Fall In Cerebral Blood Flow Research Articles

Melatonin improves cerebral circulation security margin in rats.

Because melatonin is a cerebral vasoconstrictor agent, we tested whether it could shift the lower limit of cerebral blood flow autoregulation to a lower pressure level, by improving the cerebrovascular dilatory reserve, and thus widen the security margin. Cerebral blood flow and cerebrovascular resistance were measured by hydrogen clearance in the frontal cortex of adult male Wistar rats. The cerebrovasodilatory reserve was evaluated from the increase in the cerebral blood flow under hypercapnia. The lower limit of cerebral blood flow autoregulation was evaluated from the fall in cerebral blood flow following hypotensive hemorrhage. Rats received melatonin infusions of 60, 600, or 60,000 ng . kg-1 . h-1, a vehicle infusion, or no infusion (n = 9 rats per group). Melatonin induced concentration-dependent cerebral vasoconstriction (up to 25% of the value for cerebrovascular resistance of the vehicle group). The increase in vasoconstrictor tone was accompanied by an improvement in the vasodilatory response to hypercapnia (+50 to +100% vs. vehicle) and by a shift in the lower limit of cerebral blood flow autoregulation to a lower mean arterial blood pressure level (from 90 to 50 mmHg). Because melatonin had no effect on baseline mean arterial blood pressure, the decrease in the lower limit of cerebral blood flow autoregulation led to an improvement in the cerebrovascular security margin (from 17% in vehicle to 30, 55, and 55% in the low-, medium-, and high-dose melatonin groups, respectively). This improvement in the security margin suggests that melatonin could play an important role in the regulation of cerebral blood flow and may diminish the risk of hypoperfusion-induced cerebral ischemia.

Characterization of cerebral hemodynamic phases following severe head trauma: hypoperfusion, hyperemia, and vasospasm.

The extent and timing of posttraumatic cerebral hemodynamic disturbances have significant implications for the monitoring and treatment of patients with head injury. This prospective study of cerebral blood flow (CBF) (measured using 133Xe clearance) and transcranial Doppler (TCD) measurements in 125 patients with severe head trauma has defined three distinct hemodynamic phases during the first 2 weeks after injury. The phases are further characterized by measurements of cerebral arteriovenous oxygen difference (AVDO[2]) and cerebral metabolic rate of oxygen (CMRO[2]). Phase I (hypoperfusion phase) occurs on the day of injury (Day 0) and is defined by a low CBF calculated from cerebral clearance curves integrated to 15 minutes (mean CBF 32.3 +/- 2 ml/100 g/minute), normal middle cerebral artery (MCA) velocity (mean V[MCA] 56.7 +/- 2.9 cm/second), normal hemispheric index ([HI], mean HI 1.67 +/- 0.11), and normal AVDO(2) (mean AVDO[2] 5.4 +/- 0.5 vol%). The CMRO, is approximately 50% of normal (mean CMRO(2) 1.77 +/- 0.18 ml/100 g/minute) during this phase and remains depressed during the second and third phases. In Phase II (hyperemia phase, Days 1-3), CBF increases (46.8 +/- 3 ml/100 g/minute), AVDO(2) falls (3.8 +/- 0.1 vol%), V(MCA) rises (86 +/- 3.7 cm/second), and the HI remains less than 3 (2.41 +/- 0.1). In Phase III (vasospasm phase, Days 4-15), there is a fall in CBF (35.7 +/- 3.8 ml/100 g/minute), a further increase in V(MCA) (96.7 +/- 6.3 cm/second), and a pronounced rise in the HI (2.87 +/- 0.22). This is the first study in which CBF, metabolic, and TCD measurements are combined to define the characteristics and time courses of, and to suggest etiological factors for, the distinct cerebral hemodynamic phases that occur after severe craniocerebral trauma. This research is consistent with and builds on the findings of previous investigations and may provide a useful temporal framework for the organization of existing knowledge regarding posttraumatic cerebrovascular and metabolic pathophysiology.

