Biomedical subjects

S Sadoshima

Publications and source records attributed to S Sadoshima.

At least 91 records · Page 5Linked to original sources

PubMed1991

Excitatory and inhibitory amino acid changes in ischemic brain regions in spontaneously hypertensive rats.

Excitatory (glutamate, aspartate) or inhibitory amino acids (gamma-aminobutyric acid: GABA, taurine) and glutamine contents were examined in acutely induced cerebral ischemia in spontaneously hypertensive rats. At 20 min ischemia most of these amino acids remained unchanged, but glutamine significantly decreased by 14% in the CA3 hippocampal subfield. At 60 min ischemia glutamate significantly decreased by 14% in the CA3, aspartate by 17-26% in the CA3, cingulate cortex, septum and striatum. In contrast, GABA significantly increased by 48-106% in the cortices (frontal, parietal and cingulate), striatum and nucleus accumbens, but insignificantly in hippocampal subfields. Likewise, taurine increased in the parietal cortex and nucleus accumbens. Glutamine showed heterogeneous changes (increase in the nucleus accumbens and decrease in the CA3). Amino acid levels change during ischemia, but their changes are varied in each area, implying that different reaction of amino acids may explain the selective vulnerability to cerebral ischemia.

Amino Acids↗

PubMed1991

Spontaneous recovery from non-insulin-dependent diabetes mellitus induced by neonatal streptozotocin treatment in spontaneously hypertensive rats.

We studied the long-term change in glycemic level in a model of non-insulin-dependent diabetes mellitus (NIDDM) induced by neonatal streptozotocin (STZ) treatment in spontaneously hypertensive rats (SHR). Two-day-old male SHR were intraperitoneally injected with 37.5 to 75.0 mg/kg of STZ or vehicle alone as control. According to nonfasting plasma glucose levels at 12 weeks of age, rats were divided into mild (less than 16.8 mmol/L) and severe (greater than or equal to 16.8 mmol/L) diabetes groups. In the mild diabetes group (n = 5), plasma glucose decreased significantly from 14.2 +/- 1.8 mmol/L (mean +/- SEM) at 20 weeks to 7.3 +/- 0.3 mmol/L at 52 weeks (P less than .05) with progressing age. At 52 weeks, overnight fasting plasma glucose levels were significantly lower and serum immunoreactive insulin (IRI) was higher than in controls, respectively (4.1 +/- 0.3 v 5.7 +/- 0.3 mmol/L, P less than 0.01; 625 +/- 50 v 409 +/- 50 pmol/L, P less than .05), and insulinoma was found in 60% of rats. Therefore, the recovery from hyperglycemia may be attributed to the development of insulinoma. In the severe diabetes group (n = 6), plasma glucose remained high until 28 weeks (27.2 +/- 1.5 mmol/L), but thereafter decreased with age, as it did in the mild diabetes group (13.7 +/- 3.5 mmol/L at 52 weeks, P less than .005). However, no insulinoma was found, and the mechanism for the recovery was unclear. The present study demonstrates that hyperglycemia spontaneously ameliorates in a neonatal STZ diabetes model of SHR, although this phenomenon may be strain-related.

Aging↗

PubMed1991

Evaluation of EC-IC bypass for patients with atherosclerotic occlusive cerebrovascular disease: clinical and positron emission tomographic studies.

The authors report clinical evaluations of extracranial-intracranial (EC-IC) bypass surgery for patients presenting with misery perfusion on positron emission tomography (PET) due to atherosclerotic occlusive cerebrovascular disease. Seven patients underwent PET both before and after undergoing EC-IC bypass surgery. Three of the 7 patients had transient ischaemic attacks (TIAs) and 4 had minor strokes. Five of the 7 had unilateral superficial temporal-middle cerebral artery (STA-MCA) anastomosis, one had bilateral STA-MCA anastomoses and one had STA-MCA anastomosis on one side and carotid endarterectomy on the other side. PET showed postoperative improvement in regional cerebral blood flow and metabolism in 5 of the 7 patients. In the remaining 2 patients, one showed no remarkable changes on PET and the other showed exacerbation on PET due to postoperative cerebral infarction. All three patients who had TIAs had no further TIAs after surgery. Two of the 3 patients postoperatively showed improvement in misery perfusion on PET. In the 4 patients who had minor strokes, 2 showed clinical improvements. One of the 2 showed improvement not only in motor function but also in the higher cortical functions such as verbal and performance intelligence quotients. Changes on PET correlated to the clinical improvement in 4 of 7 patients. The EC-IC bypass is therefore effective in patients with haemodynamic hypoperfusion syndromes by improving the state of low perfusion.

