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Biomedical subjects

S Sadoshima

Publications and source records attributed to S Sadoshima.

At least 37 records · Page 2Linked to original sources
PubMed1996

Mild hyperglycemia and insulin treatment in experimental cerebral ischemia in rats.

We investigated the effects of mild hyperglycemia and insulin treatment on the metabolism of the ischemic brain in spontaneously hypertensive rats with acute hyperglycemia (n = 9), acute hyperglycemia treated with insulin during ischemia (n = 10), and normoglycemia (n = 10). Cerebral blood flow was measured by the H2 clearance method. Cerebral ischemia induced by occlusion of the bilateral carotid arteries. Cerebral glycolytic metabolites were measured enzymatically. Blood glucose levels were significantly higher in hyperglycemic animals (11.8 to 13.7 mM/l) than in normoglycemic animals (6.0 mM/l). At 60 min of ischemia, the blood flow to the parietal cortex was decreased to 3% of the resting value in all groups. Blood glucose levels at 60 min of ischemia in the hyperglycemic rats were 1.9--3 times higher than the treated hyperglycemic rats and normo-glycemic rats. Glucose concentrations were significantly and positively correlated with the ATP level (p < .0001) but not with the lactate levels in the ischemic brain. Our results suggest that mild hyperglycemia may preserve glucose metabolism in the presence of ischemic insult.

Analysis of Variance↗
PubMed1996

Changes in arterioles, arteries, and local perfusion of the brain stem during hemorrhagic hypertension.

Cerebral arterioles have been regarded as the primary sites of autoregulatory responses, whereas the role of large arteries in the cerebral autoregulation is poorly understood. The goal of this study was to determine in vivo whether the basilar artery and its primary branches act as resistance vessels under hypotensive conditions by simultaneously measuring their diameters and local brain stem blood flow with laser-Doppler flowmetry. In 10 anesthetized rats, blood flow to the brain stem was well maintained during stepwise hemorrhagic hypotension when mean arterial blood pressure fell from 116 +/- 3 to 50 mmHg and decreased gradually between 50 and 30 mmHg. Diameter of the basilar artery (n = 10) and its large branches (n = 22), measured through an open cranial window, increased by 10% from the baseline value at 50 mmHg and reached their maximum at 30 mmHg (314 +/- 9 from 244 +/- 6 mum, and 149 +/- 4 from 117 +/- 3 mum, respectively). Small branches (n = 15) dilated to a larger extent compared with the larger arteries throughout hypotension and reached the maximum at 30 mmHg (69 +/- 3 from 48 +/- 2 mum). Below 30 mmHg, there was a steep fall in blood flow and reduction in diameter of all-sized arteries. Thus small vessels contribute to reductions in cerebrovascular resistance throughout the entire autoregulatory-range in the brain stem circulation. Large arteries, such as the basilar artery and its branches, also contribute to reductions in cerebrovascular resistance around the lower limits of cerebral blood flow autoregulation and may thus play a significant role in maintaining blood flow to the brain stem during severe systemic hypotension.

Animals↗
PubMed1996

Circadian blood pressure in patients in a persistent vegetative state.

We examined circadian variations in blood pressure, pulse rate, and other physiological variables, including hormone levels, in 16 patients in a persistent vegetative state (mean age -/+ SE; 66.1 -+/ 3.9 yr). Cerebrovascular accident was responsible for brain damage in 12 (75%) of the 16 patients. Blood pressure was measured for 24 h with an ambulatory blood pressure monitoring device. We monitored the temperature of the urinary bladder and measured urinary excretion of epinephrine, norepinephrine, 17-hydroxycorticosteroids, water, and sodium. When data were analyzed by analysis of variance, significant circadian changes were observed in body temperature and urinary excretion of hormones and sodium, but not in blood pressure or pulse rate. Individual analysis of rhythmicity using the cosinor method detected small but significant circadian variations in blood pressure and pulse rate in five of six patients who showed a simple organized response to noxious external stimuli. The disappearance of variation in blood pressure in patients in a vegetative state appeared to be related, in part, to the lack of response to external stimuli. Our findings suggest that the circadian variation in blood pressure may largely depend on external environmental factors.

Adult↗
PubMed1996

Distribution and physiological roles of ATP-sensitive K+ channels in the vertebrobasilar system of the rabbit.

