Effects of morphine on cerebral blood flow autoregulation CO2-reactivity in experimental subarachnoid hemorrhage.

Previous reports show that naloxone improves ischemic deficits and clinical conditions in patients after subarachnoid hemorrhage (SAH). These observations have raised concern about the routine use of morphine in the treatment of severe headache after SAH. The present study was carried out to investigate the effects of morphine on cerebral vasoreactivity after experimental SAH. Cerebral blood flow (CBF) autoregulation was studied in two groups of eight rats each with experimental SAH. A bolus intravenous injection of morphine, 1 mg/kg, was administered in one group and the other was used as a control group. During eucapnia, CBF was measured by the intracarotid 133Xenon method during decreasing mean arterial blood pressure (MABP). CO2-reactivity was investigated in two corresponding groups where CBF was measured at decreasing PaCO2 levels during constant MABP. Morphine decreased mean baseline CBF by 34% and 26% in the study of autoregulation and CO2-reactivity, respectively. Cerebral blood flow autoregulation was found impaired in both controls and the morphine group. However, the mean slope of the linear regression lines of CBF/MABP was 0.49 +/- 0.32 ml/100g/min/mm Hg in the morphine group, which was significantly lower than 1.24 +/- 0.59 ml/100g/min/mm Hg in the controls (p < 0.05). Also the mean CO2-reactivity was significantly lower, 0.64 +/- 0.53 %/0.1kPa, in the morphine group, compared to 2.36 +/- 0.87 %/0.1kPa in the controls (p < 0.001). The results show that in rats with SAH, morphine partially restores CBF autoregulation but attenuates CO2-reactivity.     

Arterial CO2 tension and cerebral vascular reactivity during the induction of acute hypertension and hypotension in the awake human

The CO2 reactivity was calculated at mean arterial blood pressure (MABP) values ranging from 40 to 140 mm Hg in 15 normotensive volunteers and in 7 patients with chronic arterial hypertension. The cerebral vascular reactivity (CVR) was estimated from indirect measurements of cerebral blood flow (CBF) by the arteriovenous oxygen saturation method. In all subjects but one of the hypertensive patients, there was a significant linear correlation of CVR with PaCO2 over the total range of MABP. The median CO2 reactivity in the volunteers and in the hypertensive patients was 2.7 and 2.8% CBF/0.1 kPa, respectively (NS). At MABP values corresponding to the plateau of CBF autoregulation (baseline MABP +/- 20%), the median CO2 reactivity was 3.0% CBF/0.1 kPa in both groups. During a cross-sectional correlation analysis of the pooled data from all volunteers, the CO2 reactivity increased with increasing MABP in the range of 50-110 mm Hg. Outside this range there was no correlation of CVR with PaCO2. In conclusion, our results confirmed that during acute hypo- and hypertension, the influence of PaCO2 on the CVR is reduced. The full CO2 reactivity of the cerebral vessel exists only at the plateau of CBF autoregulation.     

Time course of the impairment of cerebral autoregulation during chronic cerebral vasospasm after subarachnoid hemorrhage in primates.

The time course of the impairment of cerebral autoregulation during chronic cerebral vasospasm after subarachnoid hemorrhage was studied in 18 monkeys. Changes in cerebral blood flow (CBF) at the regional level and central conduction times during either graded hypo- or hypertension were evaluated in these animals at three stages (3, 7, and 14 days) following the introduction of an autologous blood clot around the right middle cerebral artery (MCA). Angiograms revealed a reduction in vessel caliber (compared to the baseline level in the involved MCA) of 30% at 3 days, 50% at 7 days, and 10% at 14 days. At all stages, CBF remained constant at mean arterial blood pressures (MABP) of 60 to 160 mm Hg in the noninvolved hemisphere. In contrast, at the 3- and 7-day stages, there was an impairment of autoregulation in the involved hemisphere at MABP of 40 to 180 mm Hg. The right hemispheric CBF was significantly (p less than 0.05) lower than that in the left throughout the period of investigation at MABP below 120 mm Hg, but rose to exceed the left CBF at MABP above 180 mm Hg at the 7-day stage and 160 mm Hg at the 14-day stage. The right-sided central conduction time showed significant (p less than 0.05) prolongation at MABP below 60 mm Hg at the 3-day stage and 40 mm Hg at the 7-day stage. It is suggested that these results may help to develop guidelines for hemodynamic therapy for vasospasm in its various stages.     

