Middle cerebral artery blood velocity during rowing

Dynamic exercise increases the transcranial Doppler determined mean blood velocity in basal cerebral arteries corresponding to the cortical representation of the active limb(s) and independent of the concomitant rise in the mean arterial pressure. In 12 rowers we evaluated the middle cerebral artery blood velocity response to ergometer rowing when regulation of the cerebral perfusion is challenged by stroke synchronous fluctuation in arterial pressure. Rowing increased mean cerebral blood velocity (57 ± 3 to 67 ± 5 cm s^?1; mean ± SE) and mean arterial (86 ± 6 to 97 ± 6 mmHg) and central venous pressures (0 ± 2 to 8 ± 2 mmHg; P < 0.05). The force on the oar triggered an averaging procedure that demonstrated stroke synchronous sinusoidal oscillations in the cerebral velocity with a 12 ± 2% amplitude upon the average exercise value. During the catch phase of the stroke, the mean velocity increased to a peak of 88 ± 7 cm s^?1 and it was in phase with the highest mean arterial pressure (125 ± 14 mmHg), while the central venous pressure was highest after the stroke (20 ± 3 mmHg). The results suggest that during rowing cerebral perfusion is influenced significantly by the rapid fluctuations in the perfusion pressure.     

Middle cerebral artery blood velocity depends on cardiac output during exercise with a large muscle mass

We tested the hypothesis that pharmacological reduction of the increase in cardiac output during dynamic exercise with a large muscle mass would influence the cerebral blood velocity/perfusion. We studied the relationship between changes in cerebral blood velocity (transcranial Doppler), rectus femoris blood oxygenation (near-infrared spectroscopy) and systemic blood flow (cardiac output from model flow analysis of the arterial pressure wave) as induced by dynamic exercise of large (cycling) vs. small muscle groups (rhythmic handgrip) before and after cardioselective β₁ adrenergic blockade (0.15 mg kg^?1 metoprolol i.v.). During rhythmic handgrip, the increments in systemic haemodynamic variables as in middle cerebral artery mean blood velocity were not influenced significantly by metoprolol. In contrast, during cycling (e.g. 113 W), metoprolol reduced the increase in cardiac output (222 ± 13 vs. 260 ± 16%), heart rate (114 ± 3 vs. 135 ± 7 beats min^?1) and mean arterial pressure (103 ± 3 vs.112 ± 4 mmHg), and the increase in cerebral artery mean blood velocity also became lower (from 59 ± 3 to 66 ± 3 vs. 60 ± 2 to 72 ± 3 cm s^?1; P < 0.05). Likewise, during cycling with metoprolol, oxyhaemoglobin in the rectus femoris muscle became reduced (compared to rest; ?4.8 ± 1.8 vs. 1.2 ± 1.7 μmol L^?1, P < 0.05). Neither during rhythmic handgrip nor during cycling was the arterial carbon dioxide tension affected significantly by metoprolol. The results suggest that as for the muscle blood flow, the cerebral circulation is also affected by a reduced cardiac output during exercise with a large muscle mass.     

Regional,segmental, and temporal heterogeneity of cerebral vascular autoregulation

Autoregulation of cerebral blood flow is heterogeneous in several ways: regional, segmental, and temporal. We have found regional heterogeneity of the autoregulatory response during both acute reductions and increases in systemic arterial presure. Changes in blood flow are less in brain stem than in cerebrum during decreases and increases in cerebral perfusion pressure. Segmental heterogeneity of autoregulation has been demonstrated in two ways. Direct determination of segmental cerebral vascular resistance indicates that, while small cerebral vessels (<200 μm in diameter) make a major contribution to autoregulation during acute increases in pressure between 80 and 100 mm Hg, the role of large cerebral arteries (>200 μm) becomes increasingly important to the autoregulatory response at pressures above 100 mm Hg. Measurement of changes in diameter of pial vessels has shown that, during acute hypotension, autoregulation occurs predominantly in small resistance vessels (<100 μm). Finally, there is temporal heterogeneity of autoregulation. Sudden increases in arterial pressure produce transient increases in blood flow, which are not observed under steady-state conditions. In addition, the blood-brain barrier is more susceptible to hypertensive disruption after rapid, compared to step-wise, increases in arterial pressure. Thus, when investigating cerebral vascular autoregulation, regional, segmental, and temporal differences in the autoregulatory response must be taken into consideration.     

