Increase In Cerebral Vascular Resistance Research Articles

Static Cerebral Autoregulation is Not Altered in Symptomatic Concussed Athletes During Acute Central Hypervolemia

Dynamic cerebral autoregulation is impaired in concussed individuals. However, less is known regarding static cerebral autoregulation in symptomatic concussed athletes during a central hypervolemic challenge that increases blood pressure. PURPOSE: We tested the hypothesis that static cerebral autoregulation during a central hypervolemic challenge is impaired in symptomatic concussed college athletes (CA) vs healthy controls (HC). METHODS: Seven CA (age: 19±2 y, 5 females) and ten HC (age: 21±2 y, 6 females) completed one study visit. After 5 min of resting baseline, 20 mmHg of lower body positive pressure (LBPP) was applied for 5 min using an airtight chamber. Beat to beat blood pressure (photoplethysmography) and middle cerebral artery blood velocity (MCAv; transcranial Doppler) were recorded continuously. Static cerebral autoregulation was calculated using Fourier transfer function analysis with 3 min segments at baseline and after mean arterial pressure (MAP) stabilized during LBPP. Cerebral vascular resistance (CVR) was calculated as MAP/MCAv. Pulsatility index (PI) was calculated as the difference of peak systolic MCAv and end diastolic MCAv, divided by mean MCAv. Values are reported as a change from baseline. RESULTS: MAP (CA: 90±6 vs HC: 92±11 mmHg; P=0.32), MCAv (CA: 58.7±19.4 vs HC: 62.6±11.1 cm/s; P=0.30), gain (CA: 0.7±0.2 vs HC: 0.8±0.2 cm/s/mmHg; P=0.17), coherence (CA: 0.5±0.1 vs HC: 0.5±0.1; P=0.21), CVR (CA: 1.7±0.6 vs HC: 1.5±0.3 mmHg/cm/s; P=0.21), and PI (CA: 0.9±0.1 vs HC: 0.9±0.2; P=0.31) were not different at baseline. The change in MAP was not different between CA (12±6 mmHg) and HC (8±6 mmHg; P=0.12). The change in MCAv was greater in CA (CA: 4.8±4.6 vs HC: -4.3±8.7 cm/s; P=0.01). There were no differences in the change from baseline for gain (CA: 0.1±0.2 vs HC: 0.1±0.5 cm/s/mmHg; P=0.49) or coherence (CA: -0.0±0.1 vs HC: -0.0±0.1; P=0.40). The increase in CVR was attenuated in CA (CA: 0.0±0.2 vs HC: 0.3±0.3 mmHg/cm/s; P=0.04). The decrease in PI was greater in CA (CA: -0.1±0.0 vs HC: 0.0±0.1; P=0.02). CONCLUSION: These data indicate that indices of static cerebral autoregulation are not different between CA and HC during an acute increase in MAP. The blunted increase in CVR and greater decrease in PI appears to allow for a rise in MCAv during an acute increase in MAP in CA.

Cerebral vascular effects of loading dose of dexmedetomidine: A Transcranial Color Doppler study.

Background:Dexmedetomidine has been widely used in critical care settings because of its property of maintaining stable hemodynamics and inducing conscious sedation. The use of dexmedetomidine is in increasing trend particularly in patients with neurological disorders. Very few studies have focused on the cerebral hemodynamic effects of dexmedetomidine. This study is aimed to address this issue.Methods:Thirty patients without any intracranial pathology were included in this study. Middle cerebral artery flow velocity obtained from transcranial color Doppler was used to assess the cerebral hemodynamic indices. Mean flow velocity (mFV), pulsatility index (PI), cerebral vascular resistant index (CVRi), estimated cerebral perfusion pressure (eCPP), and zero flow pressure (ZFP) were calculated bilaterally at baseline and after infusion of injection Dexmedetomidine 1 mcg/Kg over 10 min.Results:Twenty-six patients completed the study protocol. After administration of loading dose of dexmedetomidine, mFV and eCPP values were significantly decreased in both hemispheres (P < 0.05); PI, CVRi, and ZFP values showed significant increase (P < 0.05) after dexmedetomidine infusion.Conclusion:Increase in PI, CVRi, and ZFP suggests that there is a possibility of an increase in distal cerebral vascular resistance (CVR) with loading dose of dexmedetomidine. Decrease in mFV and eCPP along with an increase in CVR may lead to a decrease in cerebral perfusion. This effect can be exaggerated in patients with preexisting neurological illness. Further studies are needed to evaluate the effect of dexmedetomidine on various other pathological conditions involving brain like traumatic brain injury and vascular malformations.

