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Biomedical subjects

M Seguchi

Publications and source records attributed to M Seguchi.

At least 19 recordsLinked to original sources

HCO3(-)-dependent intracellular pH regulation in the premature myocardium.

This study investigated developmental changes in Na(+)-H+ exchange and HCO3(-)-Cl- exchange activities in newborn and adult rabbit hearts. pHi was measured using the fluorescent dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein in isolated myocytes. Myocardial mechanical function was measured in the isolated ventricular preparation. Intracellular acidosis with normal pHo was induced by an NH4Cl (10 mM) prepulse technique. Upon removal of NH4Cl, pHi fell transiently and then recovered toward the control level. In the HCO3-/CO2-buffered solution, the rate of recovery of pHi in the newborn was greater than in the adult. In the HCO3-/CO2-buffered solution, 5-(N-ethyl-N-isopropyl)amiloride (EIPA), an inhibitor of Na(+)-H+ exchange, inhibited the recovery of pHi completely in the adult. In the newborn, however, significant recovery of pHi was observed in the presence of EIPA. In the presence of both EIPA and 4-acetamido-4'-isothiocyanatostilbene-2',2'-disulfonic acid (SITS), an inhibitor of HCO3(-)-Cl- exchange, the recovery of pHi was not observed in the two age groups. In the HEPES-buffered solution that did not contain HCO3-/CO2, the rate of recovery of pHi after NH4Cl removal was similar in the two age groups. In the HEPES-buffered solution, the recovery of pHi was completely inhibited by EIPA in the two age groups. In the presence of EIPA in the HCO3-/CO2-buffered solution, contractile function decreased during acidosis after NH4Cl removal and did not recover in the adult. In the newborn, significant recovery of contractile function was observed after NH4Cl removal in the presence of EIPA. The recovery of mechanical function observed in the presence of EIPA in the newborn was inhibited by SITS. These data suggest that, although there is no developmental change in the Na(+)-H+ exchange activity, HCO3(-)-Cl- exchange is more active in the premature myocardium. The presence of the HCO3(-)-Cl- exchanger is important in maintaining myocardial contractile function during acidosis, especially when Na(+)-H+ exchange is inhibited and may partly explain the greater resistance of the premature myocardium to acidosis.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo

Prediction of surgical result of valve replacement for chronic isolated mitral regurgitation--the significance of preoperative estimation of postoperative left ventricular afterload.

Left ventricular (LV) afterload increases after mitral valve replacement, thus it would be useful to estimate postoperative LV afterload before surgery. We tested the usefulness of an index, wall stress, obtained from preoperative end-diastolic LV dimensions and diastolic blood pressure which would represent LV afterload after surgery. The data were compared with surgical mortality and morbidity. The wall stress ranged from 98 to 220 kdynes/cm2 and was 202 or higher in 3 patients who died. Five patients had wall stress above 200 kdynes/cm2. Among these, intra-aortic balloon pumping (IABP) was used in 4, and 3 died. Prolonged catecholamine support for greater than 10 days was given to all of the 4 patients, including two who died 14 and 23 days after surgery. Among 38 patients who had wall stress less than 200 kdynes/cm2, none died, IABP was performed in 3 patients, and prolonged catecholamine infusion was required in 5 patients. The incidence of mortality and morbidity were significantly higher in the high stress than in the low stress group (Chi-square analysis). Left ventricular end-diastolic index was larger in the high stress than in the low stress group (p less than 0.05). The mass/end-diastolic volume ratio was smaller in the high stress group than in the low stress group (P less than 0.05). In conclusion, this new index, predictive wall stress, is useful in selecting patients who would have high mortality and morbidity.

Cardiac Catheterization

A case report of familial cyclic neutropenia.