Pain response measured with arterial spin labeling

The majority of functional MRI studies of pain processing in the brain use the blood oxygenation level‐dependent (BOLD) imaging approach. However, the BOLD signal is complex as it depends on simultaneous changes in blood flow, vascular volume and oxygen metabolism. Arterial spin labeling (ASL) perfusion imaging is another imaging approach in which the magnetically labeled arterial water is used as an endogenous tracer that allows for direct measurement of cerebral blood flow. In this study, we assessed the pain response in the brain using a pulsed‐continuous arterial spin labeling (pCASL) approach and a thermal stimulation paradigm. Using pCASL, response to noxious stimulation was detected in somatosensory cortex, anterior cingulate cortex, anterior insula, hippocampus, amygdala, thalamus and precuneus, consistent with the pain response activation patterns detected using the BOLD imaging approach. We suggest that pCASL is a reliable alternative for functional MRI pain studies in conditions in which blood flow, volume or oxygen extraction are altered or compromised. Copyright © 2013 John Wiley & Sons, Ltd.     

A mathematical model of the relationship between cerebral blood volume and intracranial pressure changes: The generation of plateau waves

The relationship between intracranial pressure (ICP), cerebral blood volume (CBV), cerebrospinal fluid dynamics, and the action of cerebral blood-flow (CBF) regulatory mechanisms is examined in this work with the help of an original mathematical model. In building the model, particular emphasis is placed on reproducing the mechanical properties of proximal cerebral arteries and small pial arterioles, and their active regulatory response to perfusion pressure and cerebral blood flow changes. The model allows experimental results on cerebral vessel dilatation and cerebral blood-flow regulation, following cerebral perfusion pressure decrease, to be satisfactorily reproduced. Moreover, the effect of cerebral blood volume changes—induced by autoregulatory adjustments — on the intracranial pressure time pattern can be examined at different levels of arterial hypotension. The results obtained with normal parameter values demonstrate that, at the lower lumits of autoregulation, when dilatation of small arterioles becomes maximal, the increase in cerebral blood volume can cause a significant, transient increase in intracranial pressure. This antagonism between intracranial pressure and autoregulatory adjustments can lead to instability of the intracranial system in pathological conditions. In particular, analysis of the linearized system “in the small” demonstrates that an impairment in cerebrospinal fluid (CSF) reabsorption, a decrease in intracranial compliance and a high-regulatory capacity of the cerebrovascular bed are all conditions which can lead the system equilibrium to become unstable (i.e., the real part of at least one eigenvalue to turn out positive). Accordingly, mathematical simulation “in the large,” in the above-mentioned conditions, exhibits intracranial pressure periodic fluctuations which closely resemble, in amplitude, duration, frequency and shape, the well-known Lundberg A-waves (or plateau waves).     

A cellular mechanism for myogenic regulation of cat cerebral arteries

Autoregulation of cerebral blood flow is accomplished through integration of metabolic, neurogenic and myogenic mechanisms. Myogenic mechanisms involve activation of cerebral arterial muscle cells as transmural pressure increases, providing a means through which vessel caliber can be regulated to maintain blood flow constant. The cellular mechanisms involved in this myogenic response may involve changes in the electrical potential across the plasma membrane. When isolated cat middle cerebral arteries are cannulated and prepared in a manner allowing manipulation of transmural pressure, the muscle cell membrane depolarizes as pressure increases. The degree of membrane depolarization in response to an elevated pressure is dependent upon extracellular Ca²⁺ ([Ca]₀), increasing as [Ca]₀ is elevated and markedly decreasing as [Ca]₀ is reduced to low levels. When these arterial preparations are maintained at a physiological pressure of around 100 mm Hg, spontaneous action potentials can be recorded which increase in frequency upon further elevation in pressure. Vessels exhibiting such electrical activity can be observed to decrease in diameter as pressure is increased. Such finding suggest a membrane electrical mechanism for myogenic autoregulation of cerebral arteries.     

