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Biomedical subjects

C Kawai

Publications and source records attributed to C Kawai.

At least 55 records · Page 3Linked to original sources
PubMed1993

Emergency coronary angioplasty for acute myocardial infarction: predictors of early occlusion of the infarct-related artery after balloon inflation.

THE FACTORS RESPONSIBLE FOR EARLY OCCLUSION OF THE INFARCT VESSEL AFTER emergency percutaneous transluminal coronary angioplasty (PTCA) were retrospectively examined in 191 patients with acute myocardial infarction. During the 24-hour period after the initial balloon inflation, 47 patients (25%) had occlusion of the vessel (occlusion group), whereas 144 did not (nonocclusion group). The former patients immediately underwent repeat PTCA, which was successful in 37. Univariate correlates of early occlusion were a shorter time interval between the onset of symptoms and PTCA (3.5 +/- 2.2 vs 4.5 +/- 2.9 hours, p = 0.025), right coronary artery involvement (53% vs 30%, p = 0.015), prior thrombolytic therapy (49% vs 32%, p = 0.035), and undersized inflation (43% vs 17%, p < 0.001). With multivariate analysis the three independent predictors were undersized inflation (p < 0.001), right coronary artery involvement (p = 0.004), and a shorter time interval until PTCA (p = 0.011). Thus patients undergoing early PTCA and having right coronary artery involvement appear to be at greater risk of having early occlusion. Thrombolytic agents and undersized inflation may also play an important role in its development.

Aged↗
PubMed1993

Phospholipid requirement of epididymal testosterone 5 alpha-reductase and phospholipid composition of epididymal microsomes.

We have investigated phospholipid requirement for testosterone 5 alpha-reductase solubilized from microsomal and nuclear fractions of rat epididymis. The 5 alpha-reductase from microsomal fraction was stimulated by phosphatidylcholine (PC) with long acyl-chain lengths, but inhibited by short chain PC. The nuclear enzyme activity was weakly activated by PC with various acyl-chain lengths tested. Synthetic phosphatidylserine (PS), such as dioleoylPS, most strongly stimulated the microsomal enzyme activity, but did not exhibit any activation of the nuclear enzyme activity. Endogenous phospholipids, such as PC, PS, and phosphatidylethanolamine (PE) separated from bovine epididymal microsomes were tested for their stimulatory effects on microsomal and nuclear enzymes. Among these endogenous phospholipids, PS most greatly stimulated the microsomal 5 alpha-reductase activity, whereas both PC and PE weakly activated the enzyme activity. On the other hand, endogenous PC and PS had no ability to support the nuclear enzyme activity. The fatty acid compositions of PC and PS from bovine epididymal microsomes were determined, in order to elucidate the relationship between 5 alpha-reductase activation by these phospholipids and the structure of their acyl chains. The relative content of fatty acids in PC, in a decreasing order, was palmitate > linoleate > oleate; that in PS was stearate > oleate > palmitate. Based on these observations, the roles of microsomal PS and PC in epididymal 5 alpha-reductase reaction will be discussed.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1993

Post-exercise oxygen uptake kinetics in patients with left ventricular dysfunction.

We assessed the kinetics of oxygen uptake (VO2) after symptom-limited maximal exercise by use of cardiopulmonary exercise testing with a bicycle ergometer in normal subjects and patients with left ventricular dysfunction due to dilated cardiomyopathy. During the first few minutes after the cessation of exercise, the VO2-time relationship showed an exponential-like decrease. A monoexponential curve was fitted to this relationship of the first 3 min after exercise to obtain the time constant of the decrease in VO2 (T(VO2)). The results of exercise testing in 37 normal subjects (25 male and 12 female) revealed that T(VO2) was relatively independent of age and gender. Then, 30 male patients with dilated cardiomyopathy (10 in New York Heart Association functional class I, 12 in class II, and 8 in class III) were evaluated and the results were compared with those of 16 age-matched male control normal subjects. Although the amount of the estimated oxygen debt was smaller in the patient group, the time constant T(VO2) was 117 +/- 8 s for the controls as compared with 130 +/- 14 s for the patients in class I, 153 +/- 13 s for those in class II, and 219 +/- 49 s for those in class III. There were significant correlations between T(VO2) and anaerobic threshold (r = -0.68, p < 0.001), peak VO2 (r = -0.74, p < 0.001), and the increase in VO2 per work rate (r = -0.88, p < 0.001). T(VO2) also correlated with the ventilatory equivalent for carbon dioxide output (VE/VCO2) at peak exercise (r = 0.70, p < 0.001) and the time course of minute ventilation during the early phase of the post-exercise period (r = 0.67, p < 0.001). Thus, the time course of VO2 decrease after symptom-limited exercise is considered to be closely related to exercise capacity and also to the degree of exercise-induced hyperpnea in patients with left ventricular dysfunction.

