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Biomedical subjects

Y Shiokawa

Publications and source records attributed to Y Shiokawa.

At least 19 recordsLinked to original sources

A primate model for acute and late cerebral vasospasm: angiographic findings.

A subarachnoid haemorrhage (SAH) in the squirrel monkey was produced by injection of blood via a permanently implanted catheter connected to the cisterna magna and a cannula stereotactically inserted into the interpeduncular cistern. Repeated angiographic examinations of the vertebro-basilar and right internal carotid arteries revealed a biphasic vasospasm with a maximal acute spasm at ten minutes and maximal late spasm at six days after blood injection. The present study has shown that a reproducible biphasic vasospasm can be produced in the squirrel monkey and evaluated by repeated angiographic examinations. The model is suitable in the study of basic mechanisms underlying vasospasm in a primate and, due to the size of the animal, autoradiographic evaluation of the cerebral blood flow and metabolism can be performed at an acceptable cost.

Animals

Effect of lesioning of medullary catecholamine neurons or the median eminence on the development of cerebral vasospasm in the squirrel monkey.

Injections of blood into the interpeduncular fossa and cisterna magna in the squirrel monkey produce an angiographically demonstrable, biphasic cerebral vasospasm with a maximal acute spasm at ten minutes and a maximal late spasm at six days after the subarachnoid haemorrhage (SAH). Selective lesioning of the A2 nucleus in the medulla oblongata or the median eminence in the hypothalamus prior to the SAH prevents the development of both the acute and late cerebral vasospasm. The present data indicate that the A2 nucleus and the median eminence participate in the development of vasospasm in the squirrel monkey.

Animals

Central projections of the sensory innervation to the middle cerebral artery in the squirrel monkey.

To analyze the brainstem projections of the innervation to the middle cerebral artery (MCA) in the squirrel monkey, transganglionic tracing of wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP) was used. After application of WGA-HRP to the middle cerebral artery (MCA), labelled cell bodies were identified in the ipsilateral trigeminal and superior cervical ganglia. In the brainstem, positive labelling indicative of preterminals and terminals occurred in a discontinuous pattern throughout the trigeminal brainstem nuclear complex. At the level of the obex, nerve terminations were identified in the nucleus tractus solitarius, nucleus motorius dorsalis nervi vagi and the nucleus nervi hypoglossi. Positive WGA-HRP profiles were also observed in the periaqueductal gray matter.

Afferent Pathways

Agents for the treatment of overactive detrusor. III. Synthesis and structure-activity relationships of N-(4-amino-2-butynyl)acetamide derivatives.

A series of N-(4-amino-2-butynyl)acetamides were synthesized and examined for their inhibitory activity on detrusor contraction and mydriatic activity as an index of anticholinergic side effect. Among those compounds synthesized, (+)-2-cyclohexyl-N-(4-dimethylamino-2-butynyl)-2-hydroxy-2-phenylacet amide hydrochloride ((+)-13b.HCl), 2-cyclohexyl-2-hydroxy-N-(4-methylamino-2-butynyl)-2-phenylacetamide+ ++ hydrochloride (13c.HCl), N-(4-dimethylamino-2-butynyl)-2,2-diphenyl-2-hydroxyacetamide hydrochloride (14a.HCl), and 2,2-diphenyl-N-(4-ethylamino-2-butynyl)-2-hydroxyacetamide hydrochloride (14b.HCl) showed equipotent inhibitory activity on detrusor contraction to oxybutynin (1) and less mydriatic activity. Further evaluation of these compounds as an agent for the treatment of overactive detrusor has been examined.

Alkynes

Agents for the treatment of overactive detrusor. II. Synthesis and inhibitory activity on detrusor contraction of 1,1'-biphenyl-2,6-dicarboxylic acid diesters with an aminoalkyl group in the ester function.

A series of 1,1'-biphenyl-2,6-dicarboxylic acid diesters with an aminoalkyl group in the ester function were synthesized and examined for their inhibitory activity on detrusor contraction in vitro and in vivo. In the in vivo test, arrhythmia was observed as a side effect. Among those compounds synthesized, 2-methyl 6-[4-(1-methylpiperidinyl)] 3-hydroxy-5-methyl-2'-nitro-1,1'-biphenyl-2,6-dicarboxylate (18) showed strong inhibitory activity on detrusor contractions in vivo (ED50 = 0.54 mg/kg i.v., ED50 = 7.2mg/kg i.d.) and good separation from the side effect. Compound 18 was chosen for further pharmacological evaluation as an agent for the treatment of overactive detrusor.

Animals

Effect of unilateral pre- and postganglionic lesioning of the trigeminal nerve on the development of cerebral vasospasm in the squirrel monkey: angiographic findings.