The effect of nimodipine on autoregulation of cerebral blood flow after subarachnoid haemorrhage in rat

Summary Disturbance of the autoregulation of the cerebral blood flow (CBF) is frequently seen following subarachnoid haemorrhage (SAH) and is possibly partly caused by cerebral ischaemia. It is well-known, that the calcium channel blocker nimodipine reduces the incidence of cerebral infarction and ischaemic dysfunction after SAH.The aim of the present study was to investigate the effect of nimodipine on autoregulation of CBF in an experimental model of SAH. The autoregulation was investigated in 10 control rats with SAH and in 10 nimodipine treated rats with SAH by serial measurements of CBF using a¹³³Xenon intracarotid injection method during controlled blood pressure manipulations.In the control rats the autoregulation was severely disturbed, no plateau was found where CBF was independent of changes in the arterial blood pressure (MABP). In rats treated with intravenous nimodipine (0.03 mg/kg bodyweight/h), CBF was 33.0% higher and MABP 5.3% higher compared with the controls. CBF was found constant in the MABP interval between 60 and 100 mmHg which indicates, that nimodipine improves the autoregulation of CBF after SAH.     

Impairment of cerebral autoregulation during the development of chronic cerebral vasospasm after subarachnoid hemorrhage in primates

We studied the impairment of autoregulation of cerebral blood flow (CBF) and its effect on the electrical activity of the brain during the development of chronic cerebral vasospasm after subarachnoid hemorrhage, using a vasospasm model in primates. Fourteen animals were divided into two groups: a clot group (8) and a sham-operated group (6). To induce subarachnoid hemorrhage, all the animals underwent craniectomy, and in the clot group, the autologous blood clot was located around the arteries dissected free from the arachnoid membrane. Cerebral angiography was performed before subarachnoid hemorrhage and 7 days after (Day 7). On Day 7, regional CBF in the parietal lobe--measured by the hydrogen clearance method--and central conduction time were studied during either graded hypertension or hypotension. In the clot group, the mean vessel caliber of the cerebral arteries on the right side (clot side) of the circle of Willis showed significant (P less than 0.01) reduction (more than 40%) as compared with the values on the contralateral, non-clot side. The values for the bilateral parietal CBF in the sham-operated group and the left parietal CBF in the clot group were fairly constant when the mean arterial blood pressure (MABP) was in the range of 60 to 160 mm Hg. In the clot group, right parietal CBF was significantly (P less than 0.05) smaller than that on the left side at an MABP level of 40 to 100 mm Hg, and increased at an MABP level of 180 mm Hg. The right parietal CBF increased as the arterial blood pressure increased, showing impairment of autoregulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of nimodipine on cerebral oxygenation in patients with poor-grade subarachnoid hemorrhage

OBJECT: Nimodipine has been shown to improve neurological outcome after subarachnoid hemorrhage (SAH); the mechanism of this improvement, however, is uncertain. In addition, adverse systemic effects such as hypotension have been described. The authors investigated the effect of nimodipine on brain tissue PO2. METHODS: Patients in whom Hunt and Hess Grade IV or V SAH had occurred who underwent aneurysm occlusion and had stable blood pressure were prospectively evaluated using continuous brain tissue PO2 monitoring. Nimodipine (60 mg) was delivered through a nasogastric or Dobhoff tube every 4 hours. Data were obtained from 11 patients and measurements of brain tissue PO2, intracranial pressure (ICP), mean arterial blood pressure (MABP), and cerebral perfusion pressure (CPP) were recorded every 15 minutes. Nimodipine resulted in a significant reduction in brain tissue PO2 in seven (64%) of 11 patients. The baseline PO2 before nimodipine administration was 38.4+/-10.9 mm Hg. The baseline MABP and CPP were 90+/-20 and 84+/-19 mm Hg, respectively. The greatest reduction in brain tissue PO2 occurred 15 minutes after administration, when the mean pressure was 26.9+/-7.7 mm Hg (p < 0.05). The PO2 remained suppressed at 30 minutes (27.5+/-7.7 mm Hg [p < 0.05]) and at 60 minutes (29.7+/-11.1 mm Hg [p < 0.05]) after nimodipine administration but returned to baseline levels 2 hours later. In the seven patients in whom brain tissue PO2 decreased, other physiological variables such as arterial saturation, end-tidal CO2, heart rate, MABP, ICP, and CPP did not demonstrate any association with the nimodipine-induced reduction in PO2. In four patients PO2 remained stable and none of these patients had a significant increase in brain tissue PO2. CONCLUSIONS: Although nimodipine use is associated with improved outcome following SAH, in some patients it can temporarily reduce brain tissue PO2.     