A 34-year-old female with cyclic neutropenia is reported. Family studies showed that her three sons and her mother were also involved. Oscillations in the blood neutrophil counts were almost regular, with a periodicity of 21 days. Numbers of colony-forming unit--granulocyte macrophage (CFU-GM) formed from the bone marrow cells of normal volunteers co-cultured with the patient's serum or mononuclear cell-conditioned medium (MNC-CM) were examined. Her serum prepared during the neutropenic phase inhibited the growth of CFU-GM, while her MNC-CM stimulated it. Human granulocyte colony-stimulating factor (hG-CSF) level in her serum was persistently high, with the peak occurring during the neutropenic phase. These results suggest that some inhibitory factors in the serum may be pathophysiologically important for cyclic neutropenia. To control infections, a pharmacological dose of hG-CSF was administered for 7 days around the early neutropenic phase. Her peripheral neutrophil counts oscillated from 1,200/mm3 to 17,000/mm3 with G-CSF, and from 150/mm3 to 1,800/mm3 without G-CSF.

Adult

[A successful allogeneic bone marrow transplantation for acute promyelocytic leukemia with anthracycline-induced cardiomyopathy at relapse].

A 14-year-old girl with acute promyelocytic leukemia (APL) developed cardiomyopathy following chemotherapy for remission induction and subsequent consolidation consisting of cumulative doses of 644 mg/m2 of daunorubicin and 31 mg/m2 of mitoxantrone. Six months after the first complete remission, when relapse of APL was recognized an allogeneic bone marrow transplantation (BMT) from her HLA-identical brother was performed. A preconditioning regimen, consisting of cytarabine (Ara-C, 2 g/m2/day x 3 days and 4 g/m2/day x 3 days), total body irradiation (TBI, 1200 cGy) and etoposide (VP-16, 50 mg/kg) caused moderate gastrointestinal symptoms and transient hemorrhagic cystitis, but did not worsen her cardiac function. Both continuous intravenous administration of heparin to control DIC and continuous low dose dopamine infusion to prevent cardiac failure achieved their purpose. The patient is leukemia-free and has no symptoms related to cardiomyopathy at the eight month after BMT. A preconditioning regimen (Ara-C, TBI and VP-16) appeared to be suitable for BMT to a patient with anthracycline-induced cardiomyopathy.

Adolescent

Effect of partial Na pump and Na-H exchange inhibition on [Ca]i during acidosis in cardiac cells.

This study investigated the effects of partial Na pump inhibition and Na-H exchange inhibition on contractile function, intracellular pH (pHi), and intracellular Ca concentration ([Ca]i) during intracellular acidosis, using the fluorescent dyes 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein and fura-2 in isolated cardiac cells of adult rabbits. Intracellular acidosis with normal extracellular pH was induced by an NH4Cl (10 mM) prepulse technique. A nontoxic concentration (0.5 microM) of ouabain was used to inhibit the Na pump. 5-(N-ethyl-N-isopropyl)amiloride (EIPA) was used to inhibit Na-H exchange. In both the absence and presence of ouabain, pHi fell transiently and then recovered after removal of NH4Cl. Ouabain did not alter the pHi changes observed after removal of NH4Cl. Diastolic and systolic [Ca]i increased during acidosis after NH4Cl removal. In the presence of ouabain, the increase in [Ca]i during acidosis was greater than that in the absence of this drug. Ouabain enhanced the recovery of contractile function during acidosis. In both the absence and presence of ouabain, Na-H exchange inhibition by EIPA reduced the recovery of pHi and mechanical function and the increase in [Ca]i, which were normally observed after NH4Cl removal. These data suggest that in adult rabbit myocytes the Na pump inhibition enhances the increase in [Ca]i during acidosis, and the Na-H exchange inhibition reduces it. The [Ca]i increase during acidosis may be in part due to the altered Na-Ca exchange, which in turn results from the increased Na-H exchange.

Acidosis

[The inhibitory effect of oxatomide on oxygen radical products from human eosinophils and an eosinophilic cell line].

Recently, much attention has been paid to the role played by the allergic inflammatory reaction in the role of asthma. Eosinophils are considered to be major inflammatory cells in bronchial asthma. Therefore, in this study, eosinophil-mediated oxygen radicals were examined by means of luminol-dependent chemiluminescence. Also, the effect of oxatomide, an anti-allergic agent, which has an inhibitory effect on eosinophil-mediated natural cytotoxicity against bronchial epithelial cells, on the production of oxygen radicals from eosinophils was studied. The results revealed the inhibitory effects of oxatomide on eosinophil-mediated oxygen radicals products. Furthermore, the inhibitory effect of this agent on oxygen radical products from eosinophilic cell-line named EoL-3, which has been established recently, was observed. We concluded from these results that oxatomide not only has anti-allergic activity but also anti-inflammatory properties for eosinophils.