Characterization of cerebral hemodynamic phases following severe head trauma: hypoperfusion, hyperemia, and vasospasm

The extent and timing of posttraumatic cerebral hemodynamic disturbances have significant implications for the monitoring and treatment of patients with head injury. This prospective study of cerebral blood flow (CBF) (measured using 133Xe clearance) and transcranial Doppler (TCD) measurements in 125 patients with severe head trauma has defined three distinct hemodynamic phases during the first 2 weeks after injury. The phases are further characterized by measurements of cerebral arteriovenous oxygen difference (AVDO2) and cerebral metabolic rate of oxygen (CMRO2). Phase I (hypoperfusion phase) occurs on the day of injury (Day 0) and is defined by a low CBF15 calculated from cerebral clearance curves integrated to 15 minutes (mean CBF15 32.3 ± 2 ml/100 g/minute), normal middle cerebral artery (MCA) velocity (mean VMCA 56.7 ± 2.9 cm/second), normal hemispheric index (mean HI 1.67 ± 0.11), and normal AVDO2 (mean AVDO2 5.4 ± 0.5 vol%). The CMRO2 is approximately 50% of normal (mean CMRO2 1.77 ± 0.18 ml/100 g/minute) during this phase and remains depressed during the second and third phases. In Phase II (hyperemia phase, Days 1-3), CBF increases (46.8 ± 3 ml/100 g/minute), AVDO2 falls (3.8 ± 0.1 vol%), VMCA velocity rises (86 ± 3.7 cm/second), and the HI remains less than 3 (2.41 ± 0.1). In Phase III (vasospasm phase, Days 4-15), there is a fall in CBF (35.7 ± 3.8 ml/100 g/minute), a further increase in VMCA (96.7 ± 6.3 cm/second), and a pronounced rise in the HI (2.87 ± 0.22). This is the first study in which CBF, metabolic, and TCD measurements are combined to define the characteristics and time courses of, and to suggest etiological factors for, the distinct cerebral hemodynamic phases that occur after severe craniocerebral trauma. This research is consistent with and builds on the findings of previous investigations and may provide a useful temporal framework for the organization of existing knowledge regarding posttraumatic cerebrovascular and metabolic pathophysiology.

Augmented hypoxic cerebral vasodilation in men during 5 days at 3,810 m altitude.

The fractional increase in cerebral blood flow (CBF) velocity (VCBF) from the control value with 5-min steps of isocapnic hypoxia and hyperoxic hypercapnia was measured by transcranial Doppler in six sea-level native men before and during a 5-day sojourn at 3,810 m altitude to determine whether cerebral vasoreactivity to low arterial O2 saturation (SaO2) gradually increased [as does the hypoxic ventilatory response (HVR)] or diminished (adapted, in concert with known slow fall of CBF) at altitude. A control resting PCO2 value was chosen each day during preliminary hyperoxia to set ventilation at 140 ml.kg-1.min-1 for this and the parallel HVR study, attempting to establish control cerebrospinal fluid (CSF) and brain extracellular fluid pH values unaltered by acclimatization. The relationship of CBF to SaO2 was nonlinear, steepening at a lower SaO2. A hyperbolic equation was used to describe hypoxic cerebrovascular reactivity: fractional VCBF = x[60/ (SaO2-40)-1], where X is the fractional increase of VCBF at 70%.X rose from 0.346 +/- 0.104 (SD) at sea level to 0.463 +/- 0.084 on altitude day 5 (P < 0.05 by paired t-test, justified by the a priori experimental plan). For comparison with CO2 sensitivity, from these X values, we estimate the rise in CBF in response to a 1% fall in SaO2 at 80% to be 1.30% at sea level and 1.74% after 5 days at altitude. CBF sensitivity to increased end-tidal PCO2 rose from 4.01 +/- 0.62%/Torr at sea level to 5.12 +/- 0.79%/Torr on day 5 (P < 0.05), as expected, at the lower PCO2 due to the logarithmic relationship of PCO2 to CSF pH. This change was not significant after correction to log PCO2. We conclude that the cerebral vascular response to acute isocapnic hypoxia may increase during acclimatization at high altitude. The mechanism is unknown but is presumably unrelated to the parallel carotid chemosensitization that, in these subjects, increased the HVR by 60% in the same 5-day period from 0.91 +/- 0.38 to 1.46 +/- 0.59 l.min-1.% fall in SaO2-1).

