Search PubMed⌕ Search

Biomedical subjects

S Sadoshima

Publications and source records attributed to S Sadoshima.

At least 73 records · Page 4Linked to original sources
PubMed1993

Isradipine attenuates the ischemia-induced release of dopamine in the striatum of the rat.

We examined the effect of isradipine, a blocker of L-type voltage-sensitive Ca2+ channels (VSCCs), on the ischemia-induced release of dopamine in the rat striatum. Perfusion of 200 micrograms/ml isradipine in the striatum did not alter extracellular dopamine concentrations monitored by microdialysis. However, a marked increase (145-fold) in dopamine level during forebrain ischemia, developed by bilateral carotid artery occlusion, was attenuated significantly by 37% by isradipine whereas the intensity of ischemia, monitored by striatal blood flow, was unchanged. These results suggest that isradipine attenuates the ischemia-induced release of dopamine via blockade of L-type VSCCs on dopaminergic neurons.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Ischemia-induced changes in brain monoamine metabolism in aged spontaneously hypertensive rats.

Effects of aging on monoamine metabolism in transient cerebral ischemia were studied using adult and aged female spontaneously hypertensive rats (SHRs). Tissue monoamine contents in discrete brain areas were quantified after 20 min of cerebral ischemia with or without 30-min recirculation. Cerebral blood flow (CBF) was determined with a hydrogen clearance method in separate experiments. Dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) contents in the striatum, nucleus accumbens and septum decreased in ischemic aged SHRs, compared with those in ischemic adult SHRs. After 30-min recirculation, DA contents were actually unchanged with inconsistently increased DOPAC levels. Ischemic CBF decreased to < 20% of the resting CBF in the striatum and cortex, which was not different between the two age groups of SHRs. These results indicate that aging is primarily responsible for more severely impaired DA metabolism during cerebral ischemia in aged SHRs.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Altered cerebral hemodynamics and metabolism in Takayasu's arteritis with neurological deficits.

BACKGROUND AND PURPOSE: Takayasu's arteritis is a nonspecific arteritis involving major cerebral arteries. The aim of our study is to examine cerebral hemodynamics and metabolism in Takayasu's arteritis with neurologic symptoms. METHODS: We measured cerebral blood flow and metabolism using positron emission tomography in seven patients (14 to 59 years of age) with Takayasu's arteritis who developed transient ischemic attacks (2 patients), ischemic stroke (4) or putaminal hemorrhage with multiple brain infarction (1). RESULTS: All patients had severe stenosis or occlusion of one or more major cerebral arteries. There were no significant differences in the values of cerebral blood flow, oxygen extraction fraction, and cerebral blood volume in the infarcted and noninfarcted hemisphere. By contrast, the value of cerebral metabolic rate for oxygen in the infarcted hemisphere was markedly reduced (1.87 mL/100 mL per minute, P < .01) compared with controls. Mean transit time in the infarcted hemisphere was significantly greater than in the noninfarcted one, both in patients and controls (P < .01 and P < .05, respectively). CONCLUSIONS: Collateral blood flow to the hemisphere without brain damage may be relatively well developed in Takayasu's arteritis, although hemodynamic reserve as well as oxygen metabolism were impaired in the infarcted hemisphere with ischemic lesions.

Adolescent↗
PubMed1993

Angiotensin converting enzyme inhibitors attenuate ischemic brain metabolism in hypertensive rats.

BACKGROUND AND PURPOSE: Angiotensin converting enzyme (ACE) inhibitors are expected to modulate neuronal activities. The present study was designed to examine the beneficial effects of ACE inhibitors on microcirculation and metabolism in the ischemic brain. METHODS: Cerebral ischemia was developed for 60 minutes in spontaneously hypertensive rats (SHR, n = 35) by bilateral carotid artery occlusion. ACE inhibitor (0.1 or 10 mg/kg SQ 29,852 or captopril) were intravenously injected 15 minutes before cerebral ischemia. Cerebral blood flow to the parietal cortex was measured with the H2 clearance technique. Lactate, pyruvate, and ATP in the brain were estimated by the enzymatic method. RESULTS: Before cerebral ischemia, high doses of both SQ 29,852 and captopril significantly decreased mean arterial pressure by 15 to 25 mm Hg and reduced cerebral vascular resistance by 13% to 17% of the resting values. Cerebral blood flow and arterial pressure during ischemia were not altered by these ACE inhibitors. After 60 minutes of cerebral ischemia, tissue lactate in vehicle-treated SHR increased 6.6-fold and ATP decreased to 65% of the control values. Administration of SQ 29,852 or captopril significantly reduced the lactate levels to 1.6- to 3.1-fold and well preserved the ATP levels to 82% to 93% of the control. CONCLUSIONS: These results suggest that inhibition of ACE activities may be protective for cerebral metabolism against ischemic insult.

