Cerebrovascular Resistance Index Research Articles

Dynamic cerebral autoregulation after intracerebral hemorrhage: A case-control study

BackgroundDynamic cerebral autoregulation after intracerebral hemorrhage (ICH) remains poorly understood. We performed a case-control study to compare dynamic autoregulation between ICH patients and healthy controls.MethodsTwenty-one patients (66 ± 15 years) with early (< 72 hours) lobar or basal ganglia ICH were prospectively studied and compared to twenty-three age-matched controls (65 ± 9 years). Continuous measures of mean flow velocity (MFV) in the middle cerebral artery and mean arterial blood pressure (MAP) were obtained over 5 min. Cerebrovascular resistance index (CVRi) was calculated as the ratio of MAP to MFV. Dynamic cerebral autoregulation was assessed using transfer function analysis of spontaneous MAP and MFV oscillations in the low (0.03-0.15 Hz) and high (0.15-0.5 Hz) frequency ranges.ResultsThe ICH group demonstrated higher CVRi compared to controls (ipsilateral: 1.91 ± 1.01 mmHg·s·cm-1, p = 0.04; contralateral: 2.01 ± 1.24 mmHg·s·cm-1, p = 0.04; vs. control: 1.42 ± 0.45 mmHg·s·cm-1). The ICH group had higher gains than controls in the low (ipsilateral: 1.33 ± 0.58%/mmHg, p = 0.0005; contralateral: 1.47 ± 0.98%/mmHg, p = 0.004; vs. control: 0.82 ± 0.30%/mmHg) and high (ipsilateral: 2.11 ± 1.31%/mmHg, p < 0.0001; contralateral: 2.14 ± 1.49%/mmHg, p < 0.0001; vs. control: 0.66 ± 0.26%/mmHg) frequency ranges. The ICH group also had higher coherence in the contralateral hemisphere than the control (ICH contralateral: 0.53 ± 0.38, p = 0.02; vs. control: 0.38 ± 0.15) in the high frequency range.ConclusionsPatients with ICH had higher gains in a wide range of frequency ranges compared to controls. These findings suggest that dynamic cerebral autoregulation may be less effective in the early days after ICH. Further study is needed to determine the relationship between hematoma size and severity of autoregulation impairment.

Transcranial Doppler Studies on Cerebral Autoregulation Suggest Prolonged Cerebral Vasoconstriction in a Subgroup of Patients with Orthostatic Intolerance

We studied the cerebral autoregulation in a subgroup of patients with orthostatic intolerance, who exhibited excessively decreased middle cerebral artery flow velocity (MCAFV) on transcranial Doppler sonography (TCD) during head-up tilt (HUT) test but without orthostatic hypotension or postural tachycardia. Twenty patients and 20 age- and sex-matched controls underwent Valsalva maneuver (VM) and HUT test with simultaneous monitoring of MCAFV by TCD and blood pressure, heart rate recordings. The pulsatility index (PI), cerebrovascular resistance (CVR) and autoregulatory indices were calculated. During HUT, patients had marked MCAFV reduction (−29.0 ± 5.25% vs. −8.01 ± 4.37%), paradoxically decreased PI (0.68 ± 0.17 vs. 0.96 ± 0.28) but increased CVR (45.7 ± 16.7% vs. 14.3 ± 12.6%). The MCAFV decreased similarly during early phase II of VM in both groups but did not recover to baseline in patients during late phase II, phase III and less overshoot in phase IV (−11 ± 16.7% vs. +2.2 ± 17.9 %; −15.4 ± 16.5% vs. −2.4 ± 17.8% and 16.7 ± 22.9% vs. 38.7 ± 26.5%, respectively). We concluded that in these patients, cerebrovascular vasoconstriction in response to physiologic stimulation was normal but relaxation during and after stimulation were impaired, indicating prolonged cerebral vasoconstriction.

