Brain tolerance to middle cerebral artery occlusion during hypotension in primates

The aim of this study was to determine the duration of middle cerebral artery occlusion required to produce significant ischemic damage when the occlusion occurs during controlled systemic hypotension. In 21 anesthetized cynomolgus monkeys, an IV infusion of sodium nitroprusside was used to lower the mean arterial blood pressure to 45-50 mmHg for 90 minutes. Middle cerebral artery occlusion for 15, 30, 45, or 60 minutes was performed during the hypotensive period. Neurological function was then evaluated every 8 hours for a total of 72 hours. At the end of the observation period, the monkeys were again anesthetized, magnetic resonance imaging was performed, and the brain was perfused with 10% buffered formalin. Neurological deficits were observed after 30 minutes, but not after 15 minutes, of middle cerebral artery occlusion, and rapidly increased in incidence and severity when the duration of occlusion was increased. After 60 minutes of occlusion, all the monkeys exhibited severe deficits. Four monkeys died during the observation period--two in each of the 45- and 60-minute occlusion groups. Histopathological examination revealed that little or no ischemic damage resulted from a 15-minute occlusion during hypotension. However, severe ischemic damage began to occur after only 30 minutes of occlusion, and all monkeys subjected to middle cerebral artery occlusion for 60 minutes developed extensive regions of infarction. The size and incidence of these infarctions correlated well with the lesions observed in the magnetic resonance images. These results demonstrate that the duration of middle cerebral artery occlusion that produces cerebral infarction in primates is drastically reduced when the occlusion occurs at hypotensive levels commonly employed during neurovascular surgical procedures.     

A study of collateral circulation in acute stage of occlusion of the middle cerebral artery]

Collateral circulation of angiogram in occlusion of main trunk of the middle cerebral artery in acute stage was studied in detail, and compared with the extent of the low density area on CT. Territory of the middle cerebral artery in the lateral view of angiogram was divided into three regions. Collateral circulation time was measured with the period from the maximum filling of carotid siphon to the retrograde maximum filling of collateral circulation. With these studies, the following conclusions were obtained. 1) The degree of collateral circulation is classified into three types. One type with good collateral circulation is type I. Another type with moderate collateral circulation is type II. A further type with poor collateral circulation is type III. Angiographic circulation time in each branch of the middle cerebral artery is measured in each type. 2) There is a tendency that types with the better development of collateral circulation have the smaller low density area on CT. In type I, the smallest low density area on CT appears in the territory of basal ganglia or around corona radiata. In type II or III, the medium or large low density area on CT appears in cortical and/or subcortical territory of the middle cerebral artery. 3) There is a tendency that types with the worse development of collateral circulation have the later collateral circulation time in each region. If collateral circulation time is later than 4 seconds, it is impossible to avoid the appearance of the low density area on CT in C region. In the same way, in B region, it is later than 5 or 6 seconds, in A region, it is later than 7 seconds. But, in type II or III, there are a few cases in which it is impossible to avoid the appearance of the low density area on CT, even if collateral circulation time is earlier than those mentioned. As mentioned above, classifying of collateral circulation is possible to expect the extent of the low density area on CT, and measurement of collateral circulation time is able to estimate the appearance of the low density area on CT. In type I and II, superficial temporal artery to middle cerebral artery anastomosis is apt to make the low density area narrow on CT, and to prevent the appearance of hemorrhagic infarction.     

Emergency embolectomy in embolic occlusion of the middle cerebral artery

The natural course of embolic occlusion of the middle cerebral artery (MCA) has many variations, which include the frequent appearance of hemorrhagic infarction. There are also fatal cases among which severe ischemic edema is found. There haven's been many cases reported of MCA embolectomy in the acute stage, and findings concerning them have been very complicated and hard to analyze. Nevertheless there certainly exist cases where remarkable improvement of neurological signs is shown soon after the procedure. Five cases of emergency embolectomy have been undergone in our hospital in the past 2 years. The results were better than results obtained in cases where embolectomy was not performed. Three male and two female cases are the objectives, whose average age was 61 +/- 6 years (ranging from 54 to 67 years). The left side of the MC was involved in three cases and the right in two, and all cases had past history of heart diseases which may have been the embolic source. Each case had undergone CT scan soon after admission to make sure not to be the other type of intracranial lesion. Cerebral angiography was performed next, to discover the site of the occlusion and the degree of collateral circulation. Emergency embolectomy was performed as soon as possible in every case. The functional outcome was estimated from the ADL three months later using the international fifth degree grading. Results: The period from onset to recanalization ranges between 4.5 to 11 hours (average 6.9 +/- 2.5 hours). Good MC recanalization was demonstrated in each case angiographically within a week after the operation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodilution during cardiopulmonary bypass increases cerebral infarct volume after middle cerebral artery occlusion in rats

