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Biomedical subjects

Y Sugishita

Publications and source records attributed to Y Sugishita.

At least 19 recordsLinked to original sources
PubMed1997

Pregnancy increases ET-1-induced contraction and changes receptor subtypes in uterine smooth muscle in humans.

The purpose of the present study was to investigate whether pregnancy affects endothelin (ET)-1-induced contraction, the density ofET receptors, and the ratio of receptor subtypes (ET(A) and ET(B)) in uterine smooth muscle in humans. We also investigated which ET receptor subtypes mediate ET-1-induced contraction in the human uterus. In uterine membrane preparations, (125)I-labeled ET-1 ((125)I-ET-1) binding sites (Bmax) in pregnant women did not differ from those in age-matched nonpregnant women (596.2 +/- 107.1 vs. 512.1 +/- 167.7 fmol/mg protein). The dissociation constant (Kd) in pregnant women did not differ from that in nonpregnant women. Competitive displacement experiments with (125)I-ET-1 binding to the membranes using BQ-123 (ET(A) receptor antagonist) showed that the percentage of ET(A) receptors in uterine muscle was significantly higher in pregnant women than in nonpregnant women (P < 0.01). The calculated ratios of ET(A) to ET(B) receptors in pregnant and nonpregnant uteri were 92:8 and 68:32, respectively. Combination treatment with BQ-788 (ET(B) receptor antagonist) completely inhibited the BQ-123-resistant component of (125)I-ET-1 specific binding. ET-1 caused dose-dependent contractions in isolated human uteri from both pregnant and nonpregnant women. The maximum response was markedly greater in pregnant women than in nonpregnant women, whereas pD2 (-log[EC50]) values did not differ between pregnant and nonpregnant uteri. In pregnant human uterus, BQ-123 (10(-6) M) significantly shifted the dose-dependent curve of ET-1 response to the right, whereas BQ-3020 (ET(B) receptor agonist) did not cause contraction. These results suggested that ET-1-induced contraction of the human uterus is mediated through only ET(A) receptors and that ET-1-induced uterine contraction in humans is markedly increased during pregnancy. In addition, the present study suggests that, although (125)I-ET-1 Bmax are not altered during pregnancy, the proportion of ET(A) receptors is increased and that of ET(B) receptors is decreased in the pregnant human uterus.

Adult↗
PubMed1997

Relation of a decrease in arterial compliance to ST segment depression on exercise electrocardiograms in patients with hypertension.

Decreased arterial compliance (ACo) and increased arterial resistance are the major alterations of arterial function in patients with hypertension. The influence of decreased ACo on the heart was investigated in patients with hypertension. Patients with a systolic blood pressure of > 140 mmHg, a diastolic blood pressure of > 90 mmHg, or both, who had normal coronary arteriograms were enrolled. These patients were divided into two groups according to the value of ACo: Group I, patients with ACo > or = 0.9 ml/mmHg (n = 15); and Group II, patients with ACo < 0.9 ml/mmHg (n = 13). There were no significant differences in arterial resistance, age, gender, and body surface area between the groups. Echocardiographic, hemodynamic, and exercise stress test variables were compared between the groups. There were no differences between the groups in left ventricular (LV) wall thickness and volume, cardiac output, LV end-diastolic pressure, and LV ejection fraction. However, pulse pressure was higher in Group II than in Group I. Ergometer exercise stress testing revealed that, although exercise duration and the peak rate-pressure product were similar in the two groups, ST segment depression of > or = 1.0 mm on the exercise electrocardiograms was induced more frequently in Group II than in Group I (92% vs. 27%, p < 0.001). Thus, the decrease in ACo in patients with hypertension may not significantly affect LV wall thickness, volume, or ejection fraction; however, it may increase pulse pressure and may adversely affect coronary circulation, as suggested by the ST segment depression on exercise electrocardiograms.

Arteries↗
PubMed1996

Inhibition of myocardial endothelin pathway improves long-term survival in heart failure.

