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Biomedical subjects

S Sadoshima

Publications and source records attributed to S Sadoshima.

At least 127 records · Page 7Linked to original sources
PubMed1988

Effect of recirculation on the recovery of cerebral metabolism after experimental cerebral ischemia in male and female spontaneously hypertensive rats.

Lactate, pyruvate and adenosine triphosphate (ATP) concentrations in the brain were measured at the end of various periods of cerebral ischemia induced by bilateral carotid occlusion at 1-hour recirculation after the ischemia in spontaneously hypertensive rates (SHR). In both male and female SHR, a progressive and consistent increase in lactate and lactate/pyruvate ratio and a concomitant decrease in ATP were observed in the ischemic periods of 1, 3 or 5 h. Changes of these cerebral metabolites in females were two thirds to one half of those in males at corresponding periods of ischemia. At 1 h after recanalization of the occluded carotid arteries, metabolic derangements of the ischemic brain were little recovered in male SHR exposed to only 1-hour ischemia, whereas in female SHR the decreased ATP levels were recovered close to the nonischemic control level even after 7-hour ischemia. Furthermore, the increased lactate in female was attenuated to only one sixth of that in male at 1-hour recirculation after 5-hour ischemia. It is concluded that the recovery of the cerebral ischemic metabolism by reperfusion is better in female than male SHR, probably because of the smaller metabolic changes during the ischemic insult, and the fact that the degree as well as the duration of ischemia seem to be important factors for sufficient recovery from ischemic impairment of the brain.

Adenosine Triphosphate↗
PubMed1988

Impairment of cerebellar blood flow autoregulation during cerebral ischemia in spontaneously hypertensive rats.

Participation of the autonomic nervous system in cerebellar autoregulation during supratentorial cerebral ischemia induced by bilateral carotid ligation was studied using 23 spontaneously hypertensive rats. Cerebral and cerebellar blood flows measured by a hydrogen clearance method were evaluated under stepwise hemorrhagic hypotension before and 30 minutes after ligation and after a 30-minute recirculation period following 1 hour of ligation. alpha-Adrenergic blockade with phenoxybenzamine, beta-adrenergic blockade with propranolol, and muscarinic cholinergic blockade with atropine were selectively administered before ligation for inhibition of sympathetic and parasympathetic tone. Cerebral blood flow autoregulation was severely impaired during and after cerebral ischemia in each treatment group. During cerebral ischemia, cerebellar blood flow autoregulation was also significantly impaired in both the propranolol and atropine groups although it was better preserved in the phenoxybenzamine group. After recirculation, cerebellar blood flow autoregulation recovered almost to the normal range in the phenoxybenzamine and atropine groups but remained impaired in the propranolol group. Our results suggest that impaired cerebellar blood flow autoregulation in supratentorial cerebral ischemia is partly modulated by the alpha-adrenoceptor system, which is activated by hypertensive stimuli and cerebral ischemia, leading to vasoconstriction in the cerebellum.

Animals↗
PubMed1988

Transient encephalopathy related to rapidly and markedly elevated blood pressure in acute stage of hypertensive cerebral hemorrhage--relationship to hypertensive encephalopathy--a case report.

A seventy-two-year-old man with hypertensive cerebral hemorrhage acutely developed severe headache, nausea, vomiting, agitation, and disorientation with abrupt rise in blood pressure on the sixth day after the onset. At that time, there were no remarkable changes in focal neurologic deficits, and repeated brain CT scans revealed a small hematoma located in the right basal ganglia without further enlargement or herniation. Blood chemistry and arterial gas analysis were within the normal ranges except for a slight rise in blood urea nitrogen. Similar episodes occurred three times within two days, and each time the cerebral symptoms disappeared in accordance with lowering of blood pressure by antihypertensive therapy. Complication of hypertensive encephalopathy was strongly suggested. The authors discuss the pathophysiology of this encephalopathy in relation to cerebral hemorrhage.

Aged↗
PubMed1988

Regional cerebral blood flow in chronic stroke patients with dementia.

