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Biomedical subjects

F Gotoh

Publications and source records attributed to F Gotoh.

At least 37 records · Page 2Linked to original sources

Stroke in systemic lupus erythematosus.

We investigated the clinical and pathologic characteristics of stroke in 234 patients with systemic lupus erythematosus. Thirteen patients (5.6%) developed cerebrovascular disease. Cerebral infarction was noted in eight, cerebral hemorrhage in two, and subarachnoid hemorrhage in three. In seven (54%) of these 13 patients, stroke occurred less than or equal to 5 years after systemic lupus erythematosus was diagnosed. Among the predisposing risk factors for stroke, hypertension was the most important. Lupus anticoagulant was detected in three (38%) and anticardiolipin antibody in three (43% of seven investigated) of the patients with infarction. Evaluation of the clinical manifestations and autoantibodies indicated that renal involvement and high titers of anti-deoxyribonucleic acid antibody were more frequent in the stroke group than in the non-stroke group. Autopsy studies on six of the patients with stroke revealed small infarcts and hemorrhages in all, but in no case was true angiitis observed. Libman-Sacks endocarditis was found in two of the three patients with infarction. In conclusion, the important contributory factor to the development of stroke in patients with systemic lupus erythematosus is considered to be hypertension mediated by immunologic abnormalities. Antiphospholipid antibodies and Libman-Sacks endocarditis are closely associated with occlusive cerebrovascular disease.

Adolescent↗

Effects of nilvadipine on cerebral circulation and metabolism in cats.

Effects of nilvadipine (FK 235) on cerebral circulation and metabolism were examined measuring cerebral oxygen and carbon dioxide tension (BrPO2, BrPCO2), pH (BrpH) and mean arterial blood pressure (MABP) in cats. Nilvadipine (10 micrograms/kg) infused into the carotid artery produced a remarkable and long-lasting decrease in systemic blood pressure, whereas BrPO2 and BrPCO2 increased significantly. The present study suggests that in addition to the improvement of the cerebral circulation, nilvadipine may augment cerebral metabolism.

Animals↗

Effects of 3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine on cerebral circulation and metabolism in cats.

Effects of 3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine (KC-404) on cerebral circulation and metabolism were examined measuring cerebral oxygen and carbon dioxide tension (BrPO2, BrPCO2) and mean arterial blood pressure (MABP) in cats. KC-404 (100 micrograms/kg) infused into the carotid artery produced no significant changes in BrPO2, BrPCO2 and MABP. 300 micrograms/kg of KC-404 infused into the femoral vein produced significant decrease in MABP, whereas BrPO2 remained constant. It is suggested that a large dose of KC-404 causes preferential cerebral vasodilation and maintenance of constant blood flow despite marked reduction in MABP.

Animals↗

Effect of glycerol on the hemodynamics of acutely induced ischemic area in the cerebral cortex of cats.

The effect of glycerol on the hemodynamics of ischemic areas of the brain was examined. Employing a photoelectric apparatus, the CBV (vol%), mean transit time of blood(s), and CBF (ml/100 g/min) in the cortex of the left ectosylvian gyrus were determined in 16 anesthetized cats before, at 1 hr, and at 2 hr after left MCA occlusion. In 10 cats, 10% glycerol in 5% fructose saline was intravenously administered at a speed of 5 ml/kg/hr at 1 hr after MCA occlusion. The other animals served as the control. In the group given glycerol, the relation between the values of CBF at 1 hr after MCA occlusion (X) and those at 2 hr after MCA occlusion (Y) was curvilinear and could be expressed by the regression curve, Y = 0.04X2 - 0.26X + 7.68 (R2 = 0.86). In the control group without glycerol, however, a linear relation expressed by the equation, Y = 0.76X + 5.96 (R2 = 0.94), was obtained. Comparison between the two relations indicated that glycerol improved the hemodynamics in the mild ischemic area with a relatively higher CBF. Severely ischemic areas showed no improvement.

Animals↗

Sweating function and retinal vasomotor reactivity in migraine.

Sweating function and retinal arterial reactivity in patients with migraine were examined during headache-free intervals. The sweat glands were stimulated by intradermal injection of pilocarpine hydrochloride, and molds of sweat droplets were obtained using Silastic. The number of droplets in classic migraine was significantly lower than that in the controls. The retinal arterial response to changes in perfusion pressure was measured by means of a fundus camera. The retinal vasomotor index (-change in retinal arterial diameter (%)/change in effective MABP (mmHg)) was significantly lower in classic and in common migraine than in controls. The above results suggest that sweating function and retinal arterial reactivity are impaired in patients with migraine and that the impairment may play an important role in the pathophysiology of migraine attacks.

Adolescent↗

Effects of a selective inhibitor of cyclic AMP phosphodiesterase on the pial microcirculation in feline cerebral ischemia.

