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S Beppu

Publications and source records attributed to S Beppu.

At least 19 recordsLinked to original sources
PubMed2001

Myocardial ischemia activates the JAK-STAT pathway through angiotensin II signaling in in vivo myocardium of rats.

There have been many studies concerning the hemodynamics and physiological mechanisms in ischemic heart disease, little is known about molecular mechanisms during myocardial ischemia in in vivo study. As the signal transduction pathway responsible for myocardial hypertrophy and apoptosis, janus kinase (JAK) and signal transducers and activators of transcription (STAT) are suggested to play an important role. However, whether in vivo activation of JAK-STAT pathway occurs during myocardial ischemia is still unknown. The purpose of this study was to determine whether myocardial JAK or STAT is activated in ischemic heart, and to evaluate the angiotensin blockade on the pathway. Myocardial infarction was produced by ligation of the coronary artery in Wistar rats. After myocardial ischemia, we analysed both activated levels and total amounts of JAK1, JAK2, STAT1 and STAT3 by Western blot analyses at 0, 5, 15, 30, 60, 120 and 240 min. Compared with JAK activities at 0 min, JAK1 activities were significantly increased at 60 and 120 min (3.0- and 3.7-fold, respectively, P<0.01). JAK2 and STAT1 activities of ischemic myocardium were unchanged through the time course. STAT3 activities were increased at 5 min (3.3-fold, P<0.01) and markedly enhanced at 30, 60 and 120 min (4.6-, 7.7- and 8.7-fold, respectively, P<0.01). Pretreatment with imidapril (ACE inhibitor) and candesartan cilexitil (AT1 receptor antagonist) significantly prevented the increase in the phosphorylation of JAK1 at 120 min and STAT3 at 30 and 120 min. Sis-inducing factor (SIF) DNA complex was supershifted by specific anti-STAT3 antibody, indicating that increased SIF complex at least contained activated STAT3 proteins in ischemic myocardium. Imidapril and candesartan cilexitil inhibited the activation of SIF DNA binding at 1 day after coronary ligation. In conclusion, we showed that JAK1 and STAT3 were activated by ischemia from the basal activities in in vivo rat myocardial ischemia model. Imidapril and candesartan cilexitil prevented the increase in phosphorylated JAK1 and STAT3, thereby suggesting that angiotensin II, especially angiotensin II type I receptor, partially mediates activation of myocardial JAK-STAT pathway in acute myocardial ischemia.

Angiotensin II↗
PubMed2000

Effects of sildenafil citrate (Viagra) combined with nitrate on the heart.

BACKGROUND: Sildenafil citrate (Viagra) is indicated for the treatment of erectile dysfunction. Large and sudden decreases in systemic blood pressure were reported in a substantial number of patients taking sildenafil citrate combined with nitroglycerin. We studied the effect of sildenafil citrate on the relationship between changes in systemic blood pressure and coronary blood flow. METHODS AND RESULTS: Healthy male beagles were used to assess systemic blood pressure, pulmonary arterial pressure, and flow in the left circumflex artery (in which a critical stenosis was established) and left anterior descending coronary artery. After measurement of the hemodynamic variables, 2 mg/kg sildenafil citrate was administered via a nasogastric tube. Hemodynamic changes were monitored for 1 hour. Subsequently, the acute effect of nitrate combined with sildenafil citrate was studied by the bolus injection of 0.2 mg isosorbide dinitrate before and after sildenafil citrate. Systemic blood and pulmonary arterial pressures and circumflex flow did not change during this study; however, left anterior descending coronary arterial flow increased from 16.0+/-5.8 to 24.6+/-8.7 mL/min 1 hour after administration of sildenafil citrate. The prolongation of systemic blood pressure decrease and the circumflex flow decrement induced by isosorbide dinitrate after sildenafil citrate were significantly larger and longer than those before sildenafil citrate. CONCLUSIONS: Sildenafil citrate had the effect of vasodilation in a normal coronary artery; however, a combined effect with nitrate resulted in large and protracted decreases in systemic blood pressure and coronary blood flow in vessels with critical stenosis.

Administration, Oral↗
PubMed1999

Characteristic cardiovascular manifestation in homozygous and heterozygous familial hypercholesterolemia.

