bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Cerebral Vasoconstricting and Vasodilating Agents on Blood Flow in Regions of Focal Ischemia
Authors: HANSON E. JEROME , ANDERSON ROBERT E. , SUNDT THORALF M.
Published: June 2011

Regional cerebral blood flow (rCBF) measurements with krypton-85 (100 separate determinations) were compared in squirrel monkeys anesthetized with sodium pentobarbital (a cerebral vasoconstrictor) and halothane (a cerebral vasodilator) before, during, and after middle cerebral artery (MCA) occlusion. Prior to MCA occlusion, a normal physiological response to alterations in arterial carbon dioxide tensions (Paco
2
) was demonstrated in both groups of monkeys; the cerebral vascular resistance was significantly lower in those anesthetized with halothane. During ischemia, there was loss of autoregulation and a failure to respond to alterations in Paco
2
, in both groups. Flow in the ischemic region remained uniform in the barbiturate group but decreased progressively in the halothane group, suggesting a "paradoxical response" to the dilating agent. Reactive hyperemia (luxury perfusion) was demonstrated in both groups after restoration of flow. The use of a beta-emitting isotope ensured that measurements in regions of ischemia accurately reflected rCBF and were free of the artifacts ("look through" and Compton scatter) related to use of a gamma-emitting indicator.
The Behr Pupil Revisited
Authors: HERMAN PETER
Published: June 2011

Three hundred and sixty-three cases of cerebral infarction were reviewed; 19 had anisocoria. Eighty percent had the larger pupil contralateral to the hemispheric lesion. The mydriasis was associated with long tract signs in all instances. If the abnormal pupil and long tract signs are not on the same side, the long tract signs are the most accurate evidence of the side of the hemispheric lesions.

When the pupil was 4 mm or larger and reacted sluggishly, the prognosis was poor.

The mechanism of the production of the anisocoria is still uncertain; the lesion is probably "cortical" and in the contralateral hemisphere.
Lactate and Pyruvate Concentrations, and Acid-Base Balance of Cerebrospinal Fluid in Experimentally Induced Intracerebral and Subarachnoid Hemorrhage in Dogs
Authors: SUGI TOMEI , FUJISHIMA MASATOSHI , OMAE TERUO
Published: June 2011

The effect of blood injected into either subarachnoid space or subcortical brain tissue upon lactate and pyruvate concentrations as well as acid-base balance of cerebrospinal fluid (CSF) was studied in the anesthetized dog.

CSF lactate and lactate/pyruvate ratio (L/P ratio) increased progressively following the intracranial injection of blood and reached the maximum level at six hours after injection. These changes were significantly greater in animals with intracerebral hematoma than in those with subarachnoid hemorrhagic (SAH). An increase in CSF lactate and L/P ratio in hemorrhagic CSF seems to be caused by two different factors. Shed blood cells per se produce lactate and pyruvate, and blood in the subarachnoid space and intracerebral hematomas cause secondary changes in brain tissue metabolism by a probable reduction of cerebral blood flow. Therefore, an increase in CSF lactate with a concomitant rise in CSF L/P ratio is a useful indicator for brain tissue hypoxia, even when CSF is hemorrhagic.

The association of an increase in CSF lactate to a disproportionate decrease in CSF HCO
3
-
was also observed in these animals.
A Classification of Experimental Models of Brain Ischemia
Authors: MOLINARI G. F. , LAURENT J. P.
Published: June 2011

A system is presented for the classification of experimental models of cerebral ischemia by a mechanism of induction and distribution of the cerebral insult. Application of the proposed system to the scientific literature may help to resolve apparent conflicts in experimental findings and establish a frame of reference upon which to estimate the relevance of specific animal data to clinical phenomena. Experimental ischemic lesions and pathophysiological states must be considered the net product of variables in etiology and distribution of ischemia in the species chosen under the specific anesthesia selected.
Cerebral infarction following bilateral carotid artery ligation in normotensive and spontaneously hypertensive rats: a pathological study.
Authors: Ogata J , Fujishima M , Morotomi Y , Omae T
Published: June 2011

A pathological examination was performed on normotensive rats (NTR) and spontaneously hypertensive rats (SHR) following bilateral common carotid artery ligation. After ligation, diffuse and extensive cerebral infarcts in the carotid artery territory occurred frequently in SHR, while NTR occasionally had well-circumscribed small infarcts. The posterior communicating arteries, which are the major anastomotic channels connecting the carotid and vertebrobasilar systems, did not show any anomalies and were well developed in SHR and NTR. Vascular changes secondary to hypertension, such as fibrinoid necrosis or thickening of the wall, were not observed in SHR. Because of the paucity of structural difference of the blood vessels, the more diffuse and extensive cerebral infarcts in SHR after carotid occlusion were attributed to the hemodynamic difference rather than the morphological difference between the two groups. The results of the present experiment suggest that hypertension per se, i.e., hemodynamic factors, may be operative for the development of cerebral infarction.
Temporal profile (clinical course) of acute carotid system cerebral infarction.
Authors: Jones H J , Millikan C H
Published: June 2011

