Thromboxane synthetase inhibition in acute focal cerebral ischemia in cats

The purpose of this investigation was to study the effects of a selective thromboxane A2 (TXA2) synthetase inhibitor (TSI) upon the evolution of cerebral infarction in the cat. Adult cats, lightly anesthetized with nitrous oxide, underwent right middle cerebral artery (MCA) occlusion for 4 hours followed by a 2-hour period of reperfusion before sacrifice. Ten cats received 3 mg/kg TSI intravenously immediately before, and 10 cats received 3 mg/kg TSI intravenously immediately after MCA occlusion. Ten cats were used as controls receiving no treatment. The bleeding time was determined at baseline and at the end of each experiment. Electroencephalographic (EEG) recordings were obtained before and after MCA clipping and MCA release, and at hourly intervals thereafter. Regional cerebral blood flow (rCBF) was measured using the xenon-133 (133Xe) clearance technique before and after MCA occlusion, after MCA reopening, and before terminating each experiment. Thirty minutes before each cat was sacrificed, Evans blue dye and sodium fluorescein were given intravenously. The animals were then perfused with colloidal carbon and the brains removed and evaluated for midline shift. Evans blue dye and sodium fluorescein extravasation, carbon staining, and infarct size. The bleeding time, arterial blood pressure, rCBF changes, brain swelling, and vital dye extravasation were not statistically different between the three treatment groups. The EEG changes, carbon staining, and infarct size differences between the three groups also failed to reach statistical significance, but there was a suggestion that these parameters were adversely affected in the cats pretreated with TSI. Ten additional cats undergoing MCA occlusion and reperfusion were used for pharmacological studies. Five of them received 3 mg/kg TSI intravenously immediately after MCA occlusion, and serial drug and thromboxane B2 (TXB2) levels (a stable metabolite of TXA2) were determined. Another five cats were not treated and serial TXB2 levels were obtained. Production of TXA2 was inhibited by 95% in cats receiving TSI. In conclusion, thromboxane synthetase inhibition failed to modify favorably the evolution of cerebral infarction. When TSI was given before MCA occlusion, cerebral infarction tended to be more extensive.     

Ca++ antagonist and acute brain ischemia: effects of nilvadipine and nicardipine on middle cerebral artery occlusion in rats]

Effects of calcium antagonists, Nicardipine and Nilvadipine, on neurologic deficits and size of infarct were studied in the rat middle cerebral artery (MCA) occlusion model. Each drug was administered immediately after induction of ischemia, and neurologic grade was evaluated 1 to 24 hours after MCA occlusion. At 24 hours post-occlusion, size of the infarct was compared with that of the control group. In addition, evolution of cerebral infarction was studied at 6 hours and 12 hours post-occlusion by magnetic resonance imaging (MRI). In the Nilvadipine-treated group, neurologic deficits improved more rapidly and the size of infarct was significantly smaller than in the Nicardipine-treated group. MRI showed a progressive extension of cortical infarct in the untreated rat, whereas the infarct size remained unchanged in the Nilvadipine-treated rat. These results suggest the potential therapeutic usefulness of calcium antagonist for acute cerebral ischemia.     

Angiographic analysis of the middle cerebral artery in cerebral aneurysms--its branching pattern and so-called vascular anomalies

Branching patterns of middle cerebral artery (MCA) were angiographically analyzed in 704 cases with cerebral aneurysms. The mean age was 53 years old and the men-to-women ratio was 1.1. In addition, 13 vascular anomalies of MCA were reported and their correlation with the occurrence of cerebral aneurysm was studied. Results: MCA branching patterns were classified in 6 types. Each type was further studied by dividing into 2 subgroups, namely one with MCA aneurysms at their side and the other without MCA aneurysms. There were no differences statistically between each two groups. Vascular anomalies were consisted of 5 duplications of MCA, 4 fenestrations, 3 accessories and one case of combination of duplication and accessory in the same side. Duplications and accessories did not have any evidence of developing aneurysm more frequently at their bifurcation than any one of normal MCA branching patterns. So we concluded that duplications and accessories should be thought to have similar meanings with the ordinary branching patterns of MCA in the occurrence of aneurysms. A postmortem case of accessory MCA without aneurysm revealed that the origin of the anomaly was pathologically normal. We suggested that the origin of accessory MCA could both be an enlarged Heubner artery and a rare branching pattern of MCA. The fenestration should be a true anomaly but at this point we do not have any suggestive clue for that. Finally, we thought that the combination of duplication and accessory in a single MCA was very rare morphologically, and worthwhile to report.     