Autonomic dysfunction affects cerebral neurovascular coupling

Autonomic failure (AF) affects the peripheral vascular system, but little is known about its influence on cerebrovascular regulation. Patients with familial amyloidotic polyneuropathy (FAP) were studied as a model for AF. Ten mild (FAPm), 10 severe (FAPs) autonomic dysfunction FAP patients, and 15 healthy controls were monitored in supine and sitting positions for arterial blood pressure (ABP) and heart rate (HR) with arterial volume clamping, and for blood flow velocity (BFV) in posterior (PCA) and contralateral middle cerebral arteries (MCA) with transcranial Doppler. Analysis included resting BFV, cerebrovascular resistance parameters (cerebrovascular resistance index, CVRi; resistance area product, RAP; and critical closing pressure, CrCP), and neurovascular coupling through visually evoked BFV responses in PCA (gain, rate time, attenuation, and natural frequency). In non-stimulation conditions, in each position, there were no significant differences between the groups, regarding HR, BP, resting BFV, and vascular resistance parameters. Sitting ABP was higher than in supine in the three groups, although only significantly in controls. Mean BFV was lower in sitting in all the groups, lacking statistical significance only in FAPs PCA. CVRi and CrCP increased with sitting in all the groups, while RAP increased in controls but decreased in FAPm and FAPs. In visual stimulation conditions, FAPs comparing to controls had a significant decrease of natural frequency, in supine and sitting, and of rate time and gain in sitting position. These results demonstrate that cerebrovascular regulation is affected in FAP subjects with AF, and that it worsens with orthostasis.

Increases in cerebrovascular impedance in older adults

This study explored a novel method for measuring cerebrovascular impedance to quantify the relationship between pulsatile changes in cerebral blood flow (CBF) and arterial pressure. Arterial pressure in the internal or common carotid artery (applanation tonometry), CBF velocity in the middle cerebral artery (transcranial Doppler), and end-tidal CO(2) (capnography) were measured in six young (28 ± 4 yr) and nine elderly subjects (70 ± 6 yr). Transfer function method was used to estimate cerebrovascular impedance. Under supine resting conditions, CBF velocity was reduced in the elderly despite the fact that they had higher arterial pressure than young subjects. As expected, cerebrovascular resistance index was increased in the elderly. In both young and elderly subjects, impedance modulus was reduced gradually in the frequency range of 0.78-8 Hz. Phase was negative in the range of 0.78-4.3 Hz and fluctuated at high frequencies. Compared with the young, impedance modulus increased by 38% in the elderly in the range of 0.78-2 Hz and by 39% in the range of 2-4 Hz (P < 0.05). Moreover, increases in impedance were correlated with reductions in CBF velocity. Collectively, these findings demonstrate the feasibility of assessing cerebrovascular impedance using the noninvasive method developed in this study. The estimated impedance modulus and phase are similar to those observed in the systemic circulation and other vascular beds. Moreover, increases in impedance in the elderly suggest that arterial stiffening, besides changes in cerebrovascular resistance, contributes to reduction in CBF with age.

Impairment of Cerebral Blood Flow Regulation in Astronauts With Orthostatic Intolerance After Flight

We investigated cerebral blood flow regulation in astronauts before and after flights. We hypothesized that autoregulation would be different before flight and after flight between nonfinishers and the finishers of a stand test. Twenty-seven astronauts from shuttle missions lasting 8 to 16 days underwent a 10-minute stand test: 10 days before flight, 1 to 2 hours and 3 days after landing. Mean blood flow velocity of the middle cerebral artery (MCA) was measured using transcranial Doppler; Mean arterial pressure was measured using a Finapres (Ohmeda, Englewood, CO) and was adjusted to the level of the MCA (BP(MCA)). Cross-spectral power, gain, phase, and coherence were determined for the relation between BP(MCA) and the cerebrovascular resistance index mean blood flow velocity/BP(MCA). BP(MCA) was reduced with stand (P<0.001). Differences between finishers and nonfinishers (P=0.011) and over test days (P=0.004) were observed. Cerebrovascular conductance was affected by stand (P<0.001), by group (P<0.001) with a group by stand, and test day interaction (P<0.01). Preflight data suggest that the nonfinishers were operating at a higher cerebral vasodilation than finishers for a given BP(MCA), and on landing day the nonfinishers had a greater decrease in mean blood flow velocity as a function of BP(MCA) with standing compared to finishers and preflight. There was a significant interaction effect of gender over the test days and from supine to stand (P=0.035). Our results indicate that the cause of presyncope in astronauts may be related to a mismatch of cerebral blood flow with blood pressure. Astronaut gender may also play a role in susceptibility to orthostatic intolerance after flight.