Occlusion of the diseased coronary artery in humans causes acute myocardial infarction, survivors of which have a high risk for the development of chronic heart failure. Cardiac myocytes and vascular endothelial cells produce endothelin-1 (refs 2-4), which increases the contractility of cardiac muscle and of vascular smooth muscle cells. Endothelin-1 also exerts long-term effects such as myocardial hypertrophy, and causes cellular injury in cardiac myocytes. Production of endothelin-1 is markedly increased in the myocardium of rats with heart failure, and acute application of an endothelin-receptor antagonist decreases myocardial contractility in such rats, indicating that myocardial endothelin-1 may help to support contractility of the failing heart. But we report here that the upregulated myocardial endothelin system may contribute to the progression of chronic heart failure, because long-term treatment with an endothelin-receptor antagonist greatly improved the survival of rats with chronic heart failure. This beneficial effect was accompanied by significant amelioration of left ventricular dysfunction and prevention of ventricular remodelling, in which there is usually an increase in the ventricular mass and cavity enlargement of the ventricle.

Animals↗
PubMed1996

Pulmonary hypertension caused by congestive heart failure is ameliorated by long-term application of an endothelin receptor antagonist. Increased expression of endothelin-1 messenger ribonucleic acid and endothelin-1-like immunoreactivity in the lung in congestive heart failure in rats.

OBJECTIVES: The purpose of this study was to investigate whether 1) endothelin-1, a potent vasoconstrictor peptide, is involved in progression of pulmonary hypertension caused by congestive heart failure (CHF); and 2) whether long-term treatment with BQ-123, an endothelin receptor antagonist, ameliorates pulmonary hypertension caused by CHF. BACKGROUND: Congestive heart failure accompanies pulmonary hypertension, and the severity of pulmonary hypertension is an important determinant of prognosis. Although we reported that production of endothelin-1 is increased in the failing heart in rats with CHF, it is not known whether production of endothelin-1 in the lung is altered by CHF. METHODS: Congestive heart failure was induced by coronary artery ligation in rats. Expression of preproendothelin-1 messenger ribonucleic acid (mRNA) in the lung and kidney was determined. Endothelin-1 staining (immunoreactivity) in the lung was studied by immunohistochemical analysis. Effects of long-term BQ-123 treatment on the rats were studied. RESULTS: Two weeks postoperatively, CHF accompanied by pulmonary hypertension developed in the rats (CHF rats). Expression of preproendothelin-1 mRNA in the lung was markedly higher in the CHF rats than in the sham-operated rats, whereas that in the kidney did not differ between the two groups. Endothelin-1 staining on the pulmonary vascular endothelial cells was more intense in the CHF rats. BQ-123 treatment over a 2-week period in the CHF rats greatly reduced right ventricular systolic pressure and central venous pressure, but it did not affect blood pressure or left ventricular contractility (peak positive first derivative of left ventricular pressure) in these rats. CONCLUSIONS: Long-term BQ-123 treatment greatly ameliorated pulmonary hypertension in the CHF rats. The present study suggests that endothelin-1 plays an important role in the progression of pulmonary hypertension caused by CHF and that an endothelin receptor antagonist may be a new therapeutic agent for CHF-induced pulmonary hypertension.

Animals↗
PubMed1996

Vasoconstriction by endothelin-1 in resistance and conduit portions of isolated human mesenteric arteries.

Although physiological processes related to vascular function differ greatly between resistance arteries and conduit arteries, it is not known whether the effects of endothelin-1 on these arteries differ in humans. In the present study, the conduit portion and the resistance portion of isolated human mesenteric arteries were suspended in a Krebs-Ringer solution. Norepinephrine and endothelin-1 produced concentration-dependent contractions in both portions. The EC50 value of norepinephrine in the resistance portion (3.7 x 10(-7) M, n = 8) did not differ from that in the conduit portion (3.4 x 10(-7) M, n = 7). However, the EC50 value of endothelin-1 in the resistance portion (3.0 x 10(-9) M, n = 8) was significantly lower than that in the conduit portion (1.1 x 10(-8) M, n = 7, P < 0.05). Although the maximum response to norepinephrine in the resistance portion (calculated as the percentage of 50 mM KCl-induced contraction) did not differ from that in the conduit portion, the maximum response to endothelin-1 in the resistance portion was significantly greater than that in the conduit portion. These results indicate that endothelin-1 induces more potent constriction in resistance portion than in conduit portion in isolated human mesenteric arteries.

