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Biomedical subjects

C Kawai

Publications and source records attributed to C Kawai.

At least 127 records · Page 7Linked to original sources
PubMed1991

Hemodynamic efficacy of E-1020 in comparison with dopamine on acute mitral regurgitation in anesthetized dogs.

To evaluate the effects of a new phosphodiesterase inhibitor, E-1020 (1, 2-dihydro-6-methyl-2-oxo-5-(imidazo [1, 2-a] pyridin-6-yl)-3-pyridine carbonitrile hydrochloride monohydrate), on cardiovascular hemodynamics in acute heart failure, we compared its effects with those of dopamine on experimentally produced acute mitral regurgitation in dogs. After the production of mitral regurgitation by transmyocardial chordal sectioning and obtaining a stable state, dopamine (5 micrograms/kg/min) was infused until the peak positive dP/dt (peak (+) dP/dt) increased to about 50% of the predopamine value. After complete recovery, E-1020 (30 micrograms/kg) was infused over 5 min and the data were obtained 10 min later. Both drugs equally increased peak (+) dP/dt, decreased systemic vascular resistance, and increased cardiac output. Left ventricular (LV) end-diastolic pressure, LV end-diastolic segment length (EDL), and mean left atrial (LA) pressure decreased with both drugs. The changes in EDL and mean LA pressure were larger with E-1020 than with dopamine (p less than .01 and p less than .05). Although mean inferior vena caval blood flow volume (mIVCF) increased and mean inferior vena caval pressure decreased with both drugs, the increment of mIVCF was smaller with E-1020 (p less than .001). Thus, E-1020 had not only a positive inotropic effect but also a vasodilatory action both on resistance vessels and on capacitance vessels.

Acute Disease↗
PubMed1991

Pathogenesis of myocardial injury in myocarditis and cardiomyopathy.

The pathogenesis of myocardial cell injury in myocarditis and cardiomyopathy was investigated. The presence of viral genomes in the murine heart in experimental coxsackievirus B3 myocarditis was studied by Northern blotting analysis using a 32P-labeled cDNA probe from the 5' end sequence. The strongest signal of positive autoradiograms was always at about 7.4 kilobases, corresponding to the size of the complete genome of the virus. Successive infections with coxsackievirus and encephalomyocarditis (EMC) virus infection showed simultaneous acute myocarditis and healed myocarditis, and the results suggest that successive virus infections cause additional myocardial damage, and develop lesions similar to chronic myocarditis or dilated cardiomyopathy. Anti-heart auto-antibody, induced during EMC virus infection, reacted predominantly with myosin. Indium-111 antimyosin scintigraphy showed positive in some of the patients with cardiomyopathy, and the uptake was inversely correlated with left ventricular function. When mice were injected with antimyosin antibody, mouse immunoglobulin G was detected in hearts in the chronic stage of EMC virus myocarditis, in myocytes surrounding fibrosis and calcification, suggesting deposition of antimyosin antibody. Although further study is necessary to clarify the mechanism of uptake of antimyosin in cardiomyopathy, antimyosin antibody may accumulate in viable myocytes with ongoing degeneration as well as in necrosis.

Animals↗
PubMed1991

Evaluation and clinical use of early washout ratio of thallium-201 in normal and ischemic myocardium after dipyridamole-induced vasodilation using ring-type emission computed tomography.

Using newly developed ring-type emission computed tomography (SPECT), we investigated the washout ratio (WR) of T1-201 in the myocardium quantitatively with fast dynamic scanning after infusion of dipyridamole (0.57 mg/kg), and assessed the feasibility of early WR as a marker to detect coronary artery disease. Twenty-three patients with and 8 patients without coronary artery disease had serial SPECT images obtained every 5 min for 45 min and at 180 min after dipyridamole and subsequent T1-201 injection. The best appropriate transaxial slice was selected for WR analysis. Most appropriate diagnostic time was 25 min after infusion of T1-201 (WR-25). Normal WR-25 was 7.1 +/- 4.0%, 5.9 +/- 3.1% and 7.1 +/- 2.3% at the septum, anterior and lateral wall, respectively. Sensitivity, specificity and accuracy to identify coronary stenosis greater than 50% with a usage of abnormal WR-25, defined as WR-25 less than (mean of normals--1SD) in each region of inferest of the left ventricle (LV), were 96%, 100% and 97%, respectively. These results were better than those achieved by visual analysis (sensitivity 78%, specificity 100%, accuracy 84%). In patients with single as well as multivessel disease, the regional accuracy in assessing stenosis of more than 50% in the left anterior descending artery (LAD) and left circumflex artery (LCX) by WR-25 was 94% and 83%, respectively, which was significantly better than using visual methods (LAD 72% and LCX 50%; p less than 0.05). Thus, evaluation of early washout ratios (WR-25) after dipyridamole injection is a valuable method to increase sensitivity in assessing regional myocardial perfusion abnormality and is helpful in detection of ischemic heart disease, even with multivessel disease.