Anti-Inflammatory Agents

Induction of IgE-Fc receptor (Fc epsilon R2/CD23) expression on lymphocytes from patients with mite-allergic bronchial asthma by mite allergen.

The present study was designed to clarify whether Fc epsilon R2 can be induced on lymphocytes of patients with bronchial asthma by stimulation with specific antigen. Expression of Fc epsilon R2 on freshly isolated lymphocytes (at 0 hour) was significantly higher in both patients with mite-allergic asthma and those with nonmite-atopic asthma than in healthy individuals. In addition, expression of Fc epsilon R2 on lymphocytes was still higher in patients during acute asthma. Marked induction of Fc epsilon R2 on lymphocytes was observed 48 hours or more after addition of mite-allergen in patients with mite-allergic asthma while no Fc epsilon R2 expression was induced in patients with nonmite-atopic asthma or healthy individuals. Induction of Fc epsilon R2 expression was not observed at 30 minutes, two hours, and five hours, which are equivalent in kinetics to immediate asthmatic response and late asthmatic response in allergen inhalational challenges.

Allergens

Ostial stenosis of the left coronary artery as a sole clinical manifestation of Takayasu's arteritis: a possible cause of unexpected sudden death.

An 11-year-old girl experienced several syncopal attacks and her electrocardiogram showed ST depression with exercise. Ostial stenosis of the left coronary artery was disclosed by the coronary angiography. We suspected the coronary involvement was due to Takayasu's arteritis. On operation, aortitis in the ascending aorta involving ostium of the left coronary artery was observed. Therefore Takayasu's arteritis is considered to be one of the causes of sudden death.

Aortic Arch Syndromes

Myocardial perfusion after aortic implantation for anomalous origin of the left coronary artery from the pulmonary artery.

Postoperative myocardial perfusion and function were evaluated using thallium-201 myocardial imaging and technetium-99m cardiac pool imaging in five patients with an anomalous left coronary artery arising from the pulmonary artery. The patients underwent reimplantation of the left coronary artery at an age ranging from 10 months to 13 years. Postoperative electrocardiographic and radionuclide studies were performed both at rest and during stress 1 to 4 years after the operation. Electrocardiograms which were abnormal preoperatively returned to normal after surgery except that the T wave in lead aVL remained negative. Postoperatively, left ventricular ejection fraction measured by technetium-99m cardiac pool imaging was normal in all patients. Postoperative thallium-201 myocardial imaging, however, showed a perfusion defect with incomplete redistribution at the high-lateral or antero-lateral segment in all patients after a stress test. These data suggest that although myocardial ischaemic change decreases and global cardiac function improves after establishment of a dual coronary artery system, severe myocardial damage remains at the high-lateral or antero-lateral segment.

Adolescent

Effect of acidosis on intracellular pH and calcium concentration in the newborn and adult rabbit myocardium.

This study investigated developmental changes in the effect of acidosis on intracellular pH (pHi) and [Ca]i in the isolated heart and isolated myocyte preparations. The whole heart or myocytes of newborn (5-7 days old) and adult rabbits were loaded with the fluorescent pH indicator 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF) or calcium indicator fura-2. Left ventricular pressure in the isolated heart preparation and the magnitude of cell contraction in the single-cell preparation were monitored. The heart and single cell were illuminated with excitation lights (340 and 380 nm, respectively, for fura-2 and 438 and 490 nm for BCECF). The intensity of fluorescence from the ventricular surface or from the cell was detected. [Ca]i was estimated from the following ratio: fluorescence at 505 nm during excitation at 340 nm/fluorescence at 505 nm during excitation at 380 nm. pHi was estimated from the following ratio: fluorescence at 530 nm during excitation at 490 nm/fluorescence at 530 nm during excitation at 438 nm. In the newborn, depression of contractile function during respiratory acidosis or metabolic acidosis was less than in the adult. Diastolic and systolic [Ca]i increased during respiratory acidosis in both the newborn and adult, and the net changes in [Ca]i were similar in the two age groups. During respiratory or metabolic acidosis, pHi decreased, but the decrease in the newborn was significantly less than in the adult. These data suggest that the greater resistance of the newborn myocardium to acidosis is due to the smaller change of pHi in this age group and not due to the difference in [Ca]i alteration.