The effect of an opener (levcromakalim) and a blocker (glibenclamide) of ATP-sensitive K+ (KATP) channels was investigated in the vertebrobasilar system of the rabbit. Arterial tension and membrane potential were measured by the isometric tension recording method and the microelectrode technique, respectively. Glibenclamide (10(-6) mol/L) depolarized the membrane and potentiated the contraction to histamine in vertebral arteries. The sensitivity to the relaxant effects of levcromakalim was in the following descending order: vertebral > proximal basilar > distal basilar > superior cerebellar arteries. Vertebral arteries were approximately 50 times more sensitive to levcromakalim than were superior cerebellar arteries. The relaxation to levcromakalim was abolished by glibenclamide (10(-6) mol/L). Glibenclamide attenuated vasorelaxation to adenosine in proximal arteries (vertebral and proximal basilar) but not in superior cerebellar arteries. Levcromakalim (7 x 10(-8) mol/L) and adenosine (10(-5) mol/L) induced glibenclamide-sensitive membrane hyperpolarization in vertebral arteries but not in distal basilar arteries. These results suggest that KATP channels contribute to the determination of resting membrane potential and resting tone in vertebral arteries. Furthermore, there is a marked heterogeneity in the sensitivity to an opener of KATP channels, and the heterogeneity has a functional link to the mechanism underlying vasorelaxation to adenosine in the vertebrobasilar system of the rabbit.

Animals↗
PubMed1996

Brain ischemia following bilateral carotid occlusion during development of hypertension in young spontaneously hypertensive rats--importance of morphologic changes of the arteries of the circle of Willis.

The present study was designed to examine the effect of morphologic changes of the arteries of the circle of Willis on cerebral blood flow (CBF) and metabolism in young spontaneously hypertensive rats (SHR). CBF in the parietal cortex was measured by the hydrogen clearance method before and during a one-hour bilateral carotid artery occlusion (BCO), and supratentorial brain metabolites were determined by standard enzymatic methods at a one-hour BCO. The internal diameters of the main arteries of the circle of Willis were estimated morphologically. With increase in age, systemic arterial pressure at rest was significantly raised, while cortical CBF tended to decrease and calculated cerebral vascular resistance increased. During BCO, CBF and supratentorial metabolism (adenosine triphosphate and lactate/pyruvate ratio) tended to be better preserved in two-month-old rats as compared with those in one- or three-month-old rats. The internal diameter of the posterior communicating artery (PcomA) was significantly smaller in the one-month-old group than in the other groups, while the diameter of the internal carotid artery was significantly smaller in rats aged three months than those in rats aged one or two months. It is indicated that cortical CBF reduction and impairment of supratentorial metabolism following occlusion of carotid arteries, at least in part, depend on the morphologic changes of the arteries of the circle of Willis associated with age and development of hypertension in young SHR.

Age Factors↗
PubMed1996

Serial changes in blood pressure and neurohormone levels after the onset of lacunar stroke.

To assess serial changes in blood pressure and its circadian variation following a lacunar stroke, the authors studied 7 patients who developed a single lacunar infarction in either the internal capsule or the corona radiata. Blood pressure and pulse rate were monitored noninvasively for twenty-four hours by an ambulatory blood pressure monitoring device in the acute, subacute, and chronic phases of the strokes. In the acute and chronic phases, the authors also measured urinary excretion of catecholamines every 6 hr, and serum cortisol concentration at 9:00, 17:00, and 21:00 hr. The patients were free from antihypertensive agents during the study. The twenty-four-hour averages of both systolic and diastolic blood pressure in the chronic phase were lower than those in the acute phase (P < 0.05). A nighttime fall in blood pressure was observed in the subacute and chronic phases (P < 0.05), but not in the acute phase. Urinary excretion of epinephrine at night in the acute phase was significantly higher than that in the chronic phase (P < 0.05). Serum levels of cortisol at 17:00 and 21:00 hr in the acute phase also exceeded those in the chronic phase (P < 0.05 and P < 0.01, respectively). The authors conclude that an increased secretion of epinephrine and cortisol might, at least in part, contribute to a high blood pressure and a lack of circadian variation in blood pressure in the acute phase of lacunar stroke.

Acute Disease↗
PubMed1996

Brain infarction caused by syphilitic aortic aneurysm. A case report.

Neurosyphilis often develops brain infarction. Recently, the authors experienced a case of brain infarction caused by syphilitic aneurysm on the thoracic aorta, and its clinical significance is reported. A seventy-eight-year-old woman with strongly positive serologic tests for syphilis suddenly developed global aphasia and right hemiplegia. Brain computed tomography (CT) showed a large brain infarction in the left middle cerebral artery territory. A huge aneurysm of the ascending aorta eroded the sternum and the second and third ribs. The left common carotid artery was completely compressed by the aneurysm, and blood flow was not demonstrated on enhanced CT. A cerebrospinal fluid examination revealed normal cell counts, and the titer of a syphilis test was very low. She did not have any arrhythmia, ischemic heart disease, or valvular heart disease as an embolic source. Brain infarction may be developed by pressure of an aortic aneurysm on the left common carotid artery. They recommend consideration of syphilis as an etiology of brain infarction when luetic patients are seen in old age.

