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Biomedical subjects

S Sadoshima

Publications and source records attributed to S Sadoshima.

At least 19 recordsLinked to original sources
PubMed2000

Hypothermia inhibits ischemia-induced efflux of amino acids and neuronal damage in the hippocampus of aged rats.

Brain hypothermia has been reported to protect against ischemic damages in adult animals. Our goal in this study was to examine whether brain hypothermia attenuates ischemic neuronal damages in the hippocampus of aged animals. We also determined effects of hypothermia on ischemia-induced releases of amino acids in the hippocampus. Temperature in the hippocampus of aged rats (19-23 months) was maintained at 36 degrees C (normothermia), 33 degrees C (mild hypothermia) or 30 degrees C (moderately hypothermia) using a thermoregulator during 20 min of transient forebrain ischemia. Cerebral ischemia increased extracellular concentrations of glutamate and aspartate by 6- and 5-fold, respectively, in the normothermic group. Mild and moderate hypothermia, however, markedly inhibited the rise of these amino acids to less than 2-fold. Elevation of extracellular taurine, a putative inhibitory amino acid, was 16-fold in the normothermic rats. Mild hypothermia attenuated ischemia-induced increase in taurine (10-fold), and moderate hypothermia inhibited the increase. Ischemic damages, evaluated by histopathological grading of hippocampal CA1 area 7 days after ischemia, was significantly ameliorated in the mild (1.3+/-0.5, mean+/-S.E.M.) and moderate hypothermic rats (0.8+/-0.3) compared with the normothermic ones (3.4+/-0.4). These results suggest that brain hypothermia protects against ischemic neuronal damages even in the aged animals, and the protection is associated with inhibition of excessive effluxes of both excitatory and inhibitory amino acids.

Aging↗
PubMed2000

Calcium antagonist isradipine reduces metabolic alterations in acute cerebral ischemia in spontaneously hypertensive rats.

The present study was designed to examine the effect of a calcium antagonist isradipine (PN200-110: PN) on local cerebral blood flow and brain tissue metabolism after 1-hour supratentorial ischemia induced by bilateral carotid artery ligation (BCL) in spontaneously hypertensive rats (SHR). PN, dissolved in ethanol plus polyethylene glycol 400, diluted with saline to make the final concentration of 0.25mg/ml and 2.5mg/ml, was administered subcutaneously either 30 min prior to BCL or just after the induction of incomplete cerebral ischemia (n = 7 in each group). Vehicle injection was served as a control group (n = 7). Cerebral blood flow in the parietal cortex (CBF) and the cerebellar cortex (CeBF) was measured by hydrogen clearance technique, and the supra- and infratentorial metabolites of the brain frozen in situ were determined by the enzymatic method. Blood pressure was lowered, but CBF was increased by PN administration in pre-BCL treatment study. After 1 hour of BCL, CBF decreased to around 10% or less of the resting value, being insignificant among the groups. Brain adenosine triphosphate was better preserved in PN-administered groups. The increase in lactate level tended to reduce dose dependently by PN treatment. PN also reduced the metabolic alterations in brain tissue with significance, even when administered just after the induction of forebrain ischemia. It is considered that pre- as well as post-BCL administration of PN is beneficial to attenuate the metabolic alterations in incomplete forebrain ischemia in SHR.

Acute Disease↗
PubMed2000

Effect of selective brain hypothermia on regional cerebral blood flow and tissue metabolism using brain thermo-regulator in spontaneously hypertensive rats.

