Quantitative measurement of cerebral blood flow by (99m)Tc-HMPAO SPECT in acute ischaemic stroke: usefulness in determining therapeutic options.

OBJECTIVE: Early recanalisation by thrombolysis is a conclusive therapy for acute ischaemic stroke. But this therapy may increase the risk of intracerebral haemorrhage or severe brain oedema. The purpose was to evaluate usefulness of quantitative measurement of cerebral blood flow by single photon emission computed tomography (SPECT) in predicting the risk of haemorrhage or oedema, and determining the therapeutic options in acute hemispheric ischaemic stroke. METHODS: The relation was studied retrospectively between initial regional cerebral blood flow (rCBF) quantitatively measured by technetium-99m-labelled hexamethylpropyleneamine oxime ((99m)Tc-HMPAO) SPECT and final clinical and radiological outcome in 20 patients who presented hemispheric ischaemic stroke and were treated conservatively or received early recanalisation by local intra-arterial thrombolysis. The non-invasive Patlak plot method was used for quantitative measurement of rCBF by SPECT. RESULTS: Regions where residual rCBF was preserved over 35 ml/100 g/min had a low possibility of infarction without recanalisation and regions where residual rCBF was preserved over 25 ml/100 g/min could be recovered by early recanalisation. However, regions where residual rCBF was severely decreased (< 20 ml/100 g/min) had a risk of intracerebral haemorrhage and severe oedema. CONCLUSIONS: A quantitative assessment of residual rCBF by (99m)Tc-HMPAO SPECT is useful in predicting the risk of haemorrhage or severe oedema in acute ischaemic stroke. Therapeutic options should be determined based on the results of rCBF measurement.

Crossed cerebellar hyperperfusion in symptomatic epilepsy--two case reports.

A 74-year-old female with cerebral infarction and a 78-year-old female with cerebral glioblastoma suffered complex partial seizure. Ictal perfusion single photon emission computed tomography in these patients showed the interesting phenomenon of 'crossed cerebellar hyperperfusion,' a reversed crossed cerebellar diaschisis. The mechanism is probably spread of electrical seizure through efferent projections, and may be related to the cerebellar atrophy seen in patients with long-standing partial epilepsy.

[A case of rhinocerebral mucormycosis presenting orbital apex syndrome].

A 62-year-old man with untreated diabetes complained of diplopia and headache. Neurological examination demonstrated left abducens nerve palsy. MRI showed a mass lesion in the left orbital apex. Total left ophthalmoplegia and visual loss rapidly developed in the next two weeks. A craniotomy was performed to decompress the orbital apex and remove the mass. The optic nerve was tightly encased by fibrous tissue. The pathological diagnosis was mucormycosis. Systemic administration of amphotericin B and fluconazole was started immediately. But the lesion rapidly invaded the cavernous sinus and occluded the left internal carotid artery. Finally, the patient died with intracranial extension of mucormycosis four months after the operation. Rhinocerebral mucormycosis is a rapidly progressive fatal disease. Successful treatment seems to be based on early diagnosis, control of the underlying disease, radical surgical resection, and systemic administration of amphotericin B. Mucormycosis should be considered as a differential diagnosis of orbital apex syndrome.

[Role of arachidonic acid metabolites on development of ischemic cerebral edema in rat middle cerebral artery occlusion].

The products resulting from arachidonic acid metabolism of the both cyclo-oxygenase and lipoxygenase pathways possess strong physiological activities, such as vasoconstriction and the enhancement of vascular permeability. Therefore, it is likely that these metabolites are involved in cerebral circulatory disturbance and the formation of brain edema in cerebral ischemia. It is reported that intracerebral injection of leukotriene B4, C4, and E4 increased blood-brain barrier permeability. Thus, it is suggested that leukotrienes may induce vasogenic cerebral edema. We examined role of the products resulting from arachidonic acid of the cyclo-oxygenase and lipoxygenase pathways on the formation of ischemic cerebral edema in rats with focal cerebral ischemia. Focal cerebral ischemia was induced by the occlusion of right middle cerebral artery. Acyclo-oxygenase inhibitor, indomethacin (4mg/kg), was given intravenously 30 minutes before the occlusion of the middle cerebral artery. Also, azerastine hydrochloride (8mg/kg), which has an inhibitory effect on the production and release of leukotrienes from human neutrophil as well as an antagonistic action on leukotrienes and another inhibitory effect on the production of superoxide anion, was given intravenously 5 minutes prior to occlusion. Concentrations of prostaglandin E2 (PGE2), thromboxane B2 (TxB2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and leukotriene C4 (LTC4) measured by radioimmunoassay. The percent water content of a cerebral hemisphere was determined by the wet-dry weight method. In the occluded hemisphere, PGE2, 6-keto-PGF1 alpha, TxB2 and LTC4 significantly increased at 2, 6, 12 hours respectively, following the MCA occlusion as compared to the control levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of brain tissue leukotriene in brain oedema following cerebral ischaemia: effect of a 5-lipoxygenase inhibitor, AA-861.