BACKGROUND: The aortic valve dysfunction of patients with homozygous familial hypercholesterolemia (FH) suggests that hypercholesterolemia affects not only coronary arteries but also the aortic valve. We studied the aortic root of patients with homozygous FH and those of patients with heterozygous FH to characterize the premature atherosclerotic lesions by using histopathologic specimens. METHODS AND RESULTS: The aortic roots of 10 patients with homozygous FH, age 9 to 58 years, were studied by cardiac catheterization with several angiographies. The aortic roots of 39 patients with heterozygous FH under age 60 years were also examined for aortic and mitral valvular functions by color Doppler echocardiography, and 30 normocholesterolemic patients with coronary artery disease were examined as control subjects. In addition, in 22 patients with FH and 20 control subjects, the internal diameter of the aortic annulus and the aortic ridge in cardiac cycles were measured. Of the 10 homozygotes with FH, 8 patients had aortic regurgitation demonstrated by aortography; 3 of them showed significant transvalvular pressure gradients. Stenotic changes of coronary ostia were observed in 8 of the 10 homozygotes with moderate coronary atherosclerosis. Of the 39 heterozygotes with FH, 10 patients had aortic regurgitation shown by Doppler echocardiography, as did only 1 of the 30 control subjects (P <.05). The average diameter and distensibility of the ascending aorta were significantly reduced in the heterozygotes compared with the control subjects. The surgically resected cusp specimens of aortic valves obtained from 1 homozygous and 1 heterozygous patient showed significant thickening of the cusp with foam cell infiltration. CONCLUSIONS: Premature atherosclerosis in FH had a characteristic distribution, affecting the aortic root dominantly. The involvement of the aortic valve indicating "hypercholesterolemic valvulopathy" was a peculiar feature of FH, especially its homozygous form, but was reminiscent of ubiquitous processes caused by hypercholesterolemia.

Adolescent↗
PubMed1999

Assessment of flow mismatch with pharmacologic stress test on myocardial contrast echocardiography in a model of critical stenosis: adenosine triphosphate and dipyridamole.

Although adenosine triphosphate (ATP) is a favorable vasodilator because of its short-acting duration, the agent's effectiveness in facilitating the diagnosis of myocardial ischemia with myocardial contrast echocardiography (MCE) is not fully understood. The goal of this study was to examine the efficacy of intravenous ATP administration (0.15 to 0.30 mg/kg/min for 5 minutes) in diagnosing the flow mismatch with MCE. To achieve this, a critical stenosis was produced in the left circumflex artery in 10 anesthetized dogs. The peak intensity ratio of risk area to control area was reduced by ATP from 0.51 +/- 0.19 to 0.31 +/- 0.12 (P <.05). Systolic wall thickening of the risk area did not change significantly (32.8% +/- 9.8% to 27.5% +/- 12.8%). These changes did not differ from those obtained after dipyridamole. We conclude that MCE with intravenous ATP administration is as useful as the dipyridamole method for diagnosing critical coronary stenosis.

Adenosine Triphosphate↗
PubMed1998

Preparation and characterization of echogenic liposome as an ultrasound contrast agent: size-dependency and stabilizing effect of cholesterol on the echogenicity of gas-entrapping liposome.

The liposome entrapping CO2 gas inside the vesicle, which is called the echogenic liposome, has been made and characterized in vitro as an ultrasound contrast agent. The small unilamellar vesicle (SUV), large unilamellar vesicle (LUV) and multilamellar vesicle (MLV) as echogenic liposomes were compared in their echogenic efficiency and stability, and the effect of size and acoustic property was tested. The acoustic reflectivity increased with the increase in size of the vesicle, largest for the gas filled MLV among the three liposome suspensions. The acoustic reflectivity obtained with the echogenic MLV was larger than that of the gas bubbles enclosed within a surfactant mixture. A half-lifetime of 39 min was observed for the MLV prepared from egg-yolk phosphatidylcholine liposomes. The duration of reflectivity was prolonged drastically to a half-lifetime of 866 min by incorporating cholesterol into the MLV, although the echogenicity was decreased by such incorporation. The stabilizing effect of cholesterol for the ordinary liposomal membrane was thus ascertained in the present case of the gas-entrapping liposome. Our findings encourage the future development of improved gas-entrapping liposomes for the clinical trials of ultrasound contrast agents.

