The sequential change of local cerebral blood flow and local cerebral glucose metabolism after focal cerebral ischaemia and reperfusion in rat and the effect of MK-801 on local cerebral glucose metabolism

Summary In order to investigate the time course change of local cerebral blood flow (1CBF) and local cerebral glucose metabolism (1CGM) and the effect of MK-801 (dizocilpine), an NMDA receptor antagonist on glucose metabolism in a middle cerebral artery occlusion-reperfusion model,¹⁴C-Iodo-antipyrine and¹⁴C-Deoxyglucose autoradiographic method have been used. The 1CBF was reduced to 0–10% of the control level in the ischaemic core and to 12–40% in the ischaemic penumbra between 60 and 120 min after the onset of the ischaemia. In the ischaemic core, the marked hyperfusion appeared at 15 min and maintained about 30 to 45 min following reperfusion. In the ischaemic penumbra, the hyperfusion during reperfusion was not found. Hypermetabolism occurred at 30 min and reached to the peak at 60 min after the middle cerebral artery (MCA) occlusion both in the ischaemic core and in the penumbra. The shift from hyper- to hypometabolism was observed during the ischaemia. The reperfusion following 2 hours of MCA occlusion facilitated the decrease of cerebral glucose metabolism in the ischaemic region. The pretreatment of MK-801 (0.4 mg/kg) inhibited both increased glucose metabolism during the ischaemia and decreased glucose metabolism during the reperfusion. The effect of limiting decreased glucose metabolism during the reperfusion by MK-801 was remarkable in the ischaemic penumbra. These findings support the hypothesis that excitation-induced hypermetabolism play a major role in the ischaemic insult following focal cerebral vascular occlusion.     

Transcranial Doppler for detection of cerebral ischaemia during carotid endarterectomy.

We evaluated transcranial Doppler sonography (TCD) for the detection of cerebral ischaemia during carotid endarterectomy in 30 male and 14 female patients with ipsilateral focal cerebro-vascular symptoms. Surgery was performed during halothane-nitrous oxide anaesthesia with moderate hypocapnia. Eight patients had a temporary shunt owing to contralateral occlusion or a stump pressure below 40 mmHg, and/or EEG flattening. Transcranial Doppler sonography was followed intra-operatively together with electro-encephalography (EEG), internal carotid artery (ICA) pressures and cerebral blood flow (CBF). Middle cerebral artery mean flow velocity (Vmean) was 38 (22-96) cm s-1 (median and range) and decreased during cross-clamping to 28 (10-60) cm s-1 (p less than 0.0001). After removal of the clamp it increased to 42 (20-102) cm s-1 (p less than 0.0001). AVmean clamp of less than 30 cm s-1 together with a Vmean clamp: Vmean pre-clamp ratio of less than 0.6 showed an accuracy with respect to CBF below 20 ml 100 g-1 min-1 of 89%. AVmeanclamp:Vmean pre-clamp ratio below 0.4 detected all all patients with EEG flattening (n = 3) (accuracy 97%). The corresponding level of accuracy obtained with stump pressure was 80%. The results indicate that middle cerebral flow velocity enables an increase in the accuracy of detecting cerebral ischaemia during carotid endarterectomy.     

The effects of propofol on cerebral blood flow in correlation to cerebral blood flow velocity in dogs

