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Biomedical subjects

Teruo Takano

Publications and source records attributed to Teruo Takano.

At least 91 records · Page 5Linked to original sources

Real-time measurement of nitric oxide by luminol-hydrogen peroxide reaction in crystalloid perfused rat heart.

The objective of this study was to develop an assay system that allows continuous monitoring of nitric oxide (NO) released from crystalloid perfused hearts. We utilized chemiluminescence reaction between NO and luminol-H(2)O(2) to quantify the NO level in coronary effluent. Isolated rat hearts were subjected to ordinary Langendorff's perfusion, and the right ventricle was cannulated to sample coronary effluent. After equilibration, the coronary flow rate was set constant and the hearts were paced at 300 bpm. Coronary effluent was continuously sampled and mixed with the chemiluminescent probe containing 0.018 mmol/l luminol plus 10 mmol/l H(2)O(2). Chemiluminescence from the mixture of coronary effluent and the probe was continuously measured. NO concentration was calibrated by various concentrations (0.5-400 pmol/l) of standard NO solution. The lower detection limit of NO was 1 pmol/l. Basal NO release from isolated perfused rat heart was 0.41 +/- 0.17 pmol/min/g of heart weight, and that was significantly suppressed by 0.1 mmol/l of L-NAME to 0.18 +/- 0.10 pmol/min/g of heart weight (n = 7). Application of 0.1 and 0.3 micromol/l acetylcholine increased NO level in the coronary effluent, in a concentration-dependent manner, from 6.6 +/- 1.7 in a baseline condition to 16.3 +/- 7.4 and 30.3 +/- 16.1 pmol/l at each peak, respectively. Thrombin at 1 and 10 U/ml also increased NO level from 17.6 +/- 4.3 in control to 35.5 +/- 10.4 and 48.7 +/- 8.7 pmol/l at each peak, respectively (n = 7). Thus, this assay system is applicable to the continuous real-time measurement of NO released from crystalloid perfused hearts, and it may be useful for the study of physiological or pathophysiological role of NO in coronary circulation.

Acetylcholine↗

Assessment of left ventricular function using solid-state gamma camera equipped with a highly-sensitive collimator.

PURPOSE: The solid-state gamma camera 2020tc Imager (Digirad, CA) is now commercially available and has been clinically applied. The present study evaluates the feasibility of equilibrium radionuclide ventriculography (ERNV) within a 3 min period using this camera equipped with a highly sensitive collimator. MATERIALS AND METHODS: ERNV was performed from the best septal position (left anterior oblique view) in 20 patients with cardiac disease using a single detector anger-type gamma camera equipped with a low-energy, high-resolution collimator. Immediately thereafter, we performed a second ERNV using the solid-state gamma camera equipped with a highly sensitive collimator. Acquisition periods were 10 and 3 min, respectively. RESULTS: Significantly more counts were collected from over the left ventricle with the solid-state gamma camera over 3 min than those with the anger-type gamma camera over 10 min (817.1 +/- 387.8 k counts vs. 668.2 +/- 327.4 k counts, p < 0.01). The left ventricular ejection fraction obtained from ERNV data using the solid-state gamma camera correlated closely with those acquired by the anger-type gamma camera (r = 0.94, p < 0.0001, SEE = 5.93%). CONCLUSION: The results showed that the solid-state gamma camera could assess left ventricular function with excellent data collection efficiency and high reliability.

Equipment Failure Analysis↗

Intrapulmonary vascular dilatation and nitric oxide in hypoxemic rats with chronic bile duct ligation.

BACKGROUND/AIMS: Nitric oxide (NO) has been suggested as the major cause of pulmonary vascular dilatation and hypoxemia in hepatopulmonary syndrome (HPS). The aim of this study was to assess the effect of NO on arterial oxygenation in rats with common bile duct ligation (CBDL rats), a model of HPS. METHODS: Arterial blood gases were measured in 44 CBDL rats and 44 Sham rats under unrestrained conditions. Intrapulmonary shunting was assessed with (141)Ce-labeled microspheres (15-mum diameter) and serum nitrate/nitrite levels were measured by HPLC. The effect of NOS inhibition on A-aDO(2) was studied using L-NAME. RESULTS: A decrease of PaO(2) below 82.7 mmHg (the mean value-2sigma in Sham rats) was seen in 43% of CBDL rats. Intrapulmonary shunting was greater in CBDL rats than in Sham rats (P<0.001). A correlation between the extent of shunting and A-aDO(2) was found in all animals studied (r=0.89, P<0.001, n=16). Serum levels of nitrate/nitrite increased significantly across the lungs, and the increase was significantly correlated with A-aDO(2) in the total population of animals studied. Administration of L-NAME to CBDL rats achieved a significant improvement of A-aDO(2). CONCLUSIONS: These results suggest that pulmonary vascular dilatation due to NO leads to hypoxemia in CBDL rats.

