Blood Flow Velocity Fluctuations Research Articles

Periventricular- intraventricular hemorrhage in the premature infant- A historical perspective

The objective of this chapter is to trace the evolution of intraventricular hemorrhage in the premature infant highlighting the importance of the germinal matrix, a critical role for cerebral blood flow changes in the genesis of hemorrhage, clinical factors that increase the bleeding risk, and potential preventative strategies. In 1976, neuropathological studies demonstrated capillary rupture within the germinal matrix as the precursor of hemorrhage. In 1980, introduction of cranial ultrasound facilitated diagnosis of intraventricular hemorrhage. In 1979, loss of cerebral autoregulation in sick newborn infants was demonstrated. In the 1980’s, studies demonstrated the importance of intravascular factors in provoking hemorrhage. In 1983, the association of cerebral blood flow velocity fluctuations and subsequent hemorrhage was demonstrated. In 1994, antenatal steroids use to accelerate lung development was recommended. This was associated with an unanticipated reduction in hemorrhage. In the mid 1990’s early indomethacin administration was associated with a reduction of severe hemorrhage.

Is Dynamic Cerebral Autoregulation Bilaterally Impaired after Unilateral Acute Ischemic Stroke?

Whether dynamic cerebral autoregulation (dCA) is impaired focally in the affected hemisphere or bilaterally in both the affected and nonaffected hemispheres after ischemic stroke remains controversial. We therefore investigated the pattern of dCA in acute ischemic stroke patients with different subtypes. Sixty acute ischemic stroke patients with unilateral anterior circulation infarct [30 with large artery atherosclerosis (LAA), 13 with small vessel disease (SVD), and 17 with coexisting LAA and SVD] and 16 healthy controls were enrolled. Spontaneous arterial blood pressure and cerebral blood flow velocity fluctuations in both bilateral middle cerebral arteries using transcranial Doppler were recorded over 10 minutes. Transfer function analysis was applied to obtain autoregulatory parameters, autoregulation index (ARI), phase difference (PD), and gain. PD was significantly lower on both the ipsilateral and contralateral sides in the LAA group (ipsilateral, 30.74 degrees; contralateral, 29.17 degrees) and the coexisting LAA and SVD group (20.23 degrees; 13.10 degrees) than that in healthy controls (left side, 51.66 degrees; right side, 58.48 degrees) (all P < .05), but there were no significant differences between the 2 sides when compared with each other in all groups. However, in the coexisting LAA and SVD group, phase on both sides was significantly lower when compared with that in the LAA and SVD groups, respectively. The results of ARI were consistent with the findings in PD. The results indicate that dCA is bilaterally impaired in acute ischemic patients with LAA, and the coexisting SVD may aggravate the bilateral impairment of dCA.

Application of intermittent negative pressure on the lower extremity and its effect on macro- and microcirculation in the foot of healthy volunteers.

Intermittent negative pressure (INP) applied to the lower leg and foot may increase peripheral circulation. However, it is not clear how different patterns of INP affect macro‐ and microcirculation in the foot. The aim of this study was therefore to determine the effect of different patterns of negative pressure on foot perfusion in healthy volunteers. We hypothesized that short periods with INP would elicit an increase in foot perfusion compared to no negative pressure. In 23 healthy volunteers, we continuously recorded blood flow velocity in a distal foot artery, skin blood flow, heart rate, and blood pressure during application of different patterns of negative pressure (−40 mmHg) to the lower leg. Each participant had their right leg inside an airtight chamber connected to an INP generator. After a baseline period at atmospheric pressure, we applied four different 120 sec sequences with either constant negative pressure or different INP patterns, in a randomized order. The results showed corresponding fluctuations in blood flow velocity and skin blood flow throughout the INP sequences. Blood flow velocity reached a maximum at 4 sec after the onset of negative pressure (average 44% increase above baseline, P < 0.001). Skin blood flow and skin temperature increased during all INP sequences (P < 0.001). During constant negative pressure, average blood flow velocity, skin blood flow, and skin temperature decreased (P < 0.001). In conclusion, we observed increased foot perfusion in healthy volunteers after the application of INP on the lower limb.