Analgesic effect and mechanism of the three TCM-herbal drug-combination Tou Feng Yu Pill on treatment of migraine

It is well known that pain is one of the most important characteristics of migraine. Therefore, it is important and interesting to investigate the analgesic effect and mechanism of drugs which are used to treat migraine. Tou Feng Yu pill (TFY) is a traditional Chinese herbal medicine, consisting of the three Chinese herbal drugs Radix Angelicae dahuricae (Baizhi), Rhizome Ligustici (Chuanxiong) and Folium Camelliae sinensis (green tea) for the treatment of migraine. In this study, we found that TFY could significantly reduce the writhing times induced by acetic acid and licking foot response induced by formalin, and extend the writhing latent period. But the analgesic effect was not observed at hot-plate test. Meanwhile, experimental migrainous model induced by nitroglycerin was used to investigate the therapeutic effect of TFY. Compared with the control group, the levels of plasma calcitonin gene related to peptide (CGRP), serum nitric oxide (NO) and contents of brain dopamine (DA) in TFY administration groups were significantly decreased, and the levels of plasma endothelin (ET) and contents of brain 5-hydroxytryptamine (5-HT) and norepinephrine (NE) were remarkably increased, also the ratio of ET/NO was clearly corrected. Furthermore, the improving effect of behavior abnormality was observed in TFY administration rats. Meanwhile, isolated vascular ring test indicated that TFY had an significant effect on vasomotion, and antagonize vasospasm; moreover TFY also could increase cerebral blood flow (CBF) and reduce cerebrovascular resistance index (RI) in normal rabbits, which verified the effect of TFY on vasomotion and abnormal hemorheology. All the results indicate that TFY has an effective therapeutical action on migraine, which may be related to three aspects as following: firstly, adjusting the level of neurotransmitters, neuropeptides and vasoactive substances, relieving neurogenic inflammation; secondly, improving vasomotion, increase cerebral blood flow, then improving hemorheology; finally, increasing pain threshold, relieving or preventing headache. These findings provide additional pharmacological information and may contribute for the further study and use of TFY as a phytomedicine.

The effects of sevoflurane and propofol on cerebral hemodynamics during intracranial tumors surgery under monitoring the depth of anesthesia

Hemodynamic effects during cerebral tumor resection surgery under monitoring the depth of anesthesia and during recovery in sevoflurane- or propofol-anesthetized patients have not been previously compared. To compare cerebral hemodynamic changes using transcranial Doppler sonography during sevoflurane or propofol anesthesia under state entropy (SE) monitoring, and during recovery period. In a randomized manner, 130 patients received sevoflurane (group T-S) or propofol (group T-P) to maintain SE at 40-50. Cerebral blood flow velocity (Vmean) in the middle cerebral artery was evaluated at baseline, after tracheal intubation, opening of the dura mater, tumor resection, skin closure, extubation, and two hours after extubation. Cerebrovascular resistance index (RAP), estimated cerebral perfusion pressure (eCPP), and cerebral blood flow index (CBFI) were calculated off-line. During surgery SE was 40.6 (SD, 8.1) in the group T-S and 44.0 (SD, 7.4) in the group T-P. Blood pressure was significantly higher in the group T-P. Compared to the baseline, Vmean decreased by 16.6% and 23.5% in the groups T-S and T-P, respectively (P<0.05). RAP and eCPP were higher in the group T-P versus the group T-S: 28.9% and 5.2%, respectively, above the baseline for RAP (P<0.005) and 3.2% and 16.9% below the baseline for eCPP (P<0.005). CBFI was below the baseline by 20.1% and 24.0% in the groups T-S and T-P, respectively (P>0.05). After the extubation and 2 hours later, Vmean recovered comparably with no differences in RAP, eCPP, or CBFI between the two groups. At the comparable depth of anesthesia for intracranial tumors surgery and during recovery, sevoflurane had no major effect on cerebral circulation measured by transcranial Doppler sonography as compared with propofol. Our results add to current knowledge on the safety of sevoflurane in neuroanesthesia.