Adult↗
PubMed1991

Intravenous recombinant tissue-type plasminogen activator (rt-PA) and urokinase (UK) in patients with evolving myocardial infarction--a multicenter double-blind, randomized trial in Japan.

Intravenous administrations of 2000 x 10(4)IU (33 mg) (rt-PA2) and 3000 x 10(4)IU (50 mg) (rt-PA3) of a new recombinant tissue plasminogen activator (rt-PA:TD-2061) derived from uterine endothelial cells and urokinase (UK) 96 x 10(4)IU were compared in a double blind, randomized trial of 198 patients with evolving myocardial infarction. All patients entered the trial within 6 h of the onset of symptoms and underwent baseline coronary angiography of the infarct-related coronary artery before thrombolytic therapy was instituted. Sixty minutes following thrombolytic therapy occluded infarct-related arteries were successfully reperfused in 41.5% of 66 patients in the UK, 76.4% of 72 patients in the rt-PA2, and 74.6% of 59 patients in the rt-PA3 group. Statistically significant differences were observed between the UK and rt-PA groups (p less than 0.01). Serum fibrinogen levels declined in all 3 groups at 60 min post-therapy by averages of 35.9 +/- 3.1% in the UK, 16.8 +/- 4.8% in the rt-PA2 and 17.5 +/- 4.5% in the rt-PA3 group. The difference between the UK and the rt-PA groups was statistically significant (p less than 0.01). Plasma plasminogen and alpha 2-plasmin inhibitor levels showed the same tendencies. Bleeding was the most commonly observed complication and was most commonly seen at the catheterization site. There was no difference in the incidence among the 3 groups. Hospital deaths occurred in 5.3%, 6.3%, and 4.7% of the cases in the UK, rt-PA2 and rt-PA3 groups, respectively. We conclude, therefore, that rt-PA achieves a significantly higher rate of recanalization with less extensive systemic fibrinogenolysis at the dose employed than does UK. The optimum intravenous dose of rt-PA for Japanese patients is considered to be 2000 x 10(4)IU (33 mg).

Blood Coagulation↗
PubMed1991

Randomized trial of a selective inhibitor of thromboxane A2 synthetase, (E)-7-phenyl-7-(3-pyridyl)-6-heptenoic acid (CV-4151), for prevention of restenosis after coronary angioplasty.

A selective inhibitor of thromboxane A2 synthetase, CV-4151, has the unique property of increasing prostacyclin synthesis in addition to its anti-platelet aggregating effect. Prostacyclin inhibits the growth of smooth muscle cells which is considered to be an underlying mechanism of restenosis occurring after successful coronary angioplasty. A prospective randomized trial was conducted to determine whether CV-4151 could prevent restenosis. Administration was begun greater than or equal to 2 days before angioplasty, and continued until the follow-up study performed between 3 and 6 months after angioplasty. Follow-up angiography was performed in 58 patients (81 segments) taking the active drug and in 27 patients (35 segments) taking the placebo. The incidence of angiographic restenosis was 38.3% in the former group and 31.4% in the latter group. Thus, CV-4151 did not significantly reduce the incidence of restenosis, perhaps due to endothelial denudation after angioplasty preventing an increase of the subendothelial local prostacyclin level.

Angioplasty, Balloon, Coronary↗
PubMed1991

Detection of adriamycin cardiotoxicity with indium-111 labeled antimyosin monoclonal antibody imaging.