Cerebrovascular Abnormalities Supporting the Selfish Brain Hypothesis of Human Hypertension

The selfish brain hypothesis of hypertension suggests that brainstem hypoperfusion triggers increased sympathetic activity (SNA) and blood pressure (BP) as a mechanism to maintain cerebral perfusion. We assessed: 1) prevalence of anatomical variations in the posterior cerebral circulation, which may cause brainstem hypoperfusion, 2) relationships of SNA to cerebral vascular resistance (CVR) in hypertensive (HTN) vs normotensive (NTN) humans. The vertebral arteries (VA) and Circle of Willis (CoW) were imaged in 121 HTN (MR angiography). VA hypoplasia (VAH), defined as &lt;2mm diameter, together with CoW morphology were compared to known standards in &gt;50 NTN. In a cohort of HTN (n=50) and NTN (n=40), muscle SNA (MSNA, microneurography), blood flow in the internal carotid arteries (ICA) and VA (MR phase contrast), and BP were recorded.Prevalence of VAH and incomplete posterior CoW was higher in HTN vs NTN (51 vs 27% and 62 vs 38%, p&lt;0.05). Of the posterior CoW variants, complete disconnection of anterior/posterior CoW was higher in HTN (31 vs 10%, p&lt;0.05). Prevalence of having both VAH and incomplete posterior CoW variant was higher in HTN vs. NTN (38 vs 10%, p&lt;0.05). Total CVR and CVR in VA was higher in HTN vs. NTN (2.6 ±0.1 vs 1.1±0.1 and 9.5±0.1 vs 6.7±0.1 mmHg/mL/dl.tissue/min). CVR was related to MSNA in both groups (HTN; r=0.40, NTN; r=0.38, P&lt;0.05). CVR was more closely related to MSNA in the VA vs ICA in HTN (r=0.40 vs r=0.30, P=0.05).The higher prevalence of VAH and incomplete posterior CoW may cause the observed increase in CVR in HTN. The higher CVR in the posterior circulation was linked to higher MSNA in HTN, supporting the hypothesis of brainstem hypoperfusion as a driver of neurogenic hypertension.BHF.

Long term enhancement of cerebral vascular resistance in spontaneously hypertensive rats produces short term pressor responses and long term re‐modelling of cerebral circulation

Cushing (1901, Bull Johns Hopk Hosp 12, 290‐) discovered that acute increases in cerebral vascular resistance produced hypertension. Based on the Cushing response we propose that hypertension may result from elevated cerebral vascular resistance. We sought to determine the effect of occluding both vertebral and the right common carotid artery (3‐vessel occlusion or 3‐VO) on arterial pressure in spontaneously hypertensive rats (SHR). Given that this strain already has narrowed vertebro‐basilar arteries (Cates et al. 2011; J. Appl. Physiol. 111, 149‐), we hypothesised that the pressor response in the SHR would be larger than that in the Wistar rat. 3‐VO in SHR (n=7) produced a pressor response of 23±3mmHg, which compared with 15±2mmHg in normotensive rats (n=5). Arterial pressure returned to control levels by 8–11 days after 3‐VO. In the SHR there was marked cerebral vessel re‐modelling including dilatation of the right posterior communicating artery (+63%) and ventral spinal artery (+54%) seen from day 11 post 3‐VO. The degree of re‐modelling was associated with the magnitude of the pressure response. 3‐VO in the SHR produces a significant pressor effect and arteriogenesis of cerebral vessels that is associated with a subsequent near normalisation of arterial pressure. Cerebral vascular resistance plays a major role in determining arterial pressure set‐point in the SHR. MRC and BHF funded research.