Adult↗
PubMed1993

Intracoronary infusion of E6010 has more potent thrombolytic activity than tissue plasminogen activator (t-PA) in dogs: a higher plasma level of E6010 than t-PA causes potent thrombolytic activity.

We examined the thrombolytic properties of a novel modified human tissue plasminogen activator (PA) (E6010), in which cysteine 84 is replaced by serine, and which has a prolonged biologic half-life (t1/2). We compared the thrombolytic efficacy of continuous intracoronary (i.c.) infusion of E6010 with that of recombinant human tissue PA (rt-PA) in a canine model with copper coil-induced 1-h-old coronary artery thrombi and also compared the relation between thrombolytic efficacy and plasma clearance represented by pharmacokinetic parameters of i.c.-infused E6010 and rt-PA. Sixty-minute E6010 and rt-PA i.c. infusions were compared. The thrombolytic effects of i.c.-infused E6010 and rt-PA, represented by time to reperfusion (TR), reperfusion rate at 60 min (RR), and reocclusion rates at 60 min after reperfusion (OR) were as follows. E6010: Dose 0.06, 0.15, 0.3 (mg/kg/h); TR 25 +/- 10, 15 +/- 10, 13 +/- 5 (min); RR 100, 100, 100 (%); and OR 0, 0, 17 (%), respectively. Recombinant t-PA: Dose 0.06, 0.15, 0.3 (mg/kg/h); TR 47 +/- 12, 18 +/- 17, 14 +/- 4 (min); RR 50, 75, 100 (%); and OR 100, 33, 33 (%), respectively. These findings indicate that E6010 has more potent thrombolytic activity than rt-PA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

A stable L-arginine-dependent relaxing factor released from cytotoxic-activated macrophages.

It has been known that cytotoxic-activated macrophages release an unstable vasorelaxing substance, nitric oxide. We have found that a more stable relaxing factor is released from those cells. This factor seems to be synthesized from L-arginine. It acts through the activation of soluble guanylate cyclase without affecting membrane potential. It has little charge at nearly neutral pH, and its molecular weight is < 500.

Animals↗
PubMed1993

Antithrombotic effect and reperfusion by low molecular weight heparin in a canine model of coronary artery thrombosis.

The lability of an intracoronary thrombus, which is common in the case of unstable angina, indicates the presence of endogenous fibrinolysis. To prove our hypothesis that suppression of coagulation facilitates the thrombolytic process, low molecular weight heparin (LMWH) was given intravenously to dogs with intracoronary thrombi induced by copper coils. LMWH caused reperfusion in this model and suppressed the formation of intracoronary thrombi, thus supporting our hypothesis.

Animals↗
PubMed1993

Thrombolysis with intracoronary administration of YM866, a novel modified tissue-type plasminogen activator, in a canine model of coronary artery thrombosis.

We compared the thrombolytic activity of YM866, a novel modified tissue-type plasminogen activator, with that of t-PA by intracoronary administration in a canine thrombosis model of copper coil-induced 6-hr-old thrombi. Either drug was administered by a single injection (10 min) or multiple injection (4 x 10 min) under heparinization (300 IU/kg, i.v.). The reperfusion rate of YM866 was 4 times higher than that of t-PA when administered by single injection. Time to reperfusion of YM866 by single injection was shorter than that of either agent by multiple injection. No group showed any decrease in plasma fibrinogen levels. No acute reocclusion was seen in animals with YM866 by single injection. The improved thrombolytic activity of YM866 by single injection correlated with the relatively higher antigen levels of this agent due to its prolonged biological half-life. These results suggest that single intracoronary administration of YM866 is a safe and effective thrombolytic method for rapid recanalization and lowered acute reocclusion without activation of systemic fibrinolysis.

Animals↗
PubMed1993

Thrombolytic activity of a novel modified tissue-type plasminogen activator, YM866, in a canine model of coronary artery thrombosis.

