Sympathetic activation by lower body negative pressure decreases kidney perfusion without inducing hypoxia in healthy humans.

PURPOSE: There is ample evidence that systemic sympathetic neural activity contributes to the progression of chronic kidney disease, possibly by limiting renal blood flow and thereby inducing renal hypoxia. Up to now there have been no direct observations of this mechanism in humans. We studied the effects of systemic sympathetic activation elicited by a lower body negative pressure (LBNP) on renal blood flow (RBF) and renal oxygenation in healthy humans. METHODS: Eight healthy volunteers (age 19-31 years) were subjected to progressive LBNP at - 15 and - 30 mmHg, 15 min per level. Brachial artery blood pressure was monitored intermittently. RBF was measured by phase-contrast MRI in the proximal renal artery. Renal vascular resistance was calculated as the MAP divided by the RBF. Renal oxygenation (R2*) was measured for the cortex and medulla by blood oxygen level dependent (BOLD) MRI, using a monoexponential fit. RESULTS: With a LBNP of - 30 mmHg, pulse pressure decreased from 50 ± 10 to 43 ± 7 mmHg; MAP did not change. RBF decreased from 1152 ± 80 to 1038 ± 83 mL/min to 950 ± 67 mL/min at - 30 mmHg LBNP (p = 0.013). Heart rate and renal vascular resistance increased by 38 ± 15% and 23 ± 8% (p = 0.04) at - 30 mmHg LBNP, respectively. There was no change in cortical or medullary R2* (20.3 ± 1.2 s-1 vs 19.8 ± 0.43 s-1; 28.6 ± 1.1 s-1 vs 28.0 ± 1.3 s-1). CONCLUSION: The results suggest that an increase in sympathetic vasoconstrictor drive decreases kidney perfusion without a parallel reduction in oxygenation in healthy humans. This in turn indicates that sympathetic activation suppresses renal oxygen demand and supply equally, thus allowing adequate tissue oxygenation to be maintained.

Influence of the cardiac cycle on pCASL: cardiac triggering of the end-of-labeling.

OBJECTIVE: In arterial spin labeling (ASL), the cardiac cycle might adversely influence signal-stability by varying the amount of label created, labeling efficiency and/or transport times. Due to the long labeling duration in pseudo-Continuous ASL (pCASL), the blood labeled last contributes most to the ASLsignal. The present study investigated, using numerical simulations and in vivo experiments, the effect of the cardiac cycle on pCASL, thereby focusing on the end-of-labeling. MATERIALS AND METHODS: In the in vivo experiments the end-of-labeling was timed to a specific cardiac phase while a long labeling duration of >7 s was used to isolate the influence of the lastly labeled spins on ASL-signal stability. RESULTS: Simulations showed dependence of the ASL-signal on the cardiac phase of the end-of-labeling, and that the variation in signal was more pronounced at lower heart rates. The ASL-signal variation was small (~4%), but could be effectively reduced by simulated end-of-labeling triggering. In vivo, no difference in mean CBF (p = 0.58) nor in CBF temporal-STD (p = 0.44) could be detected between triggered and non-triggered acquisitions. CONCLUSION: Influence of the cardiac cycle on pCASL-signal stability is small and triggering the start-of-labeling and end-of-labeling can be considered not to have practical implications to improve stability.

Aging modifies the effect of cardiac output on middle cerebral artery blood flow velocity.

An association between cerebral blood flow (CBF) and cardiac output (CO) has been established in young healthy subjects. As of yet it is unclear how this association evolves over the life span. To that purpose, we continuously recorded mean arterial pressure (MAP; finger plethysmography), CO (pulse contour; CO-trek), mean blood flow velocity in the middle cerebral artery (MCAV; transcranial Doppler ultrasonography), and end-tidal CO2 partial pressure (PetCO2) in healthy young (19-27 years), middle-aged (51-61 years), and elderly subjects (70-79 years). Decreases and increases in CO were accomplished using lower body negative pressure and dynamic handgrip exercise, respectively. Aging in itself did not alter dynamic cerebral autoregulation or cerebrovascular CO2 reactivity. A linear relation between changes in CO and MCAVmean was observed in middle-aged (P < 0.01) and elderly (P = 0.04) subjects but not in young (P = 0.45) subjects, taking concurrent changes in MAP and PetCO2 into account. These data imply that with aging, brain perfusion becomes increasingly dependent on CO.

The cerebrovascular response to lower-body negative pressure vs. head-up tilt.

Lower-body negative pressure (LBNP) has been proposed as a MRI-compatible surrogate for orthostatic stress. Although the effects of LBNP on cerebral hemodynamic behavior have been considered to reflect those of orthostatic stress, a direct comparison with actual orthostasis is lacking. We assessed the effects of LBNP (-50 mmHg) vs. head-up tilt (HUT; at 70°) in 10 healthy subjects (5 female) on transcranial Doppler-determined cerebral blood flow velocity (CBFv) in the middle cerebral artery and cerebral perfusion pressure (CPP) as estimated from the blood pressure signal (finger plethysmography). CPP was maintained during LBNP but decreased after 2 min in response to HUT, leading to an ~15% difference in CPP between LBNP and HUT (P ≤ 0.020). Mean CBFv initially decreased similarly in response to LBNP and for HUT, but, from minute 3 on, the decline became ~50% smaller (P ≤ 0.029) during LBNP. The reduction in end-tidal Pco2 partial pressure (PetCO2 ) was comparable but with an earlier return toward baseline values in response to LBNP but not during HUT (P = 0.008). We consider the larger decrease in CBFv during HUT vs. LBNP attributable to the pronounced reduction in PetCO2 and to gravitational influences on CPP, and this should be taken into account when applying LBNP as an MRI-compatible orthostatic stress modality.NEW & NOTEWORTHY Lower-body negative pressure (LBNP) has the potential to serve as a MRI-compatible surrogate of orthostatic stress but a comparison with actual orthostasis was lacking. This study showed that the pronounced reduction in end-tidal Pco2 together with gravitational effects on the brain circulation lead to a larger decline in cerebral blood flow velocity in response to head-up tilt than during lower-body negative pressure. This should be taken into account when employing lower-body negative pressure as MRI-compatible alternative to orthostatic stress.

