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Z Onouchi

Publications and source records attributed to Z Onouchi.

At least 19 recordsLinked to original sources
PubMed2001

Fatal pulmonary hypertension associated with an atypical case of Hunchinson-Gilford progeria.

We report the first autopsied case of an incomplete type of Hunchinson-Gilford progeria associated with fatal pulmonary hypertension. Histopathologic findings revealed abnormal deposition of collagen and elastic fibers, as well as cellular proliferation, at intima of the coronary arteries, pulmonary small arteries, and arterioles. These changes could be underlying conditions of the association of the two diseases.

Child↗
PubMed2000

Effect of coenzyme Q10 on experimental atherosclerosis and chemical composition and quality of atheroma in rabbits.

The effects of the administration of coenzyme Q10 (3 mg/kg per day) (group A, n=10) and placebo (aluminum hydroxide, 3 mg/kg per day) (group B, n=10) were compared over 24 weeks in a randomized, single-blind, controlled trial. There were two groups of rabbits receiving a trans fatty acid (TFA)-rich diet (5-8 g/day) for 36 weeks. Oxidized rabbit chow with vitamin C plus ferric chloride was administered for 4 weeks in all rabbits. Intervention with coenzyme Q10 after feeding of TFA-rich diet was associated with a significant decline in thiobarbituric acid reactive substances (TBARS), diene conjugates and malondialdehyde, and an increase in plasma levels of vitamin E in the coenzyme Q group compared to placebo group. These changes, which were indicators of a decrease in oxidative damage, were independent of lipid lowering. The aortic and coronary artery plaque sizes, coronary atherosclerosis index, aortic and coronary atherosclerosis scores were significantly lower in the coenzyme Q group than placebo group. Aortic and coronary plaque frequencies, as well as frequencies of ulceration, thrombosis or hemorrhage, and cracks and fissures, were also significantly lower in the coenzyme Q group, indicating a better quality of atheroma compared to those in the control group. Aortic cholesterol, triglycerides and sudanophilia were significantly lower and vitamin E significantly higher in the coenzyme Q group in comparison to the placebo group indicating that coenzyme Q10 can have beneficial effect on the chemical composition of atheroma. The findings suggest that antioxidant therapy with coenzyme Q10 may be used as an adjunct to lipid lowering for additional beneficial effects related to chemical composition and quality of atheroma independent of hypolipidemic agents.

Animals↗
PubMed1999

Ultrastructural characteristics of myocardial and coronary microvascular lesions in Kawasaki disease.

Kawasaki disease (KD) is an acute febrile mucocutaneous lymph node syndrome with multisystemic vasculitis affecting mainly infants and children. Although several studies on cardiovascular lesions in KD have been done at the light microscopic level, the ultrastructural characteristics and incidences of these lesions have not been well defined. In order to investigate the myocardial and coronary microvascular sequelae in KD, we performed an ultrastructural study on endomyocardial biopsy specimens obtained during follow-up from 54 patients who had typical clinical manifestations of KD, of whom 47 had associated coronary aneurysms as demonstrated by coronary arteriography (CAG) or two-dimensional echocardiography in the acute or healed stage. The average age of onset was 2.2 years old and the duration of illness was from 2 months to 23 years. Follow-up CAG showed that the coronary aneurysms persisted in 33 of the 47 patients (8 with associated stenosis) and resolved in the remaining 14 patients. Ultrastructurally, the myocardial changes revealed hypertrophy, various degrees of degeneration, proliferation and abnormality of mitochondria, infiltration of a small number of lymphocytes, and fibrosis. The coronary microvascular lesion was characterized by microvascular dilatation, endothelial cell injury, platelet aggregation with thrombosis, and stenotic lumen with thickened walls in the small arterioles. It persisted after convalescent stage even up to 23 years and closely correlated with the myocardial sequelae. Moreover, significantly increased incidences of myocardial and coronary microvascular lesions were found in patients with coronary artery lesion. These findings suggest the coronary microvascular lesion as a possible underlying factor of persistent sequelae in KD.

Adolescent↗
PubMed1999

Effect of CABG on coronary flow reserve in atresia of the left coronary ostium.