To investigate the effect of selective hypothermia of the brain (brain cooling) on regional cerebral blood flow and tissue metabolism, we have developed a brain thermo-regulator. Brain temperature was modulated by a water-cooled metallic plate placed on the surface of the rats' scalp to get the appropriate brain temperature precisely with ease. Regional cerebral blood flow and brain temperature were measured simultaneously using a Teflon-coated platinum electrode and thermocouple probe inserted stereotaxically into the parietal cortex and thalamus in spontaneously hypertensive rats. Experimental forebrain ischemia was induced by the occlusion of bilateral common carotid artery under normo- and hypothermic brain condition, and the supratentorial brain tissue metabolites were measured enzymatically after 60 min of forebrain ischemia. When cortical temperature was set to hypothermia, cortical blood flow was significantly lowered by 40% at 30 degree C and 20% at 33 degree C as compared with that at 36 degree C (p < 0.0001 and p < 0.05, respectively). Thalamic blood flow was also significantly reduced by 20% when cortical temperature was set to 30 degree C as compared with 36 degree C (p < 0.05). There were no significant differences in arterial blood pressure and gas parameters throughout these experiments. In the rats with selective brain hypothermia (30 degree C) immediately after the induction of cerebral ischemia, the level of brain ATP concentration after 60 min of ischemia was significantly higher than that in normothermia rats (36 degree C) (p < 0.05). Our findings indicate that: 1) the metallic plate brain thermo-regulator is useful in small animal experiments; 2) regional brain temperature regulates regional cerebral blood flow; and 3) selective brain hypothermia, even started after the forebrain ischemia, ameliorates the derangement of brain metabolism, suggesting its effectiveness as a cytoprotective strategy.

Animals↗
PubMed2000

Internal jugular vein thrombosis, Lemierre's syndrome; oropharyngeal infection with antibiotic and anticoagulation therapy--a case report.

The authors present a case of Lemierre's syndrome that is an uncommon septic thrombophlebitis of the internal jugular vein. A 31-year-old man developed pharyngeal pain one month before hospital admission when he suffered from a severe headache and painful swelling of the left side of his neck. He was diagnosed with tonsillitis. Contrast-enhanced computed tomography and magnetic resonance imaging of the neck revealed the presence of an occlusive thrombosis of the left internal jugular vein and an inflamed mesopharynx. His symptoms and the jugular vein thrombus showed remarkable improvement after administration of antibiotic and anticoagulation therapy. No pulmonary embolism or other metastatic infection were observed. It was suggested that accurate diagnosis during early treatment is essential to obtain a successful prognosis for Lemierre's syndrome.

Adult↗
PubMed2000

Neurally mediated syncope induced by lung cancer--a case report.

The authors present hemodynamic and autonomic features of recurrent and episodic neurally mediated syncope in a man with lung cancer involving afferent vagus. He revealed extreme hypotension with bradycardia occurring during sitting or standing. A head-up tilt test also induced syncope. However, syncope attacks no longer occurred 2 weeks after admission. Alternatively, the paralyses of the left recurrent laryngeal nerve and the left phrenic nerve developed. It is suggested that the lung cancer involved upper rootlets of the left vagus and caused transient hypersensitivity of baroreceptor function that resulted in neurally mediated syncope.

Carcinoma, Large Cell↗
PubMed2000

Adult reversible cardiomyopathy with pituitary adrenal insufficiency caused by empty sella--a case report.

The authors report a first case of reversible cardiomyopathy in an adult with adrenal insufficiency. A 62-year-old man was administered to hospital because of congestive heart failure. The electrocardiogram showed prolonged QT interval and negative T wave on the right precordial leads and frequent multifocal ventricular premature contractions. On the echocardiogram, the left ventricle was revealed to be diffusely hypokinetic with remarkable enlargement. 201Thallium single photon emission computed tomography (SPECT) revealed multiple flow defects in the left ventricular wall. He also had pituitary adrenal insufficiency secondary to an empty sella, which was diagnosed by hormonal studies and magnetic resonance images of the brain. After the replacement therapy with hydrocortisone, heart failure was sufficiently resolved. Abnormal flow defects in the myocardium on SPECT were also improved. To the authors' knowledge, adrenal insufficiency with cardiomyopathy has not been previously described in adult patients.

Adrenal Insufficiency↗
PubMed1999

Ileal varices associated with recurrent bleeding in a patient with liver cirrhosis.