Altered Cerebral Hemodynamics in Early Alzheimer Disease: A Pilot Study Using Transcranial Doppler

Cerebrovascular disease may contribute to the development and progression of Alzheimer's disease (AD). This study investigated whether impairments in cerebral hemodynamics can be detected in early-stage AD. Nine patients with mild AD and eight cognitively normal controls matched for age underwent brain magnetic resonance imaging and neuropsychological evaluation, followed by assessment of steady-state cerebral blood flow velocity (CBFV, transcranial Doppler), blood pressure (BP, Finapres), and cerebrovascular resistance index (BP/CBFV). Cerebral hemodynamics were quantified using spectral and transfer function analysis of BP and CBFV in rest, during standing up after squat, and during repeated squat-stand maneuvers. Compared to controls, AD patients had lower CBFV and higher cerebrovascular resistance index, unexplained by brain atrophy. Low-frequency variability of BP was enhanced, suggesting impaired arterial baroreflex function. However, CBFV variability was reduced despite enhanced BP variability, and dynamic cerebral autoregulation was not impaired. In conclusion, despite a distinct pattern of altered cerebral hemodynamics, AD patients may have normal autoregulation. However, the challenges for autoregulation in AD are higher, as our data show enhanced BP fluctuations. Increased cerebral vasoconstriction or reduced vasomotion also may attenuate CBFV variability.

Dynamic pressure–flow relationship of the cerebral circulation during acute increase in arterial pressure

The physiological mechanism(s) for the regulation of the dynamic pressure-flow relationship of the cerebral circulation are not well understood. We studied the effects of acute cerebral vasoconstriction on the transfer function between spontaneous changes in blood pressure (BP) and cerebral blood flow velocity (CBFV) in 13 healthy subjects (30 +/- 7 years). CBFV was measured in the middle cerebral artery using transcranial Doppler. BP was increased stepwise with phenylephrine infusion at 0.5, 1.0 and 2.0 microg kg(-1) min(-1). Phenylephrine increased BP by 11, 23 and 37% from baseline, while CBFV increased (11%) only with the highest increase in BP. Cerebrovascular resistance index (BP/CBFV) increased progressively by 6, 17 and 23%, demonstrating effective steady-state autoregulation. Transfer function gain at the low frequencies (LF, 0.07-0.20 Hz) was reduced by 15, 14 and 14%, while the phase was reduced by 10, 17 and 31%. A similar trend of changes was observed at the high frequencies (HF, 0.20-0.35 Hz), but gain and phase remained unchanged at the very low frequencies (VLF, 0.02-0.07 Hz). Windkessel model simulation suggests that increases in steady-state cerebrovascular resistance and/or decreases in vascular compliance during cerebral vasoconstriction contribute to the changes in gain and phase. These findings suggest that changes in steady-state cerebrovascular resistance and/or vascular compliance modulate the dynamic pressure-flow relationship at the low and high frequencies, while dynamic autoregulation is likely to be dominant at the very low frequencies. Thus, oscillations in CBFV are modulated not only by dynamic autoregulation, but also by changes in steady-state cerebrovascular resistance and/or vascular compliance.

Autoregulation in the Posterior Circulation Is Altered by the Metabolic State of the Visual Cortex

Previous studies suggest that dynamic autoregulation in the posterior cerebral artery (PCA) is less efficient compared to the middle cerebral artery (MCA). We examined the role of cerebral vasodilation caused by metabolic activation (ie, visual stimulus) on autoregulatory characteristics in the 2 vascular territories. Blood flow velocity in the PCA and MCA and mean arterial pressure were measured continuously in 45 healthy volunteers (62+/-3 years) while seated with eyes open. Additional 20 subjects (60+/-5 years) were examined with eyes closed and open. Autoregulation was assessed using transfer function gains in both the PCA and MCA territories in the low (0.03-0.07 Hz), high (0.07-0.15 Hz), and cardiac (approximately 1 Hz) frequency ranges. With eyes open, gains were significantly higher in the PCA compared to the MCA in the low (PCA: 1.41+/-0.09 vs MCA: 1.18+/-0.07; P=0.003) and high (PCA: 2.06+/-0.12 vs MCA: 1.61+/-0.08; P=0.0001) frequencies. Opening eyes increased blood flow velocity and reduced cerebrovascular resistance index in the PCA but not in MCA. This vasodilation in the PCA was associated with increased gain in the low (autoregulatory) frequency, whereas MCA gain did not change (PCA: 0.89+/-0.14 vs 1.31+/-0.17, MCA: 1.24+/-0.16 vs 1.16+/-0.11; P=0.02). Dilation of the PCA territory during visual cortex activation resulted in increased PCA transfer function gain without changing MCA gain. Thus, impaired autoregulation in the PCA reported in previous literature is likely the result of metabolic vasodilation and not an inherent difference in the autoregulatory characteristics of the posterior circulation.