We evaluated the change of coronary flow reserve using a Doppler guidewire before and after coronary artery bypass grafting to assess the coronary hemodynamic effect of surgical revascularization in a 13-year-old boy with congenital atresia of the left coronary ostium, which is one of the rarest of the congenital coronary anomalies. Coronary flow reserve in the right coronary artery and left anterior descending artery increased significantly after coronary revascularization, and a microvascular bed developed in the left anterior descending artery.

Adolescent↗
PubMed1999

Overview of pharmacological treatment of Kawasaki disease.

Kawasaki disease has been researched for 32 years but its aetiology is still unknown. Conventional therapy for the disease includes corticosteroids and aspirin (acetylsalicylic acid) as anti-inflammatory and/or antithrombotic agents but they have not been proven to prevent coronary artery aneurysms. Although a high incidence of liver dysfunction in Japanese patients with Kawasaki disease receiving high dose aspirin (> or =80 mg/kg/day) suggests racial differences in salicylate sensitivity, the duration of fever in patients receiving high dose aspirin is shorter than that in patients receiving moderate dosages (30 to 50 mg/kg/day). Furthermore, most corticosteroid-resistant patients were found to develop coronary artery aneurysms, many of which were large. With the clarification of the pathogenesis and clinical features of Kawasaki disease, advances in its treatment have been achieved. The introduction of high-dose intravenous gamma-globulin (IVGG) was an epoch in this field and IVGG is now a standard therapy with the incidence of persistent coronary aneurysms 1.9% in children with the disease receiving IVGG. Today, research is mainly directed toward the treatment of IVGG-resistant patients. One to 3 days of pulsed doses of methylprednisolone (30 mg/kg/day) or readministration of IVGG 1 g/kg (once to several times) has been recommended for patients with IVGG-resistant Kawasaki disease.

Adrenal Cortex Hormones↗
PubMed1998

Evaluation of coronary flow velocity dynamics and flow reserve in patients with Kawasaki disease by means of a Doppler guide wire.

OBJECTIVES: To assess the pathophysiologic effects of the coronary sequelae of Kawasaki disease on coronary hemodynamic variables, we regionally evaluated the flow velocity dynamics and flow reserve in coronary vessels with lesions using an intracoronary Doppler flow guide wire. BACKGROUND: The pathophysiologic effects of the coronary sequelae of Kawasaki disease on coronary hemodynamic variables have not been completely clarified, and we previously reported some discrepancies between coronary angiographic findings and exercise stress tests in Kawasaki disease. METHODS: Doppler phasic coronary flow velocity was determined using an 0.018-in. (0.046-cm) intracoronary Doppler flow guide wire at rest and during the adenosine triphosphate-induced hyperemic response in 95 patients (75 male, 20 female, mean age 9.8+/-6.2 years) with Kawasaki disease. RESULTS: In 25 patients with coronary aneurysms in 29 vessels, the average peak velocity and diastolic to systolic velocity ratio were significantly (p < 0.05) decreased in the moderate-sized and large-sized aneurysms. Significantly lower values in coronary flow reserve (CFR) were noted in 3 of 10 vessels with moderate aneurysms and in 4 of 7 vessels with large aneurysms. A significant positive correlation (y = 0.53x + 14.6, r2 = 0.91) was observed between the percent diameter stenosis evaluated by angiography and that calculated from the flow velocity measurement. However, the percent diameter stenosis calculated from the flow velocity measurement was underestimated compared with that determined by angiography in the stenotic lesions of intermediate severity. A reduced CFR was noted in five of seven vessels with intermediate stenosis ranging from 50% to 75%, and also in three vessels with mild stenosis ranging from 30% to 40%. A reduced CFR was also observed in six of the eight angiographically normal vessels associated with the area of reduced perfusion on exercise thallium-201 myocardial scintigraphy. CONCLUSIONS: Abnormalities in flow dynamics and a reduction in flow reserve were revealed in coronary aneurysms of intermediate to large size and in stenotic lesions, even of mild to intermediate severity, in patients with Kawasaki disease. Abnormalities in the coronary microcirculation, as well as epicardial lesions, contribute to the pathophysiologic responses in Kawasaki disease.