We report a rare case of massive and recurrent bleeding from ileal varices in a patient with hepatitis C virus-positive liver cirrhosis. A 66-year old woman, who had undergone laparotomy and blood transfusion 36 years before (because of an extrauterine pregnancy) and endoscopic sclerotherapy for esophageal varices 1 year previously, was admitted to our hospital with loss of bright red blood per rectum. The bleeding was massive and recurrent, and frequent blood transfusions were required. Endoscopic studies failed to find the bleeding site. In the venous phase of selective superior mesenteric angiography, mesenteric varices in the lower part of the abdominal cavity were observed. Laparotomy was performed to control the repeated bleeding which had lasted for more than 1 month. Varices communicating with the right ovarian vein were found on the ileal wall and segmental resection of the ileum was performed. Histological examination demonstrated a massive varicose vein and several dilated veins in the submucosa. The patient's postoperative course was favorable, with no hemorrhagic events during a follow-up of more than 6 months after surgery. Ileal varices should be considered in the diagnosis of a patient who presents with lower gastrointestinal bleeding and portal hypertension.

Aged↗
PubMed1999

Adult T-cell leukemia/lymphoma in which the pathohistological diagnosis was identical to that of Ki-1 positive anaplastic large cell lymphoma.

A 65-year-old man developed severe lumbago and a loss of appetite two months before presentation. A computerized tomograph at admission revealed soft tissue masses destroying the Th12, L4 and L5 vertebral bones. We diagnosed the lesions to be metastatic bone tumors, but the primary focus could not be determined. Just after the irradiation treatment, abnormal lymphocytes were detected in the peripheral blood cells. Under the suspicion of adult T-cell leukemia/ lymphoma (ATL), we thus performed a lymph node biopsy. The specimens were histologically composed of Ki-1 positive anaplastic large cell lymphoma (ALCL). The lymphoma cells demonstrated a biclonal integration of HTLV-1 proviral DNA. After 6 cycles of chemotherapy, the patient has demonstrated a partial and favorable remission from ATL.

Aged↗
PubMed1998

Modulation of ischemia-evoked release of excitatory and inhibitory amino acids by adenosine A1 receptor agonist.

Adenosine has been reported to have beneficial effects against ischemic brain damage, although the mechanisms are not fully clarified. To examine the role of adenosine on the ischemia-evoked release of neurotransmitters, we applied a highly selective agonist for adenosine A1 receptor, 2-chloro-N6-cyclopentyladenosine (CCPA), into the ischemic brain using in vivo brain dialysis, which directly delivered the agonist to the local brain area. Concentrations of extracellular amino acids (glutamate, aspartate, gamma-aminobutyric acid (GABA) and taurine) and regional blood flow in the striatum of spontaneously hypertensive rats (SHRs) were monitored during cerebral ischemia elicited by bilateral carotid artery occlusion for 40 min and recirculation. Striatal blood flow and basal levels of amino acids were not affected by direct perfusion of CCPA (10 microM or 100 microM). During ischemia, concentrations of glutamate, aspartate, GABA and taurine increased up to 37-, 30-, 96- and 31-fold, respectively, when vehicle alone was administered. Administration of CCPA did not affect the changes in regional blood flow during ischemia and reperfusion. Perfusion of CCPA (100 microM), however, significantly attenuated the ischemia-evoked release of aspartate (by 70%) and glutamate (by 73%). The ischemia-induced increase of GABA tended to be decreased by CCPA, although it was not statistically significant. In contrast, both low and high concentrations of CCPA had little effect on the release of taurine during ischemia. These results suggest that stimulation of adenosine A1 receptors selectively attenuated the ischemia-evoked release of excitatory amino acids, but not of inhibitory amino acids without affecting blood flow. This modulation of the release of amino acids by adenosine A1 receptor agonists may play a protective role against ischemic neuronal damage.

Adenosine↗
PubMed1998

Calcitonin gene-related peptide affords gastric mucosal protection by activating potassium channel in Wistar rat.