Cerebral atrophy and regional cerebral blood flow (CBF) were examined in 52 chronic stroke patients with dementia, pre-dementia or non-dementia (according to the Dementia Scale). The index of cerebral atrophy was estimated on computed tomography, and CBF was determined using 133Xe inhalation method. Cerebral atrophy indices were not significantly different among various degrees of dementia except a slightly increased cella media index in pre-dementia group. Average values for CBF were bilaterally reduced in dementia, being 28.5 +/- 4.4 for affected hemisphere and 31.0 +/- 3.2 ml/100g/min for non-affected one. Compared with those, CBF were higher in pre-dementia (37.3 +/- 8.7 and 39.4 +/- 8.2 ml/100 g/min, p less than 0.05 vs dementia, respectively) and more higher in non-dementia (45.8 +/- 10.2 and 48.5 +/- 10.4 ml/100 g/min, p less than 0.01 vs pre-dementia, respectively). Of 11 recurrent stroke patients, 5 with newly developed dementia after the second attack presented the preceding CBF reduction 10 to 34 months prior to the recurrence. Present results suggest that bilateral reduction of CBF may be the primarily important factor for the initiation or development of vascular dementia, and the CBF reduction seems to precede the symptom of dementia.

Aged↗
PubMed1987

Importance of bilateral sympathetic innervation on cerebral blood flow autoregulation in the thalamus.

Effects of bilateral sympathetic innervation on the regulation of cerebral blood flow to the thalamus were examined in spontaneously hypertensive rats (SHR). The superior cervical ganglion was removed on one side or bilaterally, and blood flow in the thalamus was repeatedly measured with a hydrogen clearance technique during a stepwise increase in arterial pressure. Regional blood flow in the thalamus was unchanged following acute ganglionectomy: 55 +/- 6 ml/100 g/min in the intact rats and 56 +/- 4 in the denervated rats. Sympathectomy on one side neither had effects on the pressure-flow relationship nor on the blood pressure levels of upper limits of autoregulation in the ipsilateral thalamus. In contrast, bilateral sympathetic denervation impaired the autoregulatory function in the thalamus and the upper limits were significantly lower than those in intact rats: 206 +/- 8 vs 226 +/- 10 mm Hg, respectively (P less than 0.02). It is concluded that overlapping innervation of sympathetic nerves has an important role in regulation of blood flow to the thalamus during an acute rise in arterial pressure in SHR.

Adrenergic Fibers↗
PubMed1987

Carbon dioxide reactivity of cerebral cortical and pial arteries in spontaneously hypertensive and normotensive rats--a morphometric study.

The responsiveness of cerebral arteries to the changes in arterial carbon dioxide tension (paCO2) was studied in spontaneously hypertensive rats (SHRs) and normotensive rats (NTRs). A freeze substitution method was applied for the preparation of pial and cortical arteries for morphometrical study. Hypercapnia was induced by giving 8% CO2, and hypocapnia was provided by hyperventilation. The ratios of internal (d) to external diameter (D) (d/D ratio) of both pial and cortical arteries in SHR were not different from those in NTRs during normocapnia. In hypercapnia, the ratios of pial and larger cortical arteries (D greater than or equal to 20 micron) in SHRs were 80.9 +/- 0.8% and 78.6 +/- 0.6%, respectively, being significantly smaller than 86.2 +/- 0.7% and 82.2 +/- 0.5% in NTR. In contrast, the d/D ratio of pial arteries in hypocapnia was 72.5 +/- 1.4% in SHRs, which was significantly larger than 67.5 +/- 1.4% in NTRs. The responsiveness of smaller cortical arteries (D less than 20 micron) to paCO2 was not different between SHRs and NTRs. The present results suggest that in SHRs cerebrovascular CO2 reactivity is decreased as compared to NTRs, especially in pial and larger cortical arteries.

Animals↗
PubMed1987

Diabetes induced by neonatal streptozotocin treatment in spontaneously hypertensive and normotensive rats.

The development of non-insulin-dependent diabetes mellitus (NIDDM) induced by neonatal streptozotocin (STZ) treatment was compared between male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). The animals were intraperitoneally given 37.5, 50.0, 62.5, or 75.0 mg/kg of STZ at two days of age. At two days after STZ injection, plasma glucose was elevated in both groups of rats according to the dose of STZ, but the level was higher in SHR than in corresponding WKY. At ten days of age, plasma glucose in WKY returned to the similar level to that in vehicle-treated control irrespective of the doses of STZ, while in SHR it remained above control and its level was significantly higher than that in WKY. At 12 weeks of age, plasma glucose was within the control range in WKY, while in SHR it was markedly and dose-dependently elevated. The present study indicates that SHR are susceptible to NIDDM induced by neonatal STZ treatment. The difference in response to STZ between SHR and WKY was discussed.