Adolescent↗
PubMed1997

Antioxidant effects of lovastatin and vitamin E on experimental atherosclerosis in rabbits.

The effects of the administration of vitamin E (10 mg/day) plus lovastatin (2 mg/day; group A, n = 10), lovastatin alone (2 mg/day; group B, n = 10), and placebo (group C, n = 10) were compared over 24 weeks in a randomized, single-blind controlled trial. All groups of rabbits received a trans fatty acid (TFA)-rich diet (5-10 g/day) for 36 weeks. Treatment with vitamin E plus lovastatin (group A) and lovastatin (group B) started after 12 weeks of administration of TFA-rich diet was associated with a significant but similar decline in serum cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides in both groups at 36 weeks. Lipid peroxides and diene conjugates showed a significant decline in association with a significant increase in the plasma level of vitamin E in group A rabbits at 36 weeks. However, the lovastatin group B showed a lesser but significant decrease in lipid peroxides and diene conjugates at 36 weeks, indicating that lovastatin may have antioxidant activity. In control group C, the increase in blood lipids and oxidative stress at 36 weeks was much greater than the decrease in groups A and B. After experimental lipid peroxidation at 24 weeks in all of the rabbits, 2 of 10 group B and 3 of 10 group C rabbits died due to coronary thrombosis; there were no deaths in group A. Thus antioxidant therapy with vitamin E can provide protection against death due to free radical stress. Aortic lipids and sudanophilia indicating athorosclorosis were significantly lower in groups A and B than in group C. The atherosclerotic coronary plaque sizes were significantly smaller in group A (18.5 +/- 3.6 microns) than in groups B (41.6 +/- 4.2 microns) and C (85 +/- 6.7 microns). Aortic plaque sizes were also smaller in group A than in group B and C. It is possible that antioxidant therapy with vitamin E, as an adjunct to lipid lowering with lovastatin, can provide additional benefit in the inhibition of oxidative stress and atherosclerosis. The antioxidant activity of lovastatin has not been reported, to our knowledge.

Animals↗
PubMed1997

Effects of intracoronary adenosine triphosphate on coronary flow velocity dynamics in children.

To assess the usefulness of adenosine triphosphate (ATP) as an alternative agent for functional determination of coronary circulation in children and to reveal the dose-response kinetics of intracoronary ATP, systemic hemodynamics and spectral coronary flow velocity dynamics using Doppler guide wire were measured during hyperemic responses to an intracoronary bolus injection of ATP (0.01 microgram/kg, 0.1 microgram/kg and 1.0 microgram/kg) in consecutive 40 Kawasaki disease patients (age: 8.4 +/- 5.1 years, 30 boys and 10 girls) without angiographic coronary lesions. ATP did not produce any significant change in heart rate, systolic blood pressure and mean blood pressure, but mildly decreased diastolic blood pressure. The coronary flow reserve (CFR) calculated as a ratio of hyperemic to basal averaged peak velocity (APV) for ATP was 2.05 +/- 0.31, 2.26 +/- 0.38 and 2.50 +/- 0.51 in LAD, and 2.24 +/- 0.28, 2.44 +/- 0.41 and 2.60 +/- 0.47 in RCA, respectively, for each of the three doses. There was no statistical significance between the mean values of CFR in LAD with ATP (1.0 microgram/kg: 2.39 +/- 0.16) and papaverine (0.15 microgram/kg: 2.43 +/- 0.16) in six patients without angiographic coronary lesions. The maximal coronary hyperemia was reached rapidly after intracoronary bolus injection of ATP in all doses (10, 10-15 and 15-20 seconds in both LAD and RCA, respectively, for each of the three doses). The time required for APV to return to basal levels (< T10%) increased with the dose of ATP (30, 55 and 110 seconds in LAD and 35, 45 and 100 seconds in RCA, respectively, for each of the three doses). Three patients (3/40: 7.5%) developed transient (< 5 seconds) asymptomatic second degree atrioventricular block, but no patient had clinically significant arrhythmias. The change ratio in QTc interval after ATP injection was 1.96 +/- 1.87% (not significant). In addition, an intracoronary injection of ATP did not increase the absolute angiographic coronary luminal diameter. This study indicates that ATP is a safe alternative agent for pharmacological induction of coronary hyperemia for evaluation of coronary stenotic lesions and for the study of coronary circulation and coronary flow reserve in children.