Adult↗
PubMed1996

Endogenous endothelin-1 participates in the maintenance of cardiac function in rats with congestive heart failure. Marked increase in endothelin-1 production in the failing heart.

BACKGROUND: Although it was demonstrated that circulating endothelin-1 (ET-1) levels are elevated in congestive heart failure (CHF), the production and roles of ET-1 in the failing heart are not known. We investigated the production of ET-1 in the heart and the density of myocardial ET receptors in rats with CHF. We also investigated the effects of intravenously infused BQ-123, an endothelin(A) (ETA) receptor antagonist, on both heart and myocardial contractility in rats with CHF. METHODS AND RESULTS: We used the left coronary artery-ligated rat model of CHF (CHF rats). Three weeks after surgery, the rats developed CHF. Plasma ET-1 concentration was significantly higher in the CHF rats than in the sham-operated rats (P<.01). In the left ventricle, the expression prepro-ET-1 mRNA was markedly higher in the CHF rats than in the sham-operated rats. The peptide level of ET-1 in the left ventricle was also significantly higher in the CHF rats than in the sham-operated rats (500+/-41 versus 102+/-10 pg/g tissue, P<.01). Myocardial ET receptors were significantly higher in the CHF rats than in the sham-operated rats (243+/-20 versus 155+/-17 fmol/mg protein, P<.05). In the CHF rats, intravenous BQ-123 infusion (0.1 mg x kg(-1) x min(-1) for 120 minutes) significantly decreased both heart rate (P<.01) and LV+dP x dt(max) (P<.05) but not mean blood pressure. BQ-123 infusion did not affect these hemodynamic parameters in the sham-operated rats. CONCLUSIONS: In the present study, we demonstrated that the production of ET-1 in the heart is markedly increased and that the density of myocardial ET receptors is significantly elevated in the CHF rats. Intravenous BQ-123 infusion significantly reduced both heart rate and LV+dP/dt(max) in the CHF rats but not in the sham-operated rats. Therefore, the ET receptor-mediated signal transduction system in the heart appears to be markedly stimulated in the CHF rats, and endogenous ET-1 may be involved in the maintenance of the cardiac function in these rats.

Animals↗
PubMed1996

Pathophysiologic significance of left ventricular hypertrophy in dilated cardiomyopathy.

BACKGROUND AND HYPOTHESIS: Patients with dilated cardiomyopathy (DCM) with left ventricular hypertrophy (LVH) have been found to have a better prognosis than patients without LVH. However, the pathophysiologic mechanism for that has not been investigated. We sought to clarify the pathophysiologic significance of LVH in DCM. METHODS: We performed isoproterenol infusion echocardiography (0.02 micrograms/kg/min) in 17 patients with DCM, and measured plasma epinephrine and norepinephrine levels at rest and at the end of ergometer exercise in 14 of the 17 patients. Patients were classified into groups according to the presence (9 patients) (LVH+) or absence (8 patients) (LVH-) of LVH. Left ventricular hypertrophy was defined as an inter-ventricular thickness or posterior wall thickness > or = 13 mm. RESULTS: Although there was no significant difference between groups in fractional shortening at rest during isoproterenol infusion, fractional shortening was significantly higher in the LVH(+) group than in the LVH(-) group (29 +/- 9 vs. 17 +/- 8%; p < 0.025). Although there was no significant difference in plasma norepinephrine level, it was significantly lower in the LVH(+) group than in the LVH(-) group (233 +/- 169 vs. 519 +/- 258 pg/ml; p < 0.05) at the end point of the exercise. CONCLUSION: Systolic reserve, represented by the response to isoproterenol, is greater in patients with DCM with LVH than in those without LVH, and a lower plasma level of norepinephrine is needed to activate the myocardium during exercise in patients with DCM with LVH. This pathophysiologic characteristic could be one of the mechanisms which explain a better prognosis in patients with DCM with LVH.

Adult↗
PubMed1996

Calcitonin gene-related peptide (CGRP) induces more potent vasorelaxation in the resistance portion than in the conduit portion of mesenteric arteries in humans.