Bilateral carotid angiography was performed in the squirrel monkey before and after unilateral pre- and postganglionic trigeminal lesioning. A unilateral postganglionic lesion caused a significant constriction of about 27% of the ipsilateral cerebral arteries, while a preganglionic lesion did not change the baseline arterial diameter. Following a subarachnoid haemorrhage (SAH) the degree of vasoconstriction in the animals with a preganglionic lesion did not differ significantly from that seen in controls. In the postganglionically lesioned animals, the vasoconstriction was more pronounced (12% at both 10 min and 6 days post SAH) on the lesioned as compared with the non-lesioned side. At day 6 post SAH the degree of vasoconstriction was 19% more pronounced on the lesioned side in post- as compared with the preganglionically lesioned animals. There was no difference in the degree of spasm on the non-lesioned side between the two groups. The findings indicate that the trigeminal system has both a peripheral and a central function. The peripheral, or axon reflex mechanism, exerts a tonic effect on the cerebral vessels. Following a SAH the axon reflex seems to attenuate cerebral vasospasm.

Animals

Effect of pre- and postganglionic lesioning of the trigeminal nerve on cerebral blood flow and glucose metabolism following a subarachnoid haemorrhage in the squirrel monkey.

Simultaneous cerebral blood flow (CBF) and glucose metabolism (CMRglu) studies with a double isotope autoradiographic technique were applied to squirrel monkeys submitted to a unilateral pre- or postganglionic trigeminal lesion. The CBF values were not affected following a pre- or postganglionic lesion per se. In contrast, there was a global increase in the cerebral glucose uptake of about 50% as compared to controls following both kinds of lesions. Following a subarachnoid haemorrhage (SAH) 2-4 weeks after pre- or postganglionic trigeminal lesioning, there was a decrease in CBF similar to that seen in the control group. In the animals with a preganglionic lesion, the 50% increase in glucose uptake was not further augmented by a SAH and the increase in CMRglu was comparable to that found in control SAH animals. In the postganglionically lesioned monkeys, a SAH induced an additional increase in glucose uptake of about 50%. The findings suggest that the trigeminal system is involved in the regulation of cerebral metabolism via a brainstem centre.

Animals

[Evaluation of halothane induced HPV inhibition with analysis of pressure-flow curve].

We investigated the effect of halothane on the hypoxic pulmonary vasoconstriction using in vivo measurement of the pressure-flow curve of the left lower lobe in the dog. With hypoxic ventilation of the left lower lobe, the pressure-flow curve shifted to the right and the slope of the curve became flatter. Although inhalation of 1 MAC halothane by the left lower lobe during hypoxic ventilation had no effect on the pressure-flow curve configuration, inhalation of 3, 5 MAC made the slope steeper. We analyzed these changes by the distensibility model proposed by W. Mitzner et al, and our data support the hypothesis that hypoxic ventilation decreases the small pulmonary vessels of 1-4 orders and also increases the compliance of the orders of vessel where the constriction has occurred, and halothane antagonizes the HPV response by further increasing the compliance of the constricted vessels. The inhibitory effect of halothane on HPV was weaker in in vivo preparation compared with the effect in in vitro preparation. Some humoral factors in the perfusate could contribute to this effect.

Animals

Anomalous origin of the right pulmonary artery from the ascending aorta.

Five cases of anomalous origin of the right pulmonary artery from the ascending aorta were seen at our hospital. Patients 1 and 2 had an intact right pulmonary artery originating from a right posterior aspect (proximal form), and primary anastomosis of the right pulmonary artery and main pulmonary trunk was performed. Patients 3 and 4 showed a narrowing right pulmonary artery originating from near the base of the innominate artery (distal form). The stenotic right pulmonary artery was reconstructed with an 8-mm graft in patient 3, whereas patient 4 became inoperable because complete obstruction had developed in the right pulmonary artery during the 3 months that the patient was waiting to undergo operation. In patient 5, primary anastomosis was undertaken, but morphologically the anomalous origin was of the distal form, so the occurrence of stenosis in the reconstructed right pulmonary artery was a matter of concern. The morphological type was found to be related to the surgical options in this anomaly. Therefore, primary anastomosis was considered the best choice for a correction of the proximal form, whereas a graft interposition with a resection of the stenotic portion on the right pulmonary artery was deemed preferable in the distal form.

Aorta

Agents for the treatment of overactive detrusor. I. Synthesis and structure-activity relationships of 1,1'-biphenyl derivatives.

A series of 1,1'-biphenyl-2,6-dicarboxylic acid diesters were synthesized and examined for their inhibitory activity on guinea-pig detrusor muscle contraction at electrical field stimulation in vitro. Among them, 6-isopropyl 2-methyl 3-hydroxy-5-methyl-2'-nitro-(1,1'-biphenyl)-2,6-dicarboxylate, FR75513 (8a) was one of the potent compounds (IC50 = 3.3 x 10(-6) g/ml). This compound (8a) exhibited a strong inhibitory activity on detrusor contraction after intravenous administration in anesthetized rats (ID50 = 0.04 mg/kg).