Effects of alterations in arterial CO2 tension on cerebral blood flow during acute intracranial hypertension in rats.

Cerebrovascular reactivity to CO2 in clinical and experimental studies has been found to be impaired during increased intracranial pressure (ICP). However, from previous study results it has not been possible to estimate whether the impairment was caused by elevated ICP, or caused by decreased cerebral perfusion pressure (CPP). The current study was carried out in a group of unmanipulated control rats and in six investigation groups of six rats each: two groups with elevated ICP (30 and 50 mm Hg) and spontaneous arterial blood pressure (MABP), two groups with spontaneous ICP and arterial hypotension (77 and 64 mm Hg), and two groups with elevated ICP (30 and 50 mm Hg) and arterial hypertension (124 mm Hg). Intracranial hypertension was induced by continuous infusion of lactated Ringer's solution into the cisterna magna, arterial hypotension by controlled bleeding, and arterial hypertension by continuous administration of norepinephrine intravenously. Cerebral blood flow (CBF) was measured repetitively by the intraarterial 133Xe method at different levels of arterial PCO2. In each individual animal, CO2 reactivity was calculated from an exponential regression line obtained from the corresponding CBF/PaCO2 values. By plotting each individual value of CO2 reactivity against the corresponding CPP value from the seven investigation groups, CPP was significantly and directly related to CO2 reactivity of CBF (P < .001). No correlation was found by plotting CO2 reactivity values against the corresponding MABP values or the corresponding ICP values. Thus, the results show that CO2 reactivity is at least partially determined by CPP and that the impaired CO2 reactivity observed at intracranial hypertension and arterial hypotension may be caused by reduced CPP.     

Effects of dihydroergotamine on intracranial pressure, cerebral blood flow, and cerebral metabolism in patients undergoing craniotomy for brain tumors.

In a search for a nonsurgical intervention to control intracranial hypertension during craniotomy, the authors studied the effects of dihydroergotamine on mean arterial blood pressure (MABP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), cerebral blood flow (CBF), and cerebral metabolism in patients who underwent craniotomy for supratentorial brain tumors. Twenty patients were randomized to receive either dihydroergotamine 0.25 mg intravenously or placebo as a bolus dose during craniotomy. Anesthesia was induced with thiopental/fentanyl/atracurium, and maintained with isoflurane/N2O/fentanyl at normocapnia. After removal of the bone flap and exposure of intact dura, ICP was measured subdurally and dihydroergotamine/placebo was administered. Intracranial pressure and MABP were measured continuously. Cerebral blood flow (after intravenous administration of 133Xe) and arteriojugular venous difference of oxygen (AVDO2) were measured before, and 30 minutes after, dihydroergotamine/placebo administration. Cerebral metabolic rate of oxygen (CMRO2) was calculated. After administration of dihydroergotamine, a significant increase in MABP from 74 to 87 mm Hg (median) and CPP from 65 to 72 mm Hg (median) were found. Simultaneously to the increase in MABP, a significant increase in ICP from 9.5 to 11.5 mm Hg (median) was disclosed, whereas no significant differences in CBF, AVDO2, or CMRO2 were found. Intracranial pressure was significantly higher after dihydroergotamine than after placebo. In conclusion, no ICP decreasing effect of a bolus dose of dihydroergotamine was found when administered to patients with brain tumors during isoflurane/N2O anesthesia. Corresponding increases in MABP and ICP suggest that abolished cerebral autoregulation might explain why dihydroergotamine was associated with an ICP increase.     