Although physiological processes related to vascular function differ greatly between resistance arteries and conduit arteries, it is not known whether the effects of calcitonin gene-related peptide (CGRP), a vasodilator neuropeptide, on these arteries differ in humans. In the present study, the conduit portion and the resistance portion of isolated human mesenteric arteries were suspended in a Krebs-Ringer solution. CGRP produced vasorelaxations in both portions. The EC50 values were very low both in the resistance portion (2.4 x 10(-9) M, n = 7) and in the conduit portion (2.2 x 10(-9) M, n = 7). The maximum response to CGRP in the resistance portion was significantly greater than that in the conduit portion (94.6 +/- 4.0% vs. 64.1 +/- 2.6% relaxation of methoxamine-induced precontraction, both n = 7, p < 0.01). These data suggest that CGRP is one of the most potent endogenous vasodilators in both the resistance portion and the conduit portion of the human mesenteric arteries, and that CGRP induces more potent vasorelaxation in the resistance portion than in the conduit portion of these arteries.

Adult↗
PubMed1996

Effect of percutaneous transluminal coronary angioplasty on exercise ventilation in patients with coronary artery disease and normal left ventricular function.

We evaluated the ventilatory response to exercise before and after percutaneous transluminal coronary angioplasty (PTCA) in 22 patients with coronary artery disease (CAD) and normal left ventricular systolic function to determine the effect of exercise-induced myocardial ischemia on the ventilatory response. Subjects performed a symptom-limited maximal ergometer exercise test in the sitting position. The ventilatory response was evaluated in terms of the slopes of minute ventilation (VE) and carbon dioxide production (VCO2) during exercise (slope 1 and slope 2, defined as below and above the respiratory compensation threshold, respectively). Slope 1 of the correlation between (VE) and (VCO2) was significantly greater in patients with CAD (27.3 +/- 2.6) than in the age-matched control group (23.7 +/- 2.6; p < 0.01). Slope 2 was also significantly greater in patients (41.0 +/- 4.8) than in the control group (29.7 +/- 2.9; p < 0.01). Slope 1 of the correlation between (VE) and (VCO2) decreased significantly in the 14 patients in whom PTCA was successful but did not decrease in the 8 patients in whom PTCA failed. Our results suggest that myocardial ischemia increases exercise ventilation in patients with CAD and normal left ventricular systolic function and that its effect is reversible.

Adult↗
PubMed1996

Alterations in left ventricular wall stress and coronary circulation in patients with isolated systolic hypertension.

OBJECTIVES: To study the alterations in cardiac function and coronary circulation in patients with isolated systolic hypertension (ISH). PATIENTS: Ten patients with a history of ISH were studied and findings were compared with those of seven normotensive subjects. All of the patients had angiographically normal coronary arteries. They underwent cardiac catheterization, and haemodynamic variables and coronary flow velocity were measured. All of the patients also underwent treadmill exercise testing. MAIN OUTCOME MEASURES: Left ventricular mass was evaluated by echocardiography. The coronary flow velocity data were obtained by using the intracoronary Doppler catheter technique. ST-segment depression was observed on the exercise electrocardiogram. RESULTS: Systemic vascular resistance did not differ, whereas total arterial compliance was decreased in the ISH patients versus the controls (P < 0.001). The left ventricular mass of the ISH patients was increased slightly, but their left ventricular systolic wall stress was greater than that of the controls (P < 0.01). The coronary flow reserve ratio and the ratio of diastolic to total coronary flow were decreased in the ISH patients versus the controls (P < 0.01). ST-segment depression on the exercise electrocardiogram was frequently observed in the hypertensive patients (80 versus 0% in control subjects, P < 0.01). CONCLUSIONS: Patients with ISH were characterized haemodynamically by a decrease in arterial compliance. They showed an increase in left ventricular systolic wall stress and also showed decreases in coronary flow reserve ratio and in the relative diastolic coronary flow. Such alterations observed in patients with ISH are detrimental to the heart and may contribute to a reduced exercise capacity and the induction of subendocardial ischaemia during exercise.

Adult↗
PubMed1996

Long-term effects of doxazosin, an alpha 1-blocker, on serum lipids in hypertensive patients.