This study correlates the effects of propofol on cerebral blood flow (CBF) and middle cerebral artery blood flow velocity in dogs. CBF was measured using radioactive microspheres. Cerebral oxygen consumption (CMRO2) was measured with each CBF determination. Blood flow velocity was measured through a transtemporal window using a pulsed 8 MHz transcranial Doppler ultrasound system (TCD). Electroencephalogram (EEG) was continuously recorded over both cerebral hemispheres. Cardiac output (CO) was measured using an electromagnetic flow probe placed on the pulmonary artery. Baseline measures were made in all dogs (n = 11) with 0.7% isoflurane end tidal and 50% N2O in O2. There were two treatment groups. In group 1 (n = 6), propofol (0.8 mg/kg/min) was infused and a second measurement made at induction of EEG burst suppression (12 +/- 2 min). CBF and CMRO2 decreased by 70% and mean blood flow velocity decreased by 60%. Blood pressure, heart rate, and CO did not change. Propofol infusion was discontinued and all parameters were measured following recovery of EEG to baseline activity (48 +/- 9 min). CBF and blood flow velocity increased 35 and 25%, respectively, and CMRO2 increased by 32% during this period. A second propofol infusion (0.8 mg/kg/min) was started and all cerebral and systemic hemodynamic parameters were again determined at induction of EEG burst suppression (12 +/- 2 min). CBF decreased 35% and blood flow velocity decreased 25% to levels seen during the first propofol infusion. Over the entire study, changes in CBF correlated with changes in blood flow velocity (r = 0.86, p < 0.05). In group 2 (n = 5), four control measures were made at the same time intervals as in group 1. Baseline CBF and blood flow velocity were lower in group 2 compared to group 1 but these measures did not change over time. Our results show that propofol produces marked decreases in CBF in dogs and that these changes are closely correlated with CBF velocity.     

Comparison of measurement of stump pressure and transcranial measurement of flow velocity in the middle cerebral artery in carotid surgery

Transcranial Doppler ultrasound measurement of the velocity of blood flow in the middle cerebral artery (MCA) was performed in 24 consecutive patients undergoing carotid endarterectomy. Measurements were performed preoperatively at rest, following common carotid artery compression, and continuously during surgery. In addition, internal carotid artery stump pressures were measured and a subjective assessment of back flow was made. No relationship between MCA flow velocity and stump pressure following carotid clamping was demonstrated. Peak and mean MCA flow velocity was significantly lower in patients with stump pressures <30 mm Hg (p <0.03) and those with poor back flow (p <0.02).     

Changes in middle cerebral artery flow velocity and pulsatility index after carotid endarterectomy.

Transcranial Doppler sonography (TCD) was used in 33 patients undergoing carotid endarterectomy (CEA). Mean flow velocity (MCA MV) and the pulsatility index in the middle cerebral artery (MCA PI) were measured pre- and on six occasions postoperatively. The MCA MV was reduced by anaesthesia but was increased postoperatively (+43%, p less than 0.001) compared to the preoperative value and was still increased at late follow-up after several months. The MCA PI, which was lower preoperatively than normally reported in this age group, was not changed by anaesthesia but then rose and remained elevated, i.e. within normal limits 72 h postoperatively (+30%, p less than 0.01) as well as at late follow-up. No significant changes in MCA MV or MCA PI were noted on the contralateral side. The results from this study support earlier findings from invasive studies showing that CEA results in an increased flow in the middle cerebral artery on the operated side and an increased MCA PI suggests an increased resistance on the operated side. The findings are compatible with an increased cerebral blood flow during the first days after CEA and with the operated side supplying a greater part of the cerebral blood flow even several months after surgery.     

Transcranial Doppler sonography: halothane increases average blood flow velocity in the middle cerebral artery

Transcranial Doppler sonography (TCD) can non-invasively measure the blood flow velocity of basal cerebral arteries, especially of the middle cerebral artery (MCA). TCD has been used for monitoring the cerebral circulation during cardiopulmonary bypass or cross-clamping of the carotid artery. To date, systemic investigation of the effects of anesthetic agents on mean blood flow velocity in the MCA (vMCA) has been neglected, although their effects on cerebral blood flow are well known. Two groups of 10 patients each with minor surgical or gynecological operations were studied using TC2-64 (EME) TCD equipment. Constant artificial ventilation with N2O:O2 = 2:1 was controlled by capnometry; capillary pCO2 ranged from 35 to 40 mmHg in both groups. In group I, patients underwent general anaesthesia with approximately 0.8 vol% halothane. vMCA, blood pressure, and heart rate were determined before and during anesthesia as well as after skin incision. Group II patients received fentanyl and droperidol. Measurements were performed at time points comparable to those in group I. Halothane caused an increase in vMCA by more than one third of the preanesthetic value (from 54.4 +/- 12.2. to 84.2 +/- 23.9 (P less than 0.01]. In group II (neuroleptanesthesia), no significant alterations of vMCA or hemodynamic parameters were observed. These results show that anesthetic agents can influence vMCA as well as cerebral blood flow. Therefore, these data should be taken into account while monitoring vMCA during operative procedures. However it has to be considered that TCD only permits measurement of blood flow velocity, while the diameter of the investigated vessel remains unknown. Clinical applications of this fascinating noninvasive monitoring device are discussed.     