The records of 179 consecutive patients with acute carotid system cerebral infarction were studied to describe the temporal profile of the clinical events during the first week of the illness. Only those patients admitted to the cerebrovascular hospital service within 36 hours of the onset of the first symptom were included. The neurological status of 39% was stable (unchanged) at the end of seven days; 35% of the patients gradually improved. Nineteen percent had a progressing neurological deficit from the onset which stabilized within 48 hours of onset. Six patients (3%) had a remitting-relapsing course during the first 36 hours. Eight patients (4%) had a significant late worsening, after 48 hours of stable or improving course. Mortality was 11% for the entire group. However, a high risk of death group was identified - the mortality was 41% for those patients who had any degree of decreased level of consciousness and hemiplegia at the time of admission.
Cerebral manifestations of ergotism. Report of a case and review of the literature.
Authors: Senter H J , Lieverman A N , Pinto R
Published: June 2011

A patient with diffuse and focal cerebral dysfunction was found to have absent peripheral pulses. Cerbral angiography revealed evidence of an arteritis with bilateral high grade carotid stenosis. When there was no laboratory confirmation of the arteritis, an iatrogenic etiology (ergotism) was suspected. This was later confirmed by the patient. The pertinent literature on ergotism is reviewed, and it is emphasized that ergotism may develop in patients on therapeutic doses of the drug.
Intracranial bleeding associated with urokinase therapy for acute ischemic hemispheral stroke.
Authors: Hanaway J , Torack R , Fletcher A P , Landau W M
Published: June 2011

Four patients undergoing urokinase infusion therapy for acute occlusive cerebrovascular disease had intracerebral hemorrhage in the ischemic hemisphere. Three patients died during the acute phase of their illness and an autopsy was performed on two. The pathogenesis of cerebral bleeding in these case reports is discussed.
Diplopia and involuntary eye closure in spontaneous cerebellar hemorrhage.
Authors: Messert B , Leppik I E , Sato S
Published: June 2011

Spontaneous cerebellar hemorrhage is of difficult clinical diagnosis. The causes can be varied, but the hemorrhage is most often associated with hypertensive cardiovascular disease. The neurological symptomatology is complex and often misleading. The diagnosis is mainly dependent of familiarity of the eye signs seen in this disease. Among these, the spontaneous unilateral eye closure is presented as an additional striking manifestation. The displacement of the brain stem by the hematoma is frequently associated with a seventh nerve palsy on the side of the hemorrhage. The patient in an effort to obviate the diplopia caused by the gaze dissociations and extraocular motor palsies, has only the option to close the eye on the noninvolved side of the face, and thus the eye remaining open is on the side of the cerebellar hematoma. This paper presents reports of two patients with these symptoms.
Noninvasive angiography for the diagnosis of vertebral artery disease using Doppler ultrasound (vertebral artery Doppler).
Authors: Keller H M , Meier W E , Kumpe D A
Published: June 2011

A transoral noninvasive procedure in the oropharynx using local anesthesia was applied to detect flow in the vertebral arteries with a bidirectional continuous-wave Doppler ultrasound system. Common carotid artery compression was used to identify the vertebral artery. Flow direction, amplitude of flow signals, diastolic flow, and reaction of flow on common carotid artery compression served as diagnostic parameters. The procedure was applied in 90 patients of whom 42 underwent angiography. The method has proved to be 82% accurate. It was most reliable in the diagnosis of occlusion or aplasia, subclavian steal and normalcy, and was less reliable in the detection of stenosis or hypoplasia of a vertebral artery. Eleven patients with subclavin steal, five patients with a missing vertebral artery three patients with hypoplasia or stenosis, and 15 patients with normal angiorgraphical findings were correctly diagnosed by Doppler; normal Doppler findings were present in three patients with a mission or stenosed vertebral artery. Those patients (five) with Doppler indications of subclavian steal (one patient), missing vertebral artery (two patients), or stenosis (two patients) had normal angiograms. Application of the Doppler procedure, after 11 subclavin endarterectomies, informed the surgeon immediately about the hemodynamic effect of surgical intervention. Rethrombosis was diagnosed in two patients by postoperative Doppler examination.
Noninvasive measurement of velocity profiles and blood flow in the common carotid artery by pulsed Doppler ultrasound.
Authors: Keller H M , Meier W E , Anliker M , Kumpe D A
Published: June 2011

A computer-controlled 14-channel pulsed Doppler ultrasound instrument was used as a noninvasive means to evaluate instantaneous velocity profiles and flow in the comlon carotid arteries of 22 healthy persons and in 22 patients. Of the later, 13 had severe obstructions of the extracranial portion of the carotid artery, four had obstruction of the intracranial portion, and five had severe aortic valve insufficiency (AI), with more than 60% regurgitation in all cases. Measurements could be performed within an accuracy of about +/- 20% under clinical conditions and revealed perfusion values of 5 to 8 ml per second (300 to 480 ml per minute) in healthy persons. Of the patients, values less than 3 ml per second (180 ml per minute) were detected in nine, between 3 and 5 mm per second (180 to 300 ml per minute) in four, and normal values in another four, while significant backflow was observed only in patients with severe AI. Consecutive blood flow profiles were recorded every 4 msec; these demonstratedthat, for a period lasting from 40 msec to 280 msec after the initial systolic peak, blood flow decelerated more rapidly in the central portion of the vessel lumen than near the wall. This situation was present in all healthy persons and in most patients with pathological flow. In patients with AI, flow reinversion from reverse to normal began near the vessel wall, while in the middle third of the vessel lumen, blood was still flowing backward. These phenomena seem to be in agreement with the theoretical and experimental findings of Wormersly, Müller, and others. The AI patients who underwent artificial valve implantation were studied ten days after operation and showed no or little backflow in the common carotid artery at that time.
Doppler sonography diagnosis of cerebrovascular disease.
Authors: Katz D M , Smith R A , Otis S M , Dalessio D J
Published: June 2011

