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Biomedical subjects

S Sadoshima

Publications and source records attributed to S Sadoshima.

At least 19 recordsLinked to original sources
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↗
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↗
PubMed1995

Brain infarction developed in hypertensive and normotensive patients during hospitalization--hemodynamic factors.

To determine the effects of changes in blood pressure (BP) on the development of ischemic stroke, 17 patients who developed acute brain infarction during hospitalization were analyzed in relation to the vascular risk factors such as hypertension, previous stroke, diabetes mellitus, and hyperlipidemia. Their BPs were retrospectively referred to the onset of stroke. The average values of mean arterial blood pressure (MABP) on admission were 137 mmHg in hypertensive patients (HT; n = 9) and 101 mmHg in normotensives (NT; n = 8). HT patients received antihypertensive treatment after admission and MABP decreased by 22 mmHg (14%) prior to the ictus (three to sixty-five days after admission). MABP in NT patients remained constant before the attack (-1.4 mmHg, four to one hundred ten days after admission). Similarly, MABP decreased by 17 mmHg (four to ninety-three days) before the ictus in patients with previous stroke (n = 9), whereas it changed only a little in patients without history of stroke (n = 8). BP in each group elevated immediately after the stroke and gradually decreased to 90% of the resting level after two weeks. An excessive reduction of BP may induce brain infarction in HT or chronic stroke patients or cause it to recur.

Acute Disease↗
PubMed1995

Cerebral blood flow and metabolism in hypertensive patients with cerebral infarction.

The authors investigated, by positron emission tomography, the effect of long-standing hypertension on cerebral blood flow (CBF) and oxygen metabolism in patients with chronic atherothrombotic brain infarction. In the nonbrain infarct (non-BI) group (n = 13, mean age: sixty-two years), the regional CBF (rCBF) was decreased significantly with a rise in the mean arterial blood pressure (MABP) in the cerebral cortexes (r = -0.575) and the deep gray matter (r = -0.451), whereas the regional cerebral metabolic rate for oxygen (rCMRO2) remained unchanged. In the brain infarct (BI) group (n = 22, mean age: fifty-eight years), however, the rCBF as well as the rCMRO2 were reduced even in the normotensive patients and thus did not correlate with the MABP. These results suggest that long-standing hypertension per se causes a reduction in the rCBF but not in the oxygen metabolism with a compensatory increase in the oxygen extraction fraction. On the other hand, patients with brain infarction, even normotensives, show a diffuse decrease in cerebral circulation and metabolism, which is probably due to the more severe sclerotic changes that take place in the cerebral vessels.

Blood Pressure↗
PubMed1995

[Urinary incontinence in elderly patients in the chronic stage of stroke].

One hundred and six elderly patients with chronic stroke who were admitted to Seiai Rehabilitation Hospital were studied regarding urinary incontinence. The average age of the subjects was 74 +/- 8 years old, ranging from 60 to 94 years. Seventy three of the 106 patients (69%) had urinary incontinence which was found in 72% of brain infarction, 61% of brain hemorrhage and 67% of subarachnoid hemorrhage. The prevalence of urinary incontinence in cases of brain stem, thalamic, and putaminal hemorrhage was 80%, 67% and 46%, while that in cases of cortical infarction and infarct of perforating arteries was 84% and 68%, respectively. The rate of urinary incontinence was significantly higher in those aged 75 years or over (p < 0.05), those with poor activities of daily living (ADL, p < 0.005), or with dementia (p < 0.001). Dementia was a complicating factor more frequently in aged patients (p < 0.05) and in those with poor ADL (p < 0.001), although no correlation was seen between age and ADL (p = 0.08). These results indicated the high prevalence of urinary incontinence in elderly inpatients with chronic stroke, which is significantly related to impairment of mental and physical activities.

Activities of Daily Living↗
PubMed1995

[A diabetic patient with bilateral carotid stenosis who developed neovascular glaucoma following cataract surgery].