The thrombolytic activity of a novel modified t-PA, YM866, was compared with that of a recombinant t-PA in a canine model of copper coil-induced coronary thrombosis. The coronary thrombus was allowed to age for 1, 3 or 6 hr before either drug was administered. YM866 was administered by i.v. bolus injection, while t-PA was given by the same method, as well as by 60-min i.v. infusion. YM866 showed thrombolytic activity 2 to 4 times as potent as that of t-PA when administered by bolus injection, the difference in thrombolytic effect being obvious in the 3- and 6-hr-old thrombi. Coronary reperfusion was achieved more rapidly with YM866 than with i.v. infusion of t-PA. In animals injected with doses of more than 0.1 mg/kg of YM866, no acute reocclusion occurred. Depletion of plasma fibrinogen to 70% of baseline levels was observed in animals given 0.2 mg/kg YM866, 0.4 mg/kg t-PA by bolus, and 0.6 mg/kg t-PA via infusion. The residual plasma YM866 and t-PA antigen 30 min after bolus injection was 25% and 3% of the peak levels, respectively. YM866, administered by i.v. bolus injection, was thus confirmed to exert a thrombolytic effect superior to that of bolus injection and infusion of t-PA, without systemic fibrinolytic activation. These results suggest the potential clinical applicability of YM866 as a thrombolytic agent that can be administered by i.v. bolus injection for acute myocardial infarction.

Amino Acid Sequence↗
PubMed1993

Chronic active myocarditis simulating constrictive pericarditis-like findings: report of a case.

A 34-year-old female with rhythm disturbance and characteristic hemodynamic features of constrictive pericarditis is presented. A left ventricular wall open needle biopsy revealed mild mononuclear cell infiltration suggestive of myocarditis. The patient died of intractable heart failure seven years later. The autopsy revealed left and right ventricular dilatation, multiple foci of mononuclear cell infiltration, and diffuse replacement fibrosis in 31%, 13% and 14% of the areas of the left ventricular free wall, ventricular septum, and right ventricular wall, respectively, predominantly in the inner layers (68%). The pericardium was intact. These clinically constrictive pericarditis-like findings are considered to be secondary to chronic active myocarditis.

Adult↗
PubMed1993

Ventricular expression of atrial and brain natriuretic peptides in dilated cardiomyopathy. An immunohistocytochemical study of the endomyocardial biopsy specimens using specific monoclonal antibodies.

Although brain natriuretic peptide is expressed in ventricles of failing hearts including dilated cardiomyopathy, its morphological localization is still unclear. In this study, we analyzed the immunohistocytochemical localization of atrial and brain natriuretic peptides in ventricles of dilated cardiomyopathy at both light and electron microscopic levels. Ventricular specimens were obtained by endomyocardial biopsy in 31 patients (26 with dilated cardiomyopathy and 5 controls without any specific cardiac disease). By light microscopic immunohistochemistry using specific monoclonal antibodies, all (26 of 26) of the left ventricular endomyocardial biopsy specimens and 31% (8 of 26) of the right ventricular specimens showed immunoreactivity for both of these natriuretic peptides in dilated cardiomyopathy. In contrast, none of the normal controls showed immunoreactivity for either of these peptides. The percentage of atrial natriuretic peptide-containing or brain natriuretic peptide-containing myocytes in the left ventricular specimens showed an inverse correlation with the left ventricular ejection fraction (r = -0.72 and r = -0.69, respectively). By electron microscopy, we identified specific secretory granules in ventricular myocytes from patients with dilated cardiomyopathy, but not in those from normal controls. Double immunocytochemistry using a two-face immunogold staining method revealed brain natriuretic peptide colocalized with atrial natriuretic peptide in the same ventricular granules. These findings suggest that brain natriuretic peptide is expressed in ventricular myocytes in response to hemodynamic stress in dilated cardiomyopathy. Brain natriuretic peptide may be, at least in part, synthesized simultaneously and secreted together with atrial natriuretic peptide by granules from failing ventricles, although the secretory turnover is different between these two peptides.

Adult↗
PubMed1992

Left ventricular relaxation in dilated cardiomyopathy: relation to loading conditions and regional nonuniformity.

OBJECTIVES: The purpose of the present study was to investigate how loading conditions and regional nonuniformity affect left ventricular relaxation in dilated cardiomyopathy. BACKGROUND: Left ventricular relaxation is impaired in dilated cardiomyopathy. It has been suggested that relaxation abnormality is related to loading conditions and regional nonuniformity in the diseased heart. METHODS: Left ventriculography with simultaneous pressure manometry was performed in 10 patients with dilated cardiomyopathy before and during nitroprusside infusion. Ten normal subjects served as a control group. Left ventricular hemodynamics, regional wall motion (assessed by the area method) and regional wall stress (Janz method) were analyzed. RESULTS: When compared with control subjects, the patients with dilated cardiomyopathy had a reduced left ventricular ejection fraction (p < 0.01) and prolonged relaxation time constants (p < 0.01). Left ventricular wall motion was both hypokinetic and asynchronous in the patient group. In addition, systolic regional wall stress was significantly greater, the time to peak wall stress was longer and the regional myocardial relaxation time constant was greater for each ventricular area assessed in the patient group (each p < 0.01). Administration of nitroprusside reduced left ventricular pressure and increased ejection fraction in the 10 patients with dilated cardiomyopathy. For each region, systolic regional wall stress and the time to peak wall stress decreased, and both regional hypokinesia and asynchrony lessened. These changes in loading conditions and regional nonuniformity were accompanied by an improvement in both regional and global ventricular relaxation that was significant, particularly during the early to midrelaxation phase when regional asynchrony was greatest. CONCLUSIONS: These results suggest that myocardial relaxation is sensitive to loading conditions and regional nonuniformity in dilated cardiomyopathy and that load reduction can improve both relaxation and systolic performance of the left ventricle.