Sonographic patterns for the Doppler ophthalmic test (DOT) were determined by reviewing the type of graphic record obtained from 25 patients who had undergone angiography. Three principal patterns were identified, depending upon whether there was augmentation (Type 1), diminution (Type 2) or no change (Type 3) in the character of the supraorbital Doppler signal upon temporal artery compression. Type 1 records were seen in 28 of 33 instances where the carotid arteries remained patent. Type 2 records occurred in 10 of 14 instances where there was significant carotid stenoses or tortuosity and in two instances in a patient with a subclavian steal syndrome. A "false-positive" test was recorded in one instance in a patient with vascular headaches. There were three Type 3 records.
Pharmacological control of local oxygen regulation mechanisms in brain tissue.
Authors: Bicher H I , Marvin P
Published: June 2011

The effect of several agents active on autonomic nervous system functions was tested on brain oxygen autoregulation parameters. It was found that atropine, propranolol and isoproterenol had no influence in abolishing the measured parameters. Phenoxybenzamine, tolazoline and dibenamine all suppress autoregulation. In an additional experimental series, a phenoxybenzamine infusion was given during O2 breathing. The infusion induced, in most cases, an additional rise in TpO2 (tissue pressure of oxygen, which refers to the partial pressure [in mm Hg] of this gas at the measuring tip of the electrode). It is concluded that an alpha-adrenergic mechanism is part of the autoregulation process. Also, the increase in brain TpO2 induced by 59% O2-5% Co2 breathing seems to be blocked or reversed by alpha-adrenolytic drugs, thus supporting the thinking that the effect of CO2 on cerebral blood flow is at least in part mediated through an alpha-adrenergic response.
Prognosis of occlusive cerbrovascular diseases in normotensive and hypertensive subjects.
Authors: Fujishima M , Omae T , Takeya Y , Takeshita M , Ogata J
Published: June 2011

Comparison of the clinical features, especially prognosis, in cerebral infarction was made between nine normotensive subjects and 16 hypertensive patients with an 80% stenosis or occlusion of the intracranial or extracranial arteries. Our own criteria for evaluating hypertension were employed on the basis of the following items: a past history of hypertension, blood pressure levels on admission and during hospitalization, degree of retinopathy, and ECG changes. In 17 of 25 cases, brain circulation was measured by the intravenous RISA technique. Abnormalities of the EEG and reduction of cranial blood flow were greater, and an early prognosis for neurological deficits in the first two months after the onset of stroke was poorer in the hypertensive group than inthe normotensive group. These results are contradictory to the observations of others.
Cerebral infarction in the Mongolian gerbil exacerbated by phenoxybenzamine treatment.
Authors: McGraw C P , Pashayan A G , Wendel O T
Published: June 2011

In a double-blind study, the effects of a large dose (20 mg per kilogram) of phenoxybenzamine (PBZ) on cerebral infarction were evaluated in 120 Mongolian gerbils. The left common carotid artery was ligated in 100 animals; a sham operation was done in 20 animals. One hour later, 25 animals were given 2 mg per kilogram of PBZ, 25 animals were given 20 mg per kilogram of phenoxybenzamine, and 50 animals were given 0.5 cc of nomal saline, all doses being repeated at 24, 48, and 72 hours. Five sham-operated animals were given 2 mg per kilogram of phenoxybenzamine, five were given 20 mg per kilogram of phenoxybenzamine and ten were given 0.5 cc of normal saline on the same treatment schedule. Morbidity and mortality were recorded for one week and then all surviving animals wer killed. All brains were studied for signs of infarction. Of the saline-treated animals, 32% had cerebral infarction and 81% of these died. Of the animals treated with phenoxybenzamine, 36% of those receiving 2 mg per kilogram and 68% (p less than 0.05) of those receiving 20 mg per kilogram had cerebral infarction and all of those with infarction died during the observation period. The animals receiving phenoxybenzamine had a larger stroke index than those treated with saline. The authors concluded that phenoxybenzamine is harmful in postischemic treatment of strokes.
A new sign of occlusion of the origin of the internal carotid artery.
Authors: Millikan C H
Published: June 2011

When the origin of the internal carotid artery is occluded, the transmission of cardiac sounds along the carotid stops at the site of the occlusion. This is a new neurovascular sign which is being reported.
Autoregulation in acute focal ischemia. An experimental study.
Authors: Symon L , Branston N M , Strong A J
Published: June 2011

The autoregulatory capacity of areas of the cerebral circulation subjected to ischemia by acute middle cerebral occlusion has been assessed in experimental primates. Autoregulation was tested to a rise in blood pressure induced by aramine, and to a fall in blood pressure induced by exsanguination. Whole hemisphere autoregulation was substantially disturbed due to both increased blood pressure and lowered blood pressure, but fractionation of this response indicated that autoregulation to increased blood pressure was preserved in the parasagittal and intermediate zones of the hemisphere, and totally lost in the region of the sylvian opercula where middle cerebral occlusion had produced the most dense ischemia. In relation to reduced perfusion pressure, autoregulation was again widely impaired and assessment of the degree of impairment by areas indicated no significant difference between the areas of the sylvian opercula and the remainder of the lateral aspect of the hemisphere studied. Where the degree of ischemia in each individual electrode was assessed, however, it appeared that the degree of auto-regulatory loss to decreased perfusion pressure was dependent upon the intensity of ischemia, and autoregulation was partially preserved in electrodes whose immediate post-occulsion flow values were greater than 40% of basal flow. Retransfusion following exsanguination in animals with acute middle cerebral occlusion indicated that there was a linear relationship between the degreee of reperfusion achieved by retransfusion and the intensity of ischemia induced by exsanguination following middle cerebral occlusion. Thus there was some support for the no-reflow phenomenon in intensely ischemic areas.
Ophthalmodynamometry in internal carotid artery occlusion.
Authors: Paulson O B
Published: June 2011