Intracranial mechanisms for preserving brain blood flow in health and disease

The brain is an exceptionally energetically demanding organ with little metabolic reserve, and multiple systems operate to protect and preserve the brain blood supply. But how does the brain sense its own perfusion? In this review, we discuss how the brain may harness the cardiovascular system to counter threats to cerebral perfusion sensed via intracranial pressure (ICP), cerebral oxygenation and ischaemia. Since the work of Cushing over 100 years ago, the existence of brain baroreceptors capable of eliciting increases in sympathetic outflow and blood pressure has been hypothesized. In the clinic, this response has generally been thought to occur only in extremis, to perfuse the severely ischaemic brain as cerebral autoregulation fails. We review evidence that pressor responses may also occur with smaller, physiologically relevant increases in ICP. The incoming brain oxygen supply is closely monitored by the carotid chemoreceptors; however, hypoxia and other markers of ischaemia are also sensed intrinsically by astrocytes or other support cells within brain tissue itself and elicit reactive hyperaemia. Recent studies suggest that astrocytic oxygen signalling within the brainstem may directly affect sympathetic nerve activity and blood pressure. We speculate that local cerebral oxygen tension is a major determinant of the mean level of arterial pressure and discuss recent evidence that this may be the case. We conclude that intrinsic intra‐ and extra‐cranial mechanisms sense and integrate information about hypoxia/ischaemia and ICP and play a major role in determining the long‐term level of sympathetic outflow and arterial pressure, to optimize cerebral perfusion.     

The role of the carotid body chemoreceptors and carotid sinus baroreceptors in the control of cerebral blood vessels

1. Cerebral blood flow was measured in 17 baboons, anaesthetized with pentobarbitone, paralysed with gallamine and mechanically ventilated and in which the right sinus and both aortic nerves had been cut and the left carotid sinus vascularly isolated. Later in each experiment, the head was artificially perfused with femoral arterial blood via the innominate artery.2. Stimulation of the carotid body chemoreceptors with venous blood invariably caused a rise in regional cerebral blood flow whether the head was naturally or artificially perfused. This response was almost completely abolished if the VIIth cranial nerves were cut intracranially.3. Regional cerebral blood flow varied inversely with carotid sinus pressure.4. After the remaining (left) sinus nerve had been cut, the cerebral vascular response to hypoxia was negligible and the response to hypercapnia was markedly reduced. Blood flow then varied with perfusion pressure.5. These results provide further evidence that cerebral blood vessels are reflexly controlled and that the peripheral arterial receptors are involved. Their action is most conspicuous in the vascular response to hypoxia and together with intrinsic factors in the cerebral vascular bed, they determine the size of the vascular response to changes in CO(2) and pressure.     

Interactions between systemic hemodynamics and cerebral blood flow during attentional processing

The study explored interactions between systemic hemodynamics and cerebral blood flow during attentional processing. Using transcranial Doppler sonography, blood flow velocities in the middle cerebral arteries (MCA) of both hemispheres were recorded while 50 subjects performed a cued reaction time task. Finger arterial pressure and heart rate were also continuously monitored. Doppler sonography revealed a right dominant blood flow response. The extent of the increase measured in second two of the interstimulus interval showed a clear positive association with reaction speed. Task‐related changes in blood pressure and heart rate proved predictive of changes in MCA flow velocities in limited time windows of the response. Besides an association between cerebral blood flow and attentional performance, the results suggest a marked impact of systemic hemodynamics on the blood flow response. All observed interactions are highly dynamic in time.     