Animals↗

Hepatic chymase level in chronic hepatitis: co-localization of chymase with fibrosis.

Chymase, secreted by mast cells, is associated with angiotensin II production and fibrosis of myocardium and renal interstitium. Assuming that chymase also is involved in liver fibrosis, we previously established an enzyme-linked immunosorbent assay for chymase in human liver tissue. In the present study, we explored the localization of mast cells in the liver using antibodies against human chymase and also studied relationships between hepatic chymase level and histologic findings in 49 patients with chronic hepatitis. By the international classification, fibrosis was staged from F0 to F4 and activity was graded from A1 to A3. Cells immunoreactive for chymase were seen throughout portal areas and intralobular sinusoidal walls, largely colocalizing with inflammation and fibrosis. Hepatic chymase levels in F3 and F4 cases were greater than in F1 and F2 (F3+F4, 30.8+/-41.2 ng/mg vs. F1+F2, 5.7+/-6.6 ng/mg; P<0.01). Chymase in A3 casese (39.4+/-50.8 ng/mg) was more abundant than in A1 (3.7+/-4.3 ng/mg) or A2 (12.8+/-19.4 ng/mg); P<0.05 for each. Our findings suggest that hepatic chymase level is implicated in fibrosis and activity in human liver disease.

Journal Article↗

Electrocardiographic and electrophysiological characteristics of atrial fibrillation organized into atrial flutter by oral administration of class I antiarrhythmic agents.

The aim of this study was to evaluate the electrocardiographic (ECG) and electrophysiological characteristics of atrial fibrillation (AF) that organized into atrial flutter during oral administration of class I antiarrhythmic agents. The former clinical study included 72 consecutive patients (58 paroxysmal AF, 14 persistent AF) in whom class I antiarrhythmic agents were orally administered in the outpatient clinic for termination or prophylaxis of AF. The clinical background and ECG variables were compared between the patients with and without atrial flutter during class I antiarrhythmic agents therapy. An electrophysiological study was performed in ten patients with paroxysmal AF (five with [group A] and five without atrial flutter [group B] during oral class I antiarrhythmic agents therapy. Local electrograms from five different atrial sites (high and low right free wall, high and low septum, and distal coronary sinus) were analyzed during induced AF. The activation pattern of the right free wall during AF was also analyzed using a Halo catheter. Atrial flutter was documented during class I antiarrhythmic agents therapy in 14 (24%) patients with paroxysmal AF, whereas in none with persistent AF. The mean cycle length (f-f interval) and amplitude of the fibrillation waves in leads II and V1 from the surface ECG were significantly greater in the patients with than in those without atrial flutter. In the electrophysiological study, the mean cycle lengths for the low and high right free wall were significantly longer in group A than in group B, whereas those for the low septums and distal coronary sinus did not differ between the two groups. During the induced AF, the ratio of time exhibiting a consistent activation pattern (cranio-caudal, caudo-cranial, or undetermined) along the right free wall was significantly greater in group A than in group B. Atrial flutter newly developed during class I antiarrhythmic agents therapy in patients with coarse AF on the surface ECG and a relatively organized activation in the right atrial free wall. The observation of these findings may facilitate the identification of candidates for hybrid pharmacologic and ablative therapies.

Administration, Oral↗

Clinical significance and contributing factors of long-term variability in induced ventricular tachyarrhythmias.