Retinal artery pressure was measured by ophthalmodynamometry in 15 patients with occlusion of the internal carotid artery in its extracranial part. Nine of the patients had severe neurological deficit whereas the remaining six had slight or intermittent symptoms. Retinal artery pressure was reduced on the side of the internal carotid artery occlusion in all patients studied. Near-zero low diastolic retinal artery pressure on the affected side was a common finding among patients with severe deficit and was also seen in some patients with slight deficit. Its presence strongly suggests occlusion of the ipsilateral internal carotid artery.
Effect of intracarotid prostaglandin E1 on regional cerebral blood flow in man.
Authors: Olesen J
Published: June 2011

The effect of prostaglandin E1 on regional cerebral blood flow (rCBF) was studied with the intra-arterial 133Xe method in ten awake patients under local anesthesia. Measurements were taken from 16 areas of a hemisphere in seven patients, from 35 areas of a hemisphere in two patients and from 256 areas of a hemisphere in one patient. The prostaglandin was dissolved from the crystalline state without the aid of alcohol. It was given intracarotidly as a constant infusion at a rate of 5 ng per kilogram per minute for five minutes before the measurement and continued during the measurement. In every patient a mild increase in blood flow during the prostaglandin infusion was seen. The flow increase took place in all parts of the hemisphere. It averaged 11.2% (p less than 0.01). During the infusion, the skin supplied by the internal carotid artery and the conjunctiva on the infused side became red and sometimes swollen. A slight pressure was noted by most patients, but none had pain. No side effects of the infusion were noted.
Primary non-traumatic intracranial hemorrhage. A municipal emergency hospital viewpoint.
Authors: Yarnell P , Earnest M
Published: June 2011

The devastating natural history of 138 consecutive admissions for non-traumatic intracranial hemorrhage to a major emergency care municipal hospital is reviewed. Sixty-four percent of the patients had demonstrable intracranial hematomas while 36% had mainly subarachnoid hemorrhage. Hypertension was a related condition in 43% of the parenchymal hematoma patients, while proved aneurysms accounted for 74% of the subarachnoid hemorrhage patients. There was only a 14% survivorship for patients requiring emergent surgery. All operated hematoma patients survived delayed surgery with improved level of responsiveness. The overall mortality was 74% for intracranial hematoma patients and 58% for aneurysm-caused subarachnoid hemorrhage patients.
Granulomatous angiitis. An unusual etiology of stroke.
Authors: Burger P C , Burch J G , Vogel F S
Published: June 2011

A 43-year-old man, who died five months after the onset of left-sided sensory deficit, had angiographical and pathological evidence of an angiitis confined largely to the distribution of the right middle cerebral artery. Histological examination identified this process to be intracranial noninfectious granulomatous angiitis. Although certain clinical and pathological features of this disorder overlap with other vasculitides which effect the central nervous system, the disease nevertheless retains sufficient individuality to warrant status as an entity, and should be considered in the differential diagnosis in adults with lesions which produce focal neurological deficits and signs of increased intracranial pressure. The definitive answer regarding an infectious etiology will come only from detailed culture studies of the affected vessels.
Frequency and course of pure motor hemiparesis: a clinical study.
Authors: Richter R W , Brust J C , Bruun B , Shafer S Q
Published: June 2011

A review of 850 acute unselected stroke cases at Harlem Hospital found only 25 (3%) who met a clinical definition of pure motor hemiparesis. Compared to other cerebral infarction survivors, the 23 pure motor syndrome survivors were slightly younger, not much more often hypertensive and did not make a faster recovery. The degree of motor deficit a year later was nearly the same in both groups. Brain scans were positive in one-third of the pure motor patients, which suggests that this clinical picture may be associated with larger brain lesions than had been suspected before, as well as with lacunar infarction.
Cation activities in reversible ischemia of the cat brain.
Authors: Hossmann K A , Sakaki S , Zimmerman V
Published: June 2011

In normothermic anesthetized cats cerebral blood flow was interrupted completely for one hour by arterial clamping and induced hypotension. The effect of ischemia on the ionic gradients of the cerebral cortex was assayed by determining total cortical electrolytes and by recording the activities of extracellular potassium ([K+i1e) and subarachnoid sodium ions ([Na+])s) with ion-sensitive electrodes. During ischemia [K+]e increased from 3.3+/-0.3 to 56+/-5.4 mEq per liter (means+/-SE) and [Na+]s decreased from 133+/-3.8 to 53+/-5.8 mEq per liter. When the brains were recirculated with blood after one hour's ischemia, [K+]e and [Na+]a gradually returned to normal within 45 minutes. The calculated intracellular uptake of sodium during ischemia amounted to 139 mEq per kilogram dry weight, whereas the intracellular release of potassium was only 64 mEq per kilogram. The increase in intracellular cation was accompanied by a movement of water from the extracellular into the intracellular compartment, causing a reversible shrinkage of the extracellular space from 18.9 to 8.5 vol %. The changes in ionic gradients were related to the development and resolution of ischemic brain swelling, and to the elctrophysiological events during and after ischemia.
Cerebral blood flow regulation. II. Vasodilator mechanisms.
Authors: Levy L L , Wallace J D
Published: June 2011