A 67-year-old diabetic man suffered from right neovascular glaucoma following the ipsilateral cataract surgery. Three years later, he underwent left cataract surgery and again developed left neovascular glaucoma after the operation. Fluorescein angiogram showed a marked delay in retinal circulation. Moreover, severe stenosis of bilateral carotid origins and reflux of bilateral ophthalmic arteries were ascertained by neurosonographical examination such as duplex cervical echography and transcranial Doppler, as well as an angiogram. Brain imaging demonstrated asymptomatic watershed infarction in the left parieto-occipital cortex. Chronic ocular ischemia caused by carotid stenosis is one of the decisive risk factors for secondary glaucoma after cataract surgery. Preoperative neurosonographical screening tests are required to decrease ocular surgery complications, especially in the aged, and diabetic patients.

Aged↗
PubMed1994

Hypercoagulable state under low-intensity warfarin anticoagulation assessed with hemostatic markers in cardiac disorders.

The hemostatic condition under low-intensity anticoagulation in cardiac disorders is not fully elucidated. The aim of this study was to ascertain whether hemostatic molecular markers are a useful assessment for anticoagulation to detect the hypercoagulable state. A hematologic study was performed in 75 outpatients, without thromboembolic episodes, treated with low-intensity anticoagulation (average international normalized ratio [INR] 1.72) because of potential cardiac sources of arterial emboli, and in 40 age-matched control subjects. The average level of thrombin-antithrombin III complex (TAT) was significantly lower in patients than in control subjects (p = 0.005), and the mean value of D-dimer was not statistically different between patients and control subjects. Although TAT correlated moderately with D-dimer (r = 0.45, p = 0.0001), INR did not correlate with TAT or D-dimer. Elevated TAT > 3.0 ng/ml and/or D-dimer S 150 ng/ml were observed in 15 patients (20.0%), whereas the remaining 60 patients (80.0%) had no obvious increase in the level of TAT or D-dimer at overall INR. Antithrombin III activity did not correlate significantly with INR, but protein C activity and free protein S antigen showed a significant negative relation to INR (r = 0.82, r = 0.62, respectively, p = 0.0001). Low-intensity anticoagulation was sufficient to reduce coagulation and subsequent fibrinolytic activation in cardiac disorders, but may not be sufficient in some patients with elevated TAT or D-dimer concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Antithrombin III↗
PubMed1994

Inhibition of angiotensin-converting enzyme modulates the autoregulation of regional cerebral blood flow in hypertensive rats.

The inhibition of angiotensin-converting enzyme activities is considered to favorably modulate the hemodynamics of the brain. We designed the present study to examine the effects of angiotensin-converting enzyme inhibitors on regional differences in the lower limits of cerebral blood flow autoregulation in spontaneously hypertensive rats. Angiotensin-converting enzyme inhibitors (either 10 mg/kg captopril or SQ 29,852 in saline) were intravenously injected 15 minutes before hemorrhagic hypotension was induced. Cerebral blood flows to the parietal cortex and thalamus were simultaneously measured by hydrogen clearance. Both captopril and SQ 29,852 significantly decreased mean arterial pressure by 14 to 18 mm Hg and also reduced calculated cerebral vascular resistance by 11% to 15% of resting values, which resulted in a well-maintained cerebral blood flow. The lower limits of autoregulation were 76 +/- 2% (mean +/- SEM) and 77 +/- 2% of resting values in the cortex and thalamus, respectively, in control rats. Administration of either captopril or SQ 29,852 significantly reduced the lower limits to 65 +/- 3% (P < .01 versus control) and 67 +/- 2% (P < .05), respectively, in the cortex, which were slightly but always larger than the 71 +/- 3% and 71 +/- 2% reduction, respectively, in the thalamus. The inhibition of angiotensin-converting enzyme activities thus may be more protective against acute hypotension for cerebral microcirculation in the cortex than in the thalamus.

Angiotensin-Converting Enzyme Inhibitors↗