Using High-Field Magnetic Resonance Imaging to Estimate Distensibility of the Middle Cerebral Artery.

BACKGROUND: Although cerebral arterial stiffness may be an important marker for cerebrovascular health, there is not yet a measurement that accurately reflects the distensibility of major intracranial arteries. Herein, we aim to noninvasively measure distension of the human middle cerebral artery (MCA). METHODS: Ten healthy volunteers (age: 30.3 ± 10.8 years) underwent ultra-high-field (7-tesla) MRI scanning. Time-of-flight angiography and phase-contrast flow imaging were used to locate the M1 segment of the MCA and to determine the occurrence of systole and diastole. High-resolution cross-sectional cardiac triggered T2-weighted images of the M1 segment of the MCA were acquired in systole and diastole. RESULTS: The average distension of the MCA area from diastole to systole was 2.58% (range: 0.08%-6.48%). There was no significant correlation between MCA distension and the pulsatility index, calculated from the phase-contrast flow velocity profiles. CONCLUSION: These results lead to the first noninvasive image-based estimation of distensibility of the MCA (approx. 5.8 × 10-4 mm Hg-1) and demonstrate that ultra-high-field MRI could be a promising tool for investigating distensibility of intracranial arteries in relation to cerebrovascular pathology.

Cardiovascular Response Patterns to Sympathetic Stimulation by Central Hypovolemia.

In healthy subjects, variation in cardiovascular responses to sympathetic stimulation evoked by submaximal lower body negative pressure (LBNP) is considerable. This study addressed the question whether inter-subject variation in cardiovascular responses coincides with consistent and reproducible responses in an individual subject. In 10 healthy subjects (5 female, median age 22 years), continuous hemodynamic parameters (finger plethysmography; Nexfin, Edwards Lifesciences), and time-domain baroreflex sensitivity (BRS) were quantified during three consecutive 5-min runs of LBNP at -50 mmHg. The protocol was repeated after 1 week to establish intra-subject reproducibility. In response to LBNP, 5 subjects (3 females) showed a prominent increase in heart rate (HR; 54 ± 14%, p = 0.001) with no change in total peripheral resistance (TPR; p = 0.25) whereas the other 5 subjects (2 females) demonstrated a significant rise in TPR (7 ± 3%, p = 0.017) with a moderate increase in HR (21 ± 9%, p = 0.004). These different reflex responses coincided with differences in resting BRS (22 ± 8 vs. 11 ± 3 ms/mmHg, p = 0.049) and resting HR (57 ± 8 vs. 71 ± 12 bpm, p = 0.047) and were highly reproducible over time. In conclusion, we found distinct cardiovascular response patterns to sympathetic stimulation by LBNP in young healthy individuals. These patterns of preferential autonomic blood pressure control appeared related to resting cardiac BRS and HR and were consistent over time.

Assessment of middle cerebral artery diameter during hypocapnia and hypercapnia in humans using ultra-high-field MRI.

In the evaluation of cerebrovascular CO2 reactivity measurements, it is often assumed that the diameter of the large intracranial arteries insonated by transcranial Doppler remains unaffected by changes in arterial CO2 partial pressure. However, the strong cerebral vasodilatory capacity of CO2 challenges this assumption, suggesting that there should be some changes in diameter, even if very small. Data from previous studies on effects of CO2 on cerebral artery diameter [middle cerebral artery (MCA)] have been inconsistent. In this study, we examined 10 healthy subjects (5 women, 5 men, age 21-30 yr). High-resolution (0.2 mm in-plane) MRI scans at 7 Tesla were used for direct observation of the MCA diameter during hypocapnia, -1 kPa (-7.5 mmHg), normocapnia, 0 kPa (0 mmHg), and two levels of hypercapnia, +1 and +2 kPa (7.5 and 15 mmHg), with respect to baseline. The vessel lumen was manually delineated by two independent observers. The results showed that the MCA diameter increased by 6.8 ± 2.9% in response to 2 kPa end-tidal P(CO2) (PET(CO2)) above baseline. However, no significant changes in diameter were observed at the -1 kPa (-1.2 ± 2.4%), and +1 kPa (+1.4 ± 3.2%) levels relative to normocapnia. The nonlinear response of the MCA diameter to CO2 was fitted as a continuous calibration curve. Cerebral blood flow changes measured by transcranial Doppler could be corrected by this calibration curve using concomitant PET(CO2) measurements. In conclusion, the MCA diameter remains constant during small deviations of the PET(CO2) from normocapnia, but increases at higher PET(CO2) values.