Myocardial imaging with indium-111 labeled antimyosin monoclonal antibody (antimyosin imaging) has been reported to be useful in the noninvasive detection of myocardial cell necrosis in dilated cardiomyopathy as well as in myocardial infarction and myocarditis. We used antimyosin imaging to detect myocardial damage in 2 patients with malignant lymphoma in whom adriamycin cardiotoxicity was suspected. Patients were injected with 74 MBq of indium-111 labeled antimyosin (Fab. fraction). Forty-eight hours later, planar imaging and single-photon emission computed tomography were performed using a gamma camera with a medium energy general purpose collimator. Antimyosin imaging demonstrated diffuse myocardial uptake not only in one patient with congestive heart failure but also in another patient at the early stage without congestive heart failure. Antimyosin imaging may be a sensitive method for noninvasive visualization of myocardial cell damage and useful in the early diagnosis of specific heart muscle disease.

Aged↗
PubMed1991

The effect of cyclosporine on the immunopathogenesis of viral myocarditis in mice.

The effect of cyclosporine on the immunopathogenesis of viral myocarditis was studied using a murine viral myocarditis model. Mice in the treated group had a higher mortality rate compared with those of the infected control group before day 15 (47/67 vs. 14/31, p less than 0.05). On day 7, treated mice showed higher titers of anti-heart autoantibody than the control group (12 +/- 7 vs 4 +/- 2, p less than 0.05), but no significant difference was seen on day 14 (28 +/- 15 vs. 39 +/- 34). Histologic lesions, lymphocyte subsets in the peripheral blood and heart in situ, the neutralizing antibody, and virus concentrations in the heart showed no significant differences between these groups. This study suggests that with the use of cyclosporine the production of anti-heart autoantibody was enhanced in the early stages of viral myocarditis in mice, and was associated with higher mortality rate.

Animals↗
PubMed1991

Serum from patients with restenosis after percutaneous transluminal coronary angioplasty stimulates proliferation of bovine vascular smooth muscle cells under low extracellular calcium condition.

We compared the effects on the proliferation of bovine vascular smooth muscle cells (VSMC) of serum from 36 patients without restenosis (group A), and 21 patients with restenosis (group B) after percutaneous transluminal coronary angioplasty (PTCA). Baseline characteristics were similar in both groups, except for the greater number of patients with unstable angina at the time of PTCA (52 vs 22%, p = 0.020) and the shorter interval between PTCA and repeat angiography in group B (106 +/- 30 vs 153 +/- 112 days, p = 0.022). Cultured bovine VSMC were stimulated with patient serum (5%) obtained at repeat angiography in either Ca(2+)-containing or Ca(2+)-free culture medium. DNA synthesis was assessed by [3H]thymidine incorporation. The following indices of VSMC proliferation were used: S(+) = [3H]thymidine uptake stimulated by 5% serum in Ca(2+)-containing medium/[3H]thymidine uptake stimulated by 5% fetal calf serum (FCS) in Ca(2+)-containing medium, S(-) = [3H]thymidine uptake stimulated by 5% serum in Ca(2+)-free medium/[3H]thymidine uptake stimulated by 5% FCS in Ca(2+)-free medium, and D = S(-)-S(+). D represented the preserved DNA synthesis in Ca(2+)-deprived medium. S(-) was lower than S(+) in group A (1.35 +/- 0.56 vs 1.57 +/- 0.58, p less than 0.0001), whereas it was higher than S(+) in group B (1.64 +/- 0.66 vs 1.50 +/- 0.58, p = 0.010). D was significantly higher in group B than in group A (0.14 +/- 0.23 vs -0.22 +/- 0.28, p less than 0.0001), and was not associated with any continuous variables including serum calcium level on univariate regression analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Human serum albumin inhibits prostacyclin production by endothelial cells: the relation of the inhibitory activity to sulfhydryl groups in albumin.