Adult↗

PubMed1991

Age-related vulnerability to cerebral ischemia in spontaneously hypertensive rats.

BACKGROUND AND PURPOSE: We sought to determine the effects of aging on regional cerebral blood flow and ischemic brain damage in transient cerebral ischemia in rats. METHODS: Five adult (5-6 months) and five aged (18-22 months) female spontaneously hypertensive rats were subjected to 20 minutes of bilateral carotid occlusion and 60 minutes of recirculation under amobarbital anesthesia (100 mg/kg i.p.). Regional cerebral blood flow in the hippocampus and striatum was measured using the hydrogen clearance method. Nine adult and 14 aged rats were subjected to 20 minutes of bilateral carotid occlusion or were sham-operated under ether anesthesia. Seven days after 20 minutes of cerebral ischemia, the rats' brains were perfusion fixed. Ischemic damage in the hippocampus and striatum was graded (0 [normal] to 3 [majority of neurons damaged]). RESULTS: After 20 minutes of bilateral carotid occlusion, striatal cerebral blood flow decreased to 9.1 +/- 1.5 and 3.9 +/- 2.0 ml/100 g/min in aged and adult rats, respectively, and hippocampal cerebral blood flow decreased to 8.6 +/- 2.4 and 5.7 +/- 2.4 in aged and adult rats, respectively. Although these ischemic cerebral blood flow values were not significantly different between the two age groups, scores for ischemic damage in the hippocampus CA-1 subfield and striatum were significantly higher in aged than in adult rats (p less than 0.05, Kruskal-Wallis' h test with Bonferroni correction). CONCLUSIONS: We conclude that aging may be a primary factor in the development of greater ischemic neuronal damage observed in aged hypertensive rats.

Aging↗

PubMed1991

Cromakalim dilates rat cerebral arteries in vitro.

Using an in vitro perfusion method, we examined the effects of cromakalim, a potassium channel opener, on the superior cerebellar arteries of 24 rats. Cromakalim had no effect on contractions induced by 129 mM K+ until a concentration of 10(-5) M was reached. Contractions evoked by 10(-5) M serotonin were attenuated by cromakalim in a concentration-dependent manner (p less than 0.05). The diameter of untreated superior cerebellar arteries remained almost constant with increasing perfusion pressure. However, in the presence of cromakalim vessel diameter increased with increasing perfusion pressure. At concentrations of 3 x 10(-6) M, cromakalim also inhibited basal myogenic tone and dilated unstimulated arteries (p less than 0.01). These results suggest that cromakalim is a cerebrovascular dilator acting on both receptor-mediated and myogenic contractions.

Animals↗

PubMed1991

Babinski-Nageotte syndrome on magnetic resonance imaging.

A 70-year-old woman developed left hypoglossal nerve palsy, a right hemiparesis sparing the face, and a typical left Wallenberg's syndrome. These symptoms resulted from a lesion in the left half of the medulla oblongata, suggesting Babinski-Nageotte syndrome, a rare cerebrovascular disease. This is the first case of ischemic infarction in the territory of the left vertebral artery and posterior inferior cerebellar artery demonstrated on magnetic resonance imaging. Severe bilateral lesions of the distal vertebral arteries demonstrated on digital subtraction angiography may have contributed to the development of this syndrome.

Aged↗

PubMed1991

Effect of blood glucose level in acute cerebral ischemia in spontaneously hypertensive rats--survival and brain pathology.

The present study was designed to examine the effect of blood glucose level on survival and pathologic changes of the cortical neuronal cells during and after three-hour incomplete cerebral ischemia, which was induced by bilateral carotid artery ligation in spontaneously hypertensive rats (SHRs). Blood glucose levels were varied by intraperitoneal infusion of 50% glucose (hyperglycemia) or insulin with hypertonic saline (hypoglycemia) or hypertonic saline (normoglycemia). None of the hyperglycemic or normoglycemic animals died during three-hour ischemia, whereas 45% of hypoglycemic animals died (p greater than 0.001). The survival rate for twenty-four hours after recirculation was in the following ascending order: hypoglycemia, normoglycemia, and hyperglycemia. Neither hypoglycemia nor hyperglycemia (38-392 mg/dL) in nonischemic animals developed any morphologic changes in the cerebral cortex. However, both the ischemic and recirculated brains showed various degrees of histologic changes such as shrinkage of the neuronal cells with cytoplasmic vacuoles, perineuronal edema, and swelling of neuropils. Such ischemic damage of the brain was more marked in hypoglycemic animals than in hyperglycemic or normoglycemic ones during ischemia, as well as one hour after recirculation. The results suggest that cerebral ischemia and its outcome become more deleterious in hypoglycemic than in normoglycemic and hyperglycemic states. On the other hand, hyperglycemia is not necessarily a disadvantage in acute cerebral ischemia with or without reperfusion in this model.