Adenosine Triphosphate↗
PubMed1996

Myocardial oxygen consumption, cardiac work, and myocardial efficiency in children.

UNLABELLED: Few reports on human cardiac functional development exist, although this information is important for managing paediatric heart disease. The work and the energy usage of the heart was measured in children. A total of 58 patients (aged 1-19 years) with a history of Kawasaki disease without coronary sequelae underwent cardiac catheterization to obtain haemodynamic data and to measure myocardial oxygen consumption. Myocardial oxygen consumption (ml/min) (y = 0.63 x + 3.6, r = 0.86, P < 0.0001, x = age) and left ventricular minute work (kg m/min) (y = 0.46 x 2.4, r = 0.84, P < 0.0001, x = age) correlated positively with age. However, left ventricular minute work per body surface area (age: 2-5 years, 5.8 +/- 0.34 kg m/min/m2; age: 6-10 years, 6.9 +/- 0.59 kg m/min/m2; age: 11-15 years, 5.9 +/- 0.51 kg m/min/m2; age 16-19 years, 6.5 +/- 0.29 kg m/min/m2; and myocardial efficiency (age: 2-5 years, 40.1 +/- 4.4%; age: 6-10 years, 42.4 +/-3.9%; age: 11-15 years, 45.9 +/- 4.1%; age: 15-19 years, 42.3 +/- 6.6%) remained constant throughout childhood. CONCLUSION: In spite of the structural immaturity of the developing heart, the myocardial oxygen consumption per body surface area and myocardial efficiency led by the cardiac work are the same in adults and in children older than 1 year of age.

Adolescent↗
PubMed1995

Coronary arterial flow-velocity dynamics in children with angiographically normal coronary arteries.

BACKGROUND: There have been few reports about coronary hemodynamics in children during the process of growth. In the present study, to assess the characteristics of coronary flow dynamics in children, we examined the phasic coronary flow-velocity (CFV) patterns at rest and during peak hyperemic responses in children with angiographically normal coronary arteries. METHODS AND RESULTS: Spectral Doppler phasic coronary flow velocity was recorded with a 0.018-in intracoronary Doppler guidewire at rest and during peak responses after intracoronary bolus injection of ATP in 30 patients with Kawasaki's disease (age, 8.2 +/- 5.1 years; 24 boys and 6 girls) without angiographic coronary lesions. Average peak velocity (APV), maximum peak velocity (MPV), and diastolic-to-systolic velocity ratio (DSVR) were evaluated in the left anterior descending coronary artery (LAD), left circumflex artery (LCx), and right coronary artery (RCA). Coronary vasodilator reserve (coronary flow reserve [CFR]) was calculated as the ratio of ATP-induced hyperemic to baseline APV. Flow-velocity parameters in RCA were significantly lower than those in the LAD and LCx in both proximal and distal portions. Although the distal LCx had significantly lower values of APV and MPV than did the proximal LCx, there was no significant difference between the proximal and distal portions of the LAD and RCA for APV and MPV. All three coronary vessels showed a diastolic dominant flow pattern in each segment. This coronary flow pattern was less marked in the RCA than in the LCA. All three coronary vessels showed a significant increase in APV and a significantly decrease in DSVR after ATP administration. CFR was significantly lower in the LCx than in the LAD or RCA (P < .01: 1.93 +/- 0.34 in LCx versus 2.32 +/- 0.42 in LAD and 2.37 +/- 0.44 in RCA). From the view of aging, it was revealed that APV values in three vessels were higher in the younger group than in the older group. CFR values in the LAD and LCx were significantly lower in the younger group than in the older group (P < .001 in LAD: 2.01 +/- 0.28 in the younger versus 2.53 +/- 0.37 in the older; P < .01 in LCx: 1.61 +/- 0.15 in the younger versus 2.06 +/- 0.31 in the older). In addition, intracoronary injection of ATP did not increase the absolute angiographic coronary luminal diameter. CONCLUSIONS: With the use of an intracoronary Doppler guidewire, we demonstrated that there are some characteristic findings in CFV dynamics in childhood. These physiological characteristics in CFV dynamics that occur with aging and occur in each vessel must be taken into consideration in the study of the coronary circulation in children.