Aging↗
PubMed1987

Sex differences in diabetes induced by neonatal streptozotocin treatment in spontaneously hypertensive rats.

We examined the sex differences in the development of diabetes due to neonatal streptozotocin (STZ) treatment in spontaneously hypertensive rats (SHR) which are more prone to diabetes than normotensive rats. Male and female SHR were intraperitoneally injected with various doses of STZ at 2 days after birth. In those treated with vehicle or 25 mg/kg of STZ, there were no sex differences in plasma glucose levels, which changed little during the 12 weeks of observation. When treated with 50 mg/kg of STZ, however, male SHR developed overt hyperglycemia greater than 300 mg/dl plasma glucose after 8 weeks of age, while females showed a minimal change in plasma glucose levels. When given 75 mg/kg of STZ, female rats developed overt hyperglycemia at 4-6 weeks of age, during which time male SHR showed no apparent hyperglycemia. At 8 weeks or later, however, both males and females had similarly high levels of plasma glucose. Glycosylated hemoglobin at 12 weeks was compatible with plasma glucose levels in each group. The present results indicate that there are sex differences in susceptibility to neonatal STZ treatment and in development of hyperglycemia.

Aging↗
PubMed1987

Cerebrospinal fluid lactate in patients with hepatic encephalopathy.

Cerebrospinal fluid (CSF) lactate and pyruvate concentrations were determined in 16 patients with hepatic encephalopathy before and/or after treatment. CSF lactate was significantly increased to 1.92 +/- 0.11 mmol/l in hepatic encephalopathy before the treatment in comparison to 1.40 +/- 0.05 mmol/l in control subjects. In 9 of 11 patients with moderate or stage 2 encephalopathy, CSF lactate levels were below 2 mmol/l. In contrast, in 4 of 5 patients with stage 3-4 encephalopathy, CSF lactate levels were higher than 2 mmol/l. CSF lactate was decreased with the recovery of neurological symptoms by the treatment. These findings indicate that CSF lactate levels reflect the severity of metabolic impairment of the brain. Hypocapnia was frequently observed in these encephalopathic patients, and arterial PCO2 correlated inversely with CSF lactate and linearly with CSF HCO3-, suggesting that CSF lactic acidosis contributes to hyperventilation in hepatic encephalopathy. It is concluded from present results that metabolic disorder of neuronal cells might be one of the important factors for the development of hepatic encephalopathy.

Acid-Base Equilibrium↗
PubMed1987

Blood pressure changes in spontaneously hypertensive and normotensive rats with neonatal streptozotocin induced type 2 diabetes.

We examined the blood pressure changes in hypertensive and normotensive rats with Type 2 diabetes induced by neonatal streptozotocin (STZ) treatment. STZ was intraperitoneally injected at 2 days of age with the dose of 25, 50 and 75 mg/kg for male spontaneously hypertensive rats (SHR) and with 75, 100, 125 and 150 mg/kg for male normotensive Wistar Kyoto rats (WKY). Blood pressure was measured by indirect tail-cuff method until 12 weeks of age. STZ-treated SHR, of which plasma glucose and glycosylated hemoglobin increased and body weight decreased with the dose of STZ, developed and maintained hypertension, same as did the vehicle-treated control SHR. On the other hand, STZ-treated WKY which developed only mild hyperglycemia lost body weight with the dose of STZ but the blood pressures rose slightly, these changes being correlated with the glycemic levels. The explanation for these differences between SHR and WKY remained to be elucidated.

Animals↗
PubMed1986

Effect of chronic sympathetic denervation on cerebrovascular hypertrophy during the development of hypertension in rats.