UNLABELLED: Long-Term Variability in Induced Tachyarrhythmias. INTRODUCTION: Ventricular arrhythmias induced during electrophysiologic study (EPS) may vary over time, making arrhythmia induction studies unreliable. The aim of this prospective study was to clarify the clinical significance of long-term variability in induced arrhythmias and to elucidate factors determining this variability. METHODS AND RESULTS: Three noninvasive EPSs were performed 1, 13, and 25 months after implantation of a cardioverter defibrillator in 40 patients with ventricular tachyarrhythmias, without a change in their antiarrhythmic drug regimens. The induced ventricular arrhythmias were categorized into five grades. Long-term variability, which was defined as a variation in the grades during the three EPSs, was observed in 23 patients (group A) and not in the remaining 17 patients (group B). During the 2-year period, spontaneous sustained ventricular arrhythmias developed in 15 patients (65%) in group A but in only 4 patients (24%) in group B (P = 0.01). Inducibility of sustained tachyarrhythmias was not associated with emergence of spontaneous arrhythmias. All patients also underwent thallium-201 and iodine-123-metaiodobenzylguanidine (MIBG) scans to evaluate the extent of the regions showing normal thallium uptake with reduced MIBG uptake. Group A patients showed greater thallium/MIBG mismatched regions than did group B patients (P = 0.01). Logistic regression analysis revealed that long-term variability (relative risk [RR] 7.55, P = 0.03), amiodarone therapy (RR 0.14, P = 0.04), and left ventricular ejection fraction <35% (RR 6.26, P = 0.04) were independent predictors of spontaneous arrhythmia occurrence. CONCLUSION: In patients with ventricular tachyarrhythmias, long-term variability in induced arrhythmias, but not the inducibility of arrhythmias, is associated with a higher incidence of spontaneous arrhythmias. Regional cardiac sympathetic denervation may be an important mechanism of this variability. These results also may explain why inducibility-based antiarrhythmic drug testing does not predict patient prognosis.

Adaptation, Physiological↗

Possible contribution of the sarcoplasmic reticulum Ca(2+) pump function to electrical and mechanical alternans.

We investigated the role of the sarcoplasmic reticulum's (SR) Ca(2+) pump function of the in the mechanism of alternans. We recorded the surface ECG, monophasic action potential (MAP) and left ventricular pressure (LVP) in the canine beating heart. Alternans was induced with an abrupt shortening of the cycle length from 1000 to 350 ms. After the control studies, we administered propranolol or isoproterenol. In the presence of propranolol, we administered milrinone or 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). In the presence of isoproterenol, we administered thapsigargin. Isoproterenol and milrinone attenuated both the electrical and mechanical alternans. Thapsigargin, a specific SR Ca(2+) pump inhibitor, and propranolol magnified both types of alternans. DIDS, a Ca(2+)-activated Cl(-) current (I(Cl(Ca))) inhibitor, attenuated the MAP alternans without an affect on the LVP alternans. Thus, the delayed intracellular Ca(2+) cycling caused by the impaired SR Ca(2+) pump function might produce electrical and mechanical alternans. beta-adrenergic stimulation eliminated these alternans. The I(Cl(Ca)) contributed to the appearance of the electrical alternans.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Therapeutic monitoring of class I antiarrhythmic agents using high-resolution electrocardiography instead of blood samples.

Antiarrhythmic therapy requires monitoring of serum drug concentrations to determine a patient's optimal oral dose of medication. Repeated examination of blood samples, however, is costly and time-consuming, so the present study evaluated whether changes in serum concentrations could be estimated from changes in electrocardiographic (ECG) parameters. Of 36 patients receiving antiarrhythmic drugs for supraventricular or ventricular arrhythmias, 12 were treated with flecainide, 12 with pilsicainide, and 12 with pirmenol. Signal-averaged ECG (SAECG) were recorded before starting drug administration, 1 month later, and twice during ongoing therapy. At the time of the 2nd to the 4th recordings, serum concentrations of the drugs were also measured. As previously reported, all agents, but especially flecainide and pilsicainide, prolonged the filtered QRS (f-QRS) and the duration of low-amplitude signals at the terminal portion of the QRS complex. The SAECG parameters varied between the recordings made during therapy. Differences in the duration of the f-QRS between 2 recordings correlated significantly with differences in serum drug concentrations (r=0.91 for flecainide, r=0.70 for pilsicainide, and r=0.61 for pirmenol). No significant correlation between drug concentration and other SAECG parameters was found. Changes in the serum concentration of flecainide, pilsicainide and pirmenol can be estimated from changes in the duration of the f-QRS on the SAECG and periodic monitoring of such could help reduce the number of repeat measurements of drug concentrations in blood samples.