Adenosine Triphosphate↗
PubMed1995

Randomized, controlled trial of antioxidant vitamins and cardioprotective diet on hyperlipidemia, oxidative stress, and development of experimental atherosclerosis: the diet and antioxidant trial on atherosclerosis (DATA).

The effects of administration of guava and papaya fruit (100 g/day), vegetables, and mustard oil (5 g/day) (group A); antioxidant vitamins C (50 mg/day) and E (30 mg/day), plus betacarotene (10 mg/day) (group B); a high-fat (5-10 g/day) (group C); or a low-fat (4-5 g/day) diet (group D) were compared over 24 diet weeks in a randomized fashion, while all groups of rabbits (five in each of four groups) received a hydrogenated fat diet (5-10 g/day) for a period of 36 weeks. After 12 weeks on the high-fat diet, each group of rabbits had an increase in blood lipoproteins. The fruit and vegetable-enriched prudent diet (group A) caused a significant decline in blood lipids at 24 and 36 weeks, whereas the lipid levels increased significantly in groups C and D. Group A also had a significant rise in vitamin E (2.1 Umol/l), C (10.5 Umol/l), A (0.66 Umol/l), and carotene (0.08 Umol/l) and a decrease in lipid peroxides (0.34 nmol/ml at 36 weeks, whereas the levels were unchanged in groups C and D. Group B rabbits had a significant and greater increase than group A in plasma vitamins E, C, A, and carotene; a rise in HDL cholesterol; and a greater decrease in lipid peroxides after 24 and 36 weeks of treatment. After stimulation of lipid peroxidation in all rabbits, 3 of 5 group C and 2 of 5 group D rabbits died due to coronary thrombosis, whereas in groups A and B there were no deaths, indicating that antioxidant therapy can provide protection against lipid peroxidation and free radical generation. Aortic lipids and sudanophilia, indicating atherosclerosis, were significantly higher in groups C and D than in groups A and B. Fatty streaks and atheromatous and fibrous plaques were noted in all the rabbits in groups C and D. Intimal fibrosis and medial degeneration were also present in the group C rabbits. While group A (36.4 +/- 4.4 microns) and group B (37.1 +/- 4.2 microns) rabbits had minimal coronary artery plaque sizes, group C (75.4 +/- 10.6 microns) and group D rabbits (69.5 +/- 6.2 microns) had significantly greater plaque sizes. Aortic plaque sizes were also greater in groups C and D than in groups A and B. It is possible that combined therapy with antioxidant vitamins C, E, and carotene, and a diet rich in antioxidants, could independently inhibit free radical generation and the development of atherosclerosis.

Animals↗
PubMed1995

Optimal dosage and differences in therapeutic efficacy of IGIV in Kawasaki disease.

In an initial study, three groups of patients with Kawasaki disease received either aspirin alone or alkylated immunoglobulin G intravenous preparation (IGIV) 200 mg/kg daily x 3 days + aspirin, or 400 mg/kg alkylated IGIV daily x 3 days + aspirin. In a second study, three groups of patients were treated with either 100, 200 or 400 mg/kg of native IGIV in combination with aspirin daily for 5 days. While the regimen of 200 mg/kg native IGIV daily x 5 days was found to be effective, the incidence of coronary artery lesions (CAL) was even less on a regimen of 400 mg/kg daily x 5 days. It is therefore suggested that a better therapeutic effect can be achieved with a 400 mg/kg dose of native IGIV. Based on the results from these two studies, it is assumed that native IGIV is more effective in inhibiting CAL formation and persistence than the chemically modified preparation in which the biological activity of the Fc region in the immunoglobulin G molecule is altered.