Comparison of two mathematical models for the study of vascular reactivity

This work is based on the premise that fingertip temperature variation during arterial occlusion and subsequent reperfusion can be used as an indirect measurement of vascular reactivity, commonly assessed by directly measuring flow and its temporal alterations in response to arterial occlusion. Temperature of the fingers depends on blood perfusion and environmental factors. The temperature change experienced during hyperemia or high blood flow after occlusion depend on the capacity of the occluded arteries to restore normal circulation or vascular reactivity.This work uses two mathematical models of heat transfer to show the relationship between blood flow and changes in fingertip temperature experienced during vascular occlusion and reperfusion. The models consider different levels of complexity and anatomical detail. One model is a lumped or zero-order model that neglects tissue composition; the second model (first-order model) considers a simplified anatomy of the finger and allows the analysis of tissue composition which cannot be addressed with the lumped system.Thermal models provide a way of estimating the influence of different factors on the dynamic temperature response recorded during the reactivity tests. The models intend to increase the interest of the clinical community in the thermal study of vascular reactivity compared to other techniques that focus on the analysis of flow.The differences of the calculated dynamic temperature during arterial occlusion and reperfusion using both models were analyzed. Such comparison indicated that the zero-order model suffices to analyze the temperature variation during the reactivity test, as long as the proper variation between initial condition and environmental parameters affecting the response is used.     

Cerebrovascular transmural pressure and autoregulation

The cerebral blood flow (CBF) response to changes in perfusion pressure mediated through decreases in arterial pressure, increases in cerebrospinal fluid (CSF) pressure and increases in jugular venous pressure was studied in anesthetized dogs. A preparation was developed in which each of the three relevant pressures could be controlled and manipulated independently of each other. In this preparation, the superior vena cava and femoral vein were cannulated and drained into a reservoir. Blood was pumped from the reservoir into the right atrium. With this system, mean arterial pressure and jugular venous pressure could be independently controlled. CSF pressure (measured in the lateral ventricle) could be manipulated via a cisternal puncture. Total and regional CBF responses to alterations in perfusion pressure were studied with the radiolabelled microsphere technique. Each hemisphere was sectioned into 13 regions: spinal cord, cerebellum, medulla, pons, midbrain, diencephalon, caudate, hippocampus, parahippocampal gyrus, and occipital, temporal, parietal and frontal lobes. Despite 30 mm Hg reductions in arterial pressure or increases in jugular venous pressure or CSF pressure, little change in CBF was observed provided the perfusion pressure (arterial pressure minus jugular venous pressure or CSF pressure depending on which pressure was of greater magnitude) was greater than the lower limit for cerebral autoregulation (approximately 60 mm Hg). However, when the perfusion pressure was reduced by any of the three different methods to levels less than 60 mm Hg (average of 48 mm Hg), a comparable reduction (25–35%) in both total and regional CBF was obtained. Thus comparable changes in the perfusion pressure gradient established by decreasing arterial pressure, increasing jugular venous pressure and increasing CSF pressure resulted in similar total and regional blood flow responses. Independent alterations of arterial and CSF pressures, and jugular venous pressure produce opposite changes in vascular transmural pressure yet result in similar CBF responses. These results show that cerebral autoregulation is a function of the perfusion pressure gradient and cannot be accounted for predominantly by myogenic mechanisms.     

Effects of increasing arterial pressure on cerebral blood flow in the baboon: Influence of the sympathetic nervous system

The influence of stimulation of the cervical sympathetic chain on the response of cerebral blood flow to hypertension induced by the intravenous infusion of angiotensin was studied in anaesthetised baboons. Cerebral blood flow was measured by the intracarotid¹³³Xenon injection technique. Possible lesions of the blood-brain barrier were studied by injecting Evans blue towards the end of the experiment and ischaemic brain damage was assessed following perfusion fixation.In a control group of five baboons blood flow increased by 53±9% (mean ±S.E.) from the base line values in the arterial pressure range 130–159 mm Hg.In four baboons subjected to unilateral sympathetic stimulation flow increased by 16±4% in the same pressure range.In three babbons subjected to bilateral sympathetic stimulation there were not significant increases in flow until the arterial pressure had increased above 159 mm Hg.Disruption of the blood-brain barrier in the parietooccipital regions was only seen in the control animals but not in the stimulated baboons. Ischaemic brain damage was not observed with the exception of one small lesion in a single stimulated baboon.These findings provide strong support for the observations of Bill and Linder (1976) that activation of the cervical sympathetic can modify the level at which breakthrough of cerebral blood flow occurs in association with systemic hypertension.These investigations were supported by the Medical Research Council and Tenovus (Scotland)     