Chemical Phenomena↗
PubMed1998

[Levovist].

SH/TA-508 (Levovist) is agglomerates of microparticles consisting of galactose (99.9%) and palmitic acid (0.1%), and the active entity is the microbubbles stabilized by palmitic acid which covers the bubbles. SH/TA-508 micro-bubbles are stable under high-pressure condition and they circulate the whole body for several minutes along with blood flow after the intravenous injection. The left sided cardiac cavities and arteries are clearly opacified by using this contrast agent and the Doppler signals from the mitral, aortic and pulmonic vein are also enhanced significantly. Also microcirculating flow image of the liver, kidney and other organs are well enhanced in the clinical studies. SH/TA-508 improves the capability of ultrasound diagnosis.

Contrast Media↗
PubMed1997

Relationship between progressive microvascular damage and intramyocardial hemorrhage in patients with reperfused anterior myocardial infarction: myocardial contrast echocardiographic study.

BACKGROUND: Recent studies indicated that ischemic microvascular damage may be reversible or progressive after coronary reflow. Intramyocardial hemorrhage is a phenomenon that reflects severe microvascular injury. We examined the relationship between temporal changes in microvascular perfusion patterns detected by myocardial contrast echocardiography (MCE) and intramyocardial hemorrhage detected by magnetic resonance imaging (MRI) in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: The study population consisted of 24 patients with anterior AMI. All patients underwent MCE shortly after reflow and in the chronic stage (a mean of 31 days after reflow). Wall motion score (WMS) was determined as the sum of 16 segmental scores (dyskinetic/akinetic=3 to normal=0) at days 1 and 31. Gradient-echo acquisition and gadolinium-DTPA-enhanced spin-echo MRI were performed within 10 days after reflow. In MCE shortly after reflow, 16 patients (67%) showed contrast enhancement and the other 8 patients (33%) showed a sizable contrast defect. In the chronic stage, a persistent contrast defect was observed in 7 of 8 patients with a contrast defect shortly after reflow. Consistent contrast enhancement was observed in 12 of 16 patients (75%) with contrast enhancement shortly after reflow, indicating that a contrast defect newly appeared in 4 patients (25%). Intramyocardial hemorrhage was detected in 9 patients (38%): 5 of 7 patients with a persistent contrast defect and in all 4 patients with a new appearance of a contrast defect during the chronic stage. The patients without hemorrhage showed a significant improvement in WMS compared with patients with hemorrhage at day 31 (5+/-5 versus 19+/-6, P<.0005). CONCLUSIONS: These results suggest that irreversible microvascular damage to the ischemic myocardium may cause intramyocardial hemorrhage after reflow, associated with impaired recovery of left ventricular function. Contrast enhancement within the risk area shortly after reflow does not necessarily indicate long-term microvascular salvage.

Aged↗
PubMed1997

Extension of hemorrhage after reperfusion of occluded coronary artery: contrast echocardiographic assessment in dogs.

OBJECTIVES: The aim of this study was to elucidate the progression of intramural hemorrhage complicated by reperfusion with the use of myocardial contrast echocardiography. BACKGROUND: Although hemorrhagic infarction is known to occur in ischemia followed by reperfusion, its onset and sequence have not been well characterized. METHODS: In 20 anesthetized dogs, 3-h occlusion of the left circumflex-coronary artery was followed by reperfusion. The area at risk during coronary occlusion was approximately 25%. Myocardial contrast echocardiogram was examined, and the time-intensity curves for both ischemic and nonischemic areas were obtained at baseline, at 3 min after reperfusion and then at 15-min intervals until 90 min after reperfusion. The wall thickness of both areas was also measured. RESULTS: Gross hemorrhage in the reperfused areas was observed in five dogs (Group H) but not in seven dogs (Group NH). All wall segments were opacified at 3 min after reperfusion in both groups. However, the contrast defect spread significantly with time after reperfusion in Group H but not in Group NH (18.7 +/- 3.4% and 3.3 +/- 1.8%, respectively, at 90 min after reperfusion p < 0.005). The wall of the risk area at 90 min after reperfusion had thickened to 1.3 times baseline thickness in Group H but was unchanged in Group NH. The other eight dogs were excluded from study because of fatal arrhythmias or the existence of collateral circulation during coronary occlusion. CONCLUSIONS: Both progression of the contrast defect area on myocardial contrast echocardiography and a gradual thickening of the wall with reperfusion are characteristic of hemorrhagic infarction.