The state of cerebral hemodynamics in conditions of prolonged adaptation to hypercapnic hypoxia

Intermittent hypercapnic hypoxia was accompanied by increases in cerebral vascular resistance, decreases in the reactivity of cerebral vessels to hypercapnia, and increases in the collateral reserve and rate of autoregulation of brain blood flow. These changes were an important component of the mechanism increasing the tolerance of the brain to ischemia in response to training with hypercapnic hypoxia.

Heat stress reduces cerebral blood velocity and markedly impairs orthostatic tolerance in humans

Orthostatic tolerance is reduced in the heat-stressed human. This study tested the following hypotheses: 1) whole body heat stress reduces cerebral blood velocity (CBV) and increases cerebral vascular resistance (CVR); and 2) reductions in CBV and increases in CVR in response to an orthostatic challenge will be greater while subjects are heat stressed. Fifteen subjects were instrumented for measurements of CBV (transcranial ultrasonography), mean arterial blood pressure (MAP), heart rate, and internal temperature. Whole body heating increased both internal temperature (36.4+/-0.1 to 37.3+/-0.1 degrees C) and heart rate (59+/-3 to 90+/-3 beats/min); P<0.001. Whole body heating also reduced CBV (62+/-3 to 53+/-2 cm/s) primarily via an elevation in CVR (1.35+/-0.06 to 1.63+/-0.07 mmHg.cm-1.s; P<0.001. A subset of subjects (n=8) were exposed to lower-body negative pressure (LBNP 10, 20, 30, 40 mmHg) in both normothermic and heat-stressed conditions. During normothermia, LBNP of 30 mmHg (highest level of LBNP achieved by the majority of subjects in both thermal conditions) did not significantly alter CBV, CVR, or MAP. During whole body heating, this LBNP decreased MAP (81+/-2 to 75+/-3 mmHg), decreased CBV (50+/-4 to 39+/-1 cm/s), and increased CVR (1.67+/-0.17 to 1.92+/-0.12 mmHg.cm-1.s); P<0.05. These data indicate that heat stress decreases CBV, and the reduction in CBV for a given orthostatic challenge is greater during heat stress. These outcomes reduce the reserve to buffer further decreases in cerebral perfusion before presyncope. Increases in CVR during whole body heating, coupled with even greater increases in CVR during orthostasis and heat stress, likely contribute to orthostatic intolerance.

Differential responses to CO2 and sympathetic stimulation in the cerebral and femoral circulations in humans

The relative importance of CO2 and sympathetic stimulation in the regulation of cerebral and peripheral vasculatures has not been previously studied in humans. We investigated the effect of sympathetic activation, produced by isometric handgrip (HG) exercise, on cerebral and femoral vasculatures during periods of isocapnia and hypercapnia. In 14 healthy males (28.1 +/- 3.7 (mean +/- S.D.) years), we measured flow velocity (VP; transcranial Doppler ultrasound) in the middle cerebral artery during euoxic isocapnia (ISO, +1 mmHg above rest) and two levels of euoxic hypercapnia (HC5, end-tidal P(CO(2)), P(ET,CO2), = +5 mmHg above ISO; HC10, P(ET,CO2) = +10 above ISO). Each P(ET,CO2) level was maintained for 10 min using the dynamic end-tidal forcing technique, during which increases in sympathetic activity were elicited by a 2-min HG at 30% of maximal voluntary contraction. Femoral blood flow (FBF; Doppler ultrasound), muscle sympathetic nerve activity (MSNA; microneurography) and mean arterial pressure (MAP; Portapres) were also measured. Hypercapnia increased VP and FBF by 5.0 and 0.6% mmHg-1, respectively, and MSNA by 20-220%. Isometric HG increased MSNA by 50% and MAP by 20%, with no differences between ISO, HC5 and HC10. During the ISO HG there was an increase in cerebral vascular resistance (CVR; 20 +/- 11%), while VP remained unchanged. During HC5 and HC10 HG, VP increased (13% and 14%, respectively), but CVR was unchanged. In contrast, HG-induced sympathetic stimulation increased femoral vascular resistance (FVR) during ISO, HC5 and HC10 (17-41%), while there was a general decrease in FBF below ISO. The HG-induced increases in MSNA were associated with increases in FVR in all conditions (r = 0.76-0.87), whereas increases in MSNA were associated with increases in CVR only during ISO (r = 0.91). In summary, in the absence of hypercapnia, HG exercise caused cerebral vasoconstriction, myogenically and/or neurally, which was reflected by increases in CVR and a maintained VP. In contrast, HG increased FVR during conditions of ISO, HC5 and HC10. Therefore, the cerebral circulation is more responsive to alterations in PCO2, and less responsive to sympathetic stimulation than the femoral circulation.