Characterization of an anterior circulation rat subarachnoid hemorrhage model.

Our aim was to demonstrate the feasibility of an angiographically controlled rat model for the study of macrocirculatory and microcirculatory changes of the anterior intracranial circulation after subarachnoid hemorrhage. Subarachnoid hemorrhage was induced by transorbital injection of 0.3 mL of nonheparinized autologous arterial blood into the chiasmatic cistern. Changes in regional cerebral blood flow were continuously recorded with the use of laser-Doppler flowmetry over the parietal cortex. Angiographic verification of middle cerebral artery diameter was performed by carotid catheterization at baseline and 2 days after injection of blood or artificial cerebrospinal fluid. We monitored intracranial and systemic blood pressure during and after injections. Injection of artificial cerebrospinal fluid in the control group did not change the diameter of the middle cerebral artery. Injection of blood caused a significant arterial narrowing of 17.5%, from 0.37 +/- 0.04 mm to 0.31 +/- 0.04 mm after 2 days (P = .0001). In the control group regional cerebral blood flow decreased to 75.9 +/- 16.8% of preinjection control but quickly recovered to 99.7 +/- 19.4%. Intracranial pressure increased for 5 minutes after the injection to a maximum of 27.3 +/- 8.9 mm Hg, accompanied by a 10% decrease in mean arterial pressure. A fall in cerebral blood flow to 53.1 +/- 26.3% in blood-injected animals that recovered to only 80.7 +/- 16.9% of baseline values during the observation period of 30 minutes was noted. A peak intracranial pressure of 45.7 +/- 11.5 mm Hg occurred 2 minutes after injection with a decrease in mean arterial pressure of 13%, resulting in a markedly lower cerebral perfusion pressure than in the control group. An angiographically controlled model of subarachnoid hemorrhage primarily involving the anterior circulation is feasible in the rat. The resulting narrowing of the middle cerebral artery reflects moderate vasospasm and will allow further microcirculatory studies with cranial windows.

Changes in Cerebral Blood Flow as Monitored by Transcranial Doppler During Voluntary Hyperventilation and Their Effect on the Electroencephalogram

Hyperventilation results in a fall in carbon dioxide concentration, a fall in cerebral blood flow, and slowing of activity on the electroencephalogram. The temporal relationship and duration of these responses are uncertain, and were investigated using simultaneous monitoring of cerebral blood flow velocity and of the electroencephalograph, with end-tidal carbon dioxide monitoring. Sixteen patients and 9 normal volunteers were studied. Cerebral blood flow velocity in the middle cerebral artery was measured using transcranial Doppler sonography during 3 minutes of hyperventilation and during a 3-minute recovery period. Electroencephalographic recordings were rated by both visual score and measurement of the dominant posterior frequency. End-tidal expired carbon dioxide tension was monitored during the same hyperventilation protocol in the volunteers. Flow velocity fell rapidly during active hyperventilation. Electroencephalographic slowing closely correlated with the decrease in flow velocity (r = 0.86), but lagged behind it. In healthy volunteers capnographic records showed a very tight coupling between end-tidal carbon dioxide concentration and flow velocity (r = 0.94). Three minutes after hyperventilation, carbon dioxide concentration, cerebral blood flow velocity, and electroencephalographic activity were still not back to the resting state. The fall in both cerebral blood flow velocity and carbon dioxide concentration are related to but precede electroencephalographic slowing. The abnormalities persist for at least 3 minutes after hyperventilation and this must be taken into account in clinical electroencephalography. Transcranial Doppler sonography is well suited to monitoring short-term changes in the cerebral circulation.