We evaluated the effects of cilostazol, a selective inhibitor of cyclic adenosine monophosphate phosphodiesterase, on the pial vessels of adult cats subjected to endothelial damage followed by middle cerebral artery occlusion. Six cats were treated with cilostazol and four with 30% N,N-dimethylformamide in 70% saline (solvent). The brain surface was irradiated with ultraviolet rays through a cranial window for 3 minutes to selectively damage the endothelium of the pial vessels in both groups. Beginning 32 minutes after termination of the irradiation, the middle cerebral artery was occluded for 30 minutes. Thirty minutes before occlusion, intravenous infusion of 30 micrograms/kg/min cilostazol or 0.1 ml/kg/min solvent was begun and continued until the end of the study. Before occlusion, the infusion of cilostazol induced a significant (p less than 0.05) dilatation while the infusion of solvent produced no significant changes in the diameter of the pial arteries. The pial veins of solvent-treated cats showed significant (p less than 0.05) constriction during occlusion, whereas cilostazol-treated cats exhibited only mild constriction of the pial veins. The formation of platelet thrombi after occlusion was significantly (p less than 0.05) inhibited in the pial veins of cilostazol-treated compared with solvent-treated cats. Similarly, the microcirculation of the pial veins was effectively restored after reopening of the middle cerebral artery in cilostazol-treated compared with solvent-treated cats. Our data suggest that cilostazol is an effective antithrombotic agent as well as a potent vasodilator acting on vascular smooth muscle.

Animals↗

Enhanced erythrocyte aggregability in occlusive cerebrovascular disease.

We measured the rate of erythrocyte aggregation using our whole-blood aggregometer in 80 patients with occlusive cerebrovascular disease during the acute and chronic phases. We compared the data with values for 38 age-matched healthy controls. Mean +/- SD erythrocyte aggregability of the patients during both the acute phase (0.145 +/- 0.21/sec, n = 35) and the chronic phase (0.139 +/- 0.21/sec, n = 45) was higher than that in the controls (0.123 +/- 0.21/sec, n = 38; p less than 0.01). Erythrocyte aggregability was positively correlated with the plasma concentration of globulin and fibrinogen and inversely correlated with the albumin:globulin ratio. However, these correlations did not necessarily exclude the possibility that some unknown substance(s) released from ischemic tissue might enhance erythrocyte aggregability.

Acute Disease↗

Effects of 2-nitratopropyl 3-nitratopropyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate on cerebral circulation and metabolism in cats.

Effects of CD-349 (2-nitratopropyl 3-nitratopropyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate) on cerebral circulation and metabolism were examined measuring cerebral oxygen and carbon dioxide tension (BrPO2, BrPCO2), pH (BrpH) and mean arterial blood pressure (MABP) in cats. CD-349 of 10 micrograms/kg infused into the carotid artery produced a remarkable and long-lasting decrease in systemic blood pressure, whereas BrPO2, BrPCO2 and BrpH did not change significantly. The previous studies have already demonstrated that CD-349 increases cerebral blood flow (CBF). In addition to the improvement of the cerebral circulation, the present study suggests that C-349 may augment cerebral metabolism.

Animals↗

Colloid osmotic pressure of cat brain homogenate separated from autogenous CSF by a copper ferrocyanide membrane.

The colloid osmotic pressure (oncotic pressure) of cat brain homogenate against cerebrospinal fluid (CSF) was determined using an electronic osmometer with a rigid selectively permeable copper ferrocyanide membrane. First, the basic characteristics of the membrane were examined. The relative value of the reflexion coefficient (sigma) for polyethylene glycol (PEG) became rather stable above a molecular weight of 6000 Da, below which sigma declined. The osmometer showed a linear response to sucrose concentration, whereas it revealed a non-idealistic change with respect to concentration of high molecules (PEG). The temperature effect on sigma for albumin solution was found to be large. The membrane could thus be used for measuring the relative value of the colloid osmotic pressure of protein solutions without dilution and at the same temperature as the calibrating solution. Samples of CSF and brain cortex were freshly obtained from 5 cats. The cortex was immediately homogenized and the colloid osmotic pressure of the homogenate against the CSF was measured at room temperature within 3 min after cortex removal. The mean value was 213 +/- 11 (S.D.) mm Hg with the osmometer calibrated with respect to the colloid osmotic pressure of autogenous plasma.

Animals↗

Autoradiographic analysis of second-messenger systems in the gerbil brain.

Quantitative in-vitro autoradiographic study was performed to localize two prominent second-messenger systems (the adenylate cyclase and phosphoinositide systems) in the normal gerbil brain. [3H] Forskolin and [3H] phorbol 12, 13-dibutyrate (PDBu) were used to identify the regional distribution of adenylate cyclase and protein kinase C, respectively. The localization of the forskolin binding was not uniform, being particularly concentrated in the striatum, the accumbens nucleus, the olfactory tubercle, the substantia nigra, the CA3 region of the hippocampus and the molecular layer of the cerebellum. On the other hand, the PDBu binding was rather uniform, although the superficial layer of the cerebral neocortices, the strata oriens of the CA1 region of the hippocampus and the molecular layer of the cerebellum showed relatively dense binding. Quantitative autoradiography of the second-messenger systems in the brain is expected to provide important information concerning the role of neurotransmitters in the pathophysiology of various conditions.

Animals↗

Comparison between the photoelectric method and H2 clearance method for measuring cerebrocortical blood flow in cats.