BACKGROUND & AIMS: Calcitonin gene-related peptide (CGRP) protects the gastric mucosa against injurious stimuli in various experimental models. The underlying mechanism could be the increase in gastric mucosal blood flow (GMBF). A number of endogenous vasodilators exert their effects through the activation of adenosine triphosphate (ATP)-sensitive potassium (KATP) channels on vascular smooth muscle. The present experiments were performed to elucidate whether CGRP increases GMBF through the activation of KATP channels and whether the channels are involved in the protection by CGRP of gastric mucosa. METHODS: GMBF was determined by the hydrogen-clearance technique in male Wistar rats. Mucosal lesions were produced by intragastric superfusion with 0.15N HCland 15% ethanol for 40 minutes. Effects of an agonist (Y-26763, intra-arterially) and an inhibitor (glibenclamide, intravenously) of KATP channels were tested. RESULTS: Y-26763 increased GMBF, which was abolished by glibenclamide, and a CGRP-induced increase in GMBF was attenuated by glibenclamide. Macroscopic and microscopic lesions were exacerbated by human CGRP-(8-37) (a CGRP-1 receptor antagonist; intra-arterially) and glibenclamide but were ameliorated by exogenous CGRP (intra-arterially). CONCLUSIONS: CGRP protects the gastric mucosa against ulcerogenic stimuli, at least in part, through the activation of KATP channels in rats.

Animals↗
PubMed1998

Cerebral blood flow and metabolism in patients with silent brain infarction: occult misery perfusion in the cerebral cortex.

OBJECTIVES: Silent brain infarction (SBI) is of growing interest as a possible risk factor for symptomatic stroke. Although morphological characteristics of SBI have been well defined, their characteristic patterns of cerebral blood flow (CBF) and metabolism are in dispute. The purpose of this study was to elucidate CBF and metabolism in patients with SBI in relation to symptomatic stroke. METHODS: The patients underwent PET and were separated into three groups; control group (C group), with no lesions on CT (n=9, mean age 57), SBI group, with no neurological signs or history of stroke, but with ischaemic lesions on CT (n=9, mean age 63), and brain infarction group (BI group), with neurological deficits and compatible CT lesions in the area supplied by perforating arteries (n=19, mean age 56). Regional CBF, oxygen extraction fraction (OEF), cerebral metabolic rate for oxygen (CMRO2), and cerebral blood volume (CBV) were measured by PET. RESULTS: Mean values for CBF to the cerebral cortex and deep grey matter were lower in the SBI group (31.6 (SD 5.8) and 34.3 (SD 6.9) ml/100 g/min, respectively) and in the BI group (30.8 (SD 5.2), 33.9 (SD 5.9), respectively) than in the C group (36.0 (SD 6.6) and 43.5 (SD 9.5), respectively). Although mean CMRO2 of deep grey matter (2.36 (SD 0.52) ml/100 g/min) was significantly decreased in the SBI group compared with the C group (2.76 (SD 0.480), p<0.01), CMRO2 of the cortical area was as well preserved in the SBI patients (2.36 (SD 0.39)) as in the controls (2.48 (SD 0.32)) with a compensatory increase of mean OEF (0.45 (SD 0.06) and 0.41 (SD 0.05), respectively). CONCLUSIONS: Patients with SBI showed decreased CBF and CMRO2 in deep grey matter. On the other hand, decreased CBF with milder increased OEF, resulting in preserved CMRO2 in the cerebral cortex indicates the presence of occult misery perfusion, suggesting that patients with SBI have reduced cerebral perfusional reserves.

Adult↗
PubMed1998

Circumferential spontaneous coronary artery dissection in an elderly man: a case report.

An 82-year-old man developed acute inferior myocardial infarction. Emergent coronary angiography demonstrated thrombotic occlusion in the right coronary artery. Intracoronary thrombolytic therapy was performed with successful recanalization. However, circumferential dissection with luminal stenosis was revealed at the point of thrombus formation. Repeat angiography 6 months later showed resolution of the dissection. This is the first description of circumferential spontaneous coronary artery dissection. In addition, the present patient is older than any previous patients.

Aged↗
PubMed1997

L-arginine ameliorates recirculation and metabolic derangement in brain ischemia in hypertensive rats.