Partial pharmacologic blockade shows sympathetic connection between blood pressure and cerebral blood flow velocity fluctuations

Cerebral autoregulation (CA) dampens transfer of blood pressure (BP)-fluctuations onto cerebral blood flow velocity (CBFV). Thus, CBFV-oscillations precede BP-oscillations. The phase angle (PA) between sympathetically mediated low-frequency (LF: 0.03–0.15Hz) BP- and CBFV-oscillations is a measure of CA quality. To evaluate whether PA depends on sympathetic modulation, we assessed PA-changes upon sympathetic stimulation with and without pharmacologic sympathetic blockade.In 10 healthy, young men, we monitored mean BP and CBFV before and during 120-second cold pressor stimulation (CPS) of one foot (0°C ice-water). We calculated mean values, standard deviations and sympathetic LF-powers of all signals, and PAs between LF-BP- and LF–CBFV-oscillations. We repeated measurements after ingestion of the adrenoceptor-blocker carvedilol (25mg). We compared parameters before and during CPS, without and after carvedilol (analysis of variance, post-hoc t-tests, significance: p<0.05).Without carvedilol, CPS increased BP, CBFV, BP-LF- and CBFV-LF-powers, and shortened PA. Carvedilol decreased resting BP, CBFV, BP-LF- and CBFV-LF-powers, while PAs remained unchanged. During CPS, BPs, CBFVs, BP-LF- and CBFV-LF-powers were lower, while PAs were longer with than without carvedilol. With carvedilol, CPS no longer shortened resting PA.Sympathetic activation shortens PA. Partial adrenoceptor blockade abolishes this PA-shortening. Thus, PA-measurements provide a subtle marker of sympathetic influences on CA and might refine CA evaluation.

Cerebrovascular hemodynamic changes in multiple sclerosis patients during head-up tilt table test: effect of high-dose intravenous steroid treatment

Demyelination in multiple sclerosis (MS) may cause damage to the vegetative nervous system. Our objective was to examine cerebral autoregulation assessed via blood pressure and cerebral blood flow velocity fluctuations during head-up tilt table testing. We also investigated the effects of high-dose intravenous corticosteroid treatment. Transcranial Doppler registration of middle cerebral artery blood flow velocity and continuous blood pressure and heart rate monitoring were performed at rest and during tilt table testing in 30 MS patients. Ten age-matched healthy subjects were also examined as controls. Correlations between mean arterial blood pressure (MBP) and cerebral blood flow velocity (CBF) fluctuations were averaged, yielding the correlation coefficient index Mx. For a subgroup of 11 patients with acute exacerbations, results were also evaluated before and after methylprednisolone treatment (1 g/day intravenously for 5 days). No significant differences in the autoregulatory indices were seen between patients and controls, or between pre- and post-steroid results. Modeling CBF velocity changes associated with a 1-mmHg increase in MBP, significant differences (p < 0.05) were detected in patients vs. controls, and also after vs. before steroid administration. We conclude that cerebrovascular autoregulation impairments are detectable in early phase MS. Corticosteroid treatment has a significant effect on hemodynamic changes in acute exacerbations.

Computational study of thermal effects of large blood vessels in human knee joint

This paper is dedicated to present a comprehensive investigation on the thermal effects of large blood vessels of human knee joint during topical cooling and fomentation treatment. A three-dimensional (3D) finite element analysis by taking full use of the anatomical CAD model of human knee joint was developed to accurately simulate the treatment process. Based on the classical Pennes bio-heat transfer equation, the time evolution of knee joint's temperature distribution and heat flux from large blood vessels was obtained. In addition, we compared several influencing factors and obtained some key conclusions which cannot be easily acquired through clinical experiments. The results indicated that the thermal effects of large blood vessels could remarkably affect the temperature distribution of knee joint during treatment process. Fluctuations of blood flow velocity and metabolic heat production rate affect little on the thermal effects of large blood vessels. Changing the temperature of blood and regimes of treatment could effectively regulate this phenomenon, which is important for many physiological activities. These results provide a guideline to the basic and applied research for the thermally significant large blood vessels in the knee organism.

Dynamic cerebral autoregulation in carotid stenosis before and after carotid stenting