Adenosine Triphosphate↗
PubMed1993

Decrease in cerebral blood flow with blood pressure reductions in patients with chronic stroke.

BACKGROUND AND PURPOSE: Possible effects of changes in blood pressure on the cerebral circulation were studied in patients with chronic stroke and age-matched nonstroke control subjects at 28 +/- 10 months (mean +/- SD) (range, 18 to 54 months) and 27 +/- 6 months (range, 19 to 44 months), respectively, after the first measurement. METHODS: Cerebral blood flow was measured by the 133Xe inhalation method in 55 patients (mean +/- SD age, 62 +/- 11 years; 39 with brain infarction and 16 with hemorrhage) and 10 control subjects (mean +/- SD age, 61 +/- 9 years). Correlations between changes in cerebral blood flow and blood pressure were evaluated. RESULTS: Among brain infarctions, average cerebral blood flow did not change from the first study; however, changes in cerebral blood flow in each individual were closely related to changes in systolic and mean arterial blood pressures (P < .01 and P < .05, respectively). Of these, in 10 patients with cerebral blood flow decreased more than 15% from the initial levels, systolic and mean arterial blood pressures decreased by 25 +/- 32 mm Hg and 16 +/- 14 mm Hg (P < .05 and P < .005, respectively). In contrast, in 29 patients with unchanged or increased cerebral blood flow, changes in systolic (0 +/- 19 or -2 +/- 12 mm Hg, respectively) and mean arterial blood pressures (3 +/- 22 or -1 +/- 11 mm Hg, respectively) were not significant, and their systolic blood pressure levels were maintained above 110 mm Hg. CONCLUSIONS: Blood pressure importantly correlates with cerebral circulatory changes among patients with chronic brain infarction. Early detection of cerebral hemodynamic changes should be useful for determining the most favorable levels of blood pressure and for selecting appropriate therapy.

Adult↗
PubMed1993

Massive spinal cord infarction with multiple paradoxical embolism: a case report.

A sixty-seven-year-old man suffered from acute anterior spinal artery syndrome at the level of T-10. Transverse myelopathy developed by the eighth day. Computed tomography of the brain on the thirteenth day demonstrated hemorrhagic infarction in the left occipital lobe and fresh ischemic infarction in the right cerebellar hemisphere. Respiratory distress was the cause of death on the fifteenth day. Autopsy study showed severe ischemic necrosis of the spinal cord below T-10, and multiple infarcted lesions in the brain, lung, kidney, and heart. Saddle thromboembolism of the bilateral trunk of the pulmonary artery was the major cause of his death. Deep venous thrombosis in the pelvis was disclosed to be the primary source of multiple paradoxical embolisms through the patent foramen ovale.

Acute Disease↗
PubMed1993

Idiopathic cerebral hemorrhage during delivery in normotensive women--case reports.

Two normotensive pregnant women who developed cerebral hemorrhage during delivery are reported. The hematoma was small and subcortical in one and large and putaminal in the other. They had no history of hypertension, cerebrovascular disorders, or eclampsia. Cerebral angiography studied in one case revealed no abnormalities. Idiopathic cerebral hemorrhage during delivery without any evidence of vascular risk factors is discussed.

Adult↗
PubMed1993

[Age-related changes in intracranial artery velocity measured by transcranial Doppler sonography in normotensive, hypertensive and diabetic patients].