Functional, metabolic, and circulatory changes associated with seizure activity in the postischemic brain.

The present study was undertaken to explore how transient ischemia in rats alters cerebral metabolic capacity and how postischemic metabolism and blood flow are coupled during intense activation. After 6 h of recovery following transient forebrain ischemia 15 min in duration, bicuculline seizures were induced, and brains were frozen in situ after 0.5 or 5 min of seizure discharge. At these times, levels of labile tissue metabolites were measured, whereas the cerebral metabolic rate for oxygen (CMRO2) and cerebral blood flow (CBF) were measured after 5 min of seizure activity. After 6 h of recovery, and before seizures, animals had a 40-50% reduction in CMRO2 and CBF. However, because CMRO2 rose three-fold and CBF fivefold during seizures, CMRO2 and CBF during seizures were similar in control and postischemic rats. Changes in labile metabolites due to the preceding ischemia encompassed an increased phosphocreatine/creatine ratio, as well as raised glucose and glycogen concentrations. Seizures gave rise to minimal metabolic perturbation, essentially comprising reduced glucose and glycogen contents and raised lactate concentrations. It is concluded that although transient ischemia leads to metabolic depression and a fall in CBF, the metabolic capacity of the tissue is retained, and drug-induced seizures lead to a coupled rise in metabolic rate and blood flow.

Alterations in regional cerebral blood flow, with increased temporal interhemispheric asymmetries, in the normal elderly

Single photon emission computed tomography (SPECT) with the tracer 99Tcm-hexamethylpropyleneamine oxime (HMPAO) provides images allowing semiquantitative estimation of regional cerebral blood flow (rCBF). Despite its widespread use there is little data on patterns of rCBF obtained using this tracer in normal elderly subjects, although other methods of measurement suggest a fall in cerebral blood flow with age. Furthermore, the detection of interhemispheric asymmetries on HMPAO SPECT is often used to identify areas of pathological abnormality yet there is little data on the prevalence of asymmetries in the normal elderly. An increased prevalence of asymmetries in the elderly may explain the difficulties recently reported in using functional imaging in the diagnosis of Alzheimer's dementia. Patterns of HMPAO uptake were compared in 10 young (mean age 24.9 years; range 21-34 years) and 10 elderly (mean age 74.1 years; range 70-76 years) normal subjects. Percentage interhemispheric asymmetry ratios were calculated and found to be greater in the elderly, particularly for the temporal cortex (young 0.87%, elderly 3.73%, P < 0.001). The proportion of injected HMPAO taken up by the head was 29% higher in the younger age group. Analysis of regional uptake revealed that this trend towards reduced uptake in the elderly was a global phenomenon affecting all brain regions. The increased interhemispheric asymmetries seen in the elderly imply that a higher threshold for interpreting asymmetries as abnormal must be used in the elderly, particularly for the temporal cortex.

Hemodynamic and metabolic effects of flunarizine in experimental subarachnoid hemorrhage in dogs.