Impaired dynamic cerebral autoregulation (DCA) has been shown in patients with severe (> or =70%) internal carotid artery (ICA) stenosis, but DCA in moderate (50% to 69%) ICA stenosis, especially its response to carotid revascularization, has rarely been reported. Our study aimed to characterize DCA in severe and moderate ICA stenosis before and after carotid stenting. This study included 21 patients with ICA stenosis > or =50% who received carotid stenting. Data of arterial blood pressure and cerebral blood flow velocity of the middle cerebral artery, measured by transcranial Doppler, were collected for 10 minutes < or =24 hours before and after stenting. The DCA index, represented as aMx, was assessed by calculating the Pearson product-moment correlation coefficient of spontaneous arterial blood pressure and cerebral blood flow velocity fluctuations. The relationship between aMx and stenotic severity and also alternations of aMx before and after stenting were assessed. Carotid stenting was effective to improve the DCA in the stenting side but not in the contralateral nonstenting side. In considering individual ICAs, the average aMx (mean +/- SD) increased significantly from ICA stenosis <50% (0.117 +/- 0.091) to 50% to 69% (0.349 +/- 0.144), 70% to 99% (0.456 +/- 0.147), and total occlusion (0.557 +/- 0.210; P < .05, P < .01, and P < .01, compared with 50% to 69%, 70% to 99%, or total occlusion with <50% stenosis). The correlation between the degree of ICA stenosis and the aMx was also significant (r = 0.693, P < .005). The aMx improved significantly in the stented side after carotid stenting in both moderate and severe ICA stenosis, and this finding was not affected by age, sex, risk factors, or clinical symptoms. In addition to patients with severe carotid stenosis, patients with moderate carotid stenosis may also have impaired DCA that can be restored after carotid stenting.

An Assessment of Dynamic Autoregulation from Spontaneous Fluctuations of Cerebral Blood Flow Velocity: A Comparison of Two Models, Index of Autoregulation and Mean Flow Index

Various methods of assessment of cerebral autoregulation, using spontaneous slow fluctuations of blood flow velocity (FV), arterial blood pressure, and cerebral perfusion pressure, have been used in clinical practice. We studied the association between the dynamic index of autoregulation (ARI) and time correlation index (mean flow index, Mx) in a group of patients after head injury. Fifty head-injured patients of an average age of 31 yr, sedated, paralyzed, and ventilated (mild hypocapnia) with continuous monitoring of arterial blood pressure and intracranial pressure were studied. Cerebral blood FV was monitored daily for 3 days after injury during periods that were free from interventions (e.g., suctioning). Digitally recorded data were analyzed retrospectively. ARI was calculated as a coefficient graded from 0 (absence of autoregulation) to 9 (strongest autoregulation), describing a dynamic model of autoregulation. Mx was calculated as the correlation coefficient between 40 consecutive 6-s averages of FV and cerebral perfusion pressure and then averaged over the whole recording period. ARI and Mx values, assessed during the first 3 days after injury, were averaged for each patient. ARI and Mx showed moderately strong mutual linear relationship with correlation r = -0.62; P = 0.0001. Both indices correlated with outcome, indicating worse autoregulation in patients achieving unfavorable outcome. ARI and Mx agree relatively well in head-injured patients. Autoregulation affects outcome after head injury.

Nonlinear Assessment of Cerebral Autoregulation from Spontaneous Blood Pressure and Cerebral Blood Flow Fluctuations

Cerebral autoregulation (CA) is an most important mechanism responsible for the relatively constant blood flow supply to brain when cerebral perfusion pressure varies. Its assessment in nonacute cases has been relied on the quantification of the relationship between noninvasive beat-to-beat blood pressure (BP) and blood flow velocity (BFV). To overcome the nonstationary nature of physiological signals such as BP and BFV, a computational method called multimodal pressure-flow (MMPF) analysis was recently developed to study the nonlinear BP-BFV relationship during the Valsalva maneuver (VM). The present study aimed to determine (i) whether this method can estimate autoregulation from spontaneous BP and BFV fluctuations during baseline rest conditions; (ii) whether there is any difference between the MMPF measures of autoregulation based on intra-arterial BP (ABP) and based on cerebral perfusion pressure (CPP); and (iii) whether the MMPF method provides reproducible and reliable measure for noninvasive assessment of autoregulation. To achieve these aims, we analyzed data from existing databases including: (i) ABP and BFV of 12 healthy control, 10 hypertensive, and 10 stroke subjects during baseline resting conditions and during the Valsalva maneuver, and (ii) ABP, CPP, and BFV of 30 patients with traumatic brain injury (TBI) who were being paralyzed, sedated, and ventilated. We showed that autoregulation in healthy control subjects can be characterized by specific phase shifts between BP and BFV oscillations during the Valsalva maneuver, and the BP-BFV phase shifts were reduced in hypertensive and stroke subjects (P < 0.01), indicating impaired autoregulation. Similar results were found during baseline condition from spontaneous BP and BFV oscillations. The BP-BFV phase shifts obtained during baseline and during VM were highly correlated (R > 0.8, P < 0.0001), showing no statistical difference (paired-t test P > 0.47). In TBI patients there were strong correlations between phases of ABP and CPP oscillations (R = 0.99, P < 0.0001) and, thus, between ABP-BFV and CPP-BFV phase shifts (P < 0.0001, R = 0.76). By repeating the MMPF 4 times on data of TBI subjects, each time on a selected cycle of spontaneous BP and BFV oscillations, we showed that MMPF had better reproducibility than traditional autoregulation index. These results indicate that the MMPF method, based on instantaneous phase relationships between cerebral blood flow velocity and peripheral blood pressure, has better performance than the traditional standard method, and can reliably assess cerebral autoregulation dynamics from ambulatory blood pressure and cerebral blood flow during supine rest conditions.

