Endothelin in plasma and cerebrospinal fluid of patients with subarachnoid haemorrhage.
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Endothelins↗
Biomedical subjects
T Mima
Publications and source records attributed to T Mima.
Effect of recombinant human lipocortin I on brain oedema in a rat glioma model.
Glucocorticoids have been extensively used to treat brain oedema, but little is known on the mechanisms of steroids in the prevention and resolution of tumour-induced brain oedema. Recently, the mechanism of steroid action is thought to involve synthesis of proteins with antiphospholipase activity called lipocortins. In a previous study, we have demonstrated the efficacy of dexamethasone (DEX) in resolving peritumoural oedema in a rat glioma model. Using the same model, we studied the effect of recombinant human lipocortin I on the resolution of peritumoural oedema. Intracerebral tumours were produced in 6-week-old Wistar rats by implantation of rat glioma C6 cells. In comparison with sham-operated controls, the tumour-implanted animals showed significant increase in the cortical water content, which was reduced by DEX administration to the level in the sham-operated controls. The water content within the tumour was also significantly decreased by DEX treatment. On the other hand, there was no difference in water content between lipocortin-treated and non-treated animals. These findings suggest that tumour-induced brain oedema can be reduced by DEX treatment but not by lipocortin. In conclusion, it is doubtful whether glucocorticoids exert their action in resolving brain oedema by inducing PLA2 inhibitory proteins named lipocortins.
Animals↗
Reactive hyperaemic flow characteristics of the right coronary artery compared to the left anterior descending coronary artery in the open-chest dog.
Reactive hyperaemia, the cardiovascular response to transient occlusion of a vessel, was examined and compared in the right coronary artery (RCA) and the left anterior descending coronary artery (LAD) in the same heart of an open-chest dog. First, to study the relationship between reactive hyperaemia and occlusion time in the RCA and LAD, respective flows were measured and reactive hyperaemia was induced with different occlusion times. Occlusion time required for half the maximum peak percentage reactive hyperaemic flow (%PRH), t 1/2, for the RCA was approximately twice that of the LAD: 11.4 +/- 2.3 s versus 5.9 +/- 1.4 s. Maximum %PRH of the RCA was significantly greater than that of the LAD while the percentage repayment of the RCA was lower than that of the LAD. Augmentation of right ventricular oxygen consumption shortened t 1/2 and increased percentage repayment significantly. Second, to determine "critical pressure", which was defined as the perfusion pressure below which reactive hyperaemia was abolished completely, the RCA and LAD were perfused through a shunt from the carotid artery, perfusion pressure was varied in the range of 100 to 20 mmHg and reactive hyperaemia was induced. Critical pressure in the RCA was significantly lower than in the LAD: 32.2 +/- 5.7 mmHg versus 41.5 +/- 5.0 mmHg. These results suggest that the RCA has a greater flow reserve than the LAD. These results were consistent with the difference of oxygen metabolism between the right and left ventricles. The difference of oxygen metabolism between the two ventricles would, at least partly, account for these results.
Animals↗
High-dose dexamethasone given long before cerebral ischemia does not ameliorate edema formation.
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Animals↗
A new vasoconstrictor peptide, endothelin: profiles as vasoconstrictor and neuropeptide.
Endothelin was predictably found to be one of the endothelium-derived contraction factors (EDCFs) with the aid of advanced protein technology. It is the most potent and long-lasting vasoconstrictor peptide known to date. By analysis of the amino acid sequence, modern gene technology has made it possible to find isopeptides. These isopeptides, namely the endothelin family composed of endothelin-1, -2, and -3, have made and are achieving a breakthrough in every field of physiology and pathology. In the central nervous system, they act not only as a vasoconstrictor but also as a neuropeptide, in particular endothelin-1 and -3. Here we overview the findings obtained over the past 2 years since its discovery, and look to future progress.
Animals↗
Mechanisms of astroglial swelling in focal cerebral ischemia.
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Animals↗
Serum dipeptidyl peptidase activities as a possible marker of oral cancer.