It has been postulated that lipoxygenase metabolites of arachidonic acid play a role in the pathogenesis of cerebral ischaemia. Severe forebrain ischaemia in rats was induced by four-vessel occlusion with mild hypotension. After 30 min of ischaemia, circulation was restored by removing the arterial clamps and increasing blood pressure to preischaemic levels. During 30 min of cerebral ischaemia, free arachidonic acid increased by approximately 8.5 times compared with the preischaemic level. This accumulation was reversed within 60 min of reperfusion. The concentration of leukotriene C4 in brain tissue increased significantly during reperfusion: treatment with a 5-lipoxygenase inhibitor, AA-861, decreased the increase of brain water content associated with reperfusion. This study demonstrated that the increased arachidonic acid resulting from cerebral ischaemia in rats is metabolized to leukotrienes via the lipoxygenase pathway once circulation is restored, and these leukotrienes may play some role in the development of postischaemic cerebral oedema.

Increased extracellular concentration of norepinephrine in the hypothalamus by sinoaortic denervation.

To determine whether baroreflex can affect the norepinephrine system in the hypothalamus, the extracellular concentration of norepinephrine were measured by the brain dialysis technique in sinoaortic denervated rats (SAD). Twenty-four hours after sinoaortic denervation, systolic blood pressure and heart rate were significantly elevated, and norepinephrine concentration in perfusate of the posterior hypothalamus was significantly higher in SAD rats than in sham-operated rats. These results suggest that baroreflex could modify the activity of noradrenergic neuron projecting to the posterior hypothalamus.

The effects of salicylate concentration on the uptake of salicylate and cefmetazole into rat isolated small intestinal epithelial cells.

The uptake of salicylate into rat isolated small intestinal epithelial cells reached an equilibrium within 15 min, but that of cefmetazole alone did not. The presence of salicylate at concentrations greater than 50 mM accelerated the uptake of cefmetazole, which reached equilibrium within 5 min. At equilibrium, the uptake clearance of salicylate (mumol (g protein)-1 M-1 initial salicylate concn) was greater than that of cefmetazole. The uptake clearance of salicylate during the first several minutes was concentration-dependent, and a 'super-uptake' clearance of salicylate, greater than equilibrium values, was observed when 100 mM salicylate was present. This indicates that some mechanism, other than a simple diffusion process, may be involved in salicylate uptake into these cells.

Protective effect of salicylate against 2,4-dinitrophenol-induced protein thiol loss in the small intestine of rats.

The effect of the content of protein thiols and non-protein thiols in the tissue of the rat small intestinal loop on the absorption of cefmetazole has been investigated. 2,4-Dinitrophenol (DNP), at a concentration of 500 microM, caused rapid protein thiol loss, followed by non-protein thiol loss, along with a decrease of cefmetazole absorption by the intestine. The coadministration of 75 mM salicylate with DNP inhibited the effect of DNP on protein thiols and cefmetazole absorption but not on non-protein thiol loss by DNP.

[Brain tissue leukotrienes in cerebral ischemia and the effect of inhibitor of SRS-A release on postischemic cerebral edema].