Animals↗
PubMed1997

Functional myocardial perfusion abnormality induced by left ventricular asynchronous contraction: experimental study using myocardial contrast echocardiography.

OBJECTIVES: The aim of this study was to clarify how myocardial perfusion is impaired by asynchronous contraction. BACKGROUND: False septal hypoperfusion is noted in some patients with left bundle branch block. METHODS: Eight dogs were examined with epicardial pacing at the left ventricular posterior wall, the right ventricular anterior wall and, as a control, the right atrial appendage. The pacing rate was 80, 110 and 150 beats/min (bpm). Myocardial perfusion was assessed by contrast echocardiography. RESULTS: Left ventricular pacing at 80 and 110 bpm did not change systolic wall thickening or contrast intensity at the pacing site, although an early excitation notch was noted at the pacing site. However, at 150 bpm, systolic thickening was impaired (23.3 +/- 4.2% vs. 37.0 +/- 2.6% during atrial pacing, p < 0.05), and the peak intensity ratio of the pacing site to the ventricular septum was significantly decreased (24.1 +/- 5.7% vs. 37.0 +/- 2.8% at a pacing rate of 80 bpm, p < 0.01). The peak intensity ratio correlated with systolic wall thickening at the pacing site (y = 0.413 x -0.028, r = 0.81, p < 0.0001). However, right ventricular pacing did not change either systolic thickening or the peak intensity ratio at any pacing rate, although an early excitation notch was noted on the ventricular septum. CONCLUSIONS: Wall motion abnormalities after early excitation vary depending on the pacing mode. When tachycardia induces regional wall motion abnormalities, the ventricular wall of the pacing site is functionally hypoperfused.

Animals↗
PubMed1996

Identification of pseudonormal transmitral flow pattern using color Doppler echocardiography.

The jet size of flow in color Doppler is dependent on both jet momentum and the compliance of the receiving chamber. Thus, the jet size of left ventricular (LV) late filling standardized by its jet momentum should reflect LV compliance. We investigated the feasibility of using color Doppler echocardiography to differentiate a pseudonormal from a normal transmitral flow pattern. We divided 37 patients with ischemic heart diseases who demonstrated a "normal" transmitral flow pattern into 2 groups according to their LV end diastolic pressure (LVEDP): a pseudonormalization group (LVEDP > or = 18 mmHg, 16 patients), and a normal group (LVEDP < 18 mmHg, 21 patients). We measured the maximum color Doppler jet length (L) and the peak velocity of transmitral flow during atrial contraction (Av). Filling volume (Q) was measured as the increase in LV volume during atrial contraction. A simplified jet momentum index (M) was obtained from Av x Q, and L/M was considered to reflect LV compliance. L/M was significantly lower in the pseudonormalization group that in the normal group (1.55 +/- 0.46 x 10(-3) vs 2.72 +/- 0.59 x 10(-3) p < 0.01). On the other hand, conventional Doppler variables such as isovolumic relaxation time and the deceleration time of early diastolic filling were not sufficient for discriminating between the 2 groups. In conclusion, color Doppler echocardiogram during atrial contraction was useful for differentiating a pseudonormal from a normal transmitral flow pattern.

Adult↗
PubMed1995

[Feasibility of the left ventricular volume measurement by acoustic quantification method: comparison with ultrafast computed tomography].

