Biomedical subjects

C Kawai

Publications and source records attributed to C Kawai.

At least 325 records · Page 18Linked to original sources

PubMed1986

Acute hemodynamic effects of a new inotropic agent, OPC-8212, on severe congestive heart failure.

The hemodynamic and clinical effects of OPC-8212, a newly synthesized, orally effective inotropic agent, were assessed for the first time in ten patients with severe congestive heart failure by means of right heart catheterization with a Swan-Ganz catheter. Cardiac output was determined by the thermodilution technique. Patients received a single oral dose of 6 mg/kg. To determine the magnitude and time-course of the effects of OPC-8212, measurements were made during an observation period before and 2, 4, 8, and 12 h after administration. Blood was also taken at these times for measurement of the concentration of plasma OPC-8212. No large meals were allowed during the first 4 h. After the single oral dose of OPC-8212, plasma concentrations increased rapidly, reaching an effective level after 8 h and peaking at 12 h. Hemodynamic performance improved as the mean OPC-8212 plasma level increased, with the maximum effect being observed between 8 and 12 h after acute administration of the drug. At 8 h, the cardiac index was increased from the baseline value of 2.4 +/- 0.2 (SEM) to 2.8 +/- 0.3 1/min/m2 (P less than 0.01). The stroke work index rose from 26.2 +/- 5.1 to 31.7 +/- 60 g . m/m2. The excessive pulmonary artery diastolic pressure fell from 22 +/- 2 to 17 +/- 3 mmHg at 8 h (P less than 0.001) and to 16 +/- 2 mmHg (P less than 0.001) at 12 h. The incidence of ventricular premature beats was not increased and no other side effects were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1986

Dynamic changes in left ventricular regional wall thickness during premature ventricular contraction in conscious dogs.

The contractile pattern of the regional left ventricular wall during premature ventricular contraction was analyzed in conscious dogs instrumented with an ultrasonic dimension gauge across the anterior and posterior left ventricular walls. Aortic flow was measured with an electromagnetic flow probe. A single premature ventricular contraction was induced by stimulating either the anterior or posterior wall with varied coupling intervals from 380 to 650 msec. Stroke volume of premature ventricular contraction was significantly smaller than that of premature atrial contraction with identical coupling intervals. In premature contractions, stroke volume was linearly related to coupling intervals. Though there was no isovolumic wall thickening in premature atrial contraction, the wall started to thicken during isovolumic ventricular systole in premature ventricular contraction. There was a clear inverse correlation between the ratio of the isovolumic wall thickening to the total wall thickening and coupling intervals. In premature ventricular contractions with identical coupling intervals, the deformation of thickening characteristics was more pronounced in regions with closer proximity to the ectopic focus. Thus it is concluded that the pump function is depressed in premature ventricular contraction, in part due to the increased ratio of wall thickening during isovolumic systole before the opening of the aortic valve. Isovolumic wall thickening increases along with the shorter coupling intervals and closer proximity to the ectopic focus. These alterations in left ventricular mechanical function due to ectopic contraction might induce serious sequelae, depending upon the ectopic focus in the presence of already depressed regional function.

Animals↗

PubMed1986

Selective thromboxane A2 synthetase inhibition in vasospastic angina pectoris.