Aged↗
PubMed1996

Risk factors for brain infarction in patients with Cushing's disease. Case reports.

Two women aged 51 and 52 years old, respectively, developed a brain infarction before and after undergoing treatment for Cushing's disease. A biochemical remission was obtained more than ten years after the onset of signs or symptoms of Cushing's disease. The arteriosclerotic changes of the cerebral vessels progressed even during replacement therapy for posttreatment hypopituitarism after they underwent either ablative surgery or radiotherapy. One patient, who showed the signs of Nelson's syndrome, demonstrated severe progressive cerebrovascular sclerotic changes, especially around the irradiated site. It is thus suggested that hypercortisolemia, external pituitary irradiation, and posttreatment hypopituitarism may be risk factors for brain infarction. The early diagnosis and adequate treatment are therefore important to prevent cerebrovascular complications in patients with Cushing's disease.

Cerebral Infarction↗
PubMed1996

[Recurrent aseptic meningitis caused by rupture of a pineal cyst].

A 40-year-old woman experienced three attacks of aseptic meningitis in 19 months. Each attack was characterized by sudden onset of meningeal irritation followed by spontaneous remission in several days. The patient was free of neurological symptoms between the attacks. In the acute phase of each attack, her cerebrospinal fluid (CSF) showed mononuclear pleocytosis and increased protein concentration. Epithelial cell clusters in the CSF were evident during the third episode. No pathogenic microorganisms were identified in CSF or blood cultures. Brain imaging revealed a pineal cyst, 1 cm in diameter, and we suspected that the epithelial cell clusters represented the ruptured cystic wall and that the recurrent aseptic meningitis was triggered by spontaneous rupture of the cyst. Recently several new etiologies for the benign recurrent aseptic meningitis (Mollaret's meningitis) have been reported, but its existence as a clinical entity is still in dispute. Our case appears to support "spontaneous rupture of central nervous system epidermoid cysts" as one of the etiologies of recurrent aseptic meningitis.

Adult↗
PubMed1995

The alpha 1-adrenoceptor antagonist, doxazosin, modulates the lower limit of autoregulation of cerebral blood flow during hemorrhagic hypotension in anesthetized hypertensive rats.

The objective of the present study was to examine the effects of administration of an alpha 1-adrenoceptor antagonist, doxazosin, for 7 days on cerebral blood flow and the autoregulatory response to hypotension in anesthetized spontaneously hypertensive rats. We determined the cerebral blood flow at rest and during hemorrhagic hypotension in 14 rats of each group using laser-Doppler flowmetry, and at the same time, the absolute baseline cerebral blood flow values at the parietal cortex were also quantified in some of the rats with the hydrogen clearance method. Baseline mean arterial pressure was significantly lowered, by 41 mm Hg, in the doxazosin-treated group, while the baseline cerebral blood flow was 31 +/- 4 ml/100 g/min(mean +/- S.D.) which was almost the same as the 32 +/- 5 ml/100 G/min in the control group. The lower limits of cerebral blood flow autoregulation were 139 +/- 9 mm Hg in the control group and 96 +/- 12 mm Hg in the treated group; the difference was significant (P < 0.001). The present results demonstrated that the lower limit of cerebral blood flow autoregulation shifts to a lower level after chronic treatment with doxazosin, an effect which is favorable for the maintenance of cerebral blood flow under hypotensive conditions.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1995

L-arginine ameliorates cerebral blood flow and metabolism and decreases infarct volume in rats with cerebral ischemia.

Effects of L-arginine, 300 mg/kg, i.p., on the regional cerebral blood flow (rCBF), brain metabolism, and infarct volume were examined in spontaneously hypertensive rats subjected to occlusion of both left middle cerebral artery and left common carotid artery. Rats treated with L-arginine had higher rCBF, determined by hydrogen clearance method, in the ischemic core (7 +/- 1 ml/100 g/min, mean +/- S.E.M.) and penumbral regions (16 +/- 2) than did rats treated with saline (5 +/- 0 and 7 +/- 1, respectively). Simultaneously, L-arginine attenuated metabolic derangement in the ischemic tissue at 60 min, i.e. well maintained adenosine triphosphate (ATP) in ischemic region (1.29 +/- 0.07 mmol/kg in L-arginine group vs. 1.05 +/- 0.06 in saline group), and also close to normal levels in ATP (2.61 +/- 0.02 mmol/kg vs. 2.45 +/- 0.05), glucose (2.29 +/- 0.12 mmol/kg vs. 1.80 +/- 0.17) and lactate (1.63 +/- 0.10 mmol/kg vs. 2.24 +/- 0.21) in periischemic region. In another experiment, the effects of L-arginine on rCBF in the subcortical regions and on infarct volume were evaluated. L-arginine, compared with saline, increased rCBF by 8 ml/100 g/min in the ischemic side and reduced infarct volume by 29% at 24 h of ischemia. These findings support that L-arginine may be potentially useful for the treatment of acute cerebral ischemia.