The Effects of Hypocapnia and the Cerebral Autoregulatory Response on Cerebrovascular Resistance and Apparent Zero Flow Pressure During Isoflurane Anesthesia

Simultaneous recordings of arterial blood pressure (ABP) and middle cerebral artery blood velocity can be used to calculate the apparent zero flow pressure (aZFP). The inverse of the slope of the pressure-velocity relationship is known as resistance area product (RAP) and is an index of cerebrovascular resistance. There is little information available regarding the effects of vasoactive drugs, arterial carbon dioxide (Paco(2)), and impaired cerebral autoregulation on aZFP and RAP during general anesthesia. During isoflurane anesthesia, we investigated the effects of hypocapnia and the effects of a phenylephrine infusion, on aZFP and RAP. Radial ABP and transcranial Doppler middle cerebral artery blood velocity signals were recorded in 11 adults undergoing isoflurane anesthesia. A phenylephrine infusion was used to increase ABP and ventilation was adjusted to control Paco(2). Cerebral hemodynamic variables were compared at two levels of mean ABP (approximately 80 and 100 mm Hg) and at two levels of Paco(2): normocapnia (Paco(2) 38-43 mm Hg) and hypocapnia (Paco(2) 27-34 mm Hg). Two aZFP analysis methods were compared: one based on linear regression and one based on Fourier analysis of the waveforms. At the lower ABP, aZFP was 23 +/- 11 mm Hg and 30 +/- 13 mm Hg (mean +/- sd) with normocapnia and hypocapnia, respectively (P < 0.001) and RAP was 0.76 +/- 0.97 mm Hg x s x cm(-1) and 1.16 +/- 0.16 mm Hg x s x cm(-1) with normocapnia and hypocapnia, respectively (P < 0.001). Similar effects of hypocapnia were seen at the higher ABP. With normocapnia, isoflurane impaired cerebral autoregulation and aZFP did not change with the increase in ABP. With hypocapnia, cerebral autoregulation was not significantly impaired and increasing ABP was associated with increased aZFP (from 30 +/- 13 to 35 +/- 13 mm Hg, P < 0.01) and increased RAP (from 1.16 +/- 0.16 to 1.52 +/- 0.20 mm Hg x s x cm(-1), P < 0.001). Calculation of the relative contributions of aZFP and RAP to the cerebral hemodynamic responses indicated that changes in RAP appeared to have a greater influence than changes in aZFP. The mean difference between the two methods of determining aZFP (Fourier-regression) was 0.5 +/- 3.6 mm Hg (mean +/- 2sd). During isoflurane anesthesia, two interventions that increase cerebral arteriolar tone, hypocapnia and the autoregulatory response to increasing ABP, were associated with increased RAP and increased aZFP. The effect of changes in RAP appeared to be quantitatively greater than the effects of changes in aZFP. These results imply that arteriolar tone influences cerebral blood flow by controlling both resistance and effective downstream pressure.

Autonomic and cerebrovascular abnormalities in mild COPD are worsened by chronic smoking

Patients with chronic obstructive pulmonary disease (COPD) may develop hypercapnia and hypoxia, two main determinants of cerebral blood flow. The current authors tested whether cerebrovascular regulation was altered in mild COPD, modified by manoeuvres acutely improving autonomic cardiovascular modulation or influenced by smoking habit. In 15 eucapnic normoxic mild COPD patients (eight smokers) and 28 age-matched controls (14 smokers), midcerebral artery blood flow velocity (MCFV), end-tidal carbon dioxide tension (P(ET,CO2)), arterial oxygen saturation (S(a,O2)), ECG and blood pressure at rest were monitored during progressive hypercapnic hyperoxia, isocapnic hypoxia, slow breathing and oxygen administration. MCFV, arterial baroreflex and dynamic MCFV-blood pressure relationships were compared by phase analysis. COPD and control smokers showed higher MCFV (when corrected for P(ET,CO2)), lower cerebrovascular resistance index and lower sensitivity to hypercapnia than nonsmokers, with equal sensitivity to S(a,O2) and similar phase analysis. Arterial baroreflex was depressed in all COPD patients. Slow breathing and oxygen administration improved baroreflex sensitivity and reduced MCFV in all COPD patients. Patients with mild chronic obstructive pulmonary disease show autonomic dysfunction. Chronic smoking induces cerebral vasodilation and impairs cerebrovascular control. All abnormalities can be partly corrected by improving the cardio- and cerebrovascular autonomic modulation, suggesting that functional autonomic abnormalities are already present at an early stage of disease.