Serum glycyl-l-prolyl 4-methyl-coumaryl-7-amide (gly-pro-MCA) hydrolase (DPP IV) and L-lysyl-L-alanyl beta-naphthylamide (lys-ala-beta NA) hydrolase (assumed to be DPP II) activities were measured in patients with oral squamous cell carcinoma and healthy subjects. The mean serum DPP IV activity of all cancer patients was significantly (P less than 0.001) decreased, compared with that of healthy subjects. Although there was no significant difference between the stages by International Union Against Cancer (UICC) classification (1978), DPP IV levels tended to change dynamically, reflecting the clinical status during therapies. The serum DPP IV activity of patients with a fair prognosis was significantly elevated toward the normal range, whereas the activity of patients with a poor prognosis was significantly decreased (P less than 0.05). In contrast, the mean serum lys-ala-beta NA hydrolytic activity of cancer patients was significantly (P less than 0.001) increased, compared with that of healthy subjects, and was changed reciprocally to DPP IV activity. The correlation of these two serum enzyme activities with tumor weights also was observed in animal models using nude mice transplanted with human KB carcinoma cells and hamsters transplanted with BHK21 cells. These results indicate that these serum enzyme levels may become an aid for the diagnosis of malignant tumors and for estimating the prognosis of the patients.
Adult↗
Endothelin-1 acts in cerebral arteries from the adventitial but not from the luminal side.
The in vivo vasoconstrictor effect of endothelin-1 (ET-1) was investigated on feline and canine basilar arteries. The basilar artery caliber was angiographically measured after either vertebral artery perfusion or cisternal injection of the peptide. In both cats and dogs, ET-1 (5-500 pmol) induced a dose-dependent basilar artery contraction in vivo when applied intracisternally. The vasoconstriction was extremely long lasting; no significant recovery of vessel caliber was observed up to 12 h after injection. In contrast, bolus injection of ET-1 up to 3 nmol into the vertebral artery had no appreciable effect on the basilar artery caliber. These observations suggest that ET-1 acts in cerebral vessels from the adventitial but not from the luminal side, possibly due to the presence of the blood-brain barrier. The long-lasting nature of the ET-1-induced constriction of the cerebral arteries in vivo suggests that the peptide might be involved in the pathogenesis of cerebral vasospasm.
Animals↗
High induction of poly(ADP-ribose) polymerase activity in bleomycin-resistant HeLa cells.
Poly(ADP-ribose) polymerase activity was measured in bleomycin (BLM)-resistant HeLa (HeLa-BLMr) and the parental HeLa cells after BLM treatment. HeLa-BLMr cells, which had been subcultured in growth medium containing 1 micrograms/ml of BLM, showed a 3.75-fold higher enzyme activity than did HeLa cells, but this activity was decreased to the same level as that of HeLa cells after 48 h of BLM-free cultivation. When HeLa and HeLa-BLMr cells after a 48-h cultivation in BLM-free growth medium were treated with BLM, the enzyme activity was induced at a higher level (2.5-3.8 times) in HeLa-BLMr than in HeLa cells and was inhibited markedly in HeLa-BLMr and slightly in HeLa cells by nicotinamide, an inhibitor of this enzyme. The BLM-induced cell killing by nicotinamide was highly potentiated (about 18 times) in HeLa-BLMr as compared to HeLa cells.
Bleomycin↗
Endothelin acts in feline and canine cerebral arteries from the adventitial side.
We investigated the in vivo vasoconstrictor effect of endothelin, a recently characterized vasoconstrictor peptide from vascular endothelium, in the basilar arteries of five cats and five dogs. Basilar artery caliber was angiographically measured under anesthesia before (control) and after either vertebral artery infusion or cisternal injection of the peptide. In cats, 5-500 pmol endothelin induced a dose-dependent basilar artery contraction in vivo when injected intracisternally; within 3 minutes after injection of 500 pmol endothelin, basilar artery caliber was decreased by 73 +/- 4% compared with control diameter before injection. The vasoconstriction was extremely long-lasting; no significant recovery of basilar artery caliber was observed for up to 2 hours after injection. In contrast, infusion of up to 3,000 pmol endothelin into the vertebral artery had no appreciable effect on basilar artery caliber. Similar results were obtained in dogs; vasoconstriction was maintained for as long as 12 hours. Our observations suggest that endothelin acts in cerebral vessels from the adventitial side, not from the luminal side, possibly due to the presence of the blood-arterial wall barrier. The long-lasting nature of endothelin-induced constriction of the cerebral arteries in vivo suggests that the peptide might be involved in the pathogenesis of cerebral vasospasm.
Animals↗
Prostaglandin profiles in relation to local circulatory changes following focal cerebral ischemia in cats.