Human serum inhibited calcium ionophore-induced production of prostacyclin by cultured bovine aortic endothelial cells. The inhibitory fraction was purified from serum by anion-exchange and Blue-Sepharose affinity chromatography. The molecular weight of the purified substance was 67k dalton as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It was identified as human serum albumin by N-terminal amino acid sequence analysis. Human serum albumin was separated to two forms by high-performance liquid chromatography: mercaptalbumin (SH type) and nonmercaptalbumin (SS type). Both types of albumin inhibited the conversion of arachidonic acid to prostaglandin H2 in a dose-dependent manner without affecting phospholipase A2 or prostacyclin synthetase. This inhibition was more potent in mercaptalbumin than in nonmercaptalbumin. These results suggest that the conversion between mercaptalbumin and nonmercaptalbumin may play an important role in the modulation of prostacyclin synthesis by endothelial cells.

Adenosine Diphosphate↗
PubMed1991

Effects of cardiac sympathetic nervous system on the stunned myocardium experimental study with 123I-metaiodobenzylguanidine.

123I-Metaiodobenzylguanidine (123I-MIBG) uptake in the stunned myocardium was investigated in open chest dogs. 123I-MIBG is a tracer taken up in presynaptic adrenergic vesicles and reflects the function of the myocardial sympathetic nervous system. This study revealed that in the stunned myocardium without infarct, 123I-MIBG uptake was normal up to 40 minutes of ischemia and that exogenous noradrenaline improved deteriorated regional wall motion with increased uptake of 123I-MIBG. However, uptake of 123I-MIBG per flow decreased with infarct in ischemic areas, and it showed a linear relation with regional wall motion. Thus, in the absence of infarction 123I-MIBG is a tracer to differentiate stunning from more severe ischemia with persistent wall motion abnormality. Normal uptake and storage of 123I-MIBG in the stunned condition suggests that catecholamine release or second effector mechanism may relate to the mechanism.

3-Iodobenzylguanidine↗
PubMed1991

Decreased sulfhydryl groups of serum albumin in coronary artery disease.

We hypothesized that oxidative processes in myocardial tissues initiated by ischemia also cause the same kind of changes in blood proteins and lead to oxidation of sulfhydryl groups (SH). To test this hypothesis, the ratio (%MA) of mercaptalbumin to total albumin (= mercaptalbumin + nonmercaptalbumin) and the total SH contents of serum were measured in patients with coronary artery disease. There was a positive correlation between %MA and total SH contents and both values were reduced in proportion to the severity of the coronary artery disease. Furthermore, these values were lower early hours after the onset of acute myocardial infraction than 4 weeks later. These results support our hypothesis, and may provide a basis for the administration of agents which can counteract oxidative stress in order to protect myocardium in patients with coronary artery disease.

Adult↗
PubMed1991

Cytosolic and membrane-bound nitric oxide synthase.

Cytotoxic activated macrophages were sonicated and centrifuged. The activity of nitric oxide (NO) synthase was present in the supernatant and independent of Ca2+. The pellets were washed three times and treated with buffer containing 0.1% Triton X-100 or buffer alone, followed by centrifugation. The supernatant containing Triton X-100 showed NO synthase activity that was dependent on Ca2+, whereas the supernatant without the detergent had little activity. These data suggest that there are two forms of NO synthase: cytosolic and membrane-bound enzymes.

Amino Acid Oxidoreductases↗
PubMed1991

[Detection of human anti-mouse antibody in patients receiving 111In-antimyosin Fab: multicenter clinical study in Japan].

In the multicenter clinical study of 111In-Antimyosin Fab (74 MBq, 0.5 mg), human anti-mouse antibody (HAMA) titers have been evaluated in serum from 456 patients using the sensitive enzyme-linked immunosorbent assay. Presence of HAMA was confirmed by the neutralization test or using the size exclusion high performance liquid chromatography (HPLC) analysis in 11 of 393 patients (2.8%). HAMA was still detectable in 2 patients even 40 weeks after injection. None of 7 patients judged as positive for the intradermal test, a patient with vascular pain or 3 patients with fever or flare and itching with fever, developed detectable levels HAMA in their serum. These results suggest that patients may develop HAMA response after infusion of 111In-Antimyosin Fab, but pathogenic role of HAMA in these patients remains to be studied.

Animals↗
PubMed1991

[Value of fatty acid imaging using 123I-beta-methyl iodophenyl pentadecanoic acid (BMIPP) to assess viability of infarcted myocardium].