Postoperative central conduction time and cerebral blood flow in patients with aneurysmal subarachnoid hemorrhage: Relationship with prognosis and ischemic conditions

Cerebral blood flow (CBF) and somatosensory evoked potential (SEP) were monitored periodically on 32 patients who underwent aneurysm clipping within 3 days after subarachnoid hemorrhage (SAH). From the SEP data, central conduction time (CCT) was obtained, and CCT fluctuations were categorized into three types. Patients with CCT prolongation over 7.5 ms within 10 days after SAH tended to have poor recovery of CBF and unfavorable outcome. Therefore, periodical monitoring of CCT was considered as a useful indicator for predicting prognosis and post-SAH changes of cerebral blood flow.     

Brain hyperperfusion during cardiac operations. Cerebral blood flow measured in man by intra-arterial injection of xenon 133: evidence suggestive of intraoperative microembolism

Cerebral blood flow (CBF) was measured by intra-arterial injection of xenon 133 in 29 patients during cardiac operations. Marked changes occurred in all patients. A normal and significant correlation with temperature and plasma PCO2 (p less than 0.01) support the reliability of the method. Mean CBF measured between sternotomy and the onset of extracorporeal circulation (ECC) was 38 ml/100 gm . min. The first minute of ECC was associated with a decrease in CBF in nine of 12 patients (p less than 0.02). During steady-state hypothermic ECC (temperature 29 degrees C), CBF increased unexpectedly to 64 ml/100 gm . min (p less than 0.01). Following rewarming steady-state normothermic ECC, mean CBF decreased to 42 ml/100 gm . min with signs of impairment of cerebral autoregulation. Ten and 20 minutes after termination of ECC, mean CBF was 40 and 41 ml/100 gm . min, respectively. Arterial PCO2 was found to be important in regulating CBF. The cerebral autoregulation maintained CBF down to arterial pressures of around 55 mm Hg. Below this level, CBF was significantly correlated with perfusion pressure (p less than 0.01). Multiple small emboli with a hyperemic border zone could cause a brain hyperperfusion, as seen in our patients during bypass. Measurements of CBF during ECC hold promise as a guide toward safer cardiac operations.     

Effect on management mortality of a deliberate policy of early operation on supratentorial aneurysms

Of 736 patients with intracranial aneurysms seen at the University of Alberta from 1968 to 1985, 437 were admitted on the day of or the day after subarachnoid hemorrhage (SAH) from a supratentorial aneurysm. Of these, 205 were managed from 1968 through 1977 and 232 were managed from 1978 through early 1985 after a policy of early aneurysm operation had been implemented. Postoperative and management mortality and morbidity rates were related to the grade of the patient at the time of admission and the time interval before operation. Overall management mortality (and postoperative mortality) rates for patients treated before 1978 were 47% (19%) for all grades, 17% (12%) for Grades 1 and 2, 51% (25%) for Grades 3 and 4, and 100% (100%) for Grade 5. Since 1978, mortality has been reduced to 38% (11%) for all grades, 10% (5%) for Grades 1 and 2, 39% (17%) for Grades 3 and 4, and 96% (60%) for Grade 5. Management mortality for patients operated on Day 0 to 3 was lower than for those operated later after SAH both before and after 1978. Postoperative mortality was lowered in all patients operated from 1978 to 1985 regardless of the interval from SAH to operation, and management mortality was reduced overall, as well as for patients operated on day 0 to 3, in those treated from 1978 to 1985. The authors conclude that a policy of early aneurysm operation has contributed to a reduction of both postoperative and management mortality.     

Transluminal balloon angioplasty improves brain tissue oxygenation and metabolism in severe vasospasm after aneurysmal subarachnoid hemorrhage: case report