We measured mean blood flow velocity (MFV) and Fourier pulsatility index (PI) of the M1 portion of the middle cerebral artery (MCA) by transcranial Doppler mapping technique (2 MHz, Trans-scan, EME Co., Ltd.). The correlations between these parameters and arteriosclerotic risk factors such as aging, hypertension and diabetes mellitus were examined. Healthy volunteers as well as patients suffering from hypertension and diabetes mellitus were studied. A total of 59 persons (85 MCAs) consisting of 30 males (mean age 54.4, 24-81 years) and 29 females (mean age 54.8, 20-75 years) were enrolled in this study. Some hypertensive or diabetic subjects had previous cerebrovascular disease, therefore cases who had only minor stroke or asymptomatic infarction without significant lesions in carotid artery system were included. After excluding brain embolism, these subjects were divided into three groups as normotensive/non diabetic group (NT/non DM), hypertensive group (HT) and diabetic group (DM). In each group, MFV decreased with aging, being more evident in the HT and DM groups than in the NT/non DM group. Fourier PI also showed a significant increase with aging, and the correlation was stronger than that between MFV and age. Moreover, these trends of age-Fourier PI relationship were more highly significant in HT and DM groups than NT/non DM group. In cases with HT or DM, age-related arterial changes appeared to be more severe than in those without. Fourier PI seemed valuable for detecting arterial lesions with aging, HT and DM.

Adult↗
PubMed1992

Attenuation of ischemic and postischemic damage to brain metabolism and circulation by a novel Ca2+ channel antagonist, NC-1100, in spontaneously hypertensive rats.

We investigated the effect of a newly synthesized Ca2+ channel antagonist, NC-1100, on cerebral blood flow (CBF) and metabolism in spontaneously hypertensive rats. The rats received a bolus injection of 0.2 or 1.0 mg/kg NC-1100 i.v. and 1-h cerebral ischemia was then induced by bilateral carotid artery occlusion (group 1). The rats in group 2 were continuously infused with NC-1100 0.03 or 0.1 mg/kg per min, starting immediately after bilateral carotid artery occlusion, for the 1 h of ischemia and following 3-h recirculation. Group 1: during ischemia, CBF in all rats decreased to 6-8% of the resting values. At 1 h cerebral ischemia, brain tissue lactate increased 11.5-, 10.1- and 9.8-fold of the normal control given vehicle or NC-1100, 0.2 and 1.0 mg/kg, respectively. The ATP levels were better preserved by NC-1100 administration; 0.61 +/- 0.04 (mean +/- S.E.M.), 0.80 +/- 0.09 and 0.97 +/- 0.14 mmol/kg (P < 0.05 vs. vehicle), respectively. Group 2: during recirculation, CBF in NC-1100-treated rats returned to 83-90% of the resting values, but to only 65% in the vehicle group. Postischemic brain lactate at 3 h was less well preserved and ATP was dose dependently better preserved in NC-1100- than vehicle-treated rats. It is considered that pre- as well as postischemic administration of a Ca2+ channel antagonist, NC-1100, is beneficial to attenuate and also ameliorate the metabolic and circulatory derangement in the ischemic brain.

Adenosine Triphosphate↗
PubMed1992

Effects of acute superior cervical ganglionectomy on cerebral blood flow and metabolism in stroke-prone spontaneously hypertensive rats subjected to cerebral ischaemia.

1. The effects of acute bilateral superior cervical ganglionectomy on cerebral blood flow and metabolism were investigated in stroke-prone spontaneously hypertensive rats (SHRsp), before and during cerebral ischaemia. 2. The resting cerebral blood flow was comparable between the control and denervated animals. 3. There was no significant difference in cerebral blood flow or concentration of tissue energy metabolites (adenosine triphosphate [ATP], lactate and pyruvate) between the sham-operated control and denervated animals during ischaemia. 4. The results suggest that sympathetic innervation of cerebral vessels originating from superior cervical ganglia may not play a major role in the progression of cerebral ischaemia in SHRsp.

Animals↗
PubMed1992

Inhibition of ischemia-induced dopamine release by omega-conotoxin, a calcium channel blocker, in the striatum of spontaneously hypertensive rats: in vivo brain dialysis study.