We explored the temporal and topographic relations between local cerebral blood flow and regional brain prostaglandin profile following prolonged or transient occlusion of the middle cerebral artery in cats. Each experimental group was subjected to a sham operation, prolonged ischemia, or recirculation. Local cerebral blood flow was measured by the hydrogen clearance method. Following in situ freezing, cortical samples were obtained from each gyrus for determination of prostaglandin (PG) F2 alpha, PGE2, 6-keto-PGF1 alpha, and thromboxane (TX) B2 concentrations by radioimmunoassay. During prolonged ischemia, the concentrations of PGF2 alpha and PGE2 within the middle cerebral artery territory were significantly increased. Immediately after recirculation, there was a prominent but transient increase in PGF2 alpha and PGE2 in gyri that had been exposed to moderate ischemia (perifocal area). By contrast, the increases in these prostaglandins were slow and less prominent in gyri that had been exposed to severe ischemia (the focal area). The concentration of 6-keto-PGF1 alpha did not change during prolonged ischemia but transiently increased following recirculation in both the focal and perifocal areas. The TXB2 concentration did not change in any experimental group. Our study revealed a homogeneous increase in the regional brain content of PGE2 or PGF2 alpha in spite of the heterogeneous reduction of local cerebral blood flow during prolonged ischemia. Following recirculation, the focal and perifocal areas exhibited different patterns of prostanoid content. No correlation was found between local cerebral blood flow and the regional concentration of any prostaglandin examined.
6-Ketoprostaglandin F1 alpha↗
Effect of enhanced capillary activity on the blood-brain barrier during focal cerebral ischemia in cats.
We hypothesize that enhanced activity of capillary Na,K-ATPase promotes Na+ influx into the brain and causes early edema formation in focal cerebral ischemia. The pharmacologic suppression of brain capillary Na,K-ATPase as a means to ameliorate edema formation was examined using the middle cerebral artery occlusion model in 36 cats. With the help of a catheter inserted into the middle cerebral artery, the ischemic brain area was directly perfused with 10(-5) M ouabain. Perfusion was maintained as intermittent 15-second pulse injections given every 5 (n = 6) or 2 (n = 6) minutes. By this method, the naturally occurring circulatory conditions during ischemia were not altered. Four hours after ischemia, the cortical specific gravity at each of six locations over the ischemic area was compared with the corresponding ischemic blood flow measured by the H2 clearance technique. The results show that ouabain perfused every 2 minutes significantly ameliorated edema formation compared with six control cats perfused with Krebs-Ringer solution. In a separate series of experiments, the Na+ flux across the blood-brain barrier was studied by injecting 22NaCl together with an intravascular reference (cobalt-57-labeled microspheres 15 microns in diameter) into the ischemic area. The brain uptake index of 22Na was markedly increased in the ischemic cortex of six control cats; ouabain treatment in six cats suppressed the increase of Na+ influx. The results support our hypothesis that brain capillary Na,K-ATPase activity increases during early focal ischemia, leading to enhanced Na+ together with H2O flux across the blood-brain barrier.
Animals↗
Coronary flow reserve and oxygen metabolism of the right ventricle.
The flow reserve of the right coronary artery (RCA) and myocardial oxygen extraction are important tractors in any investigation of the mechanisms of impaired right ventricular function. The present study induced brief coronary occlusions and examined the effect on right coronary blood flow in normal dogs, and the effect on myocardial oxygen metabolism in dogs with right ventricular hypertrophy (RVH). Right coronary flow reserve, represented by occlusion duration causing a half maximum dilatation (T1/2), was greater in the RCA than in the left anterior descending coronary artery of normal dogs; 11.4 +/- 2.3 sec vs 5.9 +/- 1.4 sec. Myocardial oxygen extraction ratio (EO2) of the right ventricle (RV), 51.3 +/- 1.6%, was significantly (p less than 0.05) lower than the index of the left ventricle (LV), 60.6 +/- 1.0%, and the extraction of the RV increased significantly in association with an increase of myocardial oxygen demand. In dogs with RVH caused by chronic banding of the pulmonary artery, this dominant oxygen reserve was lost: the EO2 of the hypertrophied RV was high compared with the EO2 of the normal RV (57.3 +/- 3.4% vs 51.3 +/- 1.6%, p less than 0.05), and no further increase in EO2 was observed in the hypertrophied RV in response to the elevation of the myocardial oxygen requirement. Oxygen usage per 100g of the RV for a certain level of overall RV work, rate-pressure product, was significantly (p less than 0.02) lower in the hypertrophied RV (0.00054 mlO2/beat.mmHg) than in the normal RV (0.0012 mlO2/beat.mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[A broken needle in the pterygomandibular space].