Aspirin↗
PubMed1995

Coronary artery aneurysms develop in weanling rabbits with serum sickness but not in mature rabbits. An experimental model for Kawasaki disease in humans.

The involvement of the cardiovascular system in rabbits with serum sickness is similar of that in Kawasaki disease, both with respect to the histologic changes of the myocardium, the valves, the coronary arteries, and the aorta and to the sequence with which they appear. Although coronary arteritis appears the same histologically, aneurysms did not occur in mature rabbits, even in case of necrosis of an arterial segment with deletion of muscle and elastic tissue. On the other hand, weanling rabbits with serum sickness had a tendency to develop aneurysms of coronary arteries, despite little cellular infiltration and reactive fibrocellular hyperplasia. The age factor thus appears to play an important role in the development of coronary aneurysms in Kawasaki disease, irrespective of the underlying mechanism, be it a markedly increased permeability to mediators through degenerated endothelial cells, or primary degenerated muscle cells with marked thinning of the media without much inflammatory cellular reaction. Furthermore, this study provides an insight into the long-term prognosis of transient dilatation of coronary arteries in the acute stage of Kawasaki disease.

Age Factors↗
PubMed1995

Effect of Kawasaki disease on migration of human umbilical vein endothelial cells.

Kawasaki disease, which is characterized by systemic vasculitis causing coronary arterial involvement in childhood, shows a variety of immunoregulatory abnormalities. Especially the direct or indirect deleterious effects on endothelial cells of cytokines and anti-endothelial cell antibodies (AECA) are considered to be involved in the mechanism responsible for production of vasculitis. Intravenous administration of high doses of gamma-globulin (IVGG) has been used as an effective therapy for Kawasaki disease. To examine the behavior of endothelial cells affected by cytokines and IVGG in Kawasaki disease, we studied the effects of interferon (IFN), IL-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha on the migration of human umbilical vein endothelial cell line (tHUE01) by a modified Boyden chamber method. Plasma from patients with acute Kawasaki disease markedly enhanced the migration of tHUE01 cells. Cytokines, with the exception of TNF-alpha, also enhanced the migration of tHUE01 cells in a dose-dependent manner. Anti-IFN antibody inhibited the migratory activity in response to not only IFN-gamma but also to the plasma from patients with Kawasaki disease. Rabbit AECA (rAECA) also significantly stimulated the migration of tHUE01 cells. Plasma from patients treated with IVGG did not affect the migration of tHUE01 cells. Addition of gamma-globulin significantly inhibited the migration of tHUE01 cells induced by the cytokines or rAECA. These results suggest that cytokines and AECA are important in restructuring and destroying vessel walls in Kawasaki disease by enhancing the migration of endothelial cells, and that IVGG may be therapeutically effective for this disease by suppressing this endothelial cell migration.

Animals↗
PubMed1995

Assessment of effects of intravenous dipyridamole on regional myocardial perfusion in children with Kawasaki disease without angiographic evidence of coronary stenosis using positron emission tomography and H2(15)O.

BACKGROUND: Positron emission tomography and H2(15)O were used to characterize regional myocardial blood flow and distribution at rest and in response to dipyridamole in children with Kawasaki disease but without angiographic evidence of coronary stenosis. METHOD: Patients were classified into two groups on the basis of the results of selective coronary angiography: subjects in group I had normal coronary angiograms (n = 4): subjects in group II had aneurysms (n = 5). RESULTS: Myocardial perfusion, assessed with H2(15)O, was homogeneous over all regions at rest and at peak flow in groups I and II. Dipyridamole infusion significantly reduced myocardial perfusion reserve in group II (average 3.56 +/- 1.03 fold versus 5.06 +/- 1.37 fold in group I, P < 0.001). CONCLUSION: Our results suggest that aneurysms associated with Kawasaki disease may reduce myocardial reserve. Non-invasive quantitative assessment of myocardial blood flow with positron emission tomography and H2(15)O was useful in assessing the functional capacity of coronary artery lesions and the extent of myocardial damage in children with Kawasaki disease.

Adolescent↗