Numerical studies on the effect of lowering temperature on the oxygen transport during brain hypothermia resuscitation

There have been arguments about the advantage and shortcoming of hypothermia on the brain resuscitation during circulation arrest. People usually accepted that hypothermia may decrease the cerebral oxygen demands, which is beneficial for the patient to sustain longer time when subjected to a hypoxia. However, there are also quite a few disputes claiming that the blood viscosity would increase with the reduction of temperature, which may lead to an increase of cerebral vascular resistance and thus worsen the hypoxia state. To resolve this critical issue, a heat transfer model was established to characterize the thermal response of brain tissue during hypothermia resuscitation. Combined with this model, a compartmental model taking account of the temperature effect was further developed to analyze the transient oxygen partial pressure ( PO 2) distribution over the successive branches of the vascular network during circulation arrest. Using the morphological and physiological data of a sheep brain, effects of lowering temperature on the oxygen consumption dynamics were studied. Calculations indicated that the lower the temperature, the slower the decreasing rate for the PO 2. Although immediately lowering the brain temperature may induce an evident increase in blood viscosity and subsequently a decrease in blood flow rate, which is responsible for oxygen delivery, it seems to always result in a monotonic increase of PO 2. The results show a good qualitative accord with the experimental data. They also present better understanding on the transient oxygen transport in brain hypothermia during circulation arrest.

Nitric oxide inhibition abolishes sleep-wake differences in cerebral circulation.

Nitric oxide (NO), being produced by active neurones and also being a cerebral vasodilator, may couple brain activity and blood flow in sleep, particularly during active sleep (AS), which is characterized by widespread neural activation and markedly elevated cerebral blood flow (CBF) compared with quiet wakefulness (QW) and quiet sleep (QS). This study examined CBF and cerebral vascular resistance (CVR) in lambs (n = 6) during spontaneous sleep-wake cycles before and after infusion of N(omega)-nitro-L-arginine (L-NNA), an inhibitor of NO synthase. L-NNA infusion produced increases in CVR and decreases in CBF during all sleep-wake stages, with the greatest changes occurring in AS (DeltaCVR, 88 +/- 19%; DeltaCBF -24 +/- 8%). The characteristic CVR and CBF differences among AS, QS, and QW disappeared within 1-3 h of L-NNA infusion, but had reappeared by 24 h despite persisting cerebral vasoconstriction. These experiments show that NO promotes cerebral vasodilatation during sleep as well as wakefulness, particularly during AS. Additionally, NO is the major, although not sole, determinant of the CBF differences that exist between sleep-wake states.

Effects of betamethasone administration to the fetal sheep in late gestation on fetal cerebral blood flow.

Glucocorticoid administration to women at risk of preterm delivery to accelerate fetal lung maturation has become standard practice. Antenatal glucocorticoids decrease the incidence of intraventricular haemorrhage as well as accelerating fetal lung maturation. Little is known regarding side effects on fetal cerebral function. Cortisol and synthetic glucocorticoids such as betamethasone increase fetal blood pressure and femoral vascular resistance in sheep. We determined the effects of antenatal glucocorticoid administration on cerebral blood flow (CBF) in fetal sheep. Vehicle (n = 8) or betamethasone (n = 8) was infused over 48 h via the jugular vein of chronically instrumented fetal sheep at 128 days gestation (term 146 days). The betamethasone infusion rate was that previously shown to produce fetal plasma betamethasone concentrations similar to human umbilical vein concentrations during antenatal glucocorticoid therapy. Regional CBF was measured in 10 brain regions, using coloured microspheres, before and 24 and 48 h after onset of treatment, and during hypercapnic challenges performed before and 48 h after onset of betamethasone exposure. Betamethasone exposure decreased CBF in all brain regions measured except the hippocampus after 24 h of infusion (P < 0.05). The CBF decrease was most pronounced in the thalamus and hindbrain (45-50% decrease) and least pronounced in the cortical regions (35-40% decrease). It was mediated by an increase in cerebral vascular resistance (CVR, P < 0.05) and led to a decrease in oxygen delivery to subcortical and hindbrain structures of 30-40%, to 8.6 +/- 1.1 ml x (100 g)(-1) x min(-1), and 40-45 %, to 11.0 +/- 1.6 ml x 100 g(-1) x min(-1), respectively (P < 0.05). After 48 h of betamethasone treatment, the reduction in CBF was diminished to about 25-30 %, but was still significant in comparison to vehicle-treated fetuses in all brain regions except three of the five measured cortical regions (P < 0.05). CVR and oxygen delivery were unchanged in comparison to values at 24 h of treatment. The CBF increase in response to hypercapnia was diminished (P < 0.05). These observations demonstrate for the first time that glucocorticoids exert major vasoconstrictor effects on fetal CBF. This mechanism may protect the fetus against intraventricular haemorrhage both at rest and when the fetus is challenged. Betamethasone exposure decreased the hypercapnia-induced increase in CBF (P < 0.05) due to decreased cerebral vasodilatation (P < 0.05).