Rapid vasicular resistance adjustments in the brain and in the circle of Willis have been continuously measured and enhanced by signal averaging methods. Naftidrofuryl, a drug chemically similar to local anesthetics and to beta adrenergic blocking agents, increases local CBF by reducing resistance in brain and in extracerebral supply arteries. It has also been reported to affect brain metabolism. Other similar drugs merit study for potential effects on CBF and brain metabolism which may be useful in treatment.
Central nervous system angioendothelosis. A treatable multiple infarct dementia.
Authors: Reinglass J L , Muller J , Wissman S , Wellman H
Published: June 2011

CNS neoplastic angioendothelosis is a treatable primary proliferative disorder of the endothelial cells of blood vessels characterized by a clinical neurological picture of multiple infarct dementia and an inordinate amount of local cerebral edema, so striking that it may simulate primary or metastatic central nervous system tumor. The malignant cells remain within the lumen of the vessels and rarely if ever metastasize or occur in peripheral blood. There is remarkable improvement in symptoms by treating with high dose steroids. Antimetabolites and irradiation are suggested means of additional treatment.
Use of hydrogen for measurement of regional cerebral blood flow: problem of intercompartmental diffusion.
Authors: Halsey J H , Capra N F , McFarland R S
Published: June 2011

The extreme diffusibility of hydrogen, compared with xenon or krypton, may create serious artifacts when it is used to measure local blood flow with a tissue electrode. The errors are greatest when hydrogen is given by intra-arterial slug injection, and when the electrode is within 2mm of another tissue compartment, CSF, or air. These all appear to be a consequence of intercompartmental diffusion which can occur at rates of the same order of magnitude as clearance from the tissue by blood flow. No matter how small the electrode, the ultimate spatial resolution of the method appears to be about 2mm unless quantitative account is taken of diffusion. An important precaution in use of the method is to obtain homogeneous tissue saturation by prolonged inhalation administration.
Effect of sulfinpyrazone on platelet survival time in patients with transient cerebral ischemic attacks.
Authors: Steele P , Carroll J , Overfield D , Genton E
Published: June 2011

Platelet suppressant drugs have been suggested as beneficial for patients with transient cerebral ischemic attacks and these drugs have been shown to lengthen shortened platelet survival time. In the present study platelet survival time (autologous labeling with 51Chromium) was measured in 25 patients with transient cerebral ischemia involving a carotid distribution. Platelet survival was shortened in all patients (2.5 +/- 0.10 days; AVE t 1/2 +/- SEM; Normal 3.7 +/- 0.04 days P less than 0.001). Sulfinpyrazone increased platelet survival in 9 of 19 (47%) of patients (2.4 +/- 0.10 to 2.8 +/- 0.16 days; P less than 0.01). Of the 19 treated with sulfinpyrazone, 10 had a marked reduction in the frequency of transient ischemic episodes and an increased in platelet survival (2.6 +/- 0.16 to 3.1 +/- 0.22 days; P less than 0.01) was observed in all patients. Three patients had no benefit from sulfinpyrazone and alteration of platelet survival did not occur. Results suggest that platelet survival is shortened in patients with transient cerebral ischemia, that sulfinpyrazone increases platelet curvival and may decrease the frequency of ischemic episodes, and that there may be a relationship between clinical benefit and alteration of platelet survival time.
Relationships among intracranial pressure, blood pressure, and superficial cerebral vasculature after experimental occlusion of one middle cerebral artery.
Authors: Hayakawa T , Waltz A G , Hansen T
Published: June 2011

A cranial window conforming to the contours of the underlying cerebral cortical surface was implanted successfully in 18 cats. Subsequently the left middle cerebral artery (MCA) was occluded inside the sealed cranium and changes in the superficial cortical vasculature were related to measurements of intracranial pressure (ICP), measured extradurally, and to the resulting infarcts. Vascular changes early after MCA occlusion were not predictive of the outcome of the occlusion, except for aggregation of formed elements of the blood in arterioles, which was a bad prognostic sign. Secondary reactive hyperemia was not beneficial; increases of ICP suggested that hyperemia led to increased cerebral edema as well as to swelling.
Comparative effects of chloralose anesthesia and Sernylan analgesia on cerebral blood flow, CO2 responsiveness, and brain metabolism in the baboon.
Authors: Sándor P , Nyáry I , Reivich M , Kovách A G
Published: June 2011

A comparison was made between the effects of two different anesthetics, alpha-D-gluco-chloralose and 1-1-phenylcyclohexyl piperidine hydrochloride (Sernylan), on cerebral blood flow (CBF), brain metabolism and cerebrovascular CO2 responsiveness in primates. The experiments were carried out on immobilized and artificially ventilated baboons. Anesthesia was induced either with 100/mg/kg chloralose (i.p.) or with 1 mg/kg Sernylan (i.m.). CBF in 8 different brain regions was measured by the intra-arterial 133Xe clearance technique. The CO2 responsiveness of the cerebrovascular bed was tested by a gas mixture containing 5% CO2. Chloralose depressed total as well as regional CBF compared to the effect of Sernylan. A significant shift occurred toward lower CBF values in the grey matter while white matter flow was identical in the two groups. Brain O2 consumption was significantly higher during Sernylan analgesia (3.35 +/- 0.34 ml/100 g/min) than during chloralose anesthesia (2.42 +/- 0.22 ml/100 g/min). There were no differences in glucose uptake, lactate and pyruvate production, or in arterial and cerebral venous blood gases in the two types of anesthesia. The cerebrovascular CO2 sensitivity of the Sernylan-treated baboons was higher than that of the chloralose-anesthetized animals, in both the grey and white matter.
Oxidative metabolism in cerebral ischemia. Part 1. Measurement of oxygen extraction slopes of grey and white matter in vivo.
Authors: Fein J M , Eastman R , Moore C
Published: June 2011