The effects of L-arginine (a precursor of nitric oxide, NO) on cerebral blood flow (CBF), cerebrovascular resistance (CVR) and metabolites in the ischemic brain were examined in spontaneously hypertensive rats with bilateral carotid artery occlusion for 30 min followed by 60 min-recirculation. The administration of L-arginine (300 mg/kg, i.v.) increased the CBF by an average of 11 ml x 100 g-1 x min-1 (P < 0.05 vs. at rest), and N(omega)-nitro-L-arginine (L-NNA, an inhibitor of NO synthase, 5 mg/kg, i.v.) reduced the CBF by 5-6 ml x 100 g-1.min-1 with increase in the mean arterial pressure by 26 mmHg. During ischemia the CBF significantly decreased to below 8% of the resting values in all rats. The largest blood flow in postischemic hyperemia was 171 +/- 9% of the resting CBF in the rats with L-arginine (P < 0.05 vs. L-NNA and saline), followed by 126 +/- 5 with saline and 109 +/- 3 with L-NNA. The CVR at 60 min of recirculation was 3.291 +/- 0.144 mmHg . ml-1. 100 g-1 .min-1 in the rats with saline, remained low level of 2.711 +/- 0.124 with L-arginine (P < 0.01 vs. L-NNA and P < 0.05 vs. saline) and in contrast, significantly increased to 5.732 +/- 0.184 with L-NNA (P < 0.01 vs. L-arginine and saline, respectively). Tissue lactate with saline increased 2.3-fold at 60 min of recirculation, whereas the increase was inhibited to 1.4-fold after L-arginine treatment (P < 0.01 vs. L-NNA) and in contrast, significantly increased 5.7-fold with L-NNA. The ATP and glucose levels were better preserved in the rats with L-arginine than in those with L-NNA or saline. These findings support that the enhanced postischemic hyperemia is beneficial to the ischemic brain and the administration of L-arginine may be potentially useful for the treatment of acute stroke.

Animals↗
PubMed1997

Age-related ischemia in the brain following bilateral carotid artery occlusion--collateral blood flow and brain metabolism.

Cerebral blood flow (CBF) and cerebellar blood flow (CeBF) were measured and correlated with brain lactate, pyruvate and adenosine triphosphate concentrations from groups representing 3-week old suckling (n = 10), 18-22-week old adult (n = 9) and 70-week old aged (n = 7) Sprague-Dawley rats before and during bilateral carotid occlusion (BCO). The steal ratio, calculated as the ratio of %control CBF to %control CeBF, was 1.02 +/- 0.06 (mean +/- SEM) at 60 minutes of BCO in adult rats that exhibited normal levels of brain metabolites. By contrast, the ratios significantly decreased to 0.74 +/- 0.06 in suckling rats and 0.69 +/- 0.06 in aged rats with simultaneous increases by 2.4 to 2.9-fold of tissue lactate. Pyruvate and lactate/pyruvate ratio also increased by 1.4 to 1.8 times control in both suckling and aged rats. We conclude that there is age-related steal phenomenon occurring with blood flow during BCO. Ischemic derangement of the brain metabolism is in part related to poor blood supply from the posterior circulation in suckling and aged rats.

Adenosine Triphosphate↗
PubMed1996

Brain ischemia and gastric mucosal damage in spontaneously hypertensive rats: the role of arterial vagal adrenoceptors.

Brain ischemia is often accompanied by acute gastric lesions. To clarify the underlying mechanism, the influence of acute ischemic insult to the brain on gastric hemodynamics and mucosal integrity was examined in spontaneously hypertensive rats. One hour after brain ischemia, gastric mucosal blood flow decreased to 71% of the preischemic levels in the control rats but was preserved significantly better, at 94 and 108%, in the prazosin-treated and guanethidine-treated rats, respectively. Vagotomy almost abolished the decrease in gastric mucosal blood flow during cerebral ischemia. Intragastric 0.6 N hydrochloric acid administered just after reperfusion induced more severe hemorrhagic ulcers in the control than in the prazosin-treated and vagotomized groups. These results suggest that noradrenergic neurons acting through alpha1-adrenoceptors contributes to the decrease in gastric mucosal blood flow, and the subsequent disturbed integrity of the gastric mucosa, through the vagal adrenergic pathway during brain ischemia in spontaneously hypertensive rats.

Adrenergic Agents↗