Changes in linear dynamics of cerebrovascular system after severe traumatic brain injury.

We sought to describe the dynamic changes in the cerebrovascular system after traumatic brain injury by transfer function estimation and coherence. In 42 healthy volunteers (mean+/-SD age, 37+/-17 years; range, 17 to 65 years), spontaneous fluctuations of middle cerebral artery blood flow velocity and of finger blood pressure (BP) were simultaneously recorded over a period of 10 minutes under normocapnic and hypocapnic conditions to generate normative spectra of coherence, phase shift, and gain over the frequency range of 0 to 0.25 Hz. Similar recordings were performed in 24 patients with severe traumatic brain injury (Glasgow Coma Scale score <or=8; mean+/-SD age, 50+/-20 years) serially on days 1, 3, 5, and 8 after trauma. Cranial perfusion pressure was kept at >70 mm Hg. Each blood flow velocity/BP recording was related to the presence or absence of middle cerebral artery territory brain parenchyma lesions on cranial CT performed within a close time frame. In controls, hypocapnia decreased coherence (0.0 to 0.20 Hz), increased phase shift (0.0 to 0.17 Hz), and decreased gain in the frequency range of 0.0 to 0.11 Hz but increased gain at frequencies of 0.20 to 0.25 Hz (P<0.01 for all frequency ranges reported). In patients with traumatic brain injury, 102 investigations were possible. Compared with controls, coherence was increased in the frequency range <0.03 Hz and between 0.13 and 0.25 Hz in both normocapnia and hypocapnia, irrespective of the CT findings. Gain was unchanged in normocapnia and in the absence of a CT lesion. Gain was decreased in hypocapnia at frequencies >0.12 Hz irrespective of the presence/absence of a CT lesion. Phase shift decreased rapidly between 0.06 and 0.13 Hz under hypocapnic conditions and under normocapnic conditions in the presence of a CT lesion (P< 0.01). Use of spontaneous fluctuations of blood flow velocity and BP to assess the cerebrovascular system dynamically requires consideration of the Paco2 level. In different conditions, including severe traumatic brain injury, the cerebrovascular system behaves linearly only in parts of the investigated frequency range.

Temporal heterogeneity of the blood flow velocity at the middle cerebral artery in the normal human characterized by fractal analysis.

The objective of this study is to characterize the temporal fluctuation of the axial blood flow velocity (BFV) at the middle cerebral artery (MCA). Biological observables such as BFV present complex oscillations. The irregularity of physiological systems may be assessed by fractal analysis by computing the fractal dimension (D gamma) and the corresponding temporal correlation (r gamma). The BFV at the MCA was registered with transcranial Doppler ultrasonography (TCD) in four adult volunteers. As fractal processes are assumed to have no absolute time scale, two time scales were compared. The digitized signal was averaged respectively at 1-s intervals and for each heart beat. D gamma and r gamma were determined using relative dispersion analysis. The results were D gamma = 1.24 +/- 0.09 and r gamma = 0.45 +/- 0.19 (mean +/- SD) for the 1-s based time scale and D(r) = 1.17 +/- 0.09 and r gamma = 0.57 +/- 0.20 for the heart-beat scale. We conclude that the temporal heterogeneity of the BFV at the MCA in the normal human has fractal properties. Fractal analysis of TCD data may become useful in clinical diagnosis because loss of complexity in physiological systems has been linked to senescence or disease conditions. Wide variations of the so called normal values of BFV measured by TCD have been reported. The physiological BFV fluctuations may explain, in part, the variability of values recorded during routine TCD diagnostic examinations. Our observations may also be of value for understanding the interaction of the vascular endothelium and the blood flow stream (shear stress).

The relationship between cerebral blood flow velocity fluctuations and sleep state in normal newborns.