Regional oxidative metabolism was studied in vivo. Oxygen availability was monitored from polarographic electrodes in frontal cortical and subcortical tissue. The rate of oxygen extraction in these regions was estimated at frequencies of up to 3 measurements per minute. Transient ischemia of the frontal regions was induced and the resultant decay in the oxygen trace was analyzed kinetically. The oxygen extraction slopes (OES) were steeper in grey than in white matter. They were relatively insensitive to alterations of arterial blood gas concentrations within the physiological range. The slopes were predictably influenced by pharmacologic agents known to alter the rate of oxidative metabolism. Artifacts which may interfere with the OES measurments were considered. This method of estimating regional tissue oxygen extraction may be appropriate for studying aspects of focal CI.
Differentiation of early subarachnoid hemorrhage from traumatic lumbar puncture.
Authors: Shuttleworth E C , Parker J M , Wise G R , Stevens M E
Published: June 2011

The problem of early differentiation of "traumatic tap" from subarachnoid hemorrhage (SAH) was studied in the rabbit by determining the changes in percentage of hemolysis and in lactate concentrations in CSF within the first twenty-four hours following induced SAH. The 0.3 to 7% hemolysis which occurred was relatively independent both of the time following SAH and of the number of red blood cells (rbc) in the cerebrospinal fluid (CSF). There was, on the other hand, a significant and time-dependent increase in CSF lactate concentration early after SAH, suggesting the potential clinical value of the detection of increased lactate with a relatively normal lactate/pyruvate ratio in hemorrhagic CSF. Until this can be evaluated in human subjects, however, determination of the rbc counts or total hemoglobin concentrations in serially collected samples of CSF remains the best clinical method.
Xenon enhanced CT for analysis of cerebral integrity, perfusion, and blood flow.
Authors: Drayer B P , Wolfson S K , Reinmuth O M , Dujovny M , Boehnke M , Cook E E
Published: June 2011

Enhancement of the brain substance for CT evaluation using inhaled Xenon is confirmed. This technique was applied to the study of the normal and the embolized adolescent baboon. Healthy cerebral tissue enhances symmetrically, while abnormal areas show significantly diminished enhancement. At maximal enhancement, an indication of gross comparative cerebral perfusion to obtained. By obtaining serial CT scans over a 10 minute time interval, the clearance rate of Xenon (cerebral blood flow) may be evaluated. Xenon-enhanced CT enables a visual and numerical analysis of both brain morphology and physiology.
Is there a real treatment for stroke? Clinical and statistical comparison of different treatments in 300 patients.
Authors: Santambrogio S , Martinotti R , Sardella F , Porro F , Randazzo A
Published: June 2011

In the absence of universally accepted criteria for the medical treatment of stroke, we made a rigorously randomized comparative study of different treatments in 300 patients. One group of patients received only a general supportive treatment designed to ensure adequate supplies of water, electrolytes and calories, plus whatever was needed to prevent infection and correct extant associated pathology. Three other groups of patients were treated in the same way but were also given, respectively, one of the following medications: Hydergine (Sandoz) (a mixture of three ergot alkaloids), dexamethasone, and mannitol. No statistically significant difference emerged among any of the treatment groups and the reference group in terms of objective therapeutic results. The authors concluded that, at least with the dosage used in this study, none of the treatments proved more useful than conventional supportive therapy in the first 10 days after a stroke.
Serum lipids, platelets, and fibrinolytic activity in cerebrovascular disease.
Authors: Bansal B C , Prakash C , Arya R K , Gulati S K , Mittal S C
Published: June 2011

Fifty patients with occlusive cerebrovascular disease (ischemic thrombotic cerebrovascular disease--ITCBVC) were studied for clinical features, angiographic findings, serum lipids, platelet functions and fibrinolytic activity. Angiograms were abnormal in 24 of 36 cases. Two-thirds of these had an abnormality of the internal carotid artery in the neck; one-third had occlusion of the middle and/or anterior cerebral arteries. A statistically significant rise of serum triglycerides, pre-beta lipoproteins, platelet adhesiveness and aggregation, and a decrease in fibrinolytic activity were noticed in these patients as compared to age and sex matched controls. The correlation coefficient did not show any intercorrelation between the platelet adhesiveness and raised lipid fractions. These factors could be responsible for the atheroma resulting in large vessel occlusion.
Cerebral blood flow autoregulation in the rat.
Authors: Hernández M J , Brennan R W , Bowman G S
Published: June 2011