Cerebral blood flow and cerebral blood flow velocity during angiotensin-induced arterial hypertension in dogs

Pressure-passive perfusion beyond the upper limit of cerebral blood flow (CBF) autoregulation may be deleterious in patients with intracranial pathology. Therefore, monitoring of changes in CBF would be of clinical relevance in situations where clinical evaluation of adequate cerebral perfusion is impossible. Noninvasive monitoring of cerebral blood flow velocity using transcranial Doppler sonography (TCD) may reflect relative changes in CBF. This study correlates the effects of angiotensininduced arterial hypertension on CBF and cerebral blood flow velocity in dogs. Heart rate (HR) was recorded using standard ECG. Catheters were placed in both femoral arteries and veins for measurements of mean arterial blood pressure (MAP), blood sampling and drug administration. A left ventricular catheter was placed for injection of microspheres. Cerebral blood flow velocity was measured in the basilar artery through a cranial window using a pulsed 8 MHz transcranial Doppler ultrasound system. CBF was measured using colour-labelled microspheres. Intracranial pressure (ICP) was measured using an epidural probe. Arterial blood gases, arterial pH and body temperature were maintained constant over time. Two baseline measures of HR, MAP, CBF, cerebral blood flow velocity and ICP were made in all dogs (n = 10) using etomidate infusion (1.5 mg · kg^?1 · hr^?1) and 70% N₂O in O₂ as background anaesthesia. Following baseline measurements, a bolus of 1.25 mg angiotensin was injected iv and all variables were recorded five minutes after the injection. Mean arterial blood pressure was increased by 76%. Heart rate and ICP did not change. Changes in MAP were associated with increases in cortical CBF (78%), brainstem CBF (87%) and cerebellum CBF(64%). Systolic flow velocity increased by 27% and Vmean increased by 31% during hypertension (P < 0.05). Relative changes in CBF and blood flow velocity were correlated (CBF cortex — Vsyst: r = 0.94, CBF cortex — Vmean: r = 0.77; P < 0.001; CBF brainstem — Vsyst: r = 0.82, CBF brainstem — Vmean: r = 0.69; P < 0.05). Our results show that increases in arterial blood pressure beyond the upper limit of cerebral autoregulation increase CBF in dogs during etomidate and N₂O anaesthesia. The changes in CBF are correlated with increases in basilar artery blood flow velocity. These data suggest that TCD indicates the upper limit of the cerebral autoregulatory response during arterial hypertension. However, the amount of CBF change may be underestimated with the TCD technique.     

Monitoring middle cerebral artery blood velocity during carotid endarterectomy

Transcranial pulsed Doppler ultrasound and spectral analysis were used to monitor blood velocities in the middle cerebral artery of nineteen patients (mean age 61 +/- 9 years) during carotid endarterectomy. A Javid shunt was used in all patients. The intensity weighted mean Doppler frequency for each spectral sweep (at 5 ms intervals) was time-averaged over the cardiac cycle to obtain a mean value for blood velocity in the middle cerebral artery. The range of such values found in the 19 patients was: 12-38 cm s-1 after anaesthesia (baseline); 12-69 cm s-1 during diathermy; 0-30 cm s-1 during carotid clamping; 16-32 cm s-1 during shunting and 18-60 cm s-1 in the recovery room. The average change in middle cerebral artery blood velocity from baseline values showed significant increases during diathermy (P less than 0.005), shunting (P less than 0.05) and in the recovery room (P less than 0.005). Clamping of the internal carotid artery showed a significant decrease in middle cerebral artery blood velocities of all patients (P less than 0.005), three of whom showed no flow in the middle cerebral artery during clamping. Abnormally high amplitude Doppler signals at the commencement of shunting were detected in 17 of the 19 patients. Such Doppler signals are consistent with turbulent blood flow or the introduction of micro-air bubbles by the shunt. Backbleeding in the internal carotid artery before insertion of the shunt was associated with diminished flow in the ipsilateral middle cerebral artery of ten patients, oscillatory forward/reverse flow in three patients and cessation of flow in the remaining six patients.     