Regional cerebral ischemia by occlusion of the posterior communicating artery and the middle cerebral artery in gerbils

The authors have created an experimental model of regional cerebral ischemia in gerbils that is reproducible and has a low mortality rate. In gerbils, either the posterior communicating artery (PCoA) or the middle cerebral artery (MCA) was occluded, and the distribution of cerebral ischemia from each surgical procedure was compared with that produced by occlusion of the common carotid artery (CCA). In contrast to the widespread cortical and subcortical infarctions seen after occlusion of the CCA, occlusion of the PCoA caused infarction that was restricted to the hippocampus, the piriform cortex, and the posterior part of the thalamus, and occlusion of the MCA resulted in infarction that was restricted to the central part of the cerebral hemisphere and the caudate nucleus and putamen. Intracranial occlusion of the PCoA or MCA in the gerbil resulted in lesions that were reproducible with low mortality rates over a long-term period. Occlusion of the PCoA, MCA, or CCA also produces a model that is suitable for investigation of the postischemic period. A combination of these three experimental models is useful for investigation of regional vulnerability and for the study of regional metabolic differences in cerebral ischemia.     

Two cases of main trunk artery occlusion associated with multiple cerebral aneurysms

We report 2 cases of multiple aneurysms (AN) associated with main trunk artery occlusion. CASE 1: A 52-year-old male was admitted to our hospital with dysarthria and weakness of the right side of the body. Computed tomography (CT) showed cerebral infarction in the left corona radiata. MR angiography and conventional angiography showed occlusion of the left middle cerebral artery (MCA) and saccular aneurysms (ANs) at the origin of the anterior communicating artery (A-com) and bifurcation of the right MCA. Subsequent 123I-IMP-single photon emission tomography (SPECT) revealed marked reduction of cerebral blood flow and disturbed reactivity to acetazolamide in the left cerebral hemisphere. Superficial temporal artery (STA)-MCA anastomosis was performed to improve cerebral blood flow and reduce hemodynamic stress for AN of the A-com and right MCA. At 5 months after the first operation, neck clipping was performed successfully for the non-ruptured A-com AN and right MCA AN. CASE 2: A 65-year-old male was admitted to our hospital. CT revealed subarachnoid hemorrhage (SAH), and 3D-computed tomographic angiography (CTA) and cerebral angiography showed basilar top AN, A-com AN and right MCA AN associated with right internal carotid artery occlusion. Right ACA and MCA territories were visualized from the A-com artery and posterior cerebral artery. STA-MCA anastomosis was performed to improve cerebral blood flow and reduce hemodynamic stress for ANs. In the same operation, successful neck clipping was performed for BA top AN and right MCA AN. In such cases as these, particularly in ischemic cases associated with main trunk artery occlusion, it was important to consider surgery for AN after STA-MCA anastomosis in anticipation of improved cerebral blood flow and reduce hemodynamic stress for AN.     

Relationship between residual cerebral blood flow and oxygen metabolism as predictive of ischemic tissue viability: sequential multitracer positron emission tomography scanning of middle cerebral artery occlusion during the critical first 6 hours after stroke in pigs

OBJECT: The authors tested the hypothesis that oxygen metabolism is the key factor linking the long-term viability of ischemic brain tissue to the magnitude of residual blood flow during the first 6 hours following a stroke. METHODS: Eleven anesthetized pigs underwent a series of positron emission tomography studies to measure cerebral blood flow (CBF) and metabolism before and for 7 hours after the animals were subjected to permanent middle cerebral artery (MCA) occlusion. The extent of collateral blood supply was assessed using angiography. Abnormal metabolism of the ischemic tissue progressed as a function of time in inverse proportion to the magnitude of residual CBF, and the volume of the infarct grew in inverse proportion to the residual blood supply. Ten hours after occlusion of the MCA, the infarct topographically matched the tissue with a cerebral metabolic rate of oxygen consumption below 50% of values measured on the contralateral side. This was also the threshold for the decline of the oxygen extraction fraction below normal, which was critical for the prediction of nonviable ischemic tissue. Mildly ischemic tissue (CBF > 30 ml/100 g/min) did not reach the cerebral metabolic rate of oxygen threshold of viability during the first 6 hours after MCA occlusion; moderately ischemic tissue (CBF 12-30 m1/100 g/ min) reached the threshold of viability in 3 hours; and severely ischemic tissue (CBF < 12 ml/100 g/min) remained viable for less than 1 hour. CONCLUSIONS: The relationship between the residual CBF and both oxygen metabolism and extraction is critical to the evolution of metabolic deficiency and lesion size after stroke.     