Animals↗

PubMed1991

[Positron emission tomography (PET) before and after treatment of hyperammonemia in a patient with decompensated liver cirrhosis].

A 56 year-old-male liver cirrhosis patient was admitted because of hepatic encephalopathy with hyperammonemia. We measured cerebral blood flow (CBF), cerebral oxygen extraction fraction (OEF) and cerebral metabolic rate for oxygen (CMRO2) by using PET before and after treatment of hyperammonemia. At the time of the first PET, serum ammonia was 152 micrograms/dl and on the second PET it was 88 micrograms/dl. The electroencephalogram and number connection test also improved on the second PET. CBF and CMRO2 were decreased by 25-42% in comparison to normal control and OEF increased 1-24% at first examination. Similar abnormal reduction of both CBF and CMRO2 and increase of OEF were seen at second examination. Reduced CBF and CMRO2 regardless of serum ammonia level suggests that heptic encephalopathy may be, at least in part, associated with pathological changes in brain tissue induced by hepatic metabolic disorder.

Ammonia↗

PubMed1991

A new ergopeptide, CBM 36-733, improves ischaemic cerebral metabolism in spontaneously hypertensive rats.

The authors have examined the protective effects of CBM 36-733 (2-methyl-alpha-ergocryptine) on experimental cerebral ischaemia in spontaneously hypertensive rats (SHR). SHR aged 6 months were divided into four groups; a vehicle-treated group, and CBM 36-733 0.01, 0.1 or 1.0 mg/kg i.v. treated groups. After anaesthesia, the bilateral common carotid artery was ligated (BCL) and supratentorial cerebral ischaemia was produced for 1 h. Cerebral blood flow to the parietal cortex was repeatedly measured by the H2 clearance technique. Brain tissue lactate, adenosine triphosphate (ATP) and pyruvate were determined by enzymatic methods. By BCL, cerebral cortical blood flow decreased to 9-19% of the resting value at 30 min and further to 5-11% at 60 min. Blood flow reduction was not altered by CBM 36-733 administration. At 1 h ischaemia, brain tissue lactate greatly increased to 27.5 +/- 2.6 (mean +/- SEM) mmol/kg in the vehicle-treated SHR, while it showed less increase, to 7.5 +/- 1.4, in the CBM 36-733 0.1 mg/kg group. Brain ATP decreased to 1.31 +/- 0.05 in vehicle-treated SHR after 1 h BCL, but it changed little, retaining almost normal levels (2.60 +/- 0.19) in rats treated with 0.1 mg/kg CBM 36-733, followed by 1.0 and 0.01 mg/kg, suggesting a beneficial effect of CBM 36-733 on the ischaemic cerebral metabolism. The present results suggest that CBM 36-733 has a protective effect on the brain against ischaemia by improving cerebral metabolism while not affecting haemodynamics.

Adenosine Triphosphate↗

PubMed1991

[A case of metoclopramide-induced neuroleptic malignant syndrome with cerebrospinal fluid lactic acidosis].

A case of metoclopramide-induced neuroleptic malignant syndrome with cerebrospinal fluid (CSF) lactic acidosis was reported. A 44-year-old Japanese woman noted tarry stool on July 2, 1988 and was treated with metoclopramide and cimetidine for nausea and vomiting. Hydroxyzine pamoate was also administered for insomnia at 3:10 am and she became comatose with muscle rigidity at 3:40-4:30 am on July 3. Tachycardia and high fever (39.5 degrees C) were evident at 8:00 am on July 4. She was transferred to the Kyushu University Hospital. On admission, serum creatine kinase was elevated to 1640 IU/1; MM fraction was 100%. She was diagnosed as malignant syndrome. Cerebrospinal fluid was normocellular with protein 38 mg/dl and glucose 122 mg/dl. Cerebrospinal fluid lactate increased markedly to 3.43 mmol/l, CSF pH was 7.264, HCO3- 14.4 mEq/l, indicating CSF metabolic acidosis. She became afebrile after the 10th hospital day, and gradually but completely recovered within a month. She was discharged on August 16, 1988. The anti-dopaminergic activity of metoclopramide was considered to be primarily responsible for the development of malignant syndrome in this case. Cerebrospinal fluid lactic acidosis seemed to reflect hyperpyrexia or malignant syndrome induced derangement of the brain metabolism.