Oxygen-dependent mechanisms in cerebral autoregulation

Autoregulatory adjustments in the caliber of cerebral arterioles were studied in anesthetized cats equipped with cranial windows for the direct observation of the pial microcirculation. Increased venous pressure caused slight, but consistent, arteriolar dilation, at normal and at reduced arterial blood pressure and irrespective of whether or not intracranial pressure was kept constant or allowed to increase. Arterial hypotension caused arteriolar dilation which was inhibited partially by perfusion of the space under the cranial window with artificial CSF equilibrated with high concentrations of oxygen. This vasodilation was inhibited to a greater extent by perfusion of the space under the cranial window with fluorocarbon FC-80, equilibrated with high concentrations of oxygen. CSF or fluorocarbon equilibrated with nitrogen did not influence the vasodilation in response to arterial hypotension. The response to increased venous pressure was converted to vasoconstriction when fluorocarbon equilibrated with high concentrations of oxygen was flowing under the cranial window. The vasodilation in response to arterial hypotension was inhibited by topical application of adenosine deaminase. The results show that both metabolic and myogenic mechanisms play a role in cerebral arteriolar autoregulation. Under normal conditions, the metabolic mechanisms predominate. The presence of the myogenic mechanisms may be unmasked by preventing the operation of the metabolic mechanisms. The major metabolic mechanism seems to be dependent on changes in PO₂ within the brain with secondary release of adenosine.     

Frequency-domain analysis of cerebral autoregulation from spontaneous fluctuations in arterial blood pressure

The dynamic relationship between spontaneous fluctuations of arterial blood pressure (ABP) and corresponding changes in crebral blood flow velocity (CBFV) is studied in a population of 83 neonates. Static and dynamic methods are used to identify two subgroups showing either normal (group A, n=23) or impaired (group B, n=21) cerebral autoregulation. An FFT algorithm is used to estimate the coherence and transfer function between CBFV and ABP. The significance of the linear dependence between these two variables in demonstrated by mean values of squared coherence >0.50 for both groups in the frequency range 0.02–0.50 Hz. However, group A has significanlty smaller coherences than group B in the frequency ranges 0.02–0.10 Hz and 0.33–0.49 Hz. The phase response of group A is also significantly more positive than that of group B, with slopes of 9.3±1.05 and 1.80±1.2 rad Hz⁻¹, respectively. The amplitude frequency response is also significantly smaller for group A in relation to group B for the frequency range 0.25–0.43 Hz. These results suggest that transfer function analysis may be able to identify different components of cerebral autoregulation and also provide a deeper understanding of recent findings by other investigators.     

An instrument for measuring endometrial blood flow in the uterus, using two thermistor probes

An instrument was developed for continuous measurement of thermal conductance reflecting blood flow locally in the endometrium. The probe consists of two small thermistors, one sensing the tissue temperature, and the other working at 5 degrees C elevated temperature, sensing the heat loss caused by thermal conduction mainly due to the blood flow. The power needed to keep this temperature difference was recorded as a measure of flow. When the instrument was tested in model experiments, for measurement of flows at temperatures of 35 to 40 degrees C, stable recordings with high sensitivity were obtained and no influence of the surrounding temperature was observed. Recordings were also made in vivo in non-pregnant women by applying the instrument to the endometrium of the uterine fundus. Intrauterine pressure was recorded simultaneously. The blood flow recordings were stable over long periods in spite of changes in body temperature, but with fluctuations of up to 0.1 mW concomitant with uterine contractions. Pulse-syncronous variations in flow were recorded, indicating a high sensitivity and a short time constant of the instrument. The blood flow effects of vasoactive substances, i.e. vasopressin and a vasopressin antagonist, could readily be distinguished. It is concluded that this instrument can be used for semi-quantitative recordings of blood flow in cavities of the body, for example the uterus, which can be reached by small probes and that changes of body temperature do not effect the measurements.     