OBJECTIVE AND IMPORTANCE: The effect of transluminal balloon angioplasty on cerebral biochemical monitoring during treatment of severe cerebral vasospasm after subarachnoid hemorrhage (SAH) was investigated. CLINICAL PRESENTATION: In a 36-year-old man, an anterior communicating artery aneurysm caused an SAH (Hunt and Hess Grade IV, Fisher Grade III). After clipping, intraparenchymal monitoring (intracranial pressure, brain tissue oxygen tension [P(ti)O(2)], and microdialysis sampling of extracellular glucose, lactate, pyruvate, and glutamate) was initiated. Flow velocities obtained by transcranial Doppler sonography increased in the internal carotid artery (ICA)/middle cerebral artery bilaterally. INTERVENTION: After a decrease of P(ti)O(2) to less than 2 mm Hg and an increase of the lactate-to-pyruvate ratio to 44 in the territorial region of the left ICA, angiography demonstrated a 70 to 80% stenosis of the left ICA, which was dilated by a temporary occlusion balloon. This maneuver normalized the ICA diameter, P(ti)O(2) increased immediately from 1.5 to 40 mm Hg, the lactate-to-pyruvate ratio decreased from 44 to 30, and extracellular glucose increased from 0.4 to 0.9 mmol/L. No major changes in glutamate or intracranial pressure were seen. In the clinical follow-up, the patient showed a good recovery 6 months after SAH. CONCLUSION: Transluminal balloon angioplasty led to a continuous and effective resolution of cerebral vasospasm observed by sustained, improved cerebral biochemical parameters. Both P(ti)O(2) and lactate-to-pyruvate ratio might provide an early diagnosis of severe cerebral vasospasm after SAH and continuous surveillance of threatened tissue regions after transluminal balloon angioplasty.     

Sepsis-induced vasoparalysis does not involve the cerebral vasculature: indirect evidence from autoregulation and carbon dioxide reactivity studies

We have studied cerebral autoregulation and vasoreactivity to carbon dioxide in 10 patients with the sepsis syndrome receiving intensive therapy. All patients were sedated with infusions of midazolam and fentanyl, and their lungs were ventilated mechanically with oxygen-air to maintain normoxia and normocapnia. Inotropic support and antibiotics were administered as necessary. During a period of constant level of sedation and stable haemodynamics, cerebral autoregulation was tested by increasing mean arterial pressure (MAP) by 23 (SD 2) mm Hg from baseline with an infusion of phenylephrine and simultaneously recording middle cerebral artery blood flow velocity (vmca) using transcranial Doppler ultrasonography. Carbon dioxide reactivity was tested by varying PaCO2 between 3.0 and 7.0 kPa and simultaneously recording vmca. There was no significant change in vmca (57 (22) and 59 (23) cm s- 1) during the increase in MAP (75 (11) to 98 (10) mm Hg). The mean index of autoregulation (IOR) was 0.92 (SEM 0.03), which was not significantly different from 1, indicating near perfect autoregulation. Although absolute carbon dioxide reactivity was lower than reported previously in awake subjects, relative carbon dioxide reactivity was within normal limits for all patients (11.6 (SEM 0.8) cm s-1 and 20.3 (3) % kPa-1, respectively). We conclude that cerebral carbon dioxide reactivity and pressure autoregulation remained intact in patients with the sepsis syndrome, providing indirect evidence that at least in the early stages of the syndrome, the widespread sepsis-induced vasoparalysis does not involve the cerebral vasculature.      

Angiotensin converting enzyme inhibition,CBF autoregulation,and ICP in patients with normal-pressure hydrocephalus

Summary Fourteen patients with normal pressure hydrocephalus had the autoregulation of cerebral blood flow (CBF) and intracranial pressure (ICP) investigated. In 8 of the patients the effect of Captopril on ICP and CBF was also investigated. The mean arterial blood pressure (MABP) was 109 mmHg (intra-arterially), and ICP was 11 mmHg (intraventricularly). Changes in global CBF were estimated by the arterio-venous oxygen difference method. The autoregulation of CBF was present in 13 of the patients (p < 0.01). The lower limit of CBF autoregulation was 86% of the baseline perfusion pressure. One hour after 50 mg of captopril perorally, MABP was reduced 16 mmHg, and ICP and CBF were unchanged. The autoregulation was maintained and the lower limit was decreased 19 mmHg. Thus patients would be expected to benefit from captopril treatment in hypotensive anaesthesia.     