We encountered a case where a 30 gauge disposable dental needle was accidentally broken and inoculated into pterygomandibular space by a dentist during a block anesthesia for the inferior alveolar nerve. Several approaches including use of a guide needle and roentgenograms were made but all were unsuccessful. Eleven days later, further operation was attempted monitoring the needle on X-ray TV, resulting in that the broken needle was successfully removed. This technique may be useful for removal of mandibular broken needles.
Anesthesia, Dental↗
Improvement of reduced coronary vasodilatory response during reactive hyperemia by diltiazem.
This study was performed to reconfirm transiently-reduced vasodilatory responses of the coronary artery in the reactive hyperemic period, and also to study whether an increase in calcium influx into the coronary smooth muscle accounts for the reduced coronary vasodilatory responses. Blood flow in the circumflex coronary artery was measured with an electromagnetic flow transducer in anesthetized open-chest dogs. Two successive occlusions for 3 to 7 s performed in pairs with a brief interval were accompanied by decreasing reactive hyperemia: the maximum reduction of reactive hyperemia appeared when the occlusion period was around 5 s with a 5-s interval. Around 5 s after the release of occlusion, excess arterial inflow almost equaled the blood flow debt incurred during the first occlusion. Pretreatment with diltiazem (150 micrograms/kg), a calcium entry blocker, significantly attenuated the reduction of coronary vasodilatory responses, but glyceryl trinitrate (nitroglycerin) did not affect the phenomenon of coronary reactivity. The results suggest that excess accumulation of calcium in the smooth muscle of small coronary arteries occurred during an early period of post-occlusion hyperemia, which resulted in a reduced vasodilatory reactivity of the vessels to the second ischemic stimulus.
Animals↗
The QRS complex of the standard 12-lead electrocardiogram in septal myocardial infarction.
Interventricular septal involvement in myocardial infarction is suggested by the findings of a QS deflection in lead V1 and/or absence of the Q wave in leads I and V6, using the standard 12-lead electrocardiogram (ECG). However, these findings were not sufficiently established for the criteria of septal infarction, because several factors including anatomic position of the heart, changes of intraventricular conduction, and condition of the lung would affect the QRS complex in the leads. In this study, we analyzed the ECGs of anterior myocardial infarction with (group A) and without (group B) involvement of the first septal coronary artery. The R wave in V1 was absent in 64.7% of group A and 60.0% of group B. The Q wave was absent in 35.3% in lead I and 64.7% in lead V6 of group A, while in group B the Q wave in leads I and V6 were not observed in 60.0% and 40.0%, respectively. The prevalence rates of the R wave and the Q wave in these leads were not significantly different between the two groups. Left ventriculography revealed that the prevalence rate of the R wave in V1, and the Q wave in I and V6 was not significantly different, regardless of the presence or absence of impaired septal motion. Experimental study in anesthetized dogs confirmed the difficulty in clarifying acute septal ischemia by changes in the QRS complex. These results indicate that septal myocardial infarction is hardly detectable with changes in the QRS complex of the standard 12-lead electrocardiogram.
Coronary Vessels↗
Effect of heart rate and myocardial contractile force on coronary resistance.
The effect of the heart rate and myocardial contractile force on the extravascular resistance to blood flow of the left anterior descending coronary artery (LAD) was evaluated in 15 mongrel dogs anesthetized with sodium pentobarbital. The LAD was maximally dilated by intracoronary infusion of adenosine, which precluded the influence of vasomotor tone. Increases in the heart rate and myocardial contractile force decreased coronary blood flow in the absence of a change in coronary perfusion pressure. The changes in mean coronary resistance showed a significant linear relationship to changes in developed tension. The changes in coronary resistance caused by varying the heart rate and contractile force were so small that a normal coronary vascular tree could easily compensate for the increase in resistance. However, it is supposed that with critical stenosis of the vascular tree even a small increase in resistance might cause deleterious effects on coronary blood flow.
Adenosine↗
[A double-blind evaluation of famotidine for pre-anesthetic intramuscular administration--its effects on volume and pH of gastric juice].
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Adolescent↗