A sensitivity analysis of the step-temperature technique for measurement of local tissue blood perfusion

The step-temperature technique is a thermal technique that uses a small thermistor probe for measuring blood perfusion of tissue. The blood perfusion is derived from temperature and power measurements using equations that describe heat transfer in the integrated probe/tissue system. A numerical experiment is used to analyse the theoretical error caused by the assumptions used in the technique. The effects of the bead parameters, tissue parameters and measurement parameters are investigated. The study results are in accordance with experimental phenomena described previously. An optimal measurement time window is found to be 4 – 10 s, dependent mainly on the thermal conductivity and blood perfusion of tissue measured. This research will lead to reduce perfusion measurement errors.     

A sensitivity analysis of the step-temperature technique for measurement of local tissue blood perfusion

The step-temperature technique is a thermal technique that uses a small thermistor probe for measuring blood perfusion of tissue. The blood perfusion is derived from temperature and power measurements using equations that describe heat transfer in the integrated probe/tissue system. A numerical experiment is used to analyse the theoretical error caused by the assumptions used in the technique. The effects of the bead parameters, tissue parameters and measurement parameters are investigated. The study results are in accordance with experimental phenomena described previously. An optimal measurement time window is found to be 4-10 s, dependent mainly on the thermal conductivity and blood perfusion of tissue measured. This research will lead to reduce perfusion measurement errors.     

Acute intracranial hypertension and basilar artery blood flow velocity recorded by transcranial Doppler sonography: an experimental study in rabbits.

The relationship between intracranial hypertension and basilar artery blood flow is not well known, and it is not yet definite that the reduction of cerebral flow depends on cerebral perfusion pressure rather than microvessel compression. The purpose of the study described here was to investigate the effect of acute intracranial pressure on the basilar flow velocity, the cerebral perfusion pressure, and the systemic arterial pressure. The basilar Doppler signal was recorded continuously in 24 New Zealand rabbits by transcranial pulsed Doppler method. The acute intracranial hypertension was induced by the progressive raising, in steps of 5 mmHg, of a saline infusion bottle connected to an epidural sensor. The intracranial hypertension induced a decrease in diastolic and mean flow velocities in the basilar artery, and an increase in the resistance index. Cerebral perfusion pressure was significantly correlated with flow parameters. The basilar diastolic flow began to decrease significantly from a 35-40 mmHg intracranial pressure and for a 37 mmHg + 20 SD cerebral perfusion pressure, without significant variation of arterial pressure. Diastolic flow dropped to zero for a 53 mmHg intracranial pressure and a 30 mmHg + 15 SD cerebral perfusion pressure. These results show that high intracranial pressure values are necessary for significantly reducing basilar artery blood flow. This effect, and the increase of circulatory cerebral resistance, occurred before significant changes in systemic arterial pressure.     

Effects of Autoregulation and CO<Subscript>2</Subscript> Reactivity on Cerebral Oxygen Transport

Both autoregulation and CO₂ reactivity are known to have significant effects on cerebral blood flow and thus on the transport of oxygen through the vasculature. In this paper, a previous model of the autoregulation of blood flow in the cerebral vasculature is expanded to include the dynamic behavior of oxygen transport through binding with hemoglobin. The model is used to predict the transfer functions for both oxyhemoglobin and deoxyhemoglobin in response to fluctuations in arterial blood pressure and arterial CO₂ concentration. It is shown that only six additional nondimensional groups are required in addition to the five that were previously found to characterize the cerebral blood flow response. A resonant frequency in the pressure-oxyhemoglobin transfer function is found to occur in the region of 0.1 Hz, which is a frequency of considerable physiological interest. The model predictions are compared with results from the published literature of phase angle at this frequency, showing that the effects of changes in breathing rate can significantly alter the inferred phase dynamics between blood pressure and hemoglobin. The question of whether dynamic cerebral autoregulation is affected under conditions of stenosis or stroke is then examined.     

体外反搏对脑动脉血流量影响的建模和仿真研究

目的　研究体外反搏对脑动脉血流量的影响。方法　将实际测量的正常的颈动脉血压和进行体外反搏时的颈动脉血压作用于正常情况下和缺血情况下脑血流动力学数学模型，模拟上述情况下脑动脉血流的变化。结果　缺血和体外反搏都引起脑动脉血流的变化。结论　体外反搏可以明显增加大脑的血流灌注和改变脑动脉血流变化的时相模式。