Although the optimal hematocrit during cardiopulmonary bypass (CPB) is not defined, excessive hemodilution may lead to organ ischemia via a reduction in oxygen-carrying capacity uncompensated by autoregulatory and/or rheologic increases in organ blood flow. As a result, the consequences of hemodilution in patients at risk for cerebral ischemia are not clearly understood. We designed this study to evaluate the effects of hemodilution in the setting of focal cerebral ischemia during CPB. Wistar rats surgically prepared for CPB were randomized to either hemodilution (hemoglobin (Hb), 6 g/dL; n = 9) or control (Hb, 11 g/dL; n = 8) groups and subsequently exposed to focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO). Immediately after the onset of MCAO (maintained for 90 min), 65 min of hypothermic (28 degrees C) CPB was initiated. Twenty-four hours later, functional neurological outcome and cerebral infarct volume were determined. Compared with controls, the hemodilution group had worse neurological performance (new score = 8 [2], hemodilution; versus 10 [2], control; P = 0.030) and larger total cerebral infarct volumes (182 +/- 84 mm(3), hemodilution; versus 103 +/- 58 mm(3), control; P = 0.043). In this experimental model of CPB with reversible MCAO-induced focal cerebral ischemia, hemodilution worsened neurological function and increased cerebral infarct volume.     

Clinical course of acute middle cerebral artery occlusion

Knowledge of the natural course of stroke patients has become increasingly important since new therapeutic methods have been proposed for patients with cerebral infarction in the acute stage. In order to clarify the acute stage of this disease, 188 patients admitted within 24 hours after onset of middle cerebral artery (MCA) occlusion were followed for 2 months, and data relating to mortality and changes in disturbances of consciousness and motor function were investigated. It was shown that the prognosis for MCA occlusion cases is poor, and about 80% of these patients are unable to return to their previous lifestyle. The level of consciousness in the acute stage is a good index for estimating the patients' quality and time of survival, and motor function in the acute stage is a good indicator of functional recovery. Thus, when evaluating the effectiveness of a new therapy for cerebral infarction, rapid improvement in the acute stage before and after treatment should be carefully noted.     

Acute operation in cases of middle cerebral artery occlusion

The authors describe their personal experience with middle cerebral artery embolectomy performed in four patients within 6 hours after the start of clinical symptoms. The work is of a preliminary nature. No conclusion can be drawn as to the ultimate value of this treatment, and further clinical trials seem justified.     

Hypothermic protection following middle cerebral artery occlusion in the rat

The effects of deep hypothermia on ischemic neuronal injury were examined using a permanent middle cerebral artery occlusion model in the rat. Animals were maintained at temporalis temperatures of either 24 degrees C or 36 degrees C and killed 6 hours after arterial occlusion. Normothermic rats displayed an average infarct volume of 25.1% +/- 1.6% of the right hemisphere, whereas hypothermic rats had an average infarct volume of 4.1% +/- 1.3% (p less than 0.001). The right/left hemispheric ratio was 1.05 +/- 0.02 in the normothermic group and 1.00 +/- 0.02 in the hypothermic group (p less than 0.05). These results suggest that hypothermia to 24 degrees C may reduce cerebral infarction and edema formation following middle cerebral artery occlusion in the rat.     

Effect of mannitol on cerebral blood flow and microcirculation during experimental middle cerebral artery occlusion

Regional cerebral blood flow (rCBF) was measured during and after a 2-3 hour occlusion period of the middle cerebral artery (MCA) in cats with the hydrogen clearance technique. The effects of mannitol upon rCBF were studied. Transient hypotension during occlusion dropped the blood flow to near zero on the occluded side, leading to postischemic hypoperfusion. Mannitol failed to modify blood flow during the occlusion period, but was effective in preventing any further decrease of blood flow during hypotension. Animals receiving mannitol had an improved postischemic recovery of blood flow. The correlation of ischemic severity and postischemic brain damage and the effects of mannitol on these parameters are discussed.     