Cerebral blood flow autoregulation (CBFA) to changes in perfusion pressure has not been previously reported in the rat. A modification of the Kety and Schmidt technique employing 133Xenon was used to measure cerebral blood flow (CBF) in paralyzed adult Sprague Dawley rats passively ventilated with 70% nitrous oxide and 30% oxygen. At a mean arterial blood pressure (MABP) of 121 +/- 19 mm Hg, and a mean arterial PCO2 of 36.2 +/- 2.9 mm Hg, mean CBF was 103 +/- 22 ml/min/100 gm of brain. CBF responses to hypercarbia were 4.9 ml/min/100 gm per mm Hg change in arterial PCO2. CBF was measured during steady state levels of hypo- and hypertension induced by phlebotomy, or by intravenous metaraminol, over the MABP range of 48-205 mm Hg. From a MABP of 80 to 160 mm Hg. CBF remained nearly constant, indicating the presence of CBFA. However, when MABP exceeded 160 mm Hg, CBF became pressure dependent, indicating a "breakthrough" of autoregulation in acute severe hypertension.
Cerebrovascular CO2 reactivity: role of a cholinergic mechanism modulated by anesthesia.
Authors: Scremin O U , Rubinstein E H , Sonnenschein R R
Published: June 2011

Cerebral cortical blood flow was measured in rabbits with the hydrogen clearance technique. The reactivity to CO2, tested by changing the end tidal CO2 (ETCO2) in steps from 2 to 6 volumes %, was highly dependent on the kind of anesthesia, being greatest under halothane and least under nitrous oxide. Reactivity to CO2 in halothane-anesthetized animals also depended on arterial blood pressure, being greatest when pressure was below 70 mm Hg. Intravenous atropine blocked the increase in reactivity in halothane-anesthetized animals at low blood pressures. Conversely, intravenous eserine (physostigmine) greatly increased the reactivity to CO2 in nitrous oxide-anesthetized animals. Precollicular decerebration considerably decreased CO2 reactivity of halothane-anesthetized rabbits, while partial brain stem lesions that spared midline structures had no effect on CO2 reactivity. It is concluded that a central neurogenic mechanism with a cholinergic link may be responsible, at least in part, for the cerebrovascular effect of CO2. Moreover, the cerebrovascular effects of halothane may result from stimulation of the same system.
Controlled trial of ornithine alpha ketoglutarate (OAKG) in patients with stroke.
Authors: Woollard M L , Pearson R M , Dorf G , Griffith D , James I M
Published: June 2011

A double blind controlled trial of ornithine alpha-ketoglutarate (OAKG) was carried out on 50 patients admitted to the Royal Free and Royal Northern Hospitals, London, suffering from a recent stroke. Significant improvement was found in patients treated with OAKG when examined on the fifth day of therapy as compared to their control cases. The therapy was given for 5 days. When the patients in the treated and the control groups were compared 10 days after the beginning of treatment, there were no differences between the 2 groups. Implications of these findings are discussed.
Prevention of cerebral infarction in the monkey by omental transposition to the brain.
Authors: Goldsmith H S , Duckett S , Chen W F
Published: June 2011

The intact omentum of 13 monkeys was lengthened, placed subcutaneously, and laid on the left cerebral hemisphere prior to occluding the left middle cerebral artery. Two of these 13 monkeys developed left cerebral infarct and a right hemiparesis. Nine other monkeys had their left middle cerebral artery occluded without omental protection. All of these 9 developed a left cerebral infarct and 8 of them a right hemiparesis. Intact omentum may prevent a cerebral infarction when placed on the brain prior to MCA occlusion.
Cardiac cycle-dependent alternating flow in vertebral arteries with subclavian artery stenoses.
Authors: von Reutern G M , Pourcelot L
Published: June 2011

Continuous-wave Doppler sonography is a reliable method for detecting severe subclavian stenosis and occlusion as well as subclavian steal. Intermediate stages leading to subclavian steal can also be detected. These are characterized by a cardiac-phase-dependent alternating flow direction in the vertebral artery. Some cases of proximal subclavian or proximal vertebral artery stenosis produce a systolic deceleration of flow in the vertebral artery. Stenosis and occlusion of the subclavian artery as well as stenosis of the subclavian and vertebral arteries can be distinguished. The pulse curve changes described can be reversed by a vascular by-pass. Alternating flow direction or systolic deceleration of flow in the radial artery could also be observed or induced in a iatrogenic model using Cimino's a-v fistula in the arm in patients on dialysis. The results in beginning subclavian steal situations can be applied in principle to other collateral circulations, and in particular to the hemodynamics in the region of watersheds.
Prevention of persistent cerebral smooth muscle contraction in response to whole blood.
Authors: Linder M , Alksne J F
Published: June 2011

Using an in vitro system designed to measure arterial constriction, we have demonstrated the importance of platelet function in maintaining cerebral smooth muscle contraction after whole blood injection. We tested two agents, acetyl salicylic acid (ASA) and phthalazinol, both known to interfere with platelet function. In control tests normal rabbit and monkey blood produced a reliable and persistent arterial constriction. In experimental tests blood drawn from animals premedicated with ASA and phthalazinol failed to produce a persistent contraction. These results support the hypothesis that chemicals released during platelet aggregation may be important in persistent vasospasm.
Effect of aminophylline on cerebral infarction in the Mongolian gerbil.
Authors: McGraw C P , Crowell G F , Howard G
Published: June 2011