To investigate whether thromboxane A2 is responsible for the initiation of vasospastic angina pectoris, thromboxane B2 levels were measured in the great cardiac vein and the arterial blood of 12 patients with clinically and angiographically proved vasospastic angina and therapeutic trials were performed with selective thromboxane A2 synthetase inhibitor OKY-046, an imidazole derivative. During ergonovine-provoked (11 cases) and spontaneous (1 case) anginal attacks, great cardiac vein thromboxane B2 increased from 121 +/- 27 to 430 +/- 382 pg/ml (p less than 0.05, n = 12), arterial thromboxane B2 increased from 93 +/- 18 to 122 +/- 33 pg/ml (NS, n = 12) and thromboxane B2 production increased from 3.18 +/- 1.88 to 25.16 +/- 22.32 ng/min (p less than 0.05, n = 6). Subsequently, OKY-046, 400 mg/day orally, was administered to 7 of the 12 patients, while a continuous electrocardiogram was recorded on a dual channel Holter monitor during a 3 day placebo period and the 3 day OKY-046 regimen. Although peripheral plasma thromboxane B2 levels decreased significantly from 98 +/- 15 to 12 +/- 8 and 28 +/- 10 pg/ml (1 and 6 hours after ingestion, respectively) (p less than 0.05 for both), 6-keto-prostaglandin F1 alpha production in serum increased significantly from 0.48 +/- 0.22 to 2.3 +/- 0.72 (1 hour) and 1.8 +/- 0.46 ng/ml (6 hours) (p less than 0.05 for both) during OKY-046 administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrylates↗

PubMed1986

Myocardial relaxation in atrial fibrillation.

Although myocardial contractility has been known to vary from beat to beat in atrial fibrillation, myocardial relaxation in this arrhythmia has not been investigated. In this study, left ventricular relaxation was examined in seven patients with atrial fibrillation (four with mitral valve disease, one with aortic regurgitation, one with secundum type atrial septal defect and one with apical left ventricular hypertrophy). The left ventricular pressure was measured with a micromanometer-tipped catheter and the time constant of isovolumic left ventricular pressure decline (the relaxation time constant) was calculated by means of exponential curve fitting from more than 20 consecutive beats in each patient. The maximal rate of rise of left ventricular pressure (dP/dt) and the relaxation time constant were examined in relation to the preceding RR interval (RR2) and to the ratio of the RR2 interval to the pre-preceding RR interval (RR2/RR1), and the correlation coefficients were obtained. The dP/dt correlated better with RR2/RR1 than with the RR2 interval (0.82 +/- 0.05 versus 0.48 +/- 0.2), but the relaxation time constant did not show any correlation with RR2/RR1 or the RR2 interval (0.03 +/- 0.21 and 0.06 +/- 0.21, respectively). The relaxation time constant was fairly constant in each patient even when the RR2 interval and RR2/RR1 varied greatly. Thus, relaxation in atrial fibrillation is independent of changes in contractility as seen in the relation between postextrasystolic relaxation and postextrasystolic potentiation of contractility.

Adult↗

PubMed1986

Effects of prednisolone on acute viral myocarditis in mice.

The effect of prednisolone on viral myocarditis was studied in BALB/c mice with encephalomyocarditis virus myocarditis. Prednisolone was injected intramuscularly, 10 mg/kg once a day, on days 4 to 13 (experiment 1) and on days 8 to 17 (experiment 2). The control mice in each experiment received injections of distilled water. In experiment 1, myocardial virus titers were maximal but neutralizing antibodies were rarely present on day 4, and viral titers were still elevated and antibody titers were high on day 8. The survival rate of the prednisolone group was significantly lower (p less than 0.05) than that of the control group on days 21, 22 and 23. On day 10, the antibody titers of the prednisolone group were significantly lower (p less than 0.01) than those of the control group, and viral titers of the prednisolone group remained significantly elevated (p less than 0.01), whereas viruses were rarely isolated in the control group. In experiment 2, the survival rate and antibody titers were not significantly different in the prednisolone and control groups. In both experiments, no viruses were isolated on day 14. The present study suggests that corticosteroids given in the early stage aggravate the course of acute viral myocarditis, and that they may not have detrimental effects if given when neutralizing antibody titer levels are high, although they are not expected to have a beneficial effect.

Animals↗

PubMed1986

Animal model of silent myocarditis in athymic mice.