Cerebral blood flow and oxygen metabolism were measured and a cerebral angiography was performed in dogs with experimental subarachnoid hemorrhage to assess the relation between arterial narrowing (vasospasm) and the fall of blood flow. Cerebral blood volume and the cerebrovascular CO2 reactivity were also measured to estimate the cerebrovascular reserve. Several groups of dogs were treated with flunarizine in different regimens to assess its possible therapeutic effect. The experiments were performed in the three-hemorrhage canine model for subarachnoid hemorrhage. Cerebral blood flow and cerebral oxygen metabolism were measured in anesthetized (nitrous oxide) dogs using positron emission tomography in combination with the 15O steady-state method. Basilar artery diameter was evaluated by digital subtraction angiography. In normal dogs, cerebral blood flow, oxygen consumption, and oxygen extraction ratio were 46.4 +/- 9.0 ml/100 ml per minute, 3.65 +/- 0.76 ml/100 ml per minute, and 39.9 +/- 3.4%, respectively; basilar artery diameter was 1.33 +/- 0.25 mm. Repeated subarachnoid blood injection (3 x 5 ml) reduced basilar artery diameter to < 20% of normal (p < 0.01). Cerebral blood flow was reduced by only 25% (p < 0.001); oxygen consumption was preserved at a low normal level by a 29% compensatory increase of the oxygen extraction (p < 0.001). Cerebral blood volume and cerebrovascular CO2 reactivity remained nearly normal. Early (after the first blood injection) peroral treatment with flunarizine (0.5 mg/kg daily) resulted in less severe basilar artery narrowing (56% of normal; p < 0.05 versus untreated). However, this treatment had no effect on cerebral blood flow, blood volume, oxygen consumption, and extraction. The observed fall of cerebral blood flow in experimental subarachnoid hemorrhage is not related to arterial narrowing but to an increased cerebrovascular resistance at the level of the small parenchymal vessels, and the latter, in contrast to arterial narrowing, is unaffected by flunarizine.

Intravenous aminophylline and cerebral blood flow in preterm infants.

The effect of aminophylline on cerebral blood flow (CBF) was studied in 10 preterm infants who were receiving 6.2 mg/kg intravenously over 20 minutes followed by a maintenance infusion. CBF was measured intermittently using near infrared spectroscopy. Heart rate, blood pressure, oxygen saturation, and transcutaneously measured carbon dioxide tension (TcPCO2) were recorded continuously. Aminophylline administration was associated with a fall in CBF from a median of 15.9 ml/100 g/min to 11.2 ml/100 g/min. Median fall in CBF was 4.1 ml/100 g/min (95% confidence interval 1.7 to 6.5). Heart rate rose and TcPCO2 fell in all infants, median fall being 0.66 kPa. The reduction in CBF was greater than would be expected on the basis of the modest fall in TcPCO2.

Effects of hyperventilation, hypothermia, and altered blood viscosity on cerebral blood flow, cross-brain oxygen extraction, and cerebral metabolic rate for oxygen in cats.

Therapies including hyperventilation (HV) and hypothermia (HT) are currently simultaneously used in brain-injured children at risk for cerebral swelling to reduce cerebral blood flow (CBF) and alter cerebral metabolic rate for oxygen (CMRO2). Since HV and HT may contribute to significant patient morbidity, we evaluated the effects of these treatments in combination on CBF, CMRO2, and cross-brain oxygen extraction (CBO2) using the Kety-Schmidt technique before controlled bleeding to alter blood viscosity in 20 lightly anesthetized, paralyzed cats, and after bleeding in another 17 cats. The degree of HV (PaCO2 24 to 26 torr) and HT (32 degrees and 30 degrees C) used were representative of that employed in pediatric neurointensive care. HV at normothermia resulted in a significant decline in CBF (P less than .05) and an unchanged CMRO2. HV and HT together to 32 degrees C resulted in a further significant fall in CBF and CMRO2 (p less than .05), but an unchanged CBO2. Further cooling of the animal to 30 degrees C during HV, both before and after controlled bleeding, resulted in no further significant fall in CBF, CBO2, or CMRO2. This relationship was found despite a significant fall in Hgb (p less than .001), suggesting that blood viscosity did not significantly influence CBF at this temperature. Our data suggest that HT to 32 degrees C during HV may have therapeutic benefit by decreasing CBF and CMRO2, but further cooling to 30 degrees C may not result in further cerebral protective effects.

Indomethacin restricts cerebral blood flow during pressure ventilation of newborn pigs.