The photoelectric method using carbon black as a nondiffusible tracer of blood was compared with the hydrogen clearance (H2) method in nine anesthetized cats. A photoelectric apparatus and H2 electrode were applied to a small region of the cerebral cortex (left ectosylvian gyrus) for simultaneous measurement of the regional CBF. The values of CBF(H2) and CBF(photoelectric) were 50.7 +/- 19.2 and 52.1 +/- 14.5 ml.100 g-1.min-1, respectively. CBF(H2) and CBF(photoelectric) were found to correlate well (r = 0.588, p less than 0.01) when changes in CBF were induced by CO2 inhalation, exsanguination, hyperventilation, and occlusion of the middle cerebral artery. The correlation between CBF(H2) and CBF(photoelectric) was much better in the case of intraindividual comparisons (r = 0.957, p less than 0.01). In addition to its merits in common with the H2 clearance method, such as handiness, low cost, and strict regionality, the photoelectric method displayed the following advantages: time-to-time measurements of CBF (less than 20 s), immediate display of the microcirculatory flow pattern, and simultaneous monitoring of cerebral blood volume. However, measurements from deep structures of the brain are better performed by the H2 method despite the disadvantage of the use of a potentially explosive gas.

Animals↗

Stable prostacyclin analogue preventing microcirculatory derangement in experimental cerebral ischemia in cats.

We evaluated the effect of a stable synthetic prostacyclin analogue, TRK-100, on the microcirculatory derangement occurring in feline pial vessels with endothelial damage after middle cerebral artery occlusion. Fifteen adult cats were divided into an untreated group (Group 1, n = 8) and a treated group (Group 2, n = 7). Thirty minutes after 10 minutes of ultraviolet irradiation, which selectively damaged endothelium in the pial vessels, the middle cerebral artery was occluded in both groups and maintained for 30 minutes. In Group 2, 50 ng/kg/min TRK-100 was continuously infused intravenously following ultraviolet irradiation. In both the pial arteries and veins, platelet aggregate adhesion to the endothelium with subsequent thrombus formation was significantly (p less than 0.01 and p less than 0.05, respectively) inhibited during middle cerebral artery occlusion in Group 2 compared with Group 1. Similarly, blood flow stasis in the pial veins was effectively prevented in Group 2 during occlusion. Furthermore, the pial artery diameter returned to the control level during the late period of occlusion, whereas in Group 1 the pial artery remained constricted. Our data suggest that TRK-100 can prevent microcirculatory derangement in the acute stage of ischemic stroke.

Animals↗

Are blood platelets involved in the pathogenesis of ischemic brain edema in gerbils?

Edema formation following severe permanent or temporary cerebral ischemia in gerbils with an artificially reduced platelet count was investigated. Acute focal cerebral ischemia was produced by extracranial carotid ligation, and the local cerebral blood flow was estimated using the hydrogen clearance method. Brain tissue water and sodium and potassium contents were taken as indexes of brain edema. The platelet count was reduced in some gerbils by intravenous injection of neuraminidase. After 60 minutes of ischemia, a marked increase in tissue water and sodium contents accompanied by a decrease in potassium content was observed in untreated gerbils. However, gerbils with a reduced platelet count revealed similar but significantly smaller changes in all the measured parameters. Restoration of blood flow after 60 minutes of ischemia resulted in further accumulation of water and sodium and in depletion of potassium in both groups. These changes were significantly smaller in the gerbils with a reduced platelet count. It is concluded that platelets, activated by cerebral ischemia, may be involved in the development of ischemic brain edema in gerbils.

Animals↗

Bilateral hemispheric reduction of cerebral blood volume and blood flow immediately after experimental cerebral hemorrhage in cats.

Acute cerebral circulatory changes following experimental cerebral hemorrhage were investigated in eight cats. The cerebral hemorrhage was produced in the right basal ganglia by introducing arterial blood via a thin catheter, using the systemic arterial blood pressure of the cat as a driving force. Local cerebral blood volume was measured continuously in the bilateral parietotemporal cortexes employing photoelectric apparatuses. Carbon black dilution curves were recorded from the regions, and the mean transit time of blood was calculated. Local cerebral blood flow was estimated from mean transit time and cerebral blood volume. Intracranial pressure was monitored continuously in the right parietal epidural space. Five minutes after cerebral hemorrhage, intracranial pressure increased by 24.0 +/- 6.1 mm Hg, while mean arterial blood pressure increased by only 2.9 +/- 2.0 mm Hg. Cerebral blood volume decreased by 1.60 +/- 0.24 vol% in the hemorrhagic and 1.14 +/- 0.30 vol% in the nonhemorrhagic hemisphere. Cerebral blood flow decreased by 30.0 +/- 4.5 ml/100 g brain/min in the hemorrhagic (initially 64.5 +/- 13.6) and by 30.3 +/- 7.5 ml/100 g brain/min in the nonhemorrhagic (initially 60.9 +/- 6.9) hemisphere. Increased intracranial pressure appeared to be the main cause of the observed cerebral blood volume/flow reduction shortly after experimental hemorrhage in the basal ganglia. Several other factors and mechanisms involved are discussed.

Animals↗