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... Show morePurpose 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. Show less
The primary aim of the project “Go with the flow: the heart-brain axis” was to elucidate the interaction between heart and the brain, across the lifespan. This was done by integration of... Show moreThe primary aim of the project “Go with the flow: the heart-brain axis” was to elucidate the interaction between heart and the brain, across the lifespan. This was done by integration of physiological concepts into the MRI-environment and by monitoring brain perfusion at both the macrovascular level (using transcranial Doppler; TCD) and the tissue level (using arterial spin labeling MRI; ASL). This thesis focused on the comparison and validation of these two modalities used in this project. We found that high levels of end-tidal CO2, blood pressure and handgrip all influence the middle cerebral artery (MCA) diameter, challenging the long-held assumption of diameter constancy. Furthermore, we found that during rhythmic handgrip the flow velocity (TCD) increased, whereas no change in the MCA flow territory (ASL) could be observed. Therefore, whole-brain CBF-measurements by ASL do not support the claim that a change in flow velocity measured by TCD can be used as a proxy for regional CBF during rhythmic handgrip exercise. Finally, we found in simulations and in-vivo experiments only modest influence of the cardiac cycle on the end-of-labeling. Therefore, cardiac triggering at the start or the end of labeling has little benefit to pseudo-Continuous ASL signal stability. Show less
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... Show moreIn 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. Show less
Bronzwaer, A.S.G.T.; Verbree, J.; Buchem, M.A. van; Daemen, M.J.A.P.; Osch, M.J.P. van; Lieshout, J.J. van 2016