Animals↗
PubMed1995

Isradipine, a calcium channel blocker, attenuates the ischemia-induced release of dopamine but not glutamate in rats.

This study was designed to investigate the role of the L-type voltage sensitive calcium channel blocker, isradipine, in the ischemia-induced release of neurotransmitters. Male spontaneously hypertensive rats were subjected to cerebral ischemia for 60 min by bilateral carotid artery occlusion, and recirculated for 120 min. Isradipine (0.25 mg/kg n = 6) or vehicle (n = 6) was administered subcutaneously at 20 min before ischemia. In the striatum, cerebral blood flow was determined by the hydrogen clearance method and concentrations of extracellular dopamine and glutamate were measured by in vivo brain dialysis technique. Extracellular dopamine in the vehicle-treated group increased by 180-fold from the basal level, and glutamate by 24-fold during cerebral ischemia. Isradipine significantly attenuated the ischemic release of dopamine to 33-34% (P < 0.05) of the vehicle group, while it did not affect glutamate release. It is suggested that the release mechanism of dopamine and glutamate during cerebral ischemia may be different, especially in the dependence on the L-type calcium channels.

Animals↗
PubMed1995

Citalopram, a serotonin reuptake inhibitor, and brain ischemia in SHR.

The effects of citalopram, a serotonin (5-HT) reuptake inhibitor, on cerebral blood flow (CBF) and concentration of 5-HT and its metabolite were investigated in spontaneously hypertensives rats (SHR) subjected to forebrain ischemia. Cerebral ischemia was induced by bilateral carotid artery occlusion. The concentration of the 5-HT metabolite, 5-hydroxyindoleacetic acid (5-HIAA), increased during cerebral ischemia in most brain regions examined, while that of 5-HT increased only in the frontal cortex and the striatum. Citalopram restored the 5-HIAA concentrations to the preischemic normal levels. Citalopram had no effect on the cortical CBF, before and during ischemia. These results suggest that citalopram attenuates ischemia-induced hypermetabolism of 5-HT in the brain. The effects of citalopram are independent of hemodynamic factors including cerebral blood flow, and are likely to be mediated by a direct inhibition of the neuronal 5-HT reuptake system.

Animals↗
PubMed1995

Inhibition of acetylcholinesterase modulates the autoregulation of cerebral blood flow and attenuates ischemic brain metabolism in hypertensive rats.

We designed the present study to examine whether or not the inhibition of acetylcholinesterase modulates cerebral microcirculation in hypotension and improves brain metabolism in ischemia induced by bilateral carotid artery occlusion in hypertensive rats. Blood flow to the parietal cortex was determined by the H2 clearance method. Lactate, pyruvate, and ATP were estimated by enzymatic methods. Acetylcholinesterase inhibitor (AChEI, ENA-713), at 0.05, 0.1, or 0.5 mg/kg, was intravenously injected 10 min before either hemorrhagic hypotension or cerebral ischemia. The levels of acetylcholine in the control were 29.3 +/- 8.1 (mean +/- SD) and 39.5 +/- 8.1 pmol/mg in the cortex and hippocampus, respectively, and they were significantly decreased by 15-19% after 60 min of ischemia in the vehicle-treated rats. AChEI preserved the levels to 93-98% of the control (p < 0.05 versus vehicle). The lower limit of autoregulation was 74 +/- 9% of the resting values. The administration of AChEI helped preserve blood flow and lowered the limit to 64 +/- 6% (p < 0.05 versus control). After 60 min of ischemia, lactate increased 6.5-fold and ATP decreased to 64% of the control value. The administration of AChEI dose-dependently reduced the lactate level 1.9- to 3.9-fold and well preserved the ATP level to 94-97% of the control. The inhibition of acetylcholinesterase activity may preserve cerebral autoregulation during hypotension and protect cerebral metabolism against ischemic insult.

Acetylcholine↗
PubMed1995

Ischemia-induced release of amino acids in the hippocampus of aged hypertensive rats.

