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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↗
PubMed2001

Serial assessment of left and right ventricular filling in patients with congestive heart failure.

Serial changes in the diastolic filling of both ventricles were studied using Doppler echocardiography in 19 patients with congestive heart failure from the acute to the convalescent stage. During the acute stage, left ventricular early filling velocity (E) was high (88 +/- 17 cm/s) and atrial filling velocity (A) was low (44 +/- 23 cm/s), whereas the right ventricular E was depressed (17 +/- 8 cm/s) and A was enhanced (40 +/- 9 cm/s). As the condition improved, left ventricular E decreased (43 +/- 11 cm/s, p < 0.01) and A increased (59 +/- 24 cm/s, p < 0.01) along with a decrease in the left ventricular and atrial dimensions. In contrast to the changes in left ventricular filling, right ventricular E increased (31 +/- 10 cm/s, p < 0.01) and A decreased (32 +/- 5 cm/s, p < 0.05). There are opposite directional changes in left and right ventricular filling with clinical improvement from the acute to the convalescent stage of congestive heart failure, which suggest that the changes are related to improvement of the hemodynamic conditions of both ventricles. The changes in the right ventricular filling pattern was likely to be related to changes in right ventricular afterload, ventricular interaction and external constraint rather than a change in right ventricular filling pressure.

Adult↗
PubMed2001

[Optimal setting of focus points for myocardial contrast echocardiography with intravenous Optison (FS-69): an experimental study].

OBJECTIVES: Myocardial contrast echocardiography is useful to assess myocardil perfusion, but myocardial opacification is affected by the setup of the ultrasonic equipment. The optimal setting of focus points for adequate opacification of the myocardium was examined in myocardial contrast echocardiography. METHODS: Myocardial contrast echocardiography was performed in six dogs using triggered second harmonic technology following intravenous administration of Optison(FS-69). The short-axis view was recorded and baseline subtracted video intensity(peak intensity: PI) was calculated at three regions of the left ventricular wall, the anterior, septum, and posterior walls, to evaluate myocardial opacification. The focus point was set at near(2 cm), middle(4 cm) and far(6 cm)points. The myocardial opacification was evaluated at each focus setting. The effect of the acoustic power was also examined by changing the mechanical index to 1.6, 1.2 or 0.8. RESULTS: Myocardial opacification was recognized at all focus points, and segments near the focus points had high PI. However, the PI of the posterior wall was lowest at near focus, whereas the PI of the anterior wall was lowest at far focus. The difference of PI between the anterior and posterior walls was significant (p < 0.05, p < 0.01, respectively) at either focus point. Adequate myocardial opacification of all segments was observed when the focus was set at the middle point. The PI of the whole left ventricle increased relative to mechanical index. CONCLUSIONS: Setting up of focus points at the middle of the left ventricle provides more homogeneous myocardial opacification of the whole left ventricle in myocardial contrast echocardiography, and high acoustic power possibly improves myocardial opacification. Inadequate setting of focus points leads to inadequate estimation of myocardial perfusion by myocardial contrast echocardiography.

Albumins↗
PubMed2001

[Usefulness of intravenous myocardial contrast echocardiography in rats].

OBJECTIVES: Few intravenous myocardial contrast echocardiography trials have evaluated myocardial perfusion in small animals. The feasibility of using intravenous myocardial contrast echocardiography to assess the ischemic area in rats was investigated. METHODS: Fourteen open chest Wister male rats were examined. Intravenous myocardial contrast echocardiography was performed by fundamental and intermittent mode using a high frequency (5-12 MHz) transducer (SONOS 5500) with injection of NC100100 (20% dilution) into the femoral vein. The mechanical index was set to 1.6. Baseline-subtracted video intensity (256 level) was measured in the anterior, posterior, septal and lateral walls of the left ventricle. The left anterior descending artery was ligated in 16 rats. The area at risk was evaluated by myocardial contrast echocardiography and compared to the area of defect by Evans Blue staining. RESULTS: All wall segments were clearly opacified (anterior 63.8 +/- 24.7, posterior 27.0 +/- 11.0, septal 44.5 +/- 11.6, lateral 52.3 +/- 19.1), although the baseline-subtracted video intensity of the posterior wall was low. The area at risk was clearly observed, and there was a good correlation with the nonperfused area by Evans Blue staining (y = 1.13x-3.54, r = 0.98). CONCLUSIONS: Intravenous myocardial contrast echocardiography can detect the perfusion defect even in rats using a high frequency transducer and suitable setup of equipment.

Animals↗
PubMed2001

[Effect of oxygen inhalation on myocardial opacification using levovist: an animal experimental study].

OBJECTIVES: Levovist can opacify the myocardium via venous injection, and is widely used in the clinical field. However, left ventricular opacification deteriorates during oxygen inhalation using Albunex, one of the first generation of contrast agents. This study examines the effect of blood oxygen pressure on the myocardial opacification by Levovist. METHODS: Myocardial contrast echocardiography (Toshiba Power Vision 6000) was performed using second harmonic imaging, intermittent exposure of ultrasound (every 4 cardiac beats) and acoustic power of 1.4 mechanical index. The video intensity of the ventricular septum after venous injection of Levovist (0.5 ml of 300 mg/ml) was measured under various respiratory conditions by manipulating the respirator and oxygen inhalation. Arterial blood gas was measured and correlated with the myocardial video intensity. RESULTS: The video intensity of myocardial opacification was lower with higher oxygen pressure in the arterial blood. Visual recognition of myocardial opacification was only 14% under high oxygen pressure over 200 mmHg. Microbubbles of Levovist form from normal air, and are easily affected by the gas concentration of the surrounding blood. CONCLUSIONS: Myocardial opacification using Levovist is deteriorated under high oxygen pressure at examination.

Administration, Inhalation↗
PubMed2001

[On line display of the reconstructed pressure waves of the radial artery from the monitored output pressure waves at the same site].

The input-output relationship of transducer and catheter system is described by linear, second-order differential equation with three coefficients: inductance (L), resistance (R), and capacitance (C). Once the natural frequency (fo) and the damping ratio (beta) of the monitoring system have been measured, three coefficients of the differential equation are uniquely obtained. We measured the frequency response of the monitoring system, which we usually use in our hospital, to obtain fo and beta, and reconstructed the original input arterial pressure wave from output signal on the display using the simple time-domain approach. The analysis of this linear, second-order differential equation, is applicable in on-line bedside monitoring, because the calculation of this equation is simpler than that using Fourier's translation. The pressure waves of the radial artery both monitored (output) and restored (input) were depicted on the same display at the same time. We can evaluate the changes in systemic circulation from the changes in the wave shapes of arterial blood pressure.

Blood Pressure↗
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↗