An experimental study of the acute stage of subarachnoid hemorrhage

A baboon model of subarachnoid hemorrhage (SAH) has been developed to study the changes in cerebral blood flow (CBF), intracranial pressure (ICP), and cerebral edema associated with the acute stage of SAH. In this model, hemorrhage was caused by avulsion of the posterior communicating artery via a periorbital approach, with the orbit sealed and ICP restored to normal before SAH was produced. Local CBF was measured in six sites in the two hemispheres, and ICP monitored by an implanted extradural transducer. Following sacrifice of the animal, the effect of the induced SAH on ICP, CBF, autoregulation, and CO2 reactivity in the two hemispheres was assessed. Brain water measurements were also made in areas of gray and white matter corresponding to areas of blood flow measurements, and also in the deep nuclei. Two principal patterns of ICP change were found following SAH; one group of animals showed a return to baseline ICP quite quickly and the other maintained high ICP for over an hour. The CBF was reduced after SAH to nearly 20% of control values in all areas, and all areas showed impaired autoregulation. Variable changes in CO2 reactivity were evident, but on the side of the hemorrhage CO2 reactivity was predominantly reduced. Differential increase in pressure lasting for over 7 minutes was evident soon after SAH on the side of the ruptured vessel. There was a significant increase of water in all areas, and in cortex and deep nuclei as compared to control animals.     

Cerebral hemodynamic effects of 7.2% hypertonic saline in patients with head injury and raised intracranial pressure

The aim of the present study was to investigate the acute effects of 7.2% hypertonic saline (HS) on intracranial pressure (ICP), cerebral and systemic hemodynamics, serum sodium, and osmolality in 14 patients with moderate and severe traumatic brain injury (Glasgow Coma Scale < or =13) and raised ICP (>15 mm Hg) within the first 72 h postinjury. After CO2 reactivity and autoregulation were tested, each patient received a 15-min infusion of 7.2% HS (1,232 mEq/L, volume 1.5 mL/kg). ICP, serial hemodynamics, cerebral blood flow (CBF) estimated from cerebral arteriovenous oxygen content difference (AVDO2), and laboratory variables, including serum osmolality, electrolytes, urea, and creatinine were collected before infusion (T0) and at 5, 30, 60, and 120 min after (T5, T30, T60, T120). Urine output was measured 2 h before infusion and at T120. While CO2 reactivity was preserved in all patients, autoregulation was preserved in only four. ICP decreased to about 30% of base line (p = 0.0001) during the whole study period. During the first hour after infusion, cerebral perfusion pressure (p< or =0.04) and cardiac index (CI; p< or =0.01) increased, while systemic vascular resistance index fell (p< or =0.05). Heart rate increased (p< or =0.04) during the first 30 min. Pulmonary artery occlusion pressure (PAOP) increased (p = 0.004) at T5. There were no significant changes in mean arterial blood pressure (MABP), urine output, and estimated CBF. A significant positive correlation (r = 0.75; p = 0.02) between ICP and serum osmolality was found at T5. The administration of 7.2% HS in patients with traumatic brain injury significantly reduces ICP without significant changes in relative global CBF (expressed as 1/AVDO2), increases CI and transiently increases PAOP, without changing MABP and urine output. The correlation between changes in osmolality and ICP supports the hypothesis that HSS may in part decrease ICP by means of an osmotic mechanism.     

The hemodynamic effects of internal carotid artery stenosis and occlusion

The purpose of this study was to determine in subhuman primates whether hemodynamic mechanisms (as compared with embolic mechanisms) contribute to cerebral ischemia following carotid artery occlusion or stenosis. Following carotid artery occlusion there was loss of cerebral autoregulation: cerebral blood flow (CBF) measured with the xenon-133 technique became passively dependent upon the mean arterial blood pressure (MABP) over an MABP range of 30 to 110 mm Hg. By contrast, autoregulation was preserved in normal animals and in animals with a 90% carotid artery stenosis. Regional CBF was measured with carbon-14-labeled iodoantipyrine autoradiography in normotensive baboons, in hypotensive animals, and in hypotensive animals with carotid artery occlusion or stenosis. With carotid artery occlusion and hypotension, reduced levels of local CBF were seen ipsilaterally in the boundary zones between the anterior and middle cerebral arteries with 35% of the area of an anterior section through the hemisphere displaying a CBF value of less than 20 ml/100 gm/min. Comparable values with hypotension were 21% with carotid artery stenosis, 20% with no proximal vascular lesion, and 1% in normotensive animals. These areas of reduced CBF corresponded with areas of boundary-zone ischemia seen with light microscopy. The study suggests that while hemodynamic ischemia develops with carotid artery occlusion, it does not occur with even a 90% carotid artery stenosis or in normal animals.     