We have recently demonstrated the age-related vulnerability of hippocampal neurons to 20-min forebrain ischemia in spontaneously hypertensive rats (SHR). In the present study, we investigated the effect of aging on the release of amino acids in the hippocampus during transient cerebral ischemia for 20 min. Concentrations of extracellular amino acids and cerebral blood flow in the CA1 subfield were examined by an in vivo brain dialysis technique and a hydrogen clearance method, respectively, in adult (5-7 month) and aged (19-23 month) female SHR. During cerebral ischemia by bilateral carotid artery occlusion, cerebral blood flow to the hippocampus decreased to 20% of the resting values in both groups. After recirculation, both groups showed delayed hypoperfusion which was more prominent in the aged SHR. In the adult rats, concentrations of both aspartate and glutamate increased to approximately 8-fold of the resting values during ischemia. The elevation of these excitatory amino acids in the adult SHR was not significantly different from that in the aged rats. In contrast, the concentration of taurine increased 26-fold in the adult SHR but only 16-fold in the aged rats. Changes in other amino acids were not different between the two groups. These results indicate that an imbalance of excitatory and inhibitory amino acids, e.g., smaller release of taurine, during ischemia may, at least in part, contribute to the age-related vulnerability of hippocampal neurons to transient cerebral ischemia in SHR.

Aging↗
PubMed1995

Can transcranial Doppler really detect reduced cerebral perfusion states?

BACKGROUND AND PURPOSE: This study was designed to determine whether transcranial Doppler ultrasonography (TCD) may detect reduced perfusion states of the brain in patients with hypertension or diabetes mellitus with suspected cerebral atherosclerosis and arteriolosclerosis. METHODS: We determined blood flow velocity with TCD in the middle cerebral artery and cerebrovascular vasodilator responses to carbon dioxide in 22 patients with or without carotid artery occlusive disease and minor stroke; we compared the results with the measurements of cerebral blood flow and oxygen metabolism by positron emission tomography (PET). RESULTS: Blood flow velocity measured by TCD correlated with ipsilateral cerebral blood flow measured by PET in frontal, temporal, and striatal regions and throughout the entire hemisphere (P < .05 to P < .005). Relative changes in blood flow velocity and calculated cerebrovascular resistance tested by carbon dioxide inhalation both correlated closely with regional mean transit time (calculated as the ratio of cerebral blood volume divided by cerebral blood flow) in frontal, striatal, temporal, parietal, and occipital regions and also in the entire hemisphere (P < .05 to P < .0001). TCD variables did not correlate with hemispheric measurements of oxygen metabolism by PET. CONCLUSIONS: Although TCD is not useful in assessing impairments of cerebral metabolism, it is useful for detecting abnormalities of cerebral hemodynamics among patients with risk factors for cerebrovascular disease.

Adult↗
PubMed1995

Impact of thalamic hematoma on six-month mortality and motor and cognitive functional outcome.

BACKGROUND AND PURPOSE: In this study we examined the functional outcome of thalamic hemorrhage after 6 months as it related to neurological and computed tomographic (CT) findings in 104 patients. METHODS: Level of consciousness was determined on admission. Extension and volume of hematoma were examined with CT within 3 days. After 6 months, motor function was evaluated using hemiplegic staging by the scale of Brunnström, and cognition was assessed by the Hasegawa dementia rating scale administered in Japanese. RESULTS: Twelve patients (12%) died from stroke after 6 +/- 6 days (mean +/- SD), which correlated with volume of hematomas (P < .001), levels of consciousness (P < .005), and miosis (P < .01). Six patients (6%) died from systemic complications after 23 +/- 18 days, which correlated with age (P < .05). Initially, 88 patients (85%) had hemiparesis; which persisted in 78 (75%) patients (18 deaths and 60 survivors). After 6 months, the Brunnström scale scores were lower in patients with hematomas extending to the internal capsule (P < .01) than in those with hematomas localized within the thalamus, and scores were lowest in patients with hematomas extending to the midbrain or putamen (P < .01). Motor function was well correlated with the extension and volume of hematomas (P < .001) and with the consciousness level (P < .001). Activities of daily living were correlated with hematoma extension and advanced age. Cognitive impairment was correlated with disturbance of consciousness (P < .01) and ventricular extension of the hematoma (P < .05) in 80 nonaphasic patients. CONCLUSIONS: The extension and volume of hematomas, indicating direct cerebral damage, are useful indicators of mortality from thalamic hemorrhage, motor functional outcome, and level of activities of daily living after 6 months. The disturbance of consciousness and ventricular extension of the hematoma, suggesting diffuse brain damage, could be predictors of cognitive function.

Activities of Daily Living↗