Acoustic quantification (AQ: the real-time automated boundary detection system) allows instantaneous measurement of cardiac chamber volumes. The feasibility of this method was evaluated by comparing the left ventricular (LV) volumes obtained with AQ to those derived from ultrafast computed tomography (UFCT), which enables accurate measurements of LV volumes even in the presence of LV asynergy, in 23 patients (8 with ischemic heart disease, 5 with cardiomyopathy, 3 with valvular heart disease). Both LV end-diastolic and end-systolic volumes obtained with the AQ method were in good agreement with those obtained with UFCT (y = 1.04 x - 16.9, r = 0.95; y = 0.87x + 15.7, r = 0.91; respectively). AQ was reliable even in the presence of LV asynergy. Interobserver variability for the AQ measurement was 10.2%. AQ provides a new, clinically useful method for real-time accurate estimation of the left ventricular volume.

Feasibility Studies↗
PubMed1995

[Prediction of ineffective outcome of surgical treatment for constrictive pericarditis].

The preoperative factors predicting the outcome of surgical treatment for constrictive pericarditis were investigated in 22 patients with constrictive pericarditis who underwent pericardiectomy. The NYHA functional class was improved in nine patients after surgery (improved group), but not in the other 13 patients (unimproved group). Preoperative right and left heart catheterization data and echocardiograms were compared between these two groups. Right atrial pressure (RAP) and pulmonary capillary wedge pressure (PCWP) were significantly higher in the unimproved group. The left atrial diameter (LAD) measured by echocardiography was significantly greater in the unimproved group. These results indicate that pericardiectomy will cause a worsened immediate outcome in patients with severe pericardial constriction. LAD was the most useful parameter in predicting the ineffectiveness of the pericardiectomy. If the borderline value of LAD is taken as 40 mm, the sensitivity and specificity predicting ineffective surgery were 92% and 89%, respectively. RAP and PCWP could not separate the two groups satisfactorily. Pericardiectomy should be performed before the pericardial constriction progresses, and before LAD reaches 40 mm.

Adult↗
PubMed1994

Myocardial contrast echocardiography of coronary artery lesions due to Kawasaki disease.

In addition to coronary arteriography, myocardial contrast echocardiography (MCE) was performed in 25 patients with coronary artery lesions due to Kawasaki disease, in order to investigate its validity in the evaluation of these lesions and its safety in children. The patients' ages ranged from 1.0 to 15.9 years (mean, 8.6 years). Their coronary artery lesions included occlusion in 9 branches (9 patients), segmental stenosis in 9 (8 patients), localized stenosis in 16 (12 patients), and dilated lesions without coexistent stenotic lesions in 5 patients. Seven patients had coronary artery bypass grafts. Myocardial perfusion patterns of the stenotic lesions and coronary artery bypass grafts could be clearly demonstrated by MCE. For the assessment of safety, electrocardiograms obtained at the time of MCE and coronary arteriography in 14 patients showed no significant difference in the findings between MCE and coronary arteriography. Serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, lactic dehydrogenase, and creatine phosphokinase levels were measured before and 1 day after the procedure in 14 patients who underwent MCE and coronary arteriography, and in a group of 14 patients who underwent coronary arteriography alone. No significant difference was noted between the values of the two groups. These results suggested that MCE can be utilized in the assessment of coronary artery lesions due to Kawasaki disease, and confirmed the safety of the procedure even in young children.

Child↗
PubMed1994

Diastolic suction in the human ventricle: observation during balloon mitral valvuloplasty with a single balloon.

Diastolic suction has been demonstrated experimentally as a ventricular negative pressure when the ventricle is allowed to relax completely in the absence of filling, but it has not been extensively studied in the in vivo human heart. In balloon mitral valvuloplasty with a single balloon, the mitral orifice is occluded and inflow is considered to be completely obstructed during a balloon inflation. To demonstrate diastolic suction in the human ventricle, we measured left ventricular pressure during valvuloplasty with a high-fidelity catheter tip manometer in 17 patients. Left ventricular pressure fell below zero during a balloon inflation in all patients (-2 to -12 mm Hg). The peak negative diastolic pressure showed significant correlations with end-systolic volume index (r = 0.53, p = 0.03) and with the ejection fraction (r = 0.80, p = 0.0001). Thus diastolic suction was demonstrated in the human beating heart, and the sucking effect was potent in the heart with small end-systolic volume and high-ejection fraction.

Adult↗