Acidosis

Effect of respiratory acidosis on hypoxic newborn myocardium.

We studied the effect of respiratory acidosis (pH = 6.8) on mechanical function, tissue adenosine triphosphate (ATP), and effluent creatine kinase (CK) in isolated arterially perfused hypoxic newborn and adult rabbit hearts. In the oxygenated muscle, acidosis reduced tension (T) and maximal tension first derivative [+ dT/dt (max)] in the adult more than in the newborn. In the adult hypoxic and reoxygenated hearts, acidosis during hypoxia (not reoxygenation) improved the recovery of T, + dT/dt (max) and tissue adenosine triphosphate (ATP) and reduced CK release and the rise in the resting tension. In the newborn heart, respiratory acidosis during hypoxia had no beneficial effects on recovery of mechanical function, tissue ATP and CK release. The buffering capacity and sarcolemmal H-Na exchange rate are both higher in the newborn heart than in the adult heart. This suggests that acidosis reduces the rise in intracellular Na and Ca, that is observed during hypoxia and reoxygenation, in the adult more than in the newborn and this may explain the beneficial effect of acidosis in the adult and not in the newborn.

Acidosis, Respiratory

Inotropic effect of phenylephrine and myocardial alpha-adrenergic receptor in newborn and adult animals.

Developmental changes in the myocardial alpha-receptor density were studied using rabbit, rat and dog hearts. In all species studied, alpha-receptor density in the newborn was greater than in the adult. The inotropic effect of phenylephrine was measured using the isolated arterially perfused heart preparation of rabbit and rat. The heart was stimulated electrically at 40/min. In the presence of propranolol, phenylephrine caused a significant positive inotropic effect which was significantly less in the newborn than in the adult. Since alpha-adrenergic stimulation activates protein kinase C, the inotropic effect of protein kinase C activation was studied in the rabbit and rat using phorbol myristate acetate (PMA). PMA caused a negative inotropic effect and the decrease in contractile function in the newborn was greater than in the adult. These data suggest that myocardial alpha-receptor density decreases and the positive inotropic effect of alpha-agonist increases with development. The reasons for this discrepancy remain unclear but there may be developmental differences in the signal transduction processes of alpha-stimulation. The greater negative inotropy of protein kinase C activation in the premature heart may be one of the mechanisms of the reduced inotropy of alpha-agonist in this age group.

Animals

Development of the myocardial contractile system.

Recent studies regarding developmental changes in the myocardial contractile system from fetal, newborn, and adult animals are reviewed. From the data obtained so far, we conclude that in the early fetus myocardial contraction is mainly dependent on Ca which enters via the sarcolemma. Ca release from the sarcoplasmic reticulum is minimal. The role of the sarcoplasmic reticulum as a source of contractile Ca increases and the role of Ca influx across the sarcolemma in contractile system decreases with development.

Animals

Changes in left ventricular dimensions after pulmonary artery banding and Jatene operation in children with complete transposition of the great arteries. Echocardiographic study.

Echocardiographic left ventricular (LV) dimensions in patients with complete transposition of the great arteries (TGA's) were measured before and after the Jatene procedure and/or pulmonary artery banding (PAB). The LV posterior wall thickness at end-diastole (LVPWTD) increased from 3.5 +/- 0.4 to 4.9 +/- 0.9 mm (mean +/- 1SD) (p less than 0.01) after PAB, but it did not show a significant change following the Jatene procedure (from 4.5 +/- 1.0 to 5.3 +/- 0.8 mm). The LV end-diastolic internal dimension (LVIDD) increased from 17.7 +/- 4.0 to 22.6 +/- 6.5 mm after PAB (p less than 0.01), but remained unchanged after the Jatene procedure (from 24.5 +/- 5.0 to 25.0 +/- 3.0 mm). The LV shortening fraction (LVSF) decreased from 0.62 +/- 0.10 to 0.47 +/- 0.14 after PAB (p less than 0.01), but remained unchanged after the Jatene procedure (0.40 +/- 0.10 to 0.37 +/- 0.10). the a/b ratio at end-systole: (a/b)s, which indicates the flatness of the LV configuration, increased from 0.27 +/- 0.14 to 0.60 +/- 0.21 after PAB (p less than 0.01) and from 0.61 +/- 0.13 to 0.74 +/- 0.17 after the Jatene procedure (p less than 0.01). The data obtained became stable 1 month after operation. One patient died of low cardiac output with no evidence of myocardial infarction after the Jatene procedure. In this patient, LVPWTD was 5.7 mm, LVIDD was 26 mm, LVSF was 0.71 and the (a/b)s ratio was 0.55.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical

[J774].

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Animals

Influence of acidosis on inotropic effect of catecholamines in newborn rabbit hearts.

The influence of acidosis on the inotropic effect of isoproterenol was studied in the isolated arterially perfused heart of the newborn rabbits. Baseline mechanical function during acidosis (pH 6.8) was not different from control (pH 7.4). However, the inotropic effect of isoproterenol was significantly suppressed in the acidotic muscles. The increment of myocardial adenosine 3',5'-cyclic monophosphate (cAMP) content during isoproterenol infusion was also reduced in acidosis. Inotropic effects of Ca and dibutyryl cAMP in the acidotic muscles were not significantly different from those in the control muscles. beta-Receptor number and affinity in the respiratory acidotic muscle was similar to those in the control muscle. Effects of pH on myocardial beta-receptor and adenylate cyclase activity were further determined in the membrane fraction by changing the pH of the reaction medium from 7.4 (control) to 6.8 or 6.0. beta-Receptor numbers were significantly decreased at pH 6.0 but not at pH 6.8. Adenylate cyclase activity was depressed at pH 6.8 and 6.0. These data suggest that the inotropic effect of isoproterenol is diminished in the acidotic muscle. This may be due to the decreased activation of cAMP production, which in turn most likely results from depressed adenylate cyclase activity.

Acidosis

Developmental change in the function of sarcoplasmic reticulum.

This study investigates the developmental changes of sarcoplasmic reticulum function in rabbit heart. We used ryanodine to evaluate sarcoplasmic reticulum function in the isolated arterially perfused fetus, newborn and adult rabbit heart muscles. The magnitude of the negative inotropic effect of ryanodine was similar in the fetus and the 3-day-old newborn, and it was less than in the 7-day-old while the effect in the 7-day-old newborn was significantly less than in the adult. In the adult, and not in the newborn, ryanodine (10(-6) M) caused prolongation of half relaxation time and time to peak tension, and an increase in resting tension. In addition, ryanodine (10(-1) M was more effective in the adult, compared to the 3-day-old newborn, in the attenuation of the positive inotropism of staircase, hyperosmolarity and paired electrical stimulation. These data suggest that sarcoplasmic reticulum function dramatically changes during the perinatal period, and furthermore, suggests that the adult hearts are most likely dependent on Ca2+ release and uptake from sarcoplasmic reticulum, while the perinatal hearts are more dependent on transsarcolemmal Ca2+ influx than on sarcoplasmic reticulum Ca2+ release in excitation-contraction coupling.

Aging

Effect of Ca2+ antagonists on mechanical function in the neonatal heart.

The effect of verapamil and diltiazem on mechanical function was studied in the isolated arterially perfused neonatal and adult rabbit heart. The negative inotropic effect of these drugs in the newborn was significantly greater than in the adult. At concentrations 10(-7) M of verapamil and 10(-6) M of diltiazem, resting tension was significantly increased in the newborn, but not in the adult. In both age groups, verapamil and diltiazem inhibited the positive inotropy of staircase, but did not alter the inotropic effect of hyperosmolarity (116 mM mannitol). The positive inotropy of paired electrical stimulation was eliminated by these drugs in the newborn, but not in the adult. These data suggest that the neonatal heart as compared with the adult heart is more dependent on transsarcolemmal calcium influx for contraction and transsarcolemmal calcium efflux for relaxation.

Animals