Unanesthetized newborn pigs were studied to evaluate the immediate (10 min) and delayed (45 min) effects of increased ventilation pressure coupled with cyclooxygenase inhibition. Cardiac output and cerebral blood flow were measured at a low (5 cm H2O) and high (30 cm H2O) mean airway pressure (Paw) before and 45 min after 5 mg/kg of indomethacin. In a second group, these parameters were also measured 10 min after indomethacin was given during ventilation at a Paw of 30 cm H2O. Before treatment with indomethacin, increasing Paw decreased cardiac output without affecting cerebral blood flow. Baseline (Paw = 5 cm H2O) cerebral blood flow decreased 40% 45 min after indomethacin treatment. Adding the stress of a ventilation-induced drop in cardiac output did not further depress cerebral blood flow. When indomethacin was administered during high Paw, cerebral blood flow decreased markedly within 10 min. Cerebral oxygen consumption was maintained by increasing oxygen extraction. Therefore, indomethacin decreases cerebral blood flow at a high Paw. The fall in cerebral blood flow decreases brain oxygen delivery. However, cerebral oxygen consumption is maintained by an increase in oxygen extraction.

Base-line O2 extraction influences cerebral blood flow response to hematocrit

We have shown that the fall in cerebral blood flow (CBF) as hematocrit (Hct) rises is due to the independent effects of increasing red blood cell (RBC) concentration and arterial O2 content (CaO2). In the present study, we tested the hypothesis that the magnitude of the effect of RBC concentration depends on the base-line cerebral fractional oxygen extraction (E). E is the ratio of O2 demand (cerebral O2 consumption, CMRO2) to supply (cerebral O2 transport: OT = CBF x CaO2) and is assumed to be inversely related to tissue O2 availability. Pentobarbital-anesthetized 1- to 7-day-old sheep were first exchange transfused with plasma to lower Hct to 20%. Base-line E was set to either high or low levels by induction of hypocarbia [arterial CO2 partial pressure (PaCO2) = 15.3 +/- 0.7 mmHg, means +/- SE; n = 7] or hypercarbia (PaCO2 = 62.7 +/- 1.1 mmHg; n = 5), respectively. A second isovolemic exchange transfusion with pure methemoglobin-containing adult sheep red cells then raised Hct (to 38.5 +/- 0.5%) with no significant increase in CaO2. PaCO2 was maintained and other variables (oxyhemoglobin affinity, pH, mean arterial blood pressure) with potential effect on CBF did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of hematocrit on cerebral blood flow with induced polycythemia.

Cerebral blood flow (CBF) is lowered during polycythemia. Whether this fall is due to an increase in red blood cell concentration (Hct) or to an increase in arterial O2 content (Cao2) is controversial. We examined the independent effects of Hct and Cao2 on CBF as Hct was raised from 30 to 55% in anesthetized 1- to 7-day-old sheep. CBF was measured by the radiolabeled microsphere technique before and after isovolemic exchange transfusion with either oxyhemoglobin-containing erythrocytes (in 5 control animals) or with methemoglobin-containing erythrocytes (in 9 experimental animals). Following exchange transfusion in the control animals, Hct rose (30 +/- 1 vs. 55 +/- 1%, mean +/- SE), Cao2 increased (15.1 +/- 0.8 vs. 26.7 +/- 0.9 vol%), and CBF fell (66 +/- 9 vs. 35 +/- 5 ml X min-1 X 100 g-1). Because the fall in CBF was proportionate to the rise in Cao2, cerebral O2 transport (CBF X Cao2) was unchanged. Following exchange transfusion in the experimental animals, Hct rose (32 +/- 1 vs. 55 +/- 1%) but Cao2 did not change. Nevertheless, CBF still fell (73 +/- 4 vs. 48 +/- 2 ml X min-1 X 100 g-1) and, as a result, cerebral O2 transport also fell. The latter cannot be attributed to a fall in cerebral O2 uptake, as cerebral O2 uptake was unaffected during each of these conditions. Comparison of the two groups of animals showed that approximately 60% of the fall in CBF may be attributed to the increase in red cell concentration alone. It is probable that this effect is due largely to changes in blood viscosity.