To clarify the role of the immune system in the development of myocarditis, BALB/c-nu/nu mice (group 1), BALB/c-nu/+ mice (group 2), BALB/c-nu/nu mice injected with 5 X 10(7) spleen cells from BALB/c-nu/+ mice (group 3), and BALB/c-nu/nu mice injected with 5 X 10(7) spleen cells from BALB/c-nu/+ mice treated with rat anti-Thy-1.2 monoclonal antibody with complement (group 4) were inoculated with encephalomyocarditis virus. There were no significant differences in the incidence of myocarditis among the four groups. Virus titrations of the heart and serum neutralising antibody titres in the four groups did not show any significant differences. Fifty two per cent (26/50) of group 2 and 43% (20/46) of group 3 died on days 9-15, when congestive heart failure developed. Only 9% (5/54) of group 1 and 8% (1/12) of group 4, however, died on days 9-15. Pathological examination confirmed congestive heart failure in groups 2 and 3 but not in groups 1 and 4. Dilatation of the ventricular cavities, pleural effusion, ascites, and congestion of the lungs and liver were present in groups 2 and 3 but not in groups 1 and 4. Cellular infiltration and myocardial necrosis were severe in groups 2 and 3 but minimal in groups 1 and 4. Thus the severity of myocarditis may be regulated by T cells. So-called silent myocarditis seen in clinical settings may be similar to myocarditis in BALB/c-nu/nu mice.

Animals↗

PubMed1986

Mural thrombus in experimental viral myocarditis in mice: relation between thrombosis and congestive heart failure.

In a study of the time of appearance of mural thrombus and the relation between thrombosis and congestive heart failure in acute viral myocarditis 180 BALB/c mice were inoculated intraperitoneally with the M variant of encephalomyocarditis virus. Thirty mice were killed on day 5 and 50 mice each on days 7, 10, and 14. Of the 176 mice with myocarditis, 25 (14.2%) developed congestive heart failure after day 9 and 22 (12.5%) showed thrombi after day 6. Most of the thrombi were at the sites of endocardial lesions in the atria. The total incidence of thrombosis in mice with congestive heart failure was significantly higher than that in mice without. None of the 50 uninoculated control mice developed thrombi. The present study suggests that acute viral myocarditis carries an appreciable risk of thromboembolism and that congestive heart failure is a risk factor for thrombosis.

Animals↗

PubMed1986

Dynamic changes in plasma inactive renin levels in Bartter's syndrome after administration of captopril and angiotensin II.

Changes in plasma active and inactive renin concentration (ARC and IRC) after captopril administration and angiotensin II (AII) infusion were studied in six patients with Bartter's syndrome. A single oral dose of captopril (8-25 mg) lowered the blood pressure and increased both ARC and IRC. AII infusion elevated blood pressure, suppressed ARC and increased IRC. In this syndrome of high renin levels, infused AII appeared to increase inactive renin secretion by reducing its conversion to active renin. On the other hand, an acute fall in AII levels and/or renal perfusion pressure by captopril increased both active and inactive renin. This indicates that the increase in the secretion of inactive renin, stimulated by captopril, might exceed any increase in its conversion to active renin in patients with Bartter's syndrome, in whom the production of renin is accelerated, and conversion of inactive renin to active renin probably already operates near its maximum.

Adolescent↗

PubMed1986

Altered platelet alpha 2 adrenoreceptor in acute myocardial infarction and its relation to plasma catecholamine concentrations.

Changes in platelet alpha 2 adrenoreceptors and their relation to plasma catecholamine concentrations were studied in 11 patients with acute transmural myocardial infarction. A radiolabelled alpha 2 adrenoreceptor antagonist, [3H]-yohimbine, was used to assay alpha 2 adrenoreceptors on platelet membranes, and plasma catecholamine concentrations were measured by high performance liquid chromatography. The number of platelet alpha 2 adrenoreceptors, the dissociation constant, and plasma noradrenaline and adrenaline concentrations were studied 6.6 (3.3) (mean (SD)) hours after the onset of acute myocardial infarction and one month later. The mean (SD) number of adrenoreceptors increased significantly from 94.5 (50.5) fmol/mg protein immediately after infarction to 157.0 (65.7) fmol/mg protein one month later. The dissociation constant, however, did not change significantly (4.33 (1.40) nmol/l vs 4.37 (1.22) nmol/l). Raised noradrenaline (5.60 (4.37) nmol/l) and adrenaline (0.28 (0.14) nmol/l) concentrations had fallen significantly to normal values (1.21 (0.67) and 0.09 (0.05) nmol/l respectively) a month after infarction. The decrease in the number of alpha 2 adrenoreceptors soon after infarction may be beneficial because such a change will reduce the strength of various reactions to catecholamines, such as vasoconstriction.