Effects of propofol and nitrous oxide on middle cerebral artery flow velocity and cerebral autoregulation

We studied the effects of adding 50% nitrous oxide to propofol anaesthesia administered by target-controlled infusion on middle cerebral artery flow velocity and autoregulatory indices derived from transient hyperaemic response tests. Nine healthy (ASA 1) adult patients scheduled to undergo elective surgery were recruited. A standardised anaesthetic comprising alfentanil 10 microg x kg(-1), propofol via a target-controlled infusion pump and vecuronium 0.1 mg x kg(-1) was used. Transcranial Doppler ultrasonography was used to measure middle cerebral artery (MCA) blood flow velocity and the transient hyperaemic response test was used to assess cerebral autoregulation. These measurements were performed while awake and then at an induction target concentration of propofol (the target at which consciousness was lost, mean 6.2 (SD 1.1) microg x ml(-1)). The measurements were repeated after the addition of 50% nitrous oxide to the breathing gas mixture. Propofol caused a significant decrease in MCA flow velocity and a significant increase in the strength of autoregulation. The addition of nitrous oxide had no significant effect on MCA flow velocity or cerebral autoregulation. These results suggest that addition of 50% nitrous oxide does not influence propofol-induced changes in cerebral haemodynamics.     

Effects of normovolaemic haemodilution on middle cerebral artery blood flow velocity and oxygen delivery

BACKGROUND AND OBJECTIVE: Assessment of the effects of normovolaemic haemodilution on middle cerebral artery blood flow velocity with transcranial Doppler ultrasonography, intracranial pressure, cerebral perfusion pressure, arterial oxygen content and cerebral oxygen delivery. METHODS: Normovolaemic haemodilution was induced in rabbits under general anaesthesia, and the haematocrit was allowed to decrease to 30% in Group 1 (n = 6) and to 20% in Group 2 (n = 6). Peak systolic and diastolic velocities, mean blood flow velocity, and pulsatility and resistance indices of the middle cerebral artery were measured by transcranial Doppler ultrasonography. Changes in intracranial pressure, cerebral perfusion pressure, arterial oxygen content and cerebral oxygen delivery were also assessed. RESULTS: In Group 2, middle cerebral artery blood flow velocity increased from 0.4 +/- 0.01 to 0.51 +/- 0.02 m s(-1) after the induction of normovolaemic haemodilution (P = 0.04), while arterial oxygen content decreased from 16.2 +/- 0.1 to 8.5 +/- 0.1 mLdL(-1) (P = 0.002). The decrease in cerebral oxygen delivery from 6.5 +/- 0.2 to 4.3 +/- 0.2 was also significant (P = 0.02). However, no associated changes in intracranial pressure and cerebral perfusion pressure could be demonstrated. CONCLUSIONS: Normovolaemic haemodilution resulted in an increase in the mean blood flow velocity of the middle cerebral artery. However, this increase did not compensate for the consequences of the altered oxygen delivery to the brain when the haematocrit was reduced to 20%.     

The effects of prolonged isoflurane anaesthesia on cerebral blood flow and metabolism in the dog

To determine whether cerebral blood flow (CBF) changed with time under isoflurane anaesthesia, as has been reported for halothane, CBF and cerebral metabolic rate for oxygen (CMRO2) were studied in five dogs under prolonged isoflurane anaesthesia. CBF was measured with a modified sagittal sinus technique and CMRO2 was calculated as the product of CBF and the arteriovenous O2 difference. Maintaining this experimental dog model with 1% isoflurane in oxygen and nitrogen for 3 h in five dogs and for 4 h in three dogs did not cause any significant changes in CMRO2 or CBF. Cerebral metabolite levels were consistent with earlier reports from short-time studies and the EEG recordings showed a continuous sleep pattern with no pathological changes. It is concluded that there is no change in CBF or CMRO2 in our modified sagittal outflow model during 3-4 h of 1% isoflurane anaesthesia.     