Nowadays practical antihypertensive therapy involves not only simple normalization of blood pressure but also a reduction of the risks of cardiovascular disease. In this multicenter open-label study, the long-term effects of doxazosin, an alpha 1-adrenergic receptor blocker, on serum lipids were prospectively investigated in 253 patients with essential hypertension. They were treated with doxazosin for 1 year. The averaged the blood pressure was maintained at levels lower than 150/90 mmHg throughout 1 year, but heart rate did not increase. After 3 months of doxazosin therapy, total and low density lipoprotein-cholesterol levels in serum were significantly reduced by 3.3% and 3.4%, respectively, and these levels were maintained throughout the study period. This effect of doxazosin on serum lipids was especially prominent in patients with hypercholesterolemia. In addition, the lipid profile of these patients was favorably altered even when other antihypertensive drugs or lipid-lowering drugs had already been used or were used concurrently. These results constitute useful information for physicians who treat hypertension with alpha 1-blockers to reduce the overall risk of cardiovascular disease.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed1996

Effect of warming of exercising legs on exercise capacity in patients with impaired exercise tolerance.

OBJECTIVE: The purpose of this study was to determine whether warming of exercising legs improves exercise capacity in patients with cardiac disease and low exercise tolerance. BACKGROUND: Exercising muscle temperature reflects both muscle metabolic rate and muscle blood flow. Increase in muscle temperature in exercising legs is impaired in patients with chronic heart failure. We hypothesized that the mechanisms responsible for impairment of temperature increase in exercising muscle might be related to those responsible for low exercise tolerance. METHODS: We studied 17 patients with cardiac disease whose anaerobic threshold (AT) ranged from 6.6 to 14.8 ml/kg/min (mean 11.2 +/- 1.9 SD). Subjects performed symptom-limited sitting cycle ergometer exercise with or without warming of the thighs. Both thighs were warmed by use of hot packs fixed by supporters. To determine the effect of the supporters themselves on AT and peak VO2, the same ergometer exercise was performed by 7 patients with or without supporters. Peak VO2 and AT were determined by concomitant respiratory gas monitoring. RESULTS: 1) Warming of the thighs increased deep temperature in the thighs (1.0 approximately 2.8 degrees C). 2) AT and peak VO2 were significantly improved in the warming exercise compared with the non-warming exercise (p < 0.01, p < 0.01). 3) There was no significant difference in AT or peak VO2 between the exercise with and without supporters. CONCLUSION: The findings of this study indicate that warming of exercising legs improves exercise capacity in patients with cardiac disease and low exercise tolerance.

Aged↗
PubMed1996

[Class-I antiarrhythmic drugs].

Classification, mechanism of action, pharmacokinetic properties and clinical applications of class-I antiarrhythmic agents were summarized. Class-I drugs were subdivided into three groups, Ia, Ib, Ic. This subclassification is based on their action to modify the action potential duration. In the Cardiac Arrhythmia Suppression Trial (CAST), flecainide and encainide were associated with greater mortality than placebo in patients with non-life threatening arrhythmias. Results of CAST and other megatrials suggested that antiarrhythmic agents were unsafe in some groups of patients and the limitation of antiarrhythmic therapy. Proarrhythmia and combination therapy of antiarrhythmic agents were mentioned.

Anti-Arrhythmia Agents↗
PubMed1996

[Comparison of thrombolytic therapy and direct percutaneous transluminal coronary angioplasty for acute myocardial infarction: prospective multicenter trial at 16 clinical centers in Ibaraki prefecture TUGMI. Tsukuba University Group for Myocardial Infarction].