Cerebral Hemodynamics During Treatment With Sodium Nitroprusside Versus Labetalol in Malignant Hypertension

In patients with malignant hypertension, immediate blood pressure reduction is indicated to prevent further organ damage. Because cerebral autoregulatory capacity is impaired in these patients, a pharmacologically induced decline of blood pressure reduces cerebral blood flow with the danger of cerebral hypoperfusion. We compared the reduction in transcranial Doppler-determined middle cerebral artery blood velocity during blood pressure lowering with sodium nitroprusside with that of labetalol. Therefore, in 15 patients, fulfilling World Health Organization criteria for malignant hypertension, beat-to-beat mean arterial pressure, systemic vascular resistance (Modelflow), mean middle cerebral artery blood velocity, and cerebrovascular resistance index (mean blood pressure:mean middle cerebral artery blood flow velocity ratio), were monitored during treatment with sodium nitroprusside (n=8) or labetalol (n=7). The reduction in mean arterial blood pressure with sodium nitroprusside (-28+/-3%; mean+/-SEM) and labetalol (-28+/-4%) was comparable. With labetalol, both systemic and cerebral vascular resistance decreased proportionally (-13+/-10% and -17+/-5%), whereas with sodium nitroprusside, the decline in systemic vascular resistance was larger than that in cerebral vascular resistance (-53+/-4% and -7+/-4%). The rate of reduction in middle cerebral artery blood velocity was smaller with labetalol than with sodium nitroprusside (0.45+/-0.05% versus 0.78+/-0.04% cm.s(-1).%mm Hg(-1); P<0.05). In conclusion, sodium nitroprusside reduced systemic vascular resistance rather than cerebral vascular resistance with a larger rate of reduction in middle cerebral artery blood velocity, suggesting a preferential blood flow to the low resistance systemic vascular bed rather than the cerebral vascular bed.

WISE-2005: adrenergic responses of women following 56-days, 6° head-down bed rest with or without exercise countermeasures

We tested the hypotheses that women completing 56 days, 6 degrees head-down bed-rest (HDBR) would have changes in sensitivity of cardiovascular responses to adrenergic receptor stimulation and that frequent aerobic and resistive exercise would prevent these changes. Twenty-four women, eight controls, eight exercisers (lower body negative pressure treadmill and flywheel resistance exercise), and eight receiving nutritional supplement but no exercise were studied in baseline and during administration of the beta-agonist isoproterenol (ISO) and the alpha- and beta-agonist norepinephrine (NOR). In the control and nutrition groups, HDBR increased heart rate (HR) and reduced stroke volume (SV), and there was a significantly greater increase in HR with ISO after HDBR. In contrast, the HR and SV of the exercise group were unchanged from pre-HDBR. After HDBR, leg vascular resistance (LVR) was greater than pre-HDBR in the exercise group but reduced in control and nutrition. LVR was reduced with ISO and increased with NOR. Changes in total peripheral resistance were similar to those of LVR but of smaller magnitude, perhaps because changes in cerebrovascular resistance index were directionally opposite to those of LVR. There were no changes in sensitivity of the vascular resistance responses to adrenergic stimulation. The HR response might reflect a change in sensitivity or a necessary response to the reduction in SV after HDBR in control and nutrition groups. The reduced peripheral vascular resistance after HDBR might help to explain orthostatic intolerance in women. Exercise was an effective countermeasure to the HDBR effects.