Aged↗

PubMed1986

Quantitative analysis of myocardial fibrosis in normals, hypertensive hearts, and hypertrophic cardiomyopathy.

The distribution of fibrosis was studied quantitatively in the entire left ventricular wall of a transverse slice of the heart from 10 necropsy cases of hypertrophic cardiomyopathy, 10 cases of hypertensive heart disease, and 20 normal adults. The percentage area (mean (SD)) of fibrosis in the left ventricular wall in hypertrophic cardiomyopathy (10.5 (4.3)%) was significantly greater than that in hypertensive heart disease (2.6 (1.5)%) or in normal hearts (1.1 (0.5)%). In hypertrophic cardiomyopathy the percentage area of fibrosis was greater (13.1 (4.8)%) in the ventricular septum than in the left ventricular free wall (7.7 (4.2)%) whereas in hypertensive heart disease and normal hearts values in these two areas were similar. The percentage area of fibrosis in the left ventricular free wall (where myocardial fibre disarray was not extensive even in hypertrophic cardiomyopathy) was greater in hypertrophic cardiomyopathy than in hypertensive heart disease. The percentage area of fibrosis correlated with heart weight in hypertensive heart disease, but not in hypertrophic cardiomyopathy. These results suggest that widespread fibrosis in hypertrophic cardiomyopathy cannot be explained by cardiac hypertrophy alone, and that disarray and other factors are also important in pathogenesis. The increase in the percentage area of fibrosis from the outer to the inner third of the left ventricular free wall in hypertrophic cardiomyopathy and in hypertension probably reflected transmural gradients of wall stress and myocardial fibre diameter. Although fibrosis is not specific to hypertrophic cardiomyopathy, its quantification and analysis of its regional distribution provide information that is useful in investigating the pathophysiology of the disorder.

Adolescent↗

PubMed1986

Pathological features of hypertrophic cardiomyopathy without asymmetrical septal hypertrophy.

In a heart with hypertrophic cardiomyopathy without asymmetrical septal hypertrophy the number of transmural myocytes, the mean size of myocytes, and the percentage area of interstitial space were similar in the ventricular septum and left ventricular posterior wall, whereas in a reported series of 14 hearts with hypertrophic cardiomyopathy with asymmetrical septal hypertrophy the number of transmural myocytes was greater in the ventricular septum than in the left ventricular posterior wall. In hearts with hypertrophic cardiomyopathy without asymmetrical septal hypertrophy the mean size of myocytes was significantly greater than that of normal hearts, but the number of transmural myocytes was not increased. The extent and distribution pattern of myocardial fibre disarray and fibrosis in the left ventricle were similar in hearts with hypertrophic myopathy whether or not asymmetrical septal hypertrophy was present.

Aged↗

PubMed1986

Visualization of moving fluid: quantitative analysis of blood flow velocity using MR imaging.

A new method for the measurement of blood flow using magnetic resonance imaging has been developed. The flow velocities are calculated from the distances that the fluid has moved. The distances are directly visualized by a new pulse sequence. In a phantom study, the measured flow rates showed very good correlation with actual flow rates of up to 20 l/min (3 m/sec). In a volunteer study, pulsatile flow velocities of a large artery were measured with electrocardiographic gating. The flow pattern of a cardiac cycle at the abdominal aorta is similar to that revealed by other methods of measurement, such as Doppler ultrasound. This method allows reasonably accurate quantitative analysis of blood flow in the large arteries.