P94Fetal cerebrovascular response to chronic hypoxia

ObjectiveTo study the cerebral and umbilical hemodynamics changes in hypoxic and growth‐retarded fetuses. To determine if at long‐term, fetal brain hyperperfusion with loss of cerebral vascular flow velocity variability is associated with brain damage and poor fetal outcome.MethodsThe fetal blood flow redistribution was assessed by using Doppler cerebral‐umbilical ratio in 8 growth‐retarded fetuses, mainly every day. The evolution of the fetal hemodynamics was interpreted according to the clinical, anatomical and histological data.ResultsAll 8 fetuses had poor fetal outcome including fetal death (n = 5). Fetal blood flow redistribution with brain hyperperfusion was detected in all fetuses during the whole period of observation. The early phase of fetal deterioration was characterized by the development of oligohydramnios and the disappearance of the cerebral flow velocity variability. During the later phase of deterioration, fetal heart rate decelerations and the increase of cerebral vascular resistance with reduction of brain perfusion were detected. Histological study of the brains showed hypoxic lesions.ConclusionThe loss of variability of the cerebral resistance index, in the cases of absent umbilical end diastolic flow, and the loss of variability of the cerebral‐umbilical ratio in the other cases, identifies the beginning of the period of very high risk for the fetus. Such a pattern may be considered as a predictor of brain lesion and poor fetal outcome. These results also indicate the existence of two phases in the fetal cerebrovascular response to chronic hypoxia.

Central arterial hemodynamics in small-for-gestational-age fetuses before and during maternal hyperoxygenation: a Doppler velocimetric study with particular attention to the aortic isthmus.

Hemodynamic changes indicating a normalization of fetal blood flow redistribution during maternal oxygen administration have been suggested to be of positive prognostic value in growth-restricted fetuses. The aortic isthmus has been suggested as a site for early detection of blood flow redistribution as well as for verification of a response to maternal hyperoxygenation. The present study was performed to investigate whether this concept could be confirmed in a study involving fetuses assumed to have only a moderate disturbance in fetoplacental hemodynamics. Twenty-five singleton fetuses with an estimated weight less than -2 SD below the gestational age-related mean and without any malformation or chromosomal aberration were studied between 27 and 38 (median 34) weeks of gestation. Velocity waveforms from the mitral valve, aortic valve, middle cerebral artery, aortic isthmus and umbilical artery were recorded before and during maternal breathing of 100% oxygen. Nine fetuses demonstrated absent or reversed end-diastolic velocity (ARED) in the aortic isthmus while forward flow was present in the umbilical artery. The cerebral artery pulsatility index (PI) increased with oxygen administration and there was a decrease in the aortic isthmus PI. Variables obtained from the other recording sites did not change with maternal hyperoxygenation. ARED in the aortic isthmus appears to be an early sign of blood flow redistribution in this group of fetuses. Maternal oxygenation results in velocity waveform changes that suggest an increase of cerebral vascular resistance and a redistribution of blood from the brain to the vascular beds supplied by the descending aorta. The aortic isthmus is a suitable site to verify this response.