Aged↗

Clinicopathological characteristics of 10 patients with rupture of both ventricular free wall and septum (double rupture) after acute myocardial infarction.

Cardiac ruptures after myocardial infarction are classified as ventricular free wall ruptures (FWR), ventricular septal ruptures (VSR), and papillary muscle ruptures (PMR). A combination of any two types of rupture is called "ventricular double rupture;" (VDR) and shows a specific clinical course. 3,284 patients with acute myocardial infarction (AMI) were admitted to the CCU of our hospital between April, 1973 and December, 2001, and 10 patients (8 males and 2 female, aged 54 through 82 years) with VDR were clinicopathologically evaluated. All were diagnosed as VDR consisting of FWR and VSR. VDR was observed in 0.30% of all patients with AMI, in 3.0% of those with FWR, and in 16.1% of those with VSR. The infarct site was anteroseptal in 3 patients, anterolateral in 3, inferior in 3, and posterolateral in 1. Two patients with inferior infarction complicated RV infarction and a patient with posterolateral infarction had healed inferior infarction. The risk factors related to VDR were age, a history of hypertension, increased sympathetic tone to improve hemodynamic aggravation after perforation, cardiotonic agents, thrombolytic agents, delayed reperfusion, right ventricular volume overload by shunt and re-infarction. However, these factors might have played only a subsidiary role. The most important factor in VDR was the pathological findings. The site of septal perforation was the apex close to the septum-free wall junction in 9 patients and the site of rupture was also apical in 8 patients. Four patients already had VSR on admission to our CCU. FWR developed soon after VSR was demonstrated in 4 patients. FWR and VSR occurred simultaneously in one patient. These results suggest that VSR in the apical region is a precursor of VDR and requires the earliest surgical treatment. Surgical treatment was carried out in the operating room in 5 patients and 3 (60.0%) of them survived for 4 months or more. Two patients with rupture incidentally detected during operation for VSR were discharged and are still alive, though another one with free wall blow out rupture died 129 days after operation. Bedside thracotomy was performed in 3 patients and all of them died.

Aged↗

[An update consideration for the use of antithrombotic agents].

Despite recent introduction of catheter-based invasive strategy, the mainstay of the treatment for acute pulmonary thromboembolism is antithrombotic medication. The most standard tactics is to start intravenous unfractionated heparin (for a better substitute, low-molecular-weight heparin is available overseas), and to shift it to oral warfarin and maintain for at least 3 months. The duration of prophylactic anticoagulation may be extended longer by weighing the risks of recurrence and anticoagulant-related bleeding. Use of fibrinolytic agents should be considered first of all in patients who have hemodynamic instability or cardiogenic shock (massive type), because its effects are rapid and drastic in many cases. Recent evidence suggests that fibrinolytic therapy be also effective in patients with right ventricular pressure overload and dysfunction (sub-massive type).

Acute Disease↗

Use of cytosolic and myofibril markers in the detection of ongoing myocardial damage in patients with chronic heart failure.

PURPOSE: Measurement of serum levels of cytosolic and myofibril components of cardiac tissue could indicate ongoing myocardial damage in patients with chronic heart failure. METHODS: We correlated serum levels of a cytosolic marker (heart-type fatty acid-binding protein) and a myofibril marker (troponin T) with the severity of symptoms (based on the New York Heart Association [NYHA] class), neurohumoral derangement, and subsequent cardiac events in 56 patients with chronic heart failure. RESULTS: Mean (+/- SD) levels of heart-type fatty acid-binding protein were greater in patients with NYHA class III or IV heart failure (9.9 +/- 5.2 ng/mL) than in those with NYHA class II (4.9 +/- 1.9 ng/mL, P <0.0001). Detection of troponin T (> or =0.02 ng/mL) was also more common in patients with worse heart failure (81% [13/16] in class III or IV vs. 43% [17/40] in class II, P = 0.02). Significant correlations were found between heart-type fatty acid-binding protein levels and plasma levels of A-type natriuretic peptide (r = 0.45, P = 0.0004), B-type natriuretic peptide (r = 0.66, P <0.0001), and norepinephrine (r = 0.36, P = 0.006). Male sex (hazard ratio [HR] = 5.0; 95% confidence interval [CI]: 1.3 to 19), detectable troponin T levels (HR = 7.0; 95% CI: 1.1 to 44), heart-type fatty acid-binding protein (HR = 2.6 per 3.9-ng/mL increase; 95% CI: 1.1 to 6.5), and left ventricular ejection fraction (HR = 3.6 per 15% decrease; 95% CI: 1.2 to 11) were independently associated with subsequent cardiac events (8 deaths or 10 readmissions because of worsening heart failure). CONCLUSION: Heart-type fatty acid-binding protein and troponin T are markers of ongoing myocardial damage, and are associated with subsequent cardiac events in patients with chronic heart failure.