Acidosis, Lactic↗

PubMed1990

Acute effects of antihypertensive agents on cerebral blood flow in hypertensive rats.

The acute effects of various antihypertensive agents on cerebral blood flow and mean arterial pressure (MAP) were studied in anesthetized (amobarbital 100 mg/kg) spontaneously hypertensive rats. Cerebral blood flow in the cortex and thalamus was measured by the hydrogen clearance method before and during a 60-min i.v. infusion of calcium antagonist (nifedipine), angiotensin converting enzyme inhibitor (captopril) or beta-blocker (propranolol). Nifedipine, 30 or 150 micrograms/kg per h, decreased dose dependently the MAP by 20 or 31%, and concomitantly increased cortical blood flow by 28 or 74%, and thalamic blood flow by 51 or 64%, respectively. Captopril, 10 or 100 mg/kg per h, decreased MAP by 7 or 14%, but changed cerebral blood flow minimally. In contrast, propranolol, 1.0 or 5.0 mg/kg per h, decreased MAP by 13 or 11%, with a concomitant reduction of cortical and thalamic blood flow by 20 or 15 and 33 or 37%, respectively. It is concluded that the changes in cerebral blood flow in response to hypotension are varied by antihypertensive drugs depending on the direct or indirect effect of the drugs (dilatation or constriction) on cerebral vessels. Nifedipine seems to dilate while propranolol constricts cerebral vessels.

Animals↗

PubMed1990

Ischemic flow threshold for striatal dopamine release in rats.

To determine the level of cerebral blood flow reduction which causes striatal dopamine release, extracellular dopamine and cerebral blood flow was simultaneously determined using in vivo brain dialysis and a hydrogen clearance method, respectively, in the striatum of spontaneously hypertensive rats before and during experimental cerebral ischemia. The ischemic flow threshold for neurotransmitter dopamine release was found to be 20% of the resting value or 8-10 ml/100g/min of cerebral blood flow, being similar to those for energy and membrane failures.

Animals↗

PubMed1990

Cerebral blood flow and oxygen metabolism in patients with vascular dementia of the Binswanger type.

We performed clinical and neuroradiologic studies, including positron emission tomography, in five patients with vascular dementia of the Binswanger type. The clinical features of these cases consisted of slowly progressive dementia, together with vascular risk factors such as hypertension and often a history of minor stroke, and characteristic white matter lesions on brain computed tomograms or magnetic resonance images. Digital subtraction angiography of the cervical and intracranial arteries demonstrated no occlusive lesion in any patient. Both cerebral blood flow and the cerebral metabolic rate for oxygen were markedly reduced in the white matter (54-77% of control values), and both were decreased in the parietal (73% of control), frontal (74-80%), and temporal (74-83%) cortices, where no abnormalities were detected by brain computed tomography or magnetic resonance imaging. We conclude that vascular dementia of the Binswanger type may be caused by disconnection between the cerebral cortex and subcortical structures due to ischemic damage in the white matter.

Aged↗

PubMed1990

Cerebral blood flow and metabolism in normotensive and hypertensive patients with transient neurologic deficits.

We used positron emission tomography to examine retrospectively the effects of blood pressure on regional cerebral blood flow and oxygen metabolism in seven normotensive and eight hypertensive patients with a history of transient neurologic deficits. In the hypertensive patients, a decrease in regional cerebral blood flow was closely related to blood pressure; these changes were most pronounced in the supratentorial structures, especially the striatum and thalamus. In contrast, the regional cerebral metabolic rate for oxygen was less related to blood pressure. Consequently, the regional oxygen extraction fraction was increased in the hypertensive patients, while regional cerebral blood volume and the regional cerebral blood flow volume ratio were unchanged. Multivariate regression analysis confirmed that hypertension was an independent factor affecting regional cerebral blood flow. The analysis also disclosed that age, sex, hematocrit, smoking, and PaCO2 affected regional cerebral blood flow. These findings suggest that the hemodynamic reserve in hypertensive individuals is reduced, which may predispose them to cerebral ischemia and perhaps stroke, even during small decreases in cerebral perfusion pressure.

Blood Pressure↗

PubMed1990

Primary intraventricular hemorrhage imaged by high-field magnetic resonance imaging--a case report.