Cerebral blood flow velocity during tilt table test for pediatric syncope.

Brain hypoperfusion during neurocardiogenic syncope develops as a consequence of hypotension and bradycardia. Transcranial Doppler indicates that an increase in cerebral vascular resistance occurs before or during the loss of consciousness. Cerebral blood flow velocity was studied during tilt table testing in pediatric patients with neurocardiogenic syncope. We assessed whether a critical reduction in flow velocity (>40%) was predictive of the presyncopal manifestations during the test. A 2-MHz transcranial Doppler measured blood flow velocity in the right middle cerebral artery in 27 pediatric patients (ages, 8 to 18 years) during a three-stage 80 degrees tilt table test protocol. A positive test required development of syncope or presyncope with at least 30% decrease in systolic blood pressure and/or heart rate relative to preceding values. Patients were divided into: group I (isoproterenol-induced positive tests), group II (positive without isoproterenol), and group III (negative tests). Within the first 3 minutes of the upright position mean cerebral blood flow velocity in groups I, II, and III decreased by 18%, 29%, and 17%, respectively, as the systolic and diastolic blood pressures showed only minimal changes. A decreased mean blood flow velocity of 48% and 45% and an increase in resistance index of 42% and 26% from supine values in the absence of hypotension, were detected in groups I and II at 46 seconds (range, 30-120 seconds) and 50 seconds (range, 0-300 seconds) before any clinical symptom (presyncope latency). Mean blood flow velocity during presyncope decreased by 58% and 59%, whereas resistance index was double. A significant correlation (rho = -0.62) was found between presyncope latency and the decreased mean cerebral blood flow velocity. Similar blood flow velocity changes were not detected in group III. A sustained reduction >40% in mean cerebral blood flow velocity in the absence of hypotension always resulted in presyncopal or syncopal manifestations. It seems that once this critical threshold is identified during the tilt table testing, supine position may be resumed several seconds before the clinical manifestations of syncope.

Effects of magnesium sulphate on the noradrenaline-induced cerebral vasoconstrictor and pressor responses in the goat.

To examine the ability of magnesium sulphate to counteract the noradrenaline-induced cerebral vasoconstrictor and pressor responses in goats by using both in vivo and in vitro techniques. Cerebral blood flow was measured in vivo by means of an electromagnetic flow probe around the internal maxillary artery. Isometric tension was recorded in vitro from rings of goat middle cerebral artery maintained in an organ bath. 1. In vivo. Continuous infusion of noradrenaline (10 micrograms/min) directly into the cerebral arterial supply elicited sustained decrease in cerebral blood flow (61% [SEM 3] of control values) and increase in cerebral vascular resistance (178% [SEM 9] of control values). Magnesium sulphate, injected directly into the cerebral arterial supply (10-300 mg) or infused intravenously (0.3 g and 3 g during 15 min) at the noradrenaline-induced steady state, increased cerebral blood flow by decreasing cerebral vascular resistance in a dose-dependent manner. A similar result was obtained when intravenous magnesium sulphate (3 g/15 min) was tested against the cerebral vasoconstrictor and pressor responses induced by intravenous infusion of noradrenaline (30 micrograms/min). 2. In vitro. When compared with the response obtained in a control medium (1 mmol/L Mg2+), 10 mmol/L Mg2+ significantly inhibited the maximum contraction elicited by noradrenaline (10(-8) to 3 x 10(-3) mol/L) from 45% [SEM 4] to 26% [SEM 4]. Magnesium sulphate reverses the noradrenaline-induced cerebral vasoconstrictor and pressor responses by a direct inhibitory action of Mg2+ on the actions of noradrenaline in the cerebral and peripheral vascular beds, which leads to a decrease in vascular resistance. These results could explain, at least in part, the beneficial effects of magnesium sulphate in the management of preeclampsia and eclampsia.

Doppler echocardiographic assessment of fetal blood flow redistribution during maternal hyperoxygenation.