The effect of hypervolemic hemodilution with and without hypertension on cerebral blood flow following middle cerebral artery occlusion in rats anesthetized with isoflurane

The effect of hypervolemic hemodilution or hypervolemic hemodilution with dopamine-induced hypertension on cerebral blood flow (CBF) was investigated during 1.2 MAC isoflurane anesthesia in rats (n = 24) subjected to middle cerebral artery occlusion (MCAO). Prior to MCAO each animal was randomized to one of the following groups: 1) control, mean arterial pressure (89 +/- 10 mmHg [mean +/- SD]), blood volume, and hematocrit (46 +/- 1) were not manipulated; 2) hypervolemic hemodilution (HH), 30 min before MCAO, 5% albumin was administered to reduce the hematocrit to 29-32%; or 3) hypervolemic hemodilution/dopamine hypertension (HH/Dop), hemodilution was accomplished and dopamine (10 micrograms.kg-1.min-1) was infused during the ischemic period to achieve a mean arterial pressure of 111 +/- 10 mmHg (mean +/- SD). Ten minutes after occlusion of the left middle cerebral artery, CBF was determined using 14C-iodoantipyrine. Five coronal brain sections were analyzed to determine the area within each brain section with CBF ranges of 0-15 ml.100 g-1.min-1 and 15-23 ml.100 g-1.min-1. The area of 0-15 ml.100 g-1.min-1 CBF was less in both the HH and HH/Dop groups compared with control (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Responses of EEG, cerebral oxygen consumption and blood flow to peripheral nerve stimulation during thiopentone anaesthesia in the dog

The effects of sciatic nerve stimulation on the electroencephalogram (EEG), cerebral metabolic rate for oxygen (CMRO2) and cerebral blood flow (CBF) were investigated during thiopentone anaesthesia in dogs. Anaesthetic levels at 15, 35, 65, 95 and 125 minutes after the start of thiopentone infusion (23 mg X kg-1 X hr-1) were designated levels I, II, III, IV and V, respectively. The effects of stimulation for 5 min were tested at each level. At level I (plasma thiopentone concentration; 15 +/- 2 micrograms X ml-1), the EEG was activated with stimulation and CMRO2 and CBF increased by a maximum of 16 and 15 per cent, respectively. The increase in CMRO2 and CBF was significant for five and four minutes, respectively, though the increase became less with time. At level II (27 +/- 3 micrograms X ml-1), the CMRO2 and CBF increased at one minute by eight and nine per cent, the increase being accompanied by transient EEG activation. At the three deepest levels III, IV and V (37 +/- 6, 42 +/- 6, 49 +/- 6 micrograms X ml-1), the EEG, CMRO2 and CBF remained unchanged with stimulation. The results suggest the existence of the tight coupling between the EEG, CMRO2 and CBF and of a threshold level of thiopentone to block the response to peripheral stimulation during thiopentone anaesthesia.     

A comparison of propofol and sevoflurane anaesthesia: effects on aortic blood flow velocity and middle cerebral artery blood flow velocity

We compared systemic (aortic) blood flow and cerebral blood flow velocity in 30 patients randomly allocated to receive either propofol or sevoflurane anaesthesia. Cerebral blood flow velocity (CBFv) was measured in the middle cerebral artery using transcranial Doppler. Systemic blood flow velocity (SBFv) was measured in the aorta using transthoracic Doppler sonography at the level of the aortic valve. Bispectral index (BIS) was used to measure the depth of anaesthesia. Measurements were made in the awake patient and repeated during propofol or sevoflurane anaesthesia, with BIS measurements of 40-50. The effects of SBFv on CBFv were estimated by calculating the cerebral/systemic blood flow velocity-index (CsvI). A CsvI value of 100 indicating a 1 : 1 relationship between CBFv and SBFv. The results demonstrated that propofol anaesthesia produced a significantly greater reduction in CsvI than did sevoflurane anaesthesia [propofol: 60 (19); sevoflurane: 83 (16), p = 0.009, t-test]. This suggests a direct reduction in CBFv independent of SBFv during propofol anaesthesia. The greater reduction of CBFv occurring during propofol anaesthesia may be due to lower cerebral metabolic demand compared with sevoflurane anaesthesia at comparable depths of anaesthesia.     