Cold pressor test in tetraplegia and paraplegia suggests an independent role of the thoracic spinal cord in the hemodynamic responses to cold

Cold application to the hand (CAH) is associated in healthy people with increase in heart rate (HR) and blood pressure (BP). To study hemodynamic responses to CAH in humans following spinal cord injuries of various levels, and examine the effect of spinal cord integrity on the cold pressor response. An experimental controlled study. The spinal research laboratory, Loewenstein Hospital, Raanana, Israel. Thirteen healthy subjects, 10 patients with traumatic T(4-6) paraplegia and 11 patients with traumatic C(4-7) tetraplegia. HR, BP, HR and BP spectral components (low frequency, LF; high frequency, HF; LF/HF), cerebral blood flow velocity (CBFV) and cerebrovascular resistance index (CVRi). The outcome measures of the three subject groups monitored for HR, BP and CBFV were compared from 5 min before to 5 min after 40-150 s of CAH. The recorded signals were digitized online and analyzed offline in both the time and frequency domains. During CAH, HR and CVRi increased significantly in all subject groups (P<0.001), and BP in control subjects and in the tetraplegia group (P<0.01). BP increase was not statistically significant in paraplegia, and CBFV, HR LF, HR HF and BP LF did not change significantly during CAH in any group. The CAH effect in tetraplegia and the suppressed BP increase in paraplegia, supported by the other findings, suggest a contribution of an independent thoracic spinal mechanism to the cold pressor response.

Effects of hyperglycemia on the cerebrovascular response to rhythmic handgrip exercise

Dynamic cerebral autoregulation (CA) is challenged by exercise and may become less effective when exercise is exhaustive. Exercise may increase arterial glucose concentration, and we evaluated whether the cerebrovascular response to exercise is affected by hyperglycemia. The effects of a hyperinsulinemic euglycemic clamp (EU) and hyperglycemic clamp (HY) on the cerebrovascular (CVRI) and systemic vascular resistance index (SVRI) responses were evaluated in seven healthy subjects at rest and during rhythmic handgrip exercise. Transfer function analysis of the dynamic relationship between beat-to-beat changes in mean arterial pressure and middle cerebral artery (MCA) mean blood flow velocity (V(mean)) was used to assess dynamic CA. At rest, SVRI decreased with HY and EU (P < 0.01). CVRI was maintained with EU but became reduced with HY [11% (SD 3); P < 0.01], and MCA V(mean) increased (P < 0.05), whereas brain catecholamine uptake and arterial Pco(2) did not change significantly. HY did not affect the normalized low-frequency gain between mean arterial pressure and MCA V(mean) or the phase shift, indicating maintained dynamic CA. With HY, the increase in CVRI associated with exercise was enhanced (19 +/- 7% vs. 9 +/- 7%; P < 0.05), concomitant with a larger increase in heart rate and cardiac output and a larger reduction in SVRI (22 +/- 4% vs. 14 +/- 2%; P < 0.05). Thus hyperglycemia lowered cerebral vascular tone independently of CA capacity at rest, whereas dynamic CA remained able to modulate cerebral blood flow around the exercise-induced increase in MCA V(mean). These findings suggest that elevated blood glucose does not explain that dynamic CA is affected during intense exercise.

Cerebral Hemodynamics After Short- and Long-Term Reduction in Blood Pressure in Mild and Moderate Hypertension

This study tested the hypothesis that acute reduction in blood pressure (BP) at the initial stage of antihypertensive therapy compromises brain perfusion and dynamic cerebral autoregulation in patients with hypertension. Cerebral blood flow velocity and BP were measured in patients with mild and moderate hypertension and in healthy volunteers at baseline upon reduction of BP within 1 to 2 weeks of administration of losartan/hydrochlorothiazide and after 3 to 4 months of treatment. The transfer function between beat-to-beat changes in BP and cerebral blood flow velocity was estimated to assess dynamic autoregulation. After 1 to 2 weeks of treatment, BP was reduced in mild (143+/-7/88+/-4 versus 126+/-12/77+/-6 mm Hg) and moderate hypertension (163+/-11/101+/-9 versus 134+/-17/84+/-9 mm Hg; P<0.05). These reductions in BP were well maintained over the 3 to 4 month period. Cerebral blood flow velocity did not change, whereas cerebrovascular resistance index was reduced by 17% (P<0.05) after reduction in BP. Responses of cerebral blood flow velocity to head-up tilt remained unchanged. Baseline transfer function gain at the low frequencies (0.07 to 0.20 Hz) was reduced in moderate hypertension, consistent with cerebral vasoconstriction and/or enhanced dynamic autoregulation. However, this reduced transfer function gain was restored to the level of control subjects after reduction in BP. These findings, contrary to our hypothesis, demonstrate that there is a rapid adaptation of the cerebral vasculature to protect the brain from hypoperfusion even at the initial stage of antihypertensive therapy in patients with mild and moderate hypertension.