Disturbance of Cerebral Blood Flow Autoregulation in Hypertension is Attributable to Ischaemia Following Subarachnoid Haemorrhage in Rats: A PET Study

The effects of subarachnoid haemorrhage (SAH) on cerebral blood flow (CBF) autoregulation during induced hypertension were studied by positron emission tomography (PET) during chronic vasospasm in anaesthetized Sprague-Dawley rats. SAH was induced by intracisternal injection of autologous blood. In the control animals saline was injected instead. This method produced angiographical vasospasm of major arteries 48 h after injection. During this period, CBF was measured at each side of fronto-parietal and occipital sections using PET with or without induced hypertension. Mean arterial blood pressure (MABP) was increased from 94+/-2.4 to 140+/-0.3 mmHg by the injection of phenylephrine. An autoregulatory index (AI) expressed as delta CBF (%) per 10-mmHg increase in MABP was employed to analyse CBF response. SAH significantly reduced (p<0. 0001) basal CBF (ml/100 g/min) by 26.2% (control 60.0+/-1.9 n=24, SAH 44.3+/-4.5 n=20). A territorial CBF that decreased by 50% or more over the mean control value was used to define ischaemia and was identified in five out of 20 regions (25%) in the SAH group. AI (%/10-mmHg) was 13.5+/-2.4 in the control group (n=24). In the SAH group, AI decreased (p<0.05) to 4.5+/-2.5 in non-ischaemic areas (n=15), while in the ischaemic areas (n=5) AI increased (p<0.05) to 25.2+/-4.1. Since the spastic artery is intrinsically resistant to hypertension, the marked increase in CBF during hypertension can be attributable to ischaemia following SAH.     

Relationship between the timing of aneurysm surgery and the development of delayed cerebral ischemia

A consecutive series of 145 patients with acute aneurysmal subarachnoid hemorrhage (SAH) were operated on within 7 days of SAH and were prospectively evaluated over a 4-year period to determine if the timing of aneurysm surgery influenced the development of delayed cerebral ischemia. All patients were managed with a standardized policy of urgent surgical clipping and treatment with aggressive prophylactic postoperative volume expansion. Patients with delayed ischemic symptoms were additionally treated with induced hypertension. Forty-nine patients underwent surgery on Day 0 or 1 (Group 1) post-SAH, 60 patients on Day 2 or 3 (Group 2), and 36 patients on Days 4 through 7 (Group 3). Postoperative delayed cerebral ischemia developed in 16% of (Group 1) patients, in 22% of Group 2 patients, and in 28% of Group 3 patients. Cerebral infarction resulting from delayed cerebral ischemia developed in only 4% of Group 1 patients, 10% of Group 2 patients, and 11% of Group 3 patients. A bad clinical outcome as a result of delayed cerebral ischemia occurred in one Group 1 patient (2%), two Group 2 patients (3%), and one Group 3 patient (3%). Preoperative grade was not significantly correlated with the incidence or severity of delayed cerebral ischemia at any time interval except that patients in modified Hunt and Hess Grade I or II who underwent surgery on Day 0 or 1 after SAH had no strokes or bad outcomes from delayed cerebral ischemia. This study demonstrates that there is no rationale for delaying aneurysm surgery based on the time interval between SAH and patient evaluation.     

Cerebral blood flow autoregulation in experimental subarachnoid haemorrhage in rat

Summary Haemodynamic instability is of great importance in clinical management of patients with subarachnoid haemorrhage (SAH). The significance of angiographically demonstrable vasospasm for disturbances of cerebral blood flow (CBF) and cerebral autoregulation has not yet been clarified.The present study was designed to describe disturbances of cerebral autoregulation during the timecourse of experimental SAH (eSAH) in rats. A second aim of the study was to relate the results to a reported timecourse of angiographic vasospasm in the same animal model. Previous studies have shown that the timecourse of angiographically visible vasospasm in eSAH is biphasic with maximal spasm at 10 min and 2 days after induction of eSAH. At 5 days, the vasospasms have resolved.CBF was measured using a¹³³-Xenon intracarotid injection method which allowed serial measurements of mean hemispheric CBF during controlled manipulations of arterial blood pressure. In this way, an autoregulation curve could be constructed.The present study shows that autoregulation is severely disturbed or even totally absent at 2 and 5 days after eSAH. Thus there seems to be no direct correlation between presence of angiographic vasospasm and impairment of autoregulation, or that the impairment of autoregulation is more protracted than the presence of cerebral vasospasm, presuming a correlation exist.