Primary intraventricular hemorrhage (PIVH) imaged by magnetic resonance imaging (MRI) is reported. A fifty-seven-year-old man with long-standing hypertension suddenly developed severe headache, vomiting, and retrograde amnesia. A computed tomography scan on the same day revealed hematoma in the right posterior horn of the lateral ventricle and in the 4th ventricle. Angiography of the neck and head failed to demonstrate any vascular abnormalities. On the second day his neurological symptoms almost recovered except for the loss of the memory of the ictal day. High-field MRI on the sixteenth day demonstrated an isointense lesion surrounded by a hypointense area in the T1 weighted image or a hyperintense lesion in the T2 weighted image, suggesting subacute hematoma consistent with hypertension, just anterior to the right trigone of the lateral ventricle.

Cerebral Hemorrhage↗

PubMed1990

Hindbrain ischemia produced by bilateral vertebral artery occlusion and moderate hypotension in spontaneously hypertensive rats.

Hindbrain ischemia was induced by bilateral vertebral artery occlusion and moderate hypotension in spontaneously hypertensive rats (SHRs). Mean arterial blood pressure was lowered to 80 mmHg in SHRs and to 50 mmHg in Wistar-Kyoto rats (WKYs) by a controlled hemorrhage, and then the vertebral artery was bilaterally occluded through alar foramina of the first cervical vertebra. Following vertebral occlusion, blood flow of the cerebellum was significantly decreased to 9.4 +/- 2.0 mL/100g/min (+/- SEM) while flow of the cerebrum remained at 32.1 +/- 5.4 in SHRs. In contrast, cerebellar blood flow in WKYs was preserved at 24.2 +/- 2.9 mL/100g/min. Brain lactate, pyruvate, and adenosine triphosphate (ATP) were determined in SHRs after sixty minutes of hypotension with or without vertebral occlusion. Although infratentorial metabolites were actually unaltered in rats with hypotension alone, infratentorial lactate and lactate/pyruvate ratio significantly increased to 14.38 +/- 3.61 mmol/kg and 67.7 +/- 12.1, respectively, with a concomitant decrease in ATP in SHRs with hypotension and vertebral occlusion. Bilateral vertebral artery occlusion, together with moderate hypotension, was shown to produce a marked reduction of cerebellar blood flow and to induce ischemic metabolic changes in the infratentorial brain in SHRs.

Animals↗

PubMed1990

Suppression of the renin-angiotensin system induced by streptozotocin treatment in neonatal spontaneously hypertensive rats.

We studied whether or not neonatal streptozotocin (STZ) treatment would alter mean arterial pressure (MAP) and blood pressure regulating factors in conscious and unrestrained spontaneously hypertensive rats (SHR). Neonatal STZ administration to SHR resulted in type 2 diabetes mellitus with reduced MAP and heart rate. Plasma glucose was markedly increased in these diabetic animals and was inversely correlated with MAP. In the diabetic SHR, the hypotensive responses to captopril (SQ) or enalapril, administered intravenously, were diminished, regardless of preceding administrations of vasopressin V1-antagonist (AVPA) or hexamethonium (C6), when compared to findings in control rats. In contrast, the C6-induced hypotension was similar in rats with diabetes and control animals. AVPA led to no decrease in MAP in either group. Hypotensive responses to SQ following AVPA and C6 inversely correlated with the plasma levels of glucose in the diabetic group. The combined blockade of the renin-angiotensin system (RAS), sympathetic nervous system and vasoconstrictive action of vasopressin (AVP) abolished the differences in MAP between the groups. Pressor and bradycardic responses to intravenous noradrenaline, angiotensin II and AVP were practically identical in the diabetic and control SHR. Urinary aldosterone excretion rate was not altered by neonatal STZ treatment. In conclusion, a decrease in MAP in SHR with neonatal STZ treatment may be attributed to the suppressed pressor activity of RAS.

Angiotensin II↗

PubMed1990

Striatal glutamic acid and gamma-aminobutyric acid in transient cerebral ischemia in spontaneously hypertensive rats.

A massive striatal dopamine release (241-fold increase) was observed in a previous study during acute cerebral ischemia in rats. In this study, extracellular levels of glutamic acid (GLU), gamma-aminobutyric acid (GABA) and lactic acid were simultaneously determined using in vivo brain dialysis in the striatum of spontaneously hypertensive rats during cerebral ischemia and after recirculation. Extracellular GABA levels increased to 932 +/- 75% (mean +/- SEM) of the resting level and GLU increased to 390 +/- 63% during 20 min ischemia. Although ischemia-induced release of GLU and GABA was demonstrated in this study, the degree of increase was smaller than that of dopamine. These findings may be relevant to the pathophysiology of cerebral ischemia in the striatum.

Animals↗