Sixteen normal human fetuses were studied at both 20-23 and 30-33 weeks of gestation to investigate whether hemodynamic changes in the heart and major fetal arteries occurred in response to maternal hyperoxygenation in normal pregnancy. Velocity waveforms from the mitral valve, aortic valve, middle cerebral artery, aortic isthmus and umbilical artery were recorded before and during maternal breathing of 100% oxygen. The cerebral artery pulsatility index (PI) increased with oxygen administration at the first examination (1.56 +/- 0.25, mean +/- 1 SD, to 1.72 +/- 0.28, p < 0.05). At the second examination this increase in cerebral artery PI was more consistent (1.89 +/- 0.43 to 2.22 +/- 0.43, p < 0.001) and there was also a decrease in the aortic isthmus PI (2.64 +/- 0.43 to 2.40 +/- 0.33, p < 0.01) during oxygen administration. The variables determined from the velocity waveforms of the umbilical artery, aortic and mitral valve did not show any changes with maternal hyperoxygenation. Maternal hyperoxygenation resulted in velocity waveform changes suggesting an increase of cerebral vascular resistance and a redistribution of blood flow from the brain to the vascular beds supplied by the descending aorta in the normal human fetus in the third trimester, but this response was less obvious at mid-gestation. The middle cerebral artery and the aortic isthmus seem to be suitable sites for verification of this response.

Doppler echocardiographic assessment of changes in the central circulation of the fetal sheep induced by maternal oxygen administration

Eleven fetal sheep were studied to investigate if Doppler echocardiography could document redistribution of blood flow during maternal oxygen administration. Velocities through the pulmonary valve, aortic valve, common brachiocephalic trunk, aortic arch, descending aorta, umbilical and carotid artery were recorded before, during and after oxygen was delivered to the ewe by face mask. Indices of cardiac performance (shortening fraction, velocity of fiber shortening and systolic time intervals) were also obtained. The aortic arch was the only recording site where significant changes in mean velocity related to oxygen administration and withdrawal were demonstrated (p < 0.01). Changes in the velocity waveform suggesting an increase in cerebral vascular resistance during oxygen administration were found in the carotid artery. Thus, using Doppler velocimetry, the carotid artery and the aortic arch (equivalent to the human aortic isthmus) appear to be suitable sites to document changes induced by maternal oxygen administration.

Different Effects of Mg2+ on Endothelin-1− and 5-Hydroxytryptamine-Elicited Responses in Goat Cerebrovascular Bed

Mg2+ influences the response of cerebral arteries to several agonists, but until now its effects on endothelin-1 (ET-1) had not been studied. We recorded and compared the responses of goat cerebrovascular bed to ET-1 and 5-hydroxytryptamine (5-HT) during various Mg2+ treatments. We performed experiments in vitro by recording isometric tension in isolated goat middle cerebral arteries and in vivo by recording cerebral blood flow (CBF) and other physiologic parameters in conscious goats. Cumulative addition of ET-1 (10(-11)-3 x 10(-8) M) and 5-HT (10(-9) -10(-5) M) contracted cerebral arteries concentration dependently in bath media containing 0 (Mg(2+)-free medium), 1 (control), and 10 mM Mg2+, but the influence of Mg2+ was different: Mg2+ deprivation increased sensitivity (EC50) and Mg2+ overload reduced contractility (Emax) of cerebral arteries to 5-HT, whereas the ET-1 response did not change in these conditions. Cumulative addition of Mg2+ (10(-4)-3 x 10(-2) M) at the active tone induced by ET-1 (10(-9) M) and 5-HT (10(-5) M) elicited concentration-dependent relaxations of cerebral arteries, but the relaxant response was lower at the ET-1 precontraction. Infusions of ET-1 (0.1 nmol/min) and 5-HT (10 micrograms/min) directly into the cerebroarterial supply of the unanesthetized goats elicited a sustained decrease in CBF and an increase in cerebral vascular resistance. Magnesium sulfate, administered as increasing doses (10-300 mg) in the same way increased CBF and decreased cerebral vascular resistance, although this effect was less on ET-1-induced than on 5-HT-induced cerebral vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of increased resistance to umbilical blood flow on fetal hemodynamic changes induced by maternal oxygen administration: a Doppler velocimetric study on the sheep.