Cerebral blood flow velocity was recorded for an average of 23 4-min epochs during natural sleep in 11 normal full-term newborn babies. Intracranial pressure, core temperature, and respiration were simultaneously and non-invasively monitored. Sleep state was classified using information from EEG, pattern of respiration, and eye and body movements by a trained observer. From a total of 238 epochs, 66 were considered to occur in quiet sleep, 101 in active sleep, and in 77 the baby was awake, in a transitional state or moving excessively. Slow cyclical variations in cerebral blood flow velocity were observed with a frequency of between 2 and 6 cycles/min, and these were of significantly greater amplitude during quiet sleep (24%) compared to active sleep (16%; p < 0.0001, Mann Whitney U test). There was no difference in median cerebral blood flow velocity (7.5 cm/s). The cyclical variation observed in normal babies were similar to those described in preterm babies and adults, at a similar frequency to B waves in intracranial pressure. They may represent vasomotor waves in the small autoregulatory arteries of the brain. Reduction in sensitivity of the receptors initiating the waves may occur in active sleep or there may be competition from other oscillatory mechanisms.

The relationship between cerebral blood flow velocity fluctuations and sleep state in normal newborns

The relationship between cerebral blood flow velocity fluctuations and sleep state in normal newborns

The relationship of blood flow velocity fluctuations to intracranial pressure B waves

Intracranial pressure (ICP) and continuous transcranial Doppler ultrasound signals were monitored in 20 head-injured patients and simultaneous synchronous fluctuations of middle cerebral artery (MCA) velocity and B waves of the ICP were observed. Continuous simultaneous monitoring of MCA velocity, ICP, arterial blood pressure, and expired CO2 revealed that both velocity waves and B waves occurred despite a constant CO2 concentration in ventilated patients and were usually not accompanied by fluctuations in the arterial blood pressure. Additional recordings from the extracranial carotid artery during the ICP B waves revealed similar synchronous fluctuations in the velocity of this artery, strongly supporting the hypothesis that blood flow fluctuations produce the velocity waves. The ratio between ICP wave amplitude and velocity wave amplitude was highly correlated to the ICP (r = 0.81, p less than 0.001). Velocity waves of similar characteristics and frequency, but usually of shorter duration, were observed in seven of 10 normal subjects in whom MCA velocity was recorded for 1 hour. The findings in this report strongly suggest that B waves in the ICP are a secondary effect of vasomotor waves, producing cerebral blood flow fluctuations that become amplified in the ICP tracing, in states of reduced intracranial compliance.

Aetiological rôle of cerebral blood-flow alterations in development and extension of peri-intraventricular haemorrhage.

The aetiology and extension of peri-intraventricular haemorrhage (PIVH) are thought to be related to cerebral blood-flow alterations, and especially to increased cerebral blood-flow and fluctuating velocity of blood-flow. Using transcutaneous Doppler technique, the authors investigated cerebral blood-flow in 60 infants with gestations of less than 34 weeks. Pulsatility index (PI) and area under the velocity curve (AUVC) of the anterior cerebral arteries (ACA) were used as qualitative measures of cerebral blood-flow, and the coefficient of variation of PI and AUVC as indicators of fluctuations in blood-flow velocity. A reasonable correlation was found between PI and AUVC and their coefficients of variation in the ACA. First onset of PIVH was related to fluctuating blood-flow velocity, and extension of PIVH with both increased velocity (indicating increased blood-flow) and fluctuating velocity. Increased cerebral blood-flow and its fluctuating pattern were positively correlated with arterial carbon dioxide tension.

The effect of patent ductus arteriosus on flow velocity in the anterior cerebral arteries: Ductal steal in the premature newborn infant

Marked changes in blood flow velocity in the anterior cerebral arteries, measured by a Doppler technique, have been related to PDA in premature infants. Thus, 55 premature infants of birth weight less than 2,000 gm were studied. Ten developed PDA between days three and ten of life. A sharp decrease in diastolic flow velocity and an increase in pulse amplitude in the ACA was observed with the occurrence of PDA. Return of these values to normal occurred promptly following closure of the lesion. These changes in flow velocity and pulse amplitude in the ACA appear to be determined principally by changes in systemic diastolic pressure which accompany PDA. There was no consistent relationship between the changes in flow velocity and arterial PCO2 values. These data suggest that PDA may be involved in the genesis of ischemic and hemorrhagic cerebral injury in the premature newborn infant. Thus, the decrease in flow velocity appears to represent a "steal" of blood from the cerebral arteries, analogous to other documented steal phenomena observed in older patients. Major fluctuations of blood flow velocity in the ACA, with opening and closure of the PDA, and the increase in amplitude of each pulse with PDA may, in the presence of disturbed autoregulation, cause rupture of the capillaries of the germinal matrix and thus, IVH.