Cerebral perfusion during nonpulsatile cardiopulmonary bypass

The recording of middle cerebral artery (MCA) flow velocity by the transcranial Doppler method offers a new, noninvasive, continuous technique for studies of cerebral circulation. Comparative studies of electromagnetic internal carotid artery (ICA) flowmetry and MCA flow velocity by the transcranial Doppler technique have demonstrated that observed changes in MCA flow velocities reflect concomitant changes in cerebral circulation. Eleven high-risk patients undergoing cardiopulmonary bypass (CPB) procedures were included in a pilot study. Arterial blood pressure (BP), central venous pressure, and epidural intracranial pressure (EDP) were recorded during CPB. Cerebral electrical activity was recorded by a cerebral function monitor. Flow velocity in the MCA was increased during nonpulsatile CPB in 10 of the 11 patients. This increase was related to the degree of hemodilution, and the flow velocity during steady-state CPB was 80 to 300% of the prebypass value. The MCA flow velocity changed, however, in a pressure-passive manner with the cerebral perfusion pressure (CPP = BP - EDP) in the individual patient, which indicates that cerebral autoregulation was not operative. During the first 15 minutes after termination of bypass, the MCA flow velocity was reduced, but remained higher than the prebypass level, 110 to 210% of the level during the last 5 minutes preceding CPB.     

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.     

Acute cerebral revascularization after regional cerebral ischemia in the dog. Part 2: Clinicopathological correlation.

The efficacy of cerebral revascularization by anastomosis of the superficial temporal artery (STA) to the middle cerebral artery (MCA), performed 4 and 24 hours after a regional MCA infarction had been produced by combined occlusion of the MCA and internal carotid artery, was tested in 12 dogs. To control possible intercurrent variables, seven other dogs remained untreated and five had a sham operation. Clinical and pathological changes were recorded and analyzed. An incidence of 85% infarction was obtained in the untreated control group. The severity of the clinical deficits and pathological changes for the anastomosed groups were greater than those seen in the untreated control group. The extent of the infarction was significantly greater (p less than 0.05) in the anastomosed groups than in the sham-operated and control groups. Hemorrhagic infarcts occurred in most of the dogs in the anastomosed groups, but were not present in either control group (p less than 0.05). Two dogs in the 4-hour and one in the 24-hour group improved more than any control dog, but the difference was not statistically significant (p greater than 0.05). In two dogs with occluded anastomosis the clinical deficits and the pathological changes were less than those seen in animals with patent anastomosis. The severity of the pathological and clinical changes correlated well with the reestablishment of flow in the MCA territory. It is proposed that cerebral revascularization at 4 and 24 hours following a regional MCA infarct in the dog is followed by an exacerbation of the microcirculatory obstruction, cerebral edema, and infarction. From improvement noted in three animals the authors suggest that under special conditions the revascularization could benefit some cases following acute cerebral infarction.     

Experimental model of intracranial arteriovenous shunting in the acute stage

A model of intracranial arteriovenous (AV) shunting must incorporate local hypoperfusion and simulate the hemodynamics of arteriovenous malformations. In this study, the hemodynamics of an intracranial AV shunt model in the acute stage were clarified. End-to-side anastomoses with a femoral vein graft were performed between a cortical branch of the middle cerebral artery (MCA) and the superior sagittal sinus in anesthetized dogs. Local cerebral blood flow (l-CBF) was measured by laser Doppler blood flowmetry. l-CBF decreased suddenly by 34.2% when the shunt was opened in the ipsilateral MCA territory. Upon re-occlusion, l-CBF immediately equaled or exceeded the pre-opening value and returned to the pre-opening value within the next 15 minutes. Opening the shunt produced little change in l-CBF in the territory of the ipsilateral or contralateral anterior cerebral artery. The decrease in l-CBF was correlated with shunt volume only in the MCA territory. l-CBF manifested a PaCO(2)-dependent increase before shunt opening, but CO(2) reactivity was impaired after opening the shunt only in the MCA territory. This dog model features local hypoperfusion due to intracranial AV shunting and disturbance of CO(2) reactivity in the acute stage. The hemodynamics of this model will be confirmed in the chronic stage.     