Animals

Venous infarction following the interhemispheric approach in patients with acute subarachnoid hemorrhage.

Postoperative venous infarction following aneurysm surgery was studied in 48 patients with anterior communicating artery aneurysms operated on through the interhemispheric approach at the acute stage of subarachnoid hemorrhage (SAH). Of 23 patients whose bridging veins were sacrificed during surgery, 11 (47.8%) showed venous infarction in the frontal lobes. In contrast, only one (5.9%) of 17 patients whose bridging veins were preserved developed cerebral edema. None of eight patients who were operated on after Day 11 (the day of SAH was defined as Day 0) showed this complication, although bridging veins were sacrificed in six of them. Venous infarction following acute aneurysm surgery tended to occur more frequently in patients of higher SAH grade and/or more advanced age, but these correlations were not significant. However, the correlation between the sacrifice of veins and venous infarction was significant (p less than 0.025). Because this potential complication may compromise the benefit of acute aneurysm surgery and cause damage, it is important to preserve the venous system and in some instances to select another surgical approach based on the pattern of venous drainage in the frontal lobe.

Acute Disease

Chemotherapy of soft tissue sarcomas in the extremities.

A retrospective study on chemotherapy against soft-tissue sarcomas in the extremities was carried out on 98 patients. The local recurrence rate was 10.3% with intensive chemotherapy in post-1980 patients with high-grade sarcomas but 46.7% without chemotherapy--a fairly significant difference (P less than 0.01). The survival rate was significantly higher with intensive chemotherapy in post-1980 patients with high-grade sarcomas. Thus, intensive chemotherapy based on a new protocol should be given in cases of high-grade sarcoma. Considering surgical margin, the local recurrence rate was 33.3% in post-1980 cases inadequately operated upon but 8.6% in those adequately operated upon, which shows a significant difference (P less than 0.05).

Adolescent

[Recommendation for open heart surgery in infancy].

Progress in infant open-heart surgery last 10 years was reviewed mainly based on the surgical experiences in Fukuoka Children's Hospital. Recent advances and present problems in patient's care, cardiopulmonary bypass methods and cardioplegia were discussed. Low surgical mortality of 4.8% in 245 infant open-heart repairs between 1988 and 1990 in Fukuoka is highly suggestive of early primary repair for most of congenital heart diseases.

Cardiac Surgical Procedures

[Diagnosis and surgical treatment of accessory mitral valve with associated congenital heart disease].

Accessory mitral valve (AcMV) is a rare cardiac anomaly that may possibly cause left ventricular outflow tract (LVOT) obstruction. Five patients who underwent surgical resection of AcMV were reported. All these patients had associated cardiac anomalies, which include transposition of great arteries (TGA) in two cases, ventricular septal defect (VSD) in one, double outlet right ventricle (DORV) in one and membranous septal aneurysm (MSA) in one. Age at operation ranged from 23 days to 22 months. In these cases preoperative pressure gradient across the LVOT ranged from 10 to 35 mmHg. Resection of AcMV was performed together with radical operation for associated anomalies in all the patients. Approach for resection of AcMV consisted of trans-ventricular septum method in 3 patients of VSD, DORV or MSA and trans-pulmonary artery method in 2 cases of TGA. There was no operative death. The postoperative pressure gradient across the LVOT ranged from 0 to 13 mmHg. Two dimensional echocardiography was essential for the accurate preoperative diagnosis of AcMV in 4 out of the 5 patients. The trans-ventricular septum method, when the large VSD was present, for resection of AcMV was found to be quite useful especially for neonates in order to obtain an excellent operative field, as compared with the conventional method.

Echocardiography

Myocardial protection by retrograde cardioplegia in arterial switch operation.

Retrograde coronary sinus perfusion of cold cardioplegic solution was evaluated in infants undergoing an arterial switch operation for transposition of the great arteries. To assess myocardial injury during ischemia, hemodynamic measurements were conducted at weaning from cardiopulmonary bypass and a postoperative assay of creatine kinase isoenzyme MB was performed. In 22 infants with retrograde coronary sinus perfusion, the initial cardioplegic infusion was performed through the aortic root and additional infusion was repeated every 30 minutes by retrograde coronary sinus perfusion. The other 11 infants received additional solution by antegrade selective coronary artery perfusion. The aortic cross-clamp time in the retrograde coronary sinus perfusion group was significantly shorter than that in the antegrade selective coronary perfusion group (128 +/- 19 versus 143 +/- 21 minutes, p less than 0.05). There were no significant differences between the two groups in terms of postoperative hemodynamic variables and enzyme indexes. Eight neonates in the retrograde coronary sinus perfusion group also exhibited enzymatic and hemodynamic indexes similar to those of older infants. These results suggested that retroperfusion of cardioplegic solution was a safe and useful means of myocardial protection in infants and neonates because of the simplification of the operative procedure and the avoidance of traumatic injury to the coronary ostia.

Cardioplegic Solutions