Aged↗

Limitation of infarct size and ventricular remodeling in patients with completely reperfused anterior acute myocardial infarction--the potential role of ischemia time.

BACKGROUND: Experimental studies suggest that coronary reperfusion does not result in appreciable myocardial salvage beyond 3 to 4 h. HYPOTHESIS: The present study was undertaken to examine the potential role of ischemia time as a determinant of infarct size and cardiac function in humans. METHODS: Ninety patients (69 men, 21 women, aged 61 +/- 1 years) presented within 24 h of onset of a first anterior infarct had ST-segment elevation on electrocardiogram. All patients underwent coronary intervention within 24 h of onset of symptoms and obtained complete reperfusion of the infarct-related artery. RESULTS: Infarct size expressed as a percentage of the area at risk (IS/RA) and left ventricular end-diastolic volume (LVEDV) were significantly (p < 0.017) smaller and left ventricula rejection fraction (LVEF) assessed by left ventriculography (35 +/- 4 days) was significantly higher in patients treated within 4 h after onset (IS/RA:55 +/- 4%, LVEDV: 127 +/- 7 ml, LVEF: 62 +/- 2%) than in those treated 4 to 12 h (97 +/- 2%, 140 +/- 13 ml, 52 +/- 3%) and 12 to 24 h (93 +/- 2%,163 +/- 14 ml, 49 +/- 5%) after symptom onset. Left ventricular end-diastolic volume was significantly smaller in patients treated 4 to 12 h after onset than in those treated 12 to 24 h after onset. CONCLUSIONS: Patients with < 4 h of myocardial ischemia exhibited significant myocardial salvage and better left ventricular function and patients with 4 to 12 h of myocardial ischemia exhibited significantly smaller LVEDV than those with more prolonged ischemia, although there was no difference in final infarct size.

Cardiac Catheterization↗

Serial assessment of left ventricular performance at rest and during bicycle exercise by ECG-gated myocardial perfusion SPECT.

UNLABELLED: The present study evaluates left ventricular performance during exercise by ECG-gated myocardial perfusion SPECT with short-time data collection. METHODS: The study population consisted of 10 healthy volunteers (Group N) and 9 patients with ischemic heart disease (Group I). Seven patients in Group I had a history of prior myocardial infarction. Rest ECG-gated SPECT was performed 40 min after an injection of Tc-99m-tetrofosmin (555-740 MBq). After resting data acquisition, Group N underwent up to two 5-min stages of exercise (75 and 125 watts) on a detachable bicycle ergometer. The Group I patients all underwent symptom-limited, maximal testing on the ergometer. ECG-gated SPECT data were acquired from both groups for 3 min at rest and during the last 3 min of each exercise stage. RESULTS: Significant increases occurred in LVEF from rest to peak stress in both groups (from 55.4 +/- 5.8 to 66.6 +/- 4.1% in group N, p < 0.0001; from 49.0 +/- 12.8 to 56.7 +/- 13.8% in Group I, p < 0.001). The LVESV values significantly decreased to peak stress in Group N (from 49.9 +/- 13.1 to 37.8 +/- 10.0 ml, p < 0.0001), whereas LVEDV did not change (from 110.6 +/- 18.9 to 112.0 +/- 19.0 ml). In contrast, the LVESV values at rest and under peak stress were similar in Group I (from 52.6 +/- 23.9 to 51.7 +/- 31.4 ml) and LVEDV in Group I at peak exercise tended to increase (from 102.8 +/- 36.7 to 111.3 +/- 39.0 ml). The changes in LVESV from rest to peak stress were significantly different between Groups N and I (-12.1 +/- 6.3 vs. -0.9 +/- 11.6 ml, p < 0.02). CONCLUSION: ECG-gated SPECT with short-time data collection can assess left ventricular function during exercise and may offer useful information for evaluating patients with ischemic heart disease.

Adult↗