Dissecting aneurysms of the anterior cerebral artery and accessory middle cerebral artery. Case report

A 66-year-old woman presented with dissecting aneurysms of the anterior cerebral artery (ACA) and accessory middle cerebral artery (MCA) manifesting as subarachnoid hemorrhage but without radiological evidence of the dissecting aneurysms. Intraoperative observation revealed that the vessel walls were dark purple in color, a typical finding of dissecting aneurysm. The abnormal A1 segment was trapped and the dissecting aneurysm of the accessory MCA was wrapped. In the case of SAH of unknown origin, dissecting aneurysm should always be kept in mind even if the angiogram does not show any abnormal finding. This is the first reported case of dissecting aneurysm of the accessory MCA.     

An anatomic study for a modified technique for bypass of the external carotid artery to the proximal middle cerebral artery

We aimed to evaluate whether bypass of the external carotid artery (ECA) to the middle cerebral artery (MCA) can be established by a short saphenous vein graft in order to increase the anastomosis patency. The method was performed to ten adult cadaver sides. We described a modified technique for bypass of the ECA to the M2 segment of MCA. The diameters of the vessels and graft length were measured by using an electronic micrometer. The mean diameter of the superior, middle, and inferior trunks of the MCA with trifurcation were 1.7 +/- 0.15, 2.2 +/- 0.25, and 2.0 +/- 0.2 mm, respectively, whereas the mean diameter of the superior and inferior trunks of the MCA with bifurcation were 2.1 +/- 0.2 and 2.3 +/- 0.3 mm, respectively. The mean diameter of the ECA was 3.75 +/- 0.4 mm. The mean length of the saphenous vein graft was 71.5 +/- 3.9 mm. The high-flow ECA to proximal MCA bypass using a short venous graft can supply enough blood flow to establish cerebral revascularization with a straighter route.     

Intraoperative monitoring of the somatosensory evoked potentials and cerebral blood flow during aneurysm surgery--safety evaluation for temporary vascular occlusion.

Somatosensory evoked potentials (SEPs) and cerebral blood flow (CBF) were monitored during temporary vascular occlusion in 67 aneurysm operations to evaluate the usefulness of SEP as an indicator for cerebral ischemia. The SEP N20 component completely disappeared during temporary vascular occlusion in 24 cases, 23 of which demonstrated complete recovery following recirculation and had no postoperative neurological sequelae. The only one with postoperative sequelae demonstrated rapid, within 1 minute, loss of N20 followed by no recovery. Another eight cases showed prolongation of central conduction time during vascular occlusion and had no postoperative sequelae. The SEP N20 attenuation reflected the CBF reduction in the middle cerebral artery (MCA) territory during MCA occlusion. However, CBF changes in the internal carotid artery (ICA) territory during ICA occlusion greatly varied. No detectable changes in SEP were found during anterior cerebral artery occlusion for anterior communicating artery aneurysms. This study indicates that intraoperative SEP monitoring is useful to detect ischemia in the MCA territory and that rapid disappearance of the N20 component is a danger signal.     

The feasibility of detecting cerebral blood flow direction using the indocyanine green video angiography

The intraoperative confirmation of blood flow direction is necessary in cerebral vascular surgery. Using indocyanine green video angiography (ICG-VAG) with the FLOW 800 system, we examined the transit time of the blood vessel of interest and semiquantitatively evaluated the delay time (T1/2max) from indocyanine green (ICG) injection into the donor artery in reconstructive surgery and the middle cerebral artery (MCA) in aneurysmal surgery. The direction of cerebral blood flow (CBF), which can often be confirmed by ICG-VAG, may be more difficult to determine with faster blood flow. Here, we report our findings regarding the feasibility of detecting CBF direction using the FLOW 800 system. Twenty patients undergoing superficial temporal artery (STA) to MCA anastomosis for carotid occlusive disease and 13 patients with a small MCA aneurysm clipping were evaluated using the T1/2max, semiquantitative method with the FLOW 800 system. In STA–MCA anastomosis cases, the regions of interest (ROIs) included: the proximal donor STA and a region more than 10 mm on the distal side of the donor STA near the anastomosis site. In MCA aneurysms, the ROIs included the proximal M1 and distal M2 sides of the MCA aneurysm. T1/2max was significantly shorter for the proximal sites compared to the distal sites for all subjects (ps?<?0.01). T1/2max was shorter for all subjects in the proximal sites. The direction of CBF can be determined using the FLOW 800 system.     