The effects of aminophylline in Mongolian gerbils subjected to unilateral carotid ligation were studied. The drug was given in varying intraperitoneal doses at varying postoperative intervals and the animals observed for 5 days for clinical signs of stroke. Doses of 100 mg per kg caused early death and were discontinued. Doses of 50 mg per kg had no significant effect on morbidity, mortality, time until death, stroke incidence or lesion size, as compared to saline given as a control. Doses of 80 mg per kg caused a higher mortality, higher morbidity, and a shorter interval to death, but a smaller infarct. Thus, aminophylline did not have a protective effect against stroke in gerbils and was actually detrimental during the first 16 hours following the carotid ligation.
Responses of isolated dog cerebral and peripheral arteries to prostaglandins after application of aspirin and polyphloretin phosphate.
Authors: Toda N , Miyazaki M
Published: June 2011

In helically cut strips of dog cerebral, coronary, mesenteric and femoral arteries, the contractile response to prostaglandin (PG) F2alpha, and E2, relative to contractions induced by 30 mM K+, did not appreciably differ, whereas relaxations induced by PGE1 relative to those induced by 10(-4) M papaverine were significantly different; the least in cerebral arteries and the greatest in mesenteric arteries. The relaxation of human cerebral arteries in response to PGE1 was similar to that of dog cerebral arteries. Treatment for 60 min with polyphloretin phosphate (3 X 10(-5) and 10(-4) g/ml) suppressed the contractile response to PGF2alpha and E2 but did not alter the response to 25 mM K+. The relaxing effect of PGE1 was not influenced. Aspirin (5 X 10(-5) and 2 X 10(-4) M) significantly potentiated the contractile response to PGF2alpha and E2 but did not alter the relaxation induced by PGE1. In contrast, contractions induced by serotonin were attenuated. It is concluded that dog cerebral, coronary, mesenteric and femoral arteries relaxed differently in response to PGE1. It appears that arterial responses to vasoconstricting PGs, but not to the vasodilating PG, are significantly attenuated by polyphloretin phosphate and potentiated by aspirin.
A model study of why some intracranial aneurysms thrombose but others rupture.
Authors: Roach M R
Published: June 2011

A perspex model of a dog aortic trifurcation was machined to scale and perfused with steady flow from a constant pressure reservoir. The tail artery was plugged to produce a flow model of an intracranial saccular aneurysm. At all flow rates, no flow occurred beyond 2.5 tube diameters of the tail artery down-stream from the mouth of the aneurysm. This was assumed to explain why large aneurysms thrombose. Measurements of velocity fluctuations were made with a hot film anemometer and recorded on tape. Frequency analysis showed that the peak frequency was a function of flow rate, and suggested that eddies were shed from the origin of the aneurysm. This was presumed to be an artifact due to sharp entrance produced by machining the perspex. The total energy at any one point in the aneurysm was independent of the size of the aneurysm but increased with flow rate. The maximum fluctuations were comparable in the center and in the sides of the aneurysm, but were less on the top and bottom of it (assuming the central plane was in the plane of the trifurcation). This difference presumably would be less if the aneurysm were spherical rather than cylindrical.
RAGE-Dependent Activation of the Oncoprotein Pim1 Plays a Critical Role in Systemic Vascular Remodeling Processes
Authors: Meloche Jolyane , Paulin Roxane , Courboulin Audrey , Lambert Caroline , Barrier Marjorie , Bonnet Pierre , Bisserier Malik , Roy Mélanie , Sussman Mark A. , Agharazii Mohsen , Bonnet Sébastien
Published: June 2011

Objective—

Vascular remodeling diseases (VRD) are mainly characterized by inflammation and a vascular smooth muscle cells (VSMCs) proproliferative and anti-apoptotic phenotype. Recently, the activation of the advanced glycation endproducts receptor (RAGE) has been shown to promote VSMC proliferation and resistance to apoptosis in VRD in a signal transducer and activator of transcription (STAT)3-dependant manner. Interestingly, we previously described in both cancer and VRD that the sustainability of this proproliferative and antiapoptotic phenotype requires activation of the transcription factor NFAT (nuclear factor of activated T-cells). In cancer, NFAT activation is dependent of the oncoprotein provirus integration site for Moloney murine leukemia virus (Pim1), which is regulated by STAT3 and activated in VRD. Therefore, we hypothesized that RAGE/STAT3 activation in VSMC activates Pim1, promoting NFAT and thus VSMC proliferation and resistance to apoptosis.

Methods/Results—

In vitro, freshly isolated human carotid VSMCs exposed to RAGE activator Nε-(carboxymethyl)lysine (CML) for 48 hours had (1) activated STAT3 (increased P-STAT3/STAT3 ratio and P-STAT3 nuclear translocation); (2) increased STAT3-dependent Pim1 expression resulting in NFATc1 activation; and (3) increased Pim1/NFAT-dependent VSMC proliferation (PCNA, Ki67) and resistance to mitochondrial-dependent apoptosis (TMRM, Annexin V, TUNEL). Similarly to RAGE inhibition (small interfering RNA [siRNA]), Pim1, STAT3 and NFATc1 inhibition (siRNA) reversed these abnormalities in human carotid VSMC. Moreover, carotid artery VSMCs isolated from Pim1 knockout mice were resistant to CML-induced VSMC proliferation and resistance to apoptosis. In vivo, RAGE inhibition decreases STAT3/Pim1/NFAT activation, reversing vascular remodeling in the rat carotid artery-injured model.

Conclusion—

RAGE activation accounts for many features of VRD including VSMC proliferation and resistance to apoptosis by the activation of STAT3/Pim1/NFAT axis. Molecules aimed to inhibit RAGE could be of a great therapeutic interest for the treatment of VRD.