PET studies of changes in cerebral blood flow and oxygen metabolism after unilateral microembolization of the brain in anesthetized dogs.

Cerebral blood flow and oxygen metabolism have been measured with the steady-state oxygen-15 technique and positron emission tomography in anesthetized dogs. Regional microembolization was induced by infusing Sephadex particles (diameter, 40 micron) into one of the common carotid arteries. In the first series of experiments, 2.5 mg Sephadex was infused, and the dogs were examined within 3-4 hours after embolization. In a second series 0.55 mg Sephadex was infused, and the dogs were examined either in the first 3-4 hours or 24-48 hours after embolization. Cerebral blood flow, oxygen extraction ratio, and cerebral oxygen utilization were measured at 3 PCO2 levels. In the acute experiments, cerebral oxygen utilization in the embolized hemisphere was 6 (0.55 mg Sephadex) and 25% (2.5 mg Sephadex) lower than on the contralateral side. While cerebral blood flow was symmetrically distributed in normocapnia and hypocapnia, it was 9 (0.55 mg Sephadex) and 35% (2.5 mg Sephadex) lower in the embolized hemisphere during hypercapnia. In normocapnia and hypocapnia the lower oxygen utilization in the embolized hemisphere was characterized by a lower oxygen extraction ratio, and in hypercapnia by an unchanged (0.55 mg Sephadex) or by a higher (2.5 mg Sephadex) extraction ratio. The different effect on oxygen extraction ratio in the control and embolized hemispheres resulted in images of uncoupling between perfusion and oxygen demand that varied according to the PCO2. The experiments also showed a fall in cerebral blood flow in the embolized hemisphere after 3-4 hours, indicating delayed hypoperfusion. After 24-48 hours, blood flow was about 10% higher in the embolized hemisphere, and this was observed at the 3 PCO2 levels, while the oxygen extraction ratio was systematically lower. Oxygen utilization in the embolized hemisphere was depressed to practically the same extent as in acute experiments. It can be concluded that between 4 and 24 hours after microembolization the cerebral microcirculation shows important changes, with installation of luxury perfusion in the face of an unchanging decreased oxygen metabolism.

Cerebrospinal fluid pulse pressure and the pulsatile variation in cerebral blood volume: an experimental study in dogs.

The cerebrospinal fluid pulse pressure (CSFPP) has found application as a measure of intracranial elastance. However, CSFPP is also dependent on the magnitude of the pulsatile variation in cerebral blood volume (delta Vb). The purpose of the present study was to assess the effect on delta Vb of changes in systemic arterial pressure (SAP) and arterial carbon dioxide tension (PaCO2) as well as elevation of intracranial pressure (ICP). Therefore, delta Vb was computed from the electromagnetically measured flow profile in the vertebral artery of the dog on the assumption of a nonpulsatile cerebral venous outflow. During arterial hypotension, delta Vb was increased due to a shift of flow from diastole to systole, whereas mean flow was not affected. The reverse phenomenon was observed when SAP was raised. Changes in PaCO2 had little effect on pulsatile blood flow. The changes in total blood flow that occurred were evenly distributed over the cardiac cycle. Consequently, delta Vb was not significantly affected, although CSFPP was considerably changed. When ICP was raised, a breakpoint pressure was observed above which cerebral blood flow (CBF) decreased and CSFPP and delta Vb increased. This contradiction was explained by the finding of a decrease in diastolic flow, causing the fall in CBF, whereas systolic flow relative to mean flow was increased, resulting in an increased delta Vb. The underlying mechanisms of the pulsatile flow changes are extensively discussed. It is argued that the arterial inflow profile is largely determined by the compliance of the inflow section of the cerebral vascular bed. Vascular compliance is significantly altered by changes in SAP and ICP because they affect the transmural pressure of the vessels, whereas this is not the case during changes in PaCO2.

Comparison of fast flow and initial slope index values for cerebral blood flow following subarachnoid haemorrhage.