The effect of omega-conotoxin GVIA (CgTX), an N-and L-type voltage-sensitive calcium channel (VSCC) blocker, on the release of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum before and during transient cerebral ischemia in spontaneously hypertensive rats was studied using an in vivo brain dialysis technique. Continuous perfusion of CgTX in the striatum was started 20 min before ischemia and concentrations of dopamine and DOPAC in the dialysate were measured using HPLC with an electro-chemical detector. Before ischemia, both 10 and 100 microM CgTX significantly lowered the concentration of dopamine, to 49% of the basal values. DOPAC concentrations also decreased significantly, by 28 and 17%, respectively. Forebrain ischemia, produced by bilateral carotid artery occlusion, reduced striatal blood flow to less than 6% of the resting value in each group. During 20 min of ischemia, the vehicle group showed a marked increase in dopamine (175 times the basal concentration). In the 10 or 100 microM CgTX perfusion group, in contrast, dopamine release was significantly attenuated, to 38 or 29% of the vehicle group, respectively. DOPAC concentrations decreased during ischemia to 58% of the basal value in the vehicle group and 49% in both CgTX groups. These results indicate that the massive release of striatal dopamine during ischemia depends largely on the influx of extracellular calcium via CgTX-sensitive VSCCs.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Early computed tomographic findings for thrombolytic therapy in patients with acute brain embolism.

BACKGROUND AND PURPOSE: The benefits and safety of thrombolytic therapy was studied in patients with acute brain embolism. METHODS: We intravenously administered recombinant tissue plasminogen activator (20-30 MU for 1 hour) to 10 patients with acute (less than 6 hours) brain embolism and examined the neurological outcomes in relation to the findings on computed tomography and angiography. RESULTS: The symptoms ameliorated in four patients within 24 hours after onset, and reopening of the occluded arteries occurred in two of the patients immediately after recombinant tissue plasminogen activator infusion. On the initial computed tomographic scan (less than 3 hours), four patients had already demonstrated early indications of brain ischemia, that is, an obscure margin of the lentiform nuclei, reduced tissue attenuation, or effacement of cortical sulci. These patients failed to demonstrate reopening of the occluded arteries, and one developed a massive brain hemorrhage with clinical deterioration. Of the remaining six patients, two obtained clinical improvement with recanalization soon after the therapy and demonstrated little to slight hemorrhagic complications. The outcomes at 1 month were favorable in five patients and poor in three; death occurred in two. CONCLUSIONS: Thrombolytic therapy with recombinant tissue plasminogen activator may be safe and effective when there are no early computed tomographic findings within 3 hours from the onset of embolic stroke.

Adult↗
PubMed1992

Leukoaraiosis and dementia in hypertensive patients.

BACKGROUND AND PURPOSE: Although our previous study demonstrated that dementia of the Binswanger type may be a disconnection dementia caused by leukoaraiosis, some hypertensive patients with marked leukoaraiosis do not develop dementia. The goal of the present study is to elucidate the pathophysiology of nondemented hypertensive patients with leukoaraiosis. METHODS: We performed clinical and neuroradiological studies, including positron emission tomography, in eight hypertensive patients with leukoaraiosis. RESULTS: Four patients were demented, and two among the other four who were not demented at the first examination developed dementia during the follow-up period. Digital subtraction angiography of the cervical and intracranial arteries demonstrated stenotic lesions in only one patient. Cerebral blood flow and oxygen metabolism in patients with dementia were markedly reduced in the white matter (59-67% of control values). In contrast, cerebral blood flow in the white matter of patients without dementia was reduced less markedly (74% of control), oxygen extraction fraction in the white matter was significantly increased (130% of control), and oxygen metabolism remained at almost-normal levels not only in the white matter but also in the cortical area. CONCLUSIONS: Hypertension-caused arteriosclerotic changes of the long penetrating medullary arteries may cause misery perfusion and later ischemic damage in the periventricular white matter. Preserved oxygen metabolism in hypertensive patients with leukoaraiosis may represent the early stage of vascular dementia of the Binswanger type.

Adult↗
PubMed1992

Marked reduction of cerebral oxygen metabolism in patients with advanced cirrhosis: a positron emission tomography study.

Regional cerebral blood flow (rCBF), cerebral metabolic rate of oxygen (rCMRO2), and oxygen extraction fraction (rOEF) were measured using positron emission tomography (PET) in four patients with cirrhosis (two males and two females, aged 57 to 69 years) in comparison with those in five age-matched controls with previous transient global amnesia. PET studies were carried out when the patients were fully alert and oriented after the episodes of encephalopathy. In the patients, rCBF tended to be lower, while rCMRO2 was significantly lowered in almost all hemisphere cortices, more markedly in the frontal cortex. Our results suggest that the brain oxygen metabolism is diffusely impaired in patients with advanced cirrhosis, and the frontal cortex seems to be more susceptible to the systemic metabolic derangements induced by chronic liver disease.

Aged↗