Effects of repeated temporary clipping of the middle cerebral artery on pial arterial diameter, regional cerebral blood flow, and brain structure in cats

Temporary clipping of the major arterial trunk is an important maneuver to control excessive unexpected bleeding in neurosurgical operations; however, repeated temporary clipping can give rise to severe neurological deficits after surgery. The present study was performed to confirm and explain these clinical findings. Initially, a single 20-minute or 1-hour occlusion of the middle cerebral artery was performed in each of 5 cats. Pial arterial diameter was determined by video imaging, regional cerebral blood flow was measured by autoradiography, and cerebral edema and infarction were observed. In the 20-minute occlusion group, no abnormal changes were found 5 hours after recirculation. In the 1-hour occlusion group, pial arteries were dilated by 45%, and regional cerebral blood flow increased to more than twice the resting cortical values. The extent of cerebral edema was 41.2 +/- 7.5% (SE) and infarction was 34.5 +/- 9.5% (SE) of the hemisphere. In the second experiment, three 20-minute occlusions of the middle cerebral artery in a 1-hour interval were performed in 20 cats. In 10 of them, thiopental (40 mg/kg) was used to protect the brain. In the group without barbiturate treatment, pial arteries were dilated by 40% at the end of experiment, regional cerebral blood flow decreased to about 70% compared with single 20-minute occlusion, cerebral edema was 19.5 +/- 8.1% (SE), and infarction was 8.1 +/- 3.7% (SE) of the hemisphere. In the treated group, these were only trivial changes. The effect of repeated clipping may cumulatively cause brain damage, and barbiturates should be used whenever repeated clipping is necessary.     

Distribution of cerebral blood flow during deep isoflurane vs. pentobarbital anesthesia in rats with middle cerebral artery occlusion

While previous studies have identified a protective effect for barbiturate anesthesia during focal cerebral ischemia, no such effect has been demonstrated for isoflurane. To better understand the effects of these anesthetics on cerebral blood flow and metabolism that might have relevance to their respective potential for cerebral protection, fasted physiologically stable rats underwent autoradiographic determination of CBF and CMRglu during deep isoflurane or pentobarbital anesthesia (burst suppression of EEG). As expected, cerebral blood flow was significantly greater during isoflurane anesthesia (isoflurane = 157 +/- 18 and pentobarbital = 54 +/- 12 ml/100 g/min) while CMRglu values were nearly identical (isoflurane = 35 +/- 5 and pentobarbital = 33 +/- 4 mumol/100 g/min). Additional identically anesthetized rats underwent middle cerebral artery occlusion with CBF autoradiographically determined 1 h later. While the insult resulted in a significant reduction in the ipsilateral hemispheric and cortical blood flow in both anesthetic groups, flow remained at least twofold greater in isoflurane as opposed to pentobarbital-anesthetized rats. When regional flow was assessed, no difference between groups was observed with respect to the area of tissue with flow values falling between 0-10 ml/100 g/min. In contrast, isoflurane-anesthetized rats had significantly less hemispheric and cortical area with flow values in the ranges of 10-20 and 20-30 ml/100 g/min, respectively. These data, therefore, do not support the contention that isoflurane causes maldistribution of CBF during focal ischemia.     

Positron emission tomographic measurement of acute hemodynamic changes in primate middle cerebral artery occlusion.

Specific hemodynamic changes in acute ischemia were investigated using a middle cerebral artery occlusion primate model and positron emission tomography. The cerebral blood flow (CBF), cerebral blood volume, oxygen extraction fraction (OEF), and cerebral metabolic rate for oxygen were measured 1, 3, and 9 hours after occlusion. OEF showed an increase in ischemic areas, and especially where CBF was below 18 ml/100 gm/min 1 hour after occlusion the OEF increased significantly (0.69 +/- 0.20, p < 0.05). Nine hours after occlusion, the OEF values were lower compared to those 1 and 3 hours after occlusion. Areas where CBF ranged from 18 to 31 ml/100 gm/min showed an increase in OEF at all times (p < 0.05). Clearly, OEF changes remarkably in the acute stage.     

