0.1Hz) there was a strong coupling between all the five indices, marked by perfect alignment of their oscillatory frequencies. Results in the time domain show that a fall in MAP is followed by a fall in TPR at 1.58s SD 0.69), a rise in heart rate at 2.64s (SD 0.98), a rise in cardiac output at 3.72s (SD 0.60), a peak in MSNA at 5.71s (SD 1.27) and, finally, a rise in TPR at 7.13s (SD 1.02). A possible interpretation of the latter is that a drop in MAP first triggers a drop in TPR via a myogenic response before the expected rise in TPR via a rise in MSNA. In other words, following a drop in arterial pressure, myogenic response controls vessel diameter before this control is taken over by MSNA. These findings provide a possible resolution of a longstanding conceptual argument against attributing a significant role for the myogenic response in blood flow autoregulation.