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Background: The baroreflex regulates arterial blood pressure (BP). During periods when blood pressure changes, cerebral blood flow (CBF) is kept constant by cerebral autoregulation (CA). In patients with diabetes mellitus (DM), low baroreflex sensitivity (BRS) is associated with impaired CA. As sevoflurane-based anaesthesia obliterates BRS, we hypothesised that this could aggravate the already impaired CA in patients with DM resulting in a 'double-hit' on cerebral perfusion leading to increased fluctuations in blood pressure and cerebral perfusion., Methods: On the day before surgery, we measured CBF velocity (CBFV), heart rate, and BP to determine BRS and CA efficacy (CBFV mean -to-BP mean -phase lead) in 25 patients with DM and in 14 controls. During the operation, BRS and CA efficacy were determined during sevoflurane-based anaesthesia. Patients with DM were divided into a group with high BRS (DM BRS↑ ) and a group with low BRS (DM BRS↓ ). Values presented are median (inter-quartile range)., Results: Preoperative vs intraoperative BRS was 6.2 (4.5-8.5) vs 1.9 (1.1-2.5, P<0.001) ms mm Hg -1 for controls, 5.8 (4.9-7.6) vs 2.7 (1.5-3.9, P<0.001) ms mm Hg -1 for patients with DM BRS↑ , and 1.9 (1.5-2.8) vs 1.1 (0.6-2.5, P=0.31) ms mm Hg -1 for patients with DM BRS↓ . Preoperative vs intraoperative CA efficacy was 43° (38-46) vs 43° (38-51, P=0.30), 44° (36-49) vs 41° (32-49, P=0.52), and 34° (28-40) vs 30° (27-38, P=0.64) for controls, DM BRS↑ , and DM BRS↓ patients, respectively., Conclusions: In diabetic patients with low preoperative BRS, preoperative CA efficacy was also impaired. In controls and diabetic patients, CA was unaffected by sevoflurane-based anaesthesia. We therefore conclude that sevoflurane-based anaesthesia does not contribute to a 'double-hit' phenomenon on cerebral perfusion., Clinical Trial Registration: NCT 03071432., (Copyright © 2018. Published by Elsevier Ltd.)

Dynamic cerebral autoregulation (CA) has been studied previously using spectral analysis of oscillations in arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV). The dynamics of the CA can be modeled as a high-pass filter. The purpose of this study is to compare CA of blood pressure oscillations induced by gravitational loading to CA during resting conditions. We subjected twelve healthy subjects to repeated sinusoidal head-up (0 degrees - 60 degrees) tilts at several set frequencies (0.07 to 0.25 Hz) on a computer controlled tilt table while we recorded ABP (Finapres) and CBFV (transcranial Doppler ultrasound). We fitted the data sets to a high-pass filter model and computed an average time constant (T). Our results show similar phase leads of CBFV to ABPbrain in the rest recording and in sinusoidal tilting, in the studied frequency range. The transfer function gain of the resting spectra increased with increasing frequency, the gain of the tilting spectra did not. Fitting the phase responses of both data sets to a high pass filter model yielded similar time constants.

Head-down tilted bedrest is a ground-based microgravity simulation model. Since in this position the influence of chief external determinants of circadian blood pressure variation, i.e. activity and posture, are reduced, it may reveal endogenous oscillatory factors. The effects of 42 days of 6 degrees head-down tilt on the circadian profiles of continuous finger blood pressure, heart rate, stroke volume, cardiac output and total peripheral resistance were analysed. In seven healthy volunteers (25-31 years) twelve 22 h Portapres registrations were performed: two in an ambulatory baseline period, eight during 42 days of head-down tilt, and two during recovery. Stroke volume was estimated by a pulse contour method ('Modelflow') from the finger arterial blood pressure tracing. Head-down tilt rapidly reduced circadian BP variation, especially for diastolic blood pressure. No effect of long-term head-down tilt on blood pressure level was observed. The day-night difference in heart rate was essentially unaffected. Cardiac output was maintained through an increase of heart rate and simultaneous decline of stroke volume. Our observations confirm the overriding importance of physical activity and orthostatic load on the diurnal variation of BP. The time-frame of the changes in stroke volume and heart rate during head-down tilt might point to a contribution of other factors besides a reduction of circulating blood volume affecting cardiovascular performance under these conditions.

The condition of microgravity during spaceflight imposes a new challenge to the cardiovascular system and to its homeostatic mechanisms. Initial fluids shifts from the dependent parts to the upper parts of the body are supposed to induce a plethora of effects which eventually lead to the well-known puffy faces and chicken legs' of astronauts. At the same time some 2-3 kgs. in fluid is lost in urine and by diminished uptake. For research into these longer-term effects of spaceflight extensive physiologic experiments are required in space. In view of the high cost and the logistic problems related to space-research much work is done in simulation experiments like bedrest or head down tilt studies. For the very initial effects of micro-G parabolic flight can be used. In parabolic flights we have addressed the question of immediate cardiovascular effects of the transition into microgravity. Since a parabola will last for not more than some 25 seconds, one may expect to observe mainly changes in the outflow of the autonomic nervous system, reflecting in blood pressure and heart rate as easily measurable parameters. Such changes can be expected to be caused by the sudden disappearance of hydrostatic effects and the shifts of fluid from pools where it is kept under the influence of gravity. Hydrostatic effects will play a role in the position of the baroreceptors with respect to the heart: in the upright position the carotid sinuses are some 25 cm above heart level, consequently they observe a lower pressure than that at the heart. When this effect disappears in micro-G a suddenly increased pressure will be observed and the baroreflex is called into action. On the venous side blood will rush to the right atrium when it is no longer pulled down in the compliant vessels of the abdomen and legs. This may be expected to lead to increased pressures on the low-pressure side of the heart. Apart from changes in filling of the left heart this may lead to autonomic nervous effects on systemic blood pressure and heart rate as well.