The present study was designed to examine the trophic effect of sympathetic nerves on cerebrovascular hypertrophy in developmental hypertension. Unilateral superior cervical ganglionectomy was performed in spontaneously hypertensive rats at 4 weeks of age, and wall-to-lumen ratios of cerebral arteries were determined at 5 weeks, 2 months or 5 months after denervation. To estimate the thickness of the vessel wall, a freeze substitution technique was used for the preparation of cerebral arteries. Basal mean arterial blood pressure measured through cannulated femoral artery was 127 +/- 2, 146 +/- 7 and 168 +/- 6 mm Hg (mean +/- S.E.M.) at 9 weeks, 3 months and 6 months of age, respectively. The wall-to-lumen ratios in the denervated and innervated hemispheres were 0.124 +/- 0.004 and 0.129 +/- 0.005 at 9 weeks, 0.127 +/- 0.003 and 0.169 +/- 0.004 (P less than 0.02 vs denervated) at 3 months, and 0.194 +/- 0.007 and 0.222 +/- 0.006 (P less than 0.05 vs denervated) at 6 months. The effect of denervation was more significant in downstream vessels (diameter less than or equal to 100 microns) than larger ones. We conclude that wall-to-lumen ratio is correlated well with a rise in basal blood pressure, and chronic interruption of the sympathetic nerves attenuates normal occurrence of vascular hypertrophy during the development of hypertension.

Animals↗
PubMed1986

A new model of type 2 (non-insulin-dependent) diabetes mellitus in spontaneously hypertensive rats: diabetes induced by neonatal streptozotocin treatment.

This study was designed to develop an animal model of Type 2 (non-insulin-dependent) diabetes with persistent hypertension. Male spontaneously hypertensive rats were treated with 25.0, 37.5, 50.0, 62.5 or 75.0 mg/kg of streptozotocin given intraperitoneally at 2 days of age and maintained for 12 weeks. In the rats which received 50.0 mg/kg or more streptozotocin, overt hyperglycaemia gradually and consistently developed following incomplete recovery from an initial hyperglycaemia. Compared to vehicle-treated controls, body weight gain in these animals did not differ for the first 8 weeks; thereafter, it was slightly but significantly (p less than 0.05) reduced. The animals treated with 25.0 or 37.5 mg/kg streptozotocin developed mild to moderate hyperglycaemia, but their body weight gain was similar to controls. The relationships between streptozotocin dose and metabolic responses (plasma glucose, glycosylated haemoglobin, urinary glucose, food intake, etc.) were clearly demonstrated. Systolic blood pressure rose with progressing age in both controls and streptozotocin-treated rats, irrespective of dosage or metabolic response. This new rat model of Type 2 diabetes associated with persistent hypertension may be useful in studying these combined effects on small and large vessels.

Animals↗
PubMed1986

Cerebral venous angioma of the pons: report of a case with pontine hemorrhage.

Cerebral venous angioma in the pons associated with pontine hemorrhage in a 39-year-old normotensive woman was identified with computed tomography and angiography. Venous angioma in the brain stem is usually silent and rarely found by chance at autopsy. Only a few cases have been clinically reported. Our report indicates that in unusual cases of intracerebral hemorrhage, vascular malformations should be suspected and scrutinized with radiologic examination including angiography.

Adult↗
PubMed1986

Effects of intravenous glycerol on cerebral blood flow and tissue metabolism in acute cerebral ischemia in spontaneously hypertensive rats.

The effects of antiedematous agent with intravenous 10% glycerol on cerebral blood flow (CBF) and metabolism were studied in acute cerebral ischemia experimentally induced by bilateral carotid artery occlusion in spontaneously hypertensive rats (SHR). CBF was measured by the hydrogen clearance technique and brain tissue metabolites such as lactate, pyruvate and ATP in the ischemic brain frozen in situ were determined by the enzymatic method. In comparison with saline-infused SHR, the reduction of CBF in the thalamus following carotid occlusion was significantly small in the glycerol treated SHR. Supratentorial ATP concentration in the 3 hr-ischemic brain was reduced in both groups of rats, but its reduction was significantly smaller in the glycerol-infused group than the other. Lactate and lactate/pyruvate ratio tended to be less increased in the glycerol rats, indicating that ischemic metabolism was restrained by the treatment. The present results strongly suggest that intravenous glycerol is effective against acute cerebral ischemia from the view point of cerebral hemodynamic and metabolism.

Acute Disease↗