Cerebral hemodynamics after short and long‐term reduction in blood pressure in mild and moderate hypertension

This study tested the hypothesis that in contrast to the salutary effects of long-term antihypertensive therapy, reducing blood pressure (BP) at the initial stage of antihypertensive therapy compromises brain perfusion and dynamic cerebral autoregulation in patients with mild and moderate hypertension. Cerebral blood flow (CBF) velocity, BP, and cardiac output (CO) were measured in the supine position and during head-up tilt (HUT) in newly diagnosed patients with mild and moderate hypertension and in healthy volunteers. Beat-to-beat changes in BP and CBF velocity were quantified using transfer function analysis to evaluate dynamic autoregulation. After 1–2 week of administration of losartan/hydrochlorothiazide (50/12.5 – 100/25 mg, once daily) (short-term), BP was reduced in mild (from 143 ± 7/88 ± 4 to 126 ± 12/77 ± 6 mmHg) and moderate hypertension (from 163 ± 11/101 ± 9 to 134 ± 17/84 ± 9 mmHg, all P < 0.05). These reductions in BP were well maintained over the 3–4 month period of treatment (long-term). CBF velocity did not change after reductions in BP, while cerebrovascular resistance index was reduced by 17% (P < 0.05). During HUT, CBF velocity and CO were reduced similarly in control subjects and in patients with hypertension and these changes were not altered after reductions in BP. Before treatment, transfer function gain was reduced in moderate hypertension (P < 0.05). However, this reduced transfer function gain was restored to the level of control subjects after reductions in BP. These findings, contrary to our hypothesis, indicate that brain perfusion and dynamic autoregulation are not compromised in patients with mild and moderate hypertension after either short or long-term reduction in BP.

Cerebral autoregulation is preserved in multiple system atrophy: A transcranial Doppler study

Patients with multiple system atrophy (MSA) present large changes in blood pressure (BP) due to autonomic disturbances. We analyzed how this change may influence dynamic cerebral autoregulation (DCA). Simultaneous recordings of arterial BP (Finapres) and middle cerebral artery (MCA) blood flow velocity (BFV) (transcranial Doppler) were performed in 10 patients with MSA (61 +/- 12 yr of age) and 12 healthy volunteers (61 +/- 11 yr of age): cerebral BFV response to oscillations in mean BP was studied in the supine position by cross-spectral analysis of mean BP and mean MCA BFV. The DCA was also studied during the decrease in BP the first seconds when standing up from a sitting position by the assessment of the cerebrovascular resistance index (CR; mean BP/mean MCA BFV ratio). The MCA BFV/BP cross-spectral analysis showed a phase for the mid-frequency band (0.07-0.2 Hz) significantly larger in MSA, suggesting more active autoregulation in response to larger changes in BP. Changes in CR reflecting the rate of autoregulation, when standing did not differ between the two groups. These data suggest that dynamic cerebral autoregulation is preserved in MSA.

Heterogeneity of responses to orthostatic stress in homozygous twins

Early analysis into the role of genetics on cardiovascular regulation has been accomplished by comparing blood pressure and heart rate in homozygous twins during unstressed, resting physiological conditions. However, many variables, including cognitive and environmental factors, contribute to the regulation of cardiovascular hemodynamics. Therefore, the purpose of this study was to determine the hemodynamic response of identical twins to an orthostatic stress, ranging from supine rest to presyncope. Heart rate, arterial blood pressure, middle cerebral artery blood velocity, an index of cerebrovascular resistance, cardiac output, total peripheral resistance, and end-tidal carbon dioxide were measured in 16 healthy monozygotic twin pairs. Five minutes of supine resting baseline data were collected, followed by 5 min of 60 degrees head-up tilt. After 5 min of head-up tilt, lower body negative pressure was applied in increments of 10 mmHg every 3 min until the onset of presyncope, at which time the subject was returned to the supine position for a 5-min recovery period. The data indicate that cardiovascular regulation under orthostatic stress demonstrates a significant degree of variance between identical twins, despite similar orthostatic tolerance. As the level of stress increases, so does the difference in the cardiovascular response within a twin pair. The elevated variance with increasing stress may be due to an increase in the role of environmental factors, as the influential role of genetics nears a functional limit. Therefore, although orthostatic tolerance times were very similar between identical twins, the mechanism involved in sustaining cardiovascular function during increasing stress was different.