Ruptured infectious aneurysms of the distal MCA treated with trapping and STA-MCA bypass surgery

We describe two patients with ruptured infectious aneurysms of the distal MCA, which were successfully treated by trapping and superficial temporal artery (STA)-middle cerebral artery (MCA) bypass surgery. Our patients had not experienced any ischemic attack postoperatively. Trapping and STA-MCA bypass surgery can be a useful option.     

猫脑缺血时脑不同部位脑血流与氨基酸的变化

目的 比较缺血时猫脑不同部位脑血流、氮基酸的变化并研究两者之间的关系。方法 利用激光多普勒血流计，持续监测猫脑不同部位（颞叶、枕叶）在脑缺血时脑皮层表面的血流变化；利用微透析技术，测定相同位置细胞间隙中的氨基酸变化。结果 在阻断猫大脑中动脉（MCA）后，颞叶和枕叶部位的脑血流迅速下降，分别为正常值的21．44％和23．61％，并在2h内缓慢下降；微透析液中谷氨酸浓度迅速增加，可达到正常值的80余倍。结论 缺血时猫颞叶和枕叶的脑血流与谷氨酸浓度变化相同，差异无统计学意义。     

Ruptured anterior cerebral artery aneurysm at the origin of the accessory middle cerebral artery

A 36-year-old female patient was admitted to our hospital with a rare case of aneurysm at the origin of the accessory middle cerebral artery (MCA) manifesting as severe headache and vomiting. Neurological examination did not detect any abnormalities or consciousness disturbance. Computed tomography demonstrated diffuse subarachnoid hemorrhage. Magnetic resonance angiography showed an aneurysm in the horizontal portion of the left anterior cerebral artery (A(1)). Digital subtraction angiography and three-dimensional digital subtraction angiography demonstrated a saccular aneurysm originating at the junction of the left A(1) and accessory MCA. Another accessory MCA originated at the proximal portion of the left A(2) without an aneurysm. Two accessory MCAs were found on the left. Neck clipping was performed via a left pterional approach. One month after admission, she was discharged without neurological deficits.     

A new method for superselective middle cerebral artery infusion in the rat

OBJECT: Selective intraarterial drug delivery is used to achieve enhanced local uptake with reduced systemic side effects. In the present paper the authors describe and characterize a new microcatheter-based model of superselective perfusion of the middle cerebral artery (MCA) in rats combined with blockade of blood flow through the MCA. METHODS: Selectivity of administration was shown by infusion of Evans blue which diffusely stained the MCA territory, indicating an increased permeability of the blood-brain barrier during the blockade of blood flow to the MCA. Perfusion of autologous blood through the microcatheter resulted in a flow rate-related increase in the cerebral blood flow measured by laser Doppler flowmetry. Similarly, infusion of an artificial O2 carrier, Oxycyte, was accompanied by an increase in tissue oxygenation as measured using a Licox sensor. Blockade of blood flow to the MCA with the new microcatheter for an extended period of time resulted in the development of ischemia, which was comparable to that induced by intravascular occlusion using a silicone-coated thread. In a 24-hour MCA occlusion model, selective administration of a low dose of MK-801 (0.3 mg/kg body weight) resulted in a significantly smaller infarct volume than systemic application (339 +/- 53 mm(3) compared with 508 +/- 26 mm(3), p < 0.001). CONCLUSIONS: This new model of superselective MCA infusion is a valuable tool for investigating the effect of selective delivery and enhanced drug uptake into cerebral ischemic tissue. Without constant blockade of blood flow through the MCA it may also be useful for enhanced drug uptake, gene transfer, or application of stem cells in other neuropathological conditions.     

Aneurysms located at the proximal anterior cerebral artery and anterior communicating artery associated with middle cerebral artery aplasia: case report

BACKGROUND: Aneurysms arising from the proximal anterior cerebral artery (ACA) are quite rare. Here, we report upon such a case of aneurysms located at the proximal ACA and anterior communicating artery associated with middle cerebral artery (MCA) aplasia. CASE DESCRIPTION: A 64-year-old woman complained of severe headache. Brain computed tomography scans demonstrated acute subarachnoid hemorrhage. Angiograms showed 2 aneurysms located at the anterior communicating artery and proximal ACA, but did not show an MCA shadow on the lesion side. Instead, multiple collateral vessels ran toward the sylvian fissure and supplied the MCA territory, together with hypertrophied perforating branches. The operative findings confirmed that the cordlike rudimentary MCA had no internal blood flow. The 2 aneurysms were secured by neck clipping. CONCLUSION: The combined effects of these anomalies on the hemodynamic equilibrium of the arteries and the genesis of the aneurysms are noteworthy.