Comparison of the effect of fluosol DA and dextran 40 on regional cerebral blood flow, infarction size, and mortality in cats with temporary occlusion of the middle cerebral artery

Twenty-four cats were divided into two groups and treated with an intravenous infusion of either fluosol DA or dextran. One-half of the animals in each group were ventilated with room air and one-half with 100% oxygen. The right middle cerebral artery was occluded for a period of 4 hours through a transorbital approach. Regional blood flow by the hydrogen clearance method was measured before and after the infusion of fluosol DA or dextran, after oxygenation in the animals on 100% oxygen, three times during the period of ischemia, and after reperfusion. Regional cerebral blood flow increased slightly with the infusion of fluosol or dextran, decreased slightly with hyperoxygenation in the animals so treated, and decreased markedly in the right hemisphere during temporary occlusion of the right middle cerebral artery in all groups. With reperfusion regional flows in the right hemisphere varied considerably, with some animals showing hyperperfusion and others essentially no flow. There was no significant difference in average regional cerebral blood flow between any of the groups. The severity of infarction in all groups was directly related to the decrease in regional cerebral blood flow in the right hemisphere during temporary occlusion. There was also a strong correlation between the regional cerebral blood flow in the right hemisphere after reperfusion and the severity of infarction. In general, the animals showing normal or increased flow after reperfusion had small infarcts and those showing no reflow had large infarcts. Mortality was high in all groups, was not significantly different between any of the groups, and was highly correlated to the size of infarction. In brief, in this study fluosol offered no advantage over dextran, and probably neither agent, in the dose used, offered any protection against cerebral ischemia.     

Multimodal quantitation of the effects of endovascular therapy for vasospasm on cerebral blood flow,transcranial doppler ultrasonographic velocities,and cerebral artery diameters

OBJECTIVE: The goal of this study was to quantify the effects of endovascular therapy on vasospastic cerebral vessels. METHODS: We reviewed the medical records for 387 patients with ruptured intracranial aneurysms who were treated at a single institution (University of California, Los Angeles) between May 1, 1993, and March 31, 2001. Patients who developed cerebral vasospasm and underwent cerebral arteriographic, transcranial Doppler ultrasonographic, and cerebral blood flow (CBF) studies before and after endovascular therapy for cerebral arterial spasm (vasospasm) were included in this study. RESULTS: Forty-five patients fulfilled the aforementioned criteria and were treated with either papaverine infusion, papaverine infusion with angioplasty, or angioplasty alone. After balloon angioplasty (12 patients), CBF increased from 27.8 +/- 2.8 ml/100 g/min to 28.4 +/- 3.0 ml/100 g/min (P = 0.87); the middle cerebral artery blood flow velocity was 1 57.6 +/- 9.4 cm/s and decreased to 76.3 +/- 9.3 cm/s (P < 0.05), with a mean increase in cerebral artery diameters of 24.4%. Papaverine infusion (20 patients) transiently increased the CBF from 27.5 +/- 2.1 ml/100 g/min to 38.7 +/- 2.8 ml/100 g/min (P < 0.05) and decreased the middle cerebral artery blood flow velocity from 109.9 +/- 9.1 cm/s to 82.8 +/- 8.6 cm/s (P < 0.05). There was a mean increase in vessel diameters of 30.1% after papaverine infusion. Combined treatment (13 patients) significantly increased the CBF from 33.3 +/- 3.2 ml/100 g/min to 41.7 +/- 2.8 ml/100 g/min (P< 0.05) and decreased the transcranial Doppler velocities from 148.9 +/- 12.7 cm/s to 111.4 +/- 10.6 cm/s (P < 0.05), with a mean increase in vessel diameters of 42.2%. CONCLUSION: Balloon angioplasty increased proximal vessel diameters, whereas papaverine treatment effectively dilated distal cerebral vessels. In our small series, we observed no correlation between early clinical improvement or clinical outcomes and any of our quantitative or physiological data (CBF, transcranial Doppler velocities, or vessel diameters).