A fetal lamb model was used to investigate whether the effects of maternal O2 administration on fetal blood gases and hemodynamics were modified when the fetoplacental circulation was compromised by stepwise compression of both umbilical veins. At basal state, O2 administration increased O2 saturation (SaO2) and the pulsatility index (PI) of the carotid artery Doppler wave form (p < 0.01). The first compression decreased left ventricular output (-21 +/- 16%, mean +/- 1 SD, p < 0.01) and umbilical mean velocity (-22 +/- 28%, p < 0.01) but did not modify carotid pH, SaO2, or the PI in any of the arteries studied. At this level of compression, O2 administration increased carotid SaO2 (p < 0.01) but did not affect carotid PI. After a second compression, left ventricular output and umbilical mean velocity were even more reduced [-39 +/- 21% (p < 0.01) and -53 +/- 23% (p < 0.01), respectively]. With this compression, carotid pH, SaO2, and PI decreased, whereas umbilical and descending aorta PI increased. O2 administration at this level of compression increased carotid SaO2 (p < 0.01) but did not modify carotid PI. Throughout the three stages of the experiment, O2 administration did not affect umbilical PI, descending aorta PI, or umbilical mean velocity. A good linear relationship (r = 0.77, p < 0.001) was demonstrated between left ventricular O2 delivery and carotid PI. Thus, at basal state, O2 administration induced velocity changes compatible with an increase in cerebral vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Dexmedetomidine decreases cerebral blood flow velocity in humans.

This study was designed to determine the effects of dexmedetomidine on CBF velocity as measured by transcranial Doppler sonography in human volunteers. Dexmedetomidine, a potent alpha-2 adrenergic agonist, was administered by computer-driven infusion pump to six male volunteers. Serial measurements of middle cerebral artery blood flow velocity at four steady-state plasma concentrations of dexmedetomidine were made with a 2-MHz transcranial Doppler transducer via the temporal window. The targeted plasma concentrations were 0.49, 0.65, 0.81, and 0.97 ng/ml. These represent 60, 80, 100, and 120%, respectively, of the mean peak concentration following the intramuscular administration of 2 micrograms/kg of dexmedetomidine. Subjects experienced a significant degree of sedation at the highest infusion rates. Mean CBF velocity decreased with each increase in plasma concentration of dexmedetomidine and then began to return to basal levels after termination of the infusion. A trend toward an increase in the pulsatility index at the higher levels of dexmedetomidine suggests that the observed decrement in CBF velocity was due to an increase in cerebral vascular resistance. Upon initiation of the drug infusion, mean arterial pressure decreased from approximately 95 mm Hg to 78 mm Hg. There were no further decreases in arterial pressure with subsequent increases in plasma concentrations of dexmedetomidine. Arterial carbon dioxide tension increased to a maximum of 45 mm Hg during the drug infusion, but this increase from baseline was not statistically significant. These studies are in agreement with previous animal studies which demonstrate a decrease in CBF after administration of dexmedetomidine.

Focal brain injury results in severe cerebral ischemia despite maintenance of cerebral perfusion pressure.

Severe head injury often causes an increase in intracranial pressure (ICP) and decreases in cerebral blood flow (CBF) and cerebral oxygen delivery (CO2del). To determine if this reduction in CBF and CO2del would produce cerebral ischemia and if this reduction would be abrogated by maintaining global cerebral perfusion pressure (CPP), we studied CPP, ICP, CBF, CO2del, cerebral oxygen extraction ratio (CO2ER), and cortical water content (CWC) in a porcine model of focal cryogenic brain injury. Fifteen mature swine were randomized to two groups. The experimental group (n = 7) had a brain lesion and was studied for 24 hours. The control group (n = 8) was instrumented only. Cryogenic injury significantly increased ICP and decreased CBF and CO2del compared with controls. There were no significant differences in CPP between the groups for the entire experiment, and the CPP was well above the ischemic threshold. The CO2ER significantly increased in the first three hours after brain injury. However, CO2ER in experimental animals tended to decrease 12 hours after brain injury and was not significantly different from that in controls. Cryogenic injury significantly increased the CWC in the lesioned hemisphere. These data indicate that focal brain injury results in persistent ischemia despite the normalization of CPP, suggesting that a significant increase in cerebral vascular resistance (CVR) occurs after brain injury. We conclude that in addition to maintenance of CPP, intervention to reduce CVR may be important in the management of brain injury.