Forty five patients with subarachnoid haemorrhage proved by lumbar puncture underwent serial measurements of cerebral blood flow and central conduction time. When the initial slope index (ISI) value for cerebral blood flow is considered there is a clear relationship between reduction of cerebral blood flow and deteriorating clinical grade. This relationship is not so clearly demonstrated using the fast flow (f1) value for cerebral blood flow. When cerebral blood flow is compared to central conduction time those patients with a central conduction time longer than 6 X 4 ms have a significantly lower CBFisi but not a significant lower CBFf1. Furthermore, using the ISI value, there is a linear relationship between the fall in cerebral blood flow and the lengthening of CCT below a threshold blood flow of about 35 ml/100 g/min. This relationship is not demonstrated with the CBFf1 value. It therefore appears that the ISI value for cerebral blood flow shows a greater correlation between clinical and electrophysiological events than the f1 value.

The risk-benefit ratio of intraoperative shunting during carotid endarterectomy. Relevancy to operative and postoperative results and complications.

The relative risk of shunting versus not shunting during carotid endarterectomy was analyzed retrospectively in 1935 cases undergoing carotid endarterectomy for carotid ulcerative stenosis. The need for shunting was based on a correlation between electroencephalographic changes and a fall in cerebral blood flow below the critical level required for adequate perfusion during the period of carotid occlusion. Patients were divided into four risk categories for surgery, based on medical and neurological risks and angiographic findings. Shunts were required in 30% of the low risk group and 56% of the high risk group. Based on the severity of reductions of cerebral blood flow during the period of carotid occlusion it is concluded that 12% of all patients would have sustained a major deficit, 15% a minor or transient deficit, and 20% a transient deficit without shunting. The risk of shunting 792 cases in this series was 0.5%. Overall minor morbidity, major morbidity, and mortality each approximated 1% in this series.

The dopamine withdrawal test following surgery for intracranial aneurysms.

Cerebral blood flow was measured in eight patients who were being treated with dopamine in order to maintain cerebral perfusion after the onset of delayed postoperative ischaemia following intracranial aneurysm surgery. Measurements were made whilst on treatment and repeated either during a reduction in the dosage or withdrawal of dopamine. There was a significant fall in cerebral blood flow in both hemispheres in all eight patients. Clinical deterioration was observed in seven of nine instances in which cerebral blood flow fell by 25% or more of the value while on dopamine treatment. There were no episodes of deterioration in six tests where the fall in cerebral blood flow was less than 25% of the starting value. It is suggested that cerebral blood flow measurement can be useful in predicting when it is safe to withdraw dopamine treatment in these patients. Hypertensive treatment should be maintained if a withdrawal test is associated with a fall in cerebral blood flow of 25% or more.

The effects of hyperglycaemia on changes during reperfusion following focal cerebral ischaemia in the cat.

The effects of isosmolar loads of glucose and saline after onset of focal cerebral ischaemia (middle cerebral artery occlusion) were compared in cats. In cats given saline cerebral blood flow (CBF) fell and then rose slightly on the marginal gyrus (infarct penumbra). There was a sustained fall in CBF on the suprasylvian and ectosylvian gyri (infarct core). Reperfusion restored blood flow to preocclusion levels with no overall postischaemic hypoperfusion. Below ischaemic flows of 14 ml/100 g/min brain specific gravity was reduced in a smaller proportion of gyri by contrast with non reperfused cortex, suggesting that in some gyri resolution of cerebral oedema had taken place. GABA uptake was normal in the infarct core, but was reduced within the ischaemic penumbra. In animals given glucose after occlusion, CBF fell on the marginal gyrus during reperfusion. The degree of resolution of cerebral oedema was less than in saline infused cats. GABA uptake showed a pattern of abnormality similar to that seen in saline infused cats, except that uptake values were lower in the infarct core. Pial surface potassium activity remained elevated in the penumbra following reperfusion in glucose infused cats, but returned to normal in saline infused cats. Implications for the management of cerebral ischaemia in man are discussed.