The efficacies of direct percutaneous transluminal coronary angioplasty (PTCA) and thrombolysis for the treatment of acute myocardial infarction were investigated in 80 patients treated within 12 hours of the onset of myocardial infarction by either PTCA (39 patients) or thrombolytic therapy (41 patients) followed by conservative care. The therapeutic approach was selected according to the treatment strategy at each of the 16 participating centers before the admission of the patients. The two treatment groups were closely matched in clinical characteristics except for the history of hypertension which occurred more in the thrombolysis group (22/39 vs 12/41, p = 0.026). The mean time before starting reperfusion therapy from the onset of symptoms was shorter in the thrombolysis group (2.3 +/- 1.5 vs 5.3 +/- 5.7 hours, p = 0.0001). Chest pain resolved more quickly in the PTCA group. Serial changes in the mean numbers of abnormal Q waves and mean values of the sum of elevated ST-segments on the electrocardiograms were similar in both groups. Serial changes of wall motion abnormality index on echocardiograms were similar in both groups. Coronary angiography after 4 weeks showed the thrombolysis group had greater residual luminal stenosis in the infarct-related artery. Left ventriculography after 4 weeks showed the PTCA group had better mean ejection fraction (68.1 +/- 11.2% vs 58.7 +/- 14.2%, p = 0.0263). Death (3/39 vs 1/41) and cardiac events (6/39 vs 6/41) after 4 weeks were similar in both groups. There was no significant difference in death and cardiac events between these two groups. However, the PTCA group had less severe residual luminal stenosis in the infarct-related artery and better left ventricular function after 4 weeks than the thrombolysis group.

Aged↗
PubMed1995

Response to isoproterenol as a prognostic indicator of evolution from hypertrophic cardiomyopathy to a phase resembling dilated cardiomyopathy.

OBJECTIVES: We sought to assess whether isoproterenol stress echocardiography could detect in advance in which patients hypertrophic cardiomyopathy would progress to a phase resembling dilated cardiomyopathy. BACKGROUND: In a few patients, hypertrophic cardiomyopathy has been reported to progress to a phase characterized by systolic dysfunction and left ventricular dilation, resembling dilated cardiomyopathy. METHODS: Echocardiograms were recorded before and immediately after intravenous infusion of isoproterenol (0.02 microgram/kg body weight per min) for 5 min in 18 patients with typical hypertrophic cardiomyopathy (i.e., hypertrophied, hyperdynamic and nondilated) to determine the difference in fractional shortening. The patients were categorized into those with a good response (difference in fractional shortening > 7%, 14 patients) and those with a poor response (difference < or = 7%, 4 patients). Changes in left ventricular end-diastolic diameter and fractional shortening were evaluated by using serial echocardiography over an average follow-up period of 5.4 years. RESULTS: In the good response group, neither end-diastolic diameter nor fractional shortening changed significantly during the follow-up period. In the poor response group, end-diastolic diameter significantly increased from a mean +/- SD of 41 +/- 5 to 53 +/- 5 mm (p < 0.05), and fractional shortening significantly decreased from 40 +/- 12% to 29 +/- 10% (p < 0.05). All patients in the poor response group showed a substantial decrease (> or = 5%) in fractional shortening and an increase (> or = 5 mm) in end-diastolic diameter. One patient developed congestive heart failure due to systolic dysfunction during the observation period. CONCLUSIONS: The present study confirmed that impaired responses to isoproterenol infusion are related to future deterioration of left ventricular performance in patients with typical hypertrophic cardiomyopathy.

Cardiomyopathy, Dilated↗
PubMed1995

Malignant hyperthermia in a patient with Becker muscular dystrophy: dystrophin analysis and caffeine contracture study.

We present a 17-year-old boy with Becker muscular dystrophy (BMD) who developed hyperthermia and heart failure after general anesthesia. He presented clinical features of malignant hyperthermia (MH), and had masseter spasm and elevated body temperature (38.7 degrees C) with very high serum CK activity (107,000 IUl-1). Dystrophin tests confirmed a clinical diagnosis of BMD in the patient, i.e. faint and patchy immunostaining pattern of skeletal muscle, truncated dystrophin protein and a deletion of exons 3 and 4 of the dystrophin gene. To inquire into the mechanism of MH associated in the patient, we tested caffeine contracture reaction by the skinned fiber method. We found an increased sensitivity to caffeine only in type 1 muscle fibers. The rate of Ca(2+)-induced Ca2+ release (CICR) was normal, suggesting that the mechanism of "MH" observed in our patient with BMD is not the same as that of classical MH. A possible mechanism might be related to derangements of the sarcoplasmic reticulum membrane in BMD, which sensitize the membrane to caffeine or other agents.

Adolescent↗