Blood Flow Velocity↗

PubMed1986

Quantification of thallium-201 myocardial uptake using serial dynamic imaging at rest and during exercise.

The thallium-201 myocardial uptake ratio was measured using serial dynamic imaging of the initial uptake phase following an intravenous bolus injection. It revealed no significant difference at rest between non-coronary heart disease and coronary artery disease, while it was greater in cases with left ventricular hypertrophy. With exercise loading, this value significantly increased in non-coronary heart disease, whereas less increase was observed in coronary artery disease. This increasing capability was lower in multivessel disease compared with single-vessel disease.

Adult↗

PubMed1986

A clinicopathologic study of patients with hemorrhagic myocardial infarction treated with selective coronary thrombolysis with urokinase.

Hemorrhagic acute myocardial infarction (AMI) was studied after selective intracoronary thrombolysis (SICT) in 30 patients undergoing autopsy. Urokinase, 240,000 to 1,200,000 U, was selectively injected into the infarct-related coronary artery at 2 to 9 hr (4 +/- 2 hr) after the onset of AMI. The infarct-related coronary artery showed complete occlusion in 21, 99% stenosis in eight, and 90% stenosis in one patient before SICT. After SICT, complete occlusion was seen in only five, 99% stenosis in 22, and 90% stenosis in three patients. Twenty-eight patients had transmural infarction and the other two had subendocardial infarction. Macroscopically and microscopically, the degree of hemorrhage was classified as no, slight, moderate, or marked bleeding and the hemorrhagic infarction was defined as moderate or marked diffuse bleeding in the infarct area. According to the interval from SICT to death, patients were also classified into stage I (early acute stage, 1 to 4 hr after SICT and 4 to 13 hr after the onset of AMI; n = 7), stage II (late acute stage, 9 hr to 11 days after SICT and 15 hr to 11 days after the onset of AMI; n = 18), or stage III (old infarction stage, over 17 days after AMI and SICT; n = 5). There were no significant differences with respect to the frequency of recanalization, the time from the onset of AMI to SICT, the dose of urokinase, or other clinical parameters among patients at the three stages. Only the hearts of patients in stage II showed hemorrhagic infarction, and it was found in 15 of 18 of these hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1986

Stimulation of cholesteryl ester synthesis in mouse peritoneal macrophages by cholesterol-rich very low density lipoproteins from the Watanabe heritable hyperlipidemic rabbit, an animal model of familial hypercholesterolemia.

Cholesterol-rich very low density lipoproteins (VLDL) from the homozygous Watanabe heritable hyperlipidemic (WHHL) rabbit induced marked cholesteryl ester accumulation in mouse peritoneal macrophages. This WHHL rabbit, an animal model of human familial hypercholesterolemia, has severe hypercholesterolemia, cutaneous xanthomas, and fulminant atherosclerosis due to the deficiency of the low density lipoprotein (LDL) receptor. When incubated with mouse peritoneal macrophages, the VLDL from WHHL rabbit (WHHL-VLDL) stimulated cholesteryl [14C]oleate synthesis 124-fold more than did VLDL from the normal Japanese White rabbit (control-VLDL). The enhancement in cholesteryl ester synthesis and accumulation of WHHL-VLDL was due to the presence of a high affinity binding receptor site on the macrophage cell surface that mediated the uptake and lysosomal degradation of WHHL-VLDL. Competition studies showed that the uptake and degradation of 125I-WHHL-VLDL was inhibited by unlabeled excess WHHL-VLDL and beta-migrating VLDL (beta-VLDL), but not LDL. Furthermore, the degradation of WHHL-VLDL was not blocked by either fucoidin, polyinosinic acid, or polyguanylic acid, potent inhibitors of the acetylated (acetyl)-LDL binding site, or by acetyl-LDL. These results suggest that macrophages possess a high affinity receptor that recognizes the cholesterol-rich VLDL present in the plasma of the WHHL rabbit and that the receptor which mediates ingestion of WHHL-VLDL seems to be the same as that for beta-VLDL and leads to cholesteryl ester deposition within macrophages. Thus the uptake of the cholesterol-rich VLDL from the WHHL rabbit by macrophages in vivo may play a significant role in the pathogenesis of atherosclerosis in the WHHL rabbit.