High-dose ibuprofen for reduction of striatal infarcts during middle cerebral artery occlusion in rats

OBJECT: Ibuprofen is an antiinflammatory drug that disrupts leukocyte-endothelial cell interactions by limiting expression of endothelial adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), also known as CD54. The authors hypothesized that ibuprofen could reduce the size of the infarct associated with transient focal ischemia by inhibition of ICAM-1 expression, and they evaluated its effects in rats treated with middle cerebral artery (MCA) occlusion. Ibuprofen treatment was compared with mild systemic hypothermia, which is known to be neuroprotective and is commonly used during neurosurgical procedures. METHODS: The maximum ibuprofen dose (240 mg/kg/day) that could be tolerated with no systemic toxicity was established in the initial experiments. In the efficacy experiment, rats were pretreated with vehicle, ibuprofen, or hypothermia (33 degrees C) prior to 2 hours of MCA occlusion; then their brains were harvested at 24 hours of reperfusion for histological studies. End-ischemic cerebral blood flow (CBF) was evaluated using [14C]iodoantipyrine autoradiography in additional cohorts. Expression of ICAM-1 within ischemic compared with nonischemic caudate nucleus and putamen (striatum) or cortex was evaluated using immunohistochemical studies. Compared with vehicle treatment, ibuprofen produced a 46.2% reduction (p = 0.01) in striatal infarcts, which was comparable to hypothermia (48.7% reduction, p = 0.02). Ibuprofen did not alter end-ischemic CBF in any region studied, and the ibuprofen treatment group had the lowest proportion of animals with marked ICAM-1 staining. CONCLUSIONS: Ibuprofen given in maximum tolerated doses reduces the striatal infarct size after focal cerebral ischemia. The neuroprotective mechanism does not work through preservation of intraischemic CBF and is consistent with inhibition of ICAM-1 expression; however, at the doses used in this study, other effects of ibuprofen on platelet and endothelial function are possible.     

Somatosensory evoked potential monitoring of temporary middle cerebral artery occlusion during aneurysm operation

Somatosensory evoked potentials (SEPs) in response to median nerve stimulation were used as a guide to cortical function during temporary occlusion of the distal M1 segment of the middle cerebral artery (MCA) in the surgical treatment of five large aneurysms of the MCA bifurcation. MCA occlusion times ranged from 8 to 19 minutes under moderate hypothermia at 28.8 degrees to 30.3 degrees C. SEPs were preserved for variable times during MCA occlusion, ranging from no increase in latency after 13 minutes of occlusion to severe deterioration after 6 minutes. In no case was MCA occlusion maintained for longer than 3 minutes in the presence of a severely disturbed SEP. Recovery of the SEP to its preoperative relationship with that of the nonoperated hemisphere was seen in all cases before the end of operation. All patients were awake after rewarming at the end of operation without any neurological deficit. Monitoring the SEP pertaining to the territory of a cerebral artery during its temporary occlusion can help avoid ischemic damage and will allow the surgeon to take advantage of the several benefits of this technique in aneurysm surgery.     

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.     

Immunohistochemical investigation of cerebral ischemia after middle cerebral artery occlusion in gerbils

Progression and recovery of ischemic and postischemic damage after occlusion of the middle cerebral artery and subsequent reperfusion were investigated in the gerbil. This study was performed by immunohistochemical reaction testing for tubulin and creatine kinase BB-isoenzyme to visualize the neuronal structure and by immunohistochemical reaction testing for astroprotein (an astrocyte-specific protein) to visualize reactive astrocytes. The earliest ischemic lesion became visible in the frontoparietal cortex after 7 minutes of ischemia as a laminar loss of the reaction for tubulin involving the neuropil, neuronal perikarya, and dendrites. The earliest lesion in the caudoputamen evolved after 30 minutes of ischemia. After reestablishment of cerebral circulation, the immunohistochemical ischemic lesions in the neuronal structure disappeared if the ischemic period was 10 minutes or less and partially disappeared even after ischemia for 15 minutes in the cerebral cortex, while the postischemic lesion in the caudoputamen disappeared even after ischemia for 15 minutes. Reactive astrocytes were detected in the cerebral cortex and caudoputamen as early as 24 hours after reperfusion, both in the areas with and without the neuronal lesions. No lesion was identified in the hippocampus or thalamus. This experimental model is suitable for investigation of rapidly progressive regional ischemia in the cerebral cortex and for comparison with other regional or global cerebral ischemia in the gerbil or other animal species.     