To evaluate clinical value of a new fatty acid imaging tracer, 123I-beta-methyl iodophenyl pentadecanoic acid (BMIPP), 27 patients with myocardial infarction (MI) underwent BMIPP imaging at rest. The results were compared with those of thallium-201 imaging and contrast ventriculography. Of 100 hypoperfused segments on thallium-201 imaging, 34 segments (34%) showed lower BMIPP uptake than thallium-201, and remaining 66 segments showed similar distribution of those tracers. This discrepancy was more often observed in a patients with acute or subacute stages of MI (less than 4 weeks from onset) than those with chronic stage of MI (greater than 4 weeks) (75% vs. 47%; p less than 0.005). In addition, in the patients with chronic stage of MI, the regional wall motion abnormality was less severe in those showing discrepant BMIPP uptake than those showing concordant distribution (the wall motion score: 1.33 +/- 0.62 vs. 0.63 +/- 0.99; p less than 0.05). Furthermore, redistribution on stress thallium-201 imaging was more often observed in than those showing concordant distribution (12%) than those showing concordant distribution (12%) (p less than 0.005). These preliminary study indicates that discrepant distribution of BMIPP and thallium-201 may be often observed, particularly in recent MI and those showing less wall motion abnormality and redistribution on stress thallium-201 imaging. Thus, the combined study of BMIPP and thallium-201 has a potential for assessing tissue viability in patients with MI.

Adult↗
PubMed1991

[Comparison of 99mTc-hexakis 2-methoxy-2-isobutyl isonitrile and 201Tl SPECT imaging for evaluation of coronary artery disease].

To evaluate clinical value of 99mTc-hexakis 2-methoxy-2-isobutyl isonitrile (MIBI) imaging for assessing coronary artery disease (CAD), 99mTc-MIBI SPECT imaging at post-exercise and at rest was compared with 201Tl SPECT imaging at post-exercise and 3 hours redistribution in 27 patients suspected with CAD. The sensitivities for detecting CAD patients were 94% (17/18) by both studies. The specificities were 71% (5/7) by 99mTc-MIBI and 57% (4/7) by 201Tl (p = NS). The sensitivities for detecting stenosed coronary arteries (greater than or equal to 75% stenosis) were also similar between 99mTc-MIBI (78%) and 201Tl (74%) (p = NS). The similar specificity values were obtained by 99mTc-MIBI (84%) and by 201Tl (82%) (p = NS). The patterns of abnormality (normal, ischemia and scar) were similar between 99mTc-MIBI and 201Tl images in 22 of the 25 cases (88%) and 117 of the 125 segments (94%). However, these patterns were occasionally different particularly in patients who received PTCA or CABG. Thus, 99mTc-MIBI SPECT imaging seems to be as accurate as 201Tl SPECT imaging for the detecting and evaluating CAD.

Adult↗
PubMed1991

[Expression of atrial natriuretic polypeptide in ventricles of heart with hypertrophic cardiomyopathy: an immunohistochemical study of endomyocardial specimens].

To investigate the ventricular expression of atrial natriuretic polypeptide (ANP) in human hypertrophic heart, we conducted an immunohistochemical study using endomyocardial biopsy specimens obtained from the right side of the interventricular septum (RVB), left ventricular free wall (LVB), or both of 39 patients with hypertrophic cardiomyopathy (HCM), and 9 control subjects without hypertrophy. No HCM patients had apparent congestive heart failure. ANP was not present in control subjects' RVB or LVB specimens, but was found in HCM patients', showing its characteristic distribution patterns (RVB > LVB, p < 0.05); it was present in 15 of 36 RVB (42%) and 2 of 25 LVB (8%). No clinical data, including echocardiographic, hemodynamic and angiographic data, were directly related to ventricular ANP expression in HCM. According to histological data, however, ANP-present RVB specimens of HCM had larger myocytes, severer fibrosis and myofiber disarray than the specimens without ANP. This indicates that a failing state may not be a prerequisite for ANP expression in human hypertrophic ventricles, but that ventricular ANP expression may occur concomitantly with myocyte hypertrophy as an adaptive response to focal stress due to "histological overloads" such as disarray and fibrosis in HCM, which may be reflected in the characteristic distribution patterns of intraventricular ANP.

Atrial Natriuretic Factor↗