Animals↗

PubMed1986

Mechanisms of pharmacokinetic interaction between ajmaline and quinidine in rats.

In order to elucidate the mechanism of ajmaline-quinidine interaction previously observed in humans, the effects of quinidine on pharmacokinetics of ajmaline were investigated in rats. Concurrent oral administration of 10 mg/kg of quinidine markedly increased the plasma concentration of ajmaline at a dose of 2 mg/kg. On the other hand, it did not affect the pharmacokinetics of ajmaline after intravenous dose. The availability of ajmaline after oral dose showed an increase from 13% to nearly 100% by the presence of quinidine, which suggests a change in the presystemic clearance of ajmaline. In fact, when ajmaline was administered into the intestinal loop, its concentration in mesenteric venous plasma increased approximately 5-fold by the combination with quinidine. Furthermore, quinidine delayed the elimination rate of ajmaline from the perfused rat liver. These results indicate that quinidine prevents presystemic elimination of ajmaline in the intestine and liver, and increases the systemic availability of ajmaline.

Ajmaline↗

PubMed1986

The in vivo cardiotoxic effect of eosinophilic cationic protein in an animal preparation.

We studied the in vivo effects of eosinophilic cationic protein (ECP) on DBA/2 mice, and compared the cardiac lesions caused by ECP with those caused by encephalomyocarditis (EMC) virus. ECP caused myocarditis in two of five mice (40%), and EMC virus did so in five of five mice (100%). Cardiac lesions of ECP were mild and limited to the right ventricular wall, which differed from those in the mice with EMC virus inoculation, where both the right and left ventricles were involved. This experiment is the first demonstration of the in vivo cardiotoxicity of ECP.

Animals↗

PubMed1986

Prevention of nephrosclerosis and cardiac hypertrophy by captopril treatment of spontaneously hypertensive rats.

The relationship between hypertension and cardiovascular damage was assessed in three groups of spontaneously hypertensive rats (SHR): 1. stroke prone SHR (SHR-SP) treated orally with an angiotensin I converting enzyme inhibitor (captopril) (100-400 mg/L in the drinking water) from 6 to 35 weeks of age, 2. SHR-SP maintained on tap water until 30 weeks of age, 3. stroke resistant SHR (SHR-SR) maintained on tap water. The controls were Wister Kyoto rats (WKY) maintained on tap water. Captopril-treated SHR-SP showed blood pressure lower than that of untreated SHR-SP, similar to SHR-SR. The ratio of heart weight to body weight was 0.55% in SHR-SP, 0.39% in captopril-treated SHR-SP, 0.46% in SHR-SR, and 0.39% in WKY. The kidneys of SHR-SP showed glomerular sclerosis, glomerular fibrosis, tubular casts, interstitial cell infiltration and vascular wall thickening or hyperplasia of the small arteries and arterioles. The severe glomerular sclerosis was mostly distributed in the inner and middle portions of cortex. Immunohistological study showed IgG, C3 and fibrinogen in the glomeruli and arterioles in SHR-SP. In captopril-treated SHR-SP, similar to SHR-SR, only minor histological changes were seen and there was no deposition of IgG, C3 or fibrinogen. No changes were seen in WKY. Thus, it was concluded that nephrosclerosis and cardiac hypertrophy in SHR-SP are prevented by captopril. The role of the renin-angiotensin and kallikrein-kinin systems in organ pathogenesis in SHR-SP is discussed.

Animals↗