The neuroprotective effect of xenon administration during transient middle cerebral artery occlusion in mice

BACKGROUND: Xenon has been shown to be neuroprotective in several models of in vitro and in vivo neuronal injury. However, its putative neuroprotective properties have not been evaluated in focal cerebral ischemia. The purpose of this study was to determine if xenon offers neuroprotection in a mouse model of middle cerebral artery occlusion. METHODS: C57BL/6 mice underwent 60 min of middle cerebral artery occlusion. The animals (n = 21 per group) were randomized to receive either 70% xenon + 30% O2, 70% N2O + 30% O2, or 35% xenon + 35% N2O + 30% O2. After 24 h, functional neurologic outcome (on three independent scales: four-point, general, and focal deficit scales) and cerebral infarct size were evaluated. RESULTS: The 70% xenon + 30% O2 group showed improved functional outcome (median [interquartile range], four-point scale: 2 [2], 70% xenon + 30% O2 versus 3 [2], 70% N2O + 30% O2, P = 0.0061; general deficit scale: 9 [6], 70% xenon + 30% O2 versus 10 [4], 70% N2O + 30% O2, P = 0.0346). Total cerebral infarct volumes were reduced in the 70% xenon + 30% O2 group compared with the 70% N2O + 30% O2 group (45 +/- 17 mm3 versus 59 +/- 11 mm3, respectively; P = 0.0009). CONCLUSIONS: In this model of transient focal cerebral ischemia, xenon administration improved both functional and histologic outcome.     

Results of hyperbaric oxygen therapy during temporary middle cerebral artery occlusion in unanesthetized cats

We evaluated the effect of hyperbaric oxygen (HBO) therapy on neurological function and infarct size in 33 unanesthetized cats subjected to temporary 6-hour or 24-hour occlusion of the middle cerebral artery (MCA) 7 to 10 days after transorbital implantation of a vessel occluder. HBO therapy (100% oxygen at 1.5 atmospheres absolute) was administered for 40 minutes during or after 6-hour occlusions and before, during, and after 24-hour occlusions. Neurological function was graded on a scale of 0 to 10 every 30 minutes before, during, and after occlusion and HBO treatments until it stabilized and then daily until the cats were killed 10 days after occlusion. The results were compared with observations in 13 untreated controls and 6 cats that received 100% O2 at atmospheric pressure during a 6-hour MCA occlusion. HBO therapy during the 1st or 3rd hour of a 6-hour MCA occlusion resulted in a four-grade improvement of the initial neurological function; this effect persisted during the remainder of the occlusion. The average grade of neurological deficit at death was 94% less than in the untreated cats (P less than 0.03). Infarct size in the HBO-treated group was 58% less than in controls (P less than 0.03). There was no significant difference in infarct size between the untreated cats and those treated with 100% O2 at atmospheric pressure. HBO therapy during the 4th hour of a 6-hour MCA occlusion had no statistically significant effect on infarct size, even though the mean neurological deficit was 73% less than in controls (P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

Emergency embolectomy for acute occlusion of the middle cerebral artery

Twenty cases treated with emergency embolectomy for acute occlusion of the middle cerebral artery were reviewed. There were 10 males and 10 females, with an average age of 55 years. The left middle cerebral artery was involved in 17 patients and the right in three. Flow was restored in 16 patients (75%). The embolus originated in the heart in seven, the carotid artery in seven, the aorta in three, an aneurysm in one, and an indeterminate source in two. It was technically most difficult to achieve patency with atheromatous emboli from the aorta. Two patients (10%) had an excellent result with no neurological deficit, five (25%) were left with a minimal deficit but were employable, seven (35%) had a fair result but were still independent and employable, four (20%) did poorly, and two (10%) died. Patients with an associated ipsilateral carotid artery occlusion did poorly. Collateral flow, as judged from preoperative angiograms, was the best predictor of outcome.