Arachidonic acid metabolites are postulated to play a role in the pathogenesis of cerebral ischemia. In order to test the development of lipoxygenase metabolites of arachidonic acid in cerebral ischemia, we measured free arachidonic acid and slow reacting substance of anaphylaxis (SRS-A) and leukotriene C4 in the brain tissue. Moreover, we studied the influence of inhibitor of SRS-A release on postischemic cerebral edema. Severe forebrain ischemia in rats was induced by the modification of the method described by Pulsinelli and Brierley. Both vertebral arteries were electrocauterized through the alar foramen and then bilateral common carotid arteries were clamped by aneurysmal clips and mean arterial pressure was reduced to 80-90 mmHg. EEG activity was isoelectric throughout the period of carotid clamping. After forebrain ischemia had been maintained for 30 minutes, recirculation was started by removal of the arterial clamps and by increasing blood pressure to the preischemic level. Following the desired ischemic or postischemic periods, the brains were frozen in situ with liquid nitrogen. The brains were then chiselled out during irrigation with liquid nitrogen and stored at -80 degrees C until analysis. The brain extracts were analysed by high performance liquid chromatography for free arachidonic acid, by bioassay using the ileum of guinea pig for SRS-A and by radioimmunoassay for leukotriene C4. Brain water content was calculated with dry weight method. Inhibitor of SRS-A release, tranilast, was given intraperitoneally, 100 mg/kg 30 minutes before induction of ischemia and 50 mg/kg immediately before recirculation.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of phenothiazines, disodium ethylenediaminetetraacetic acid and diethyl maleate on in vitro rat colonic transport of cefmetazole and inulin.

An in vitro rat colonic sac method developed in this study was found to be suitable for frequent collection of samples and determination of transport of compounds from serosal and mucosal medium, since the volume of both was large. Under no a treatment condition, both cefmetazole and inulin penetrated the intestinal mucosa via the paracellular route, but did so very poorly. Phenothiazines as well as disodium ethylenediaminetetraacetic acid increased the transport of cefmetazole and inulin, probably via the paracellular route, while diethyl maleate increased the transport of only cefmetazole, probably via the intracellular route. The effect of phenothiazines in increasing the clearance rate for both cefmetazole and inulin showed dependency on their initial concentrations in the mucosal medium with maximum action at a concentration of 30 microM for trifluoperazine, 20 microM for perphenazine, 75 microM for profenemine and 50 microM for propericiazine.

Effects of phenothiazines and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide on rat colonic absorption of cefmetazole.

Rat colonic absorption of cefmetazole was increased significantly by calmodulin inhibitors such as phenothiazines and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) when they were coadministered at a concentration between 1 and 100 microM. The bioavailability of cefmetazole, determined by area under the blood concentration curve method, increased 20 to 30% by the coadministration of calmodulin inhibitors. It is speculated that the enhancing action of agents on rat colonic absorption of cefmetazole takes place by a paracellular route and coadministration of sodium ion increases their actions.

Changes in intestinal mucosal permeability caused by nonprotein thiol loss in rats.

The barrier selectivity of the intestinal mucosal membrane permeability may be impaired in certain disease conditions. Membrane permeability was previously shown to be correlated with changes in nonprotein thiol in rat intestinal tissue by the everted sac method. In the present study, the mucosal effects of alloxan-induced diabetes and chronic alcohol administration to intact rats, as well as pre-treatment with diethyl maleate, ethanol, and salicylate, were investigated. In each case, a drop of mucosal nonprotein thiol was associated with an increased absorption of cefoxitin, cefmetazole, and phenol red, hydrophilic compounds that are poorly absorbed through intact membrane, and with a decreased absorption of L-phenylalanine. The effect of nonprotein thiol loss on rectal absorption of cefoxitin, cefmetazole, and phenol red was greater than that on the small intestinal absorption. The increase in phenol red absorption by diethyl maleate in the in vitro everted sac method correlated with Ca(2+) release from the intestinal mucosa, which was induced by nonprotein thiol loss. Resistance to the effect of nonprotein thiol loss on Ca(2+) homeostasis was greater in rat ileum than in rat colon (including rectum). The administration of cysteamine as an exogenous nonprotein thiol restored non-protein thiol levels in the mucosa along with the barrier function of the intestinal mucosa to the absorption of cefoxitin, cefmetazole, and phenol red. In contrast, the transport of L-phenylalanine in the small intestinal mucosa was not restored by cysteamine treatment.