Analysis of Variance↗
PubMed1992

Spin-echo M-mode NMR imaging.

A nuclear magnetic resonance (NMR) imaging and display method for the observation of the continuous motion of objects is presented. By modifying a line scan technique, the spin-density distribution along a line is displayed in succession. Although spatial information is limited to only one dimension, the motion of the object is recorded at intervals of 55 ms by using a commercially available NMR imaging system. In a phantom study, this method yielded accurate velocity measurements along a single axis. When the method was applied to the human chest, an image analogous to that of M-mode echocardiography was obtained. This method, which can be called spin-echo M-mode NMR imaging, approaches the functional analysis of cardiac wall motion in regions where echocardiography is not possible. The effects of respiratory motion on the left ventricular wall were recorded in addition to its intrinsic contractile motion in an image obtained along a line parallel to the cranio-caudal axis of the body. The advantages of this method to assess cardiac wall motion in a patient with an arrhythmia were also demonstrated.

Atrial Fibrillation↗
PubMed1992

Successive infection of coxsackievirus B3 and encephalomyocarditis virus: an animal model of chronic myocarditis.

Successive infection of coxsackievirus B3 and encephalomyocarditis virus was investigated as a disease model of chronic myocarditis. Four-week-old C3H/He mice were inoculated with coxsackievirus B3 and then inoculated with encephalomyocarditis virus at 8 weeks old. The hearts were evaluated on histopathological changes compared with those of non-infected mice and mice infected with either virus alone. At 10 weeks old, the hearts of the mice infected successively with both viruses showed co-existence of fibrosis surrounding calcified lesions and marked cellular infiltration with myocardial necrosis. These findings resembled chronic active myocarditis in humans, unlike the lesions due to either virus alone. At 12 weeks old, the hearts of all the infected mice showed fibrosis with scarce cellular infiltration. The successively infected hearts also showed a significantly higher heart weight to body weight ratio than that of the non-infected control mice, and localized wall thinning in the damaged regions. Thus, we conclude that successive infection additively causes myocardial damage that resembles chronic myocarditis and may produce a heart condition similar to dilated cardiomyopathy.

Animals↗
PubMed1992

Pharmacotherapy of dilated cardiomyopathy: current status and future directions.

The current status and future directions of the pharmacotherapy of dilated cardiomyopathy are reviewed. The Japanese multicenter study on the effect of beta-blockers revealed significant improvement of NYHA functional classification, LV end-diastolic dimension, ejection fraction, and exercise tolerance time in patients with dilated cardiomyopathy. From our study using normal rabbits, metoprolol augmented adenylate cyclase activity without upregulation of the beta-adrenergic receptor number. Carteolol, a beta-adrenergic blocker with intrinsic sympathomimetic action, prevented the development of dilatation and hypertrophy of the heart in the chronic stage following murine encephalomyocarditis (EMC) viral myocarditis. Metoprolol exerted no such effect. Animal experiments indicated that immunosuppressive treatment for inflammatory myocarditis may aggravate the clinical course of the disease. However, immunosuppressive treatment in acute myocarditis should be reevaluated with the use of newly developed antiviral agents. A new synthetic immunoactive peptide FK 565, given before or simultaneously with viral inoculation, proved effective in inhibiting myocardial virus replication and myocardial damage in murine EMC viral myocarditis. Beneficial effects of captopril on survival rate and myocardial injury were demonstrated dose dependently in murine EMC viral myocarditis, even when the treatment was started around the peak of virus replication, namely, on day 4-14 after inoculation. Captopril may be promising for the treatment of acute myocarditis, and hopefully for prevention of the progression from myocarditis to dilated cardiomyopathy.

Adrenergic beta-Antagonists↗
PubMed1992

Effect of immunostimulant therapy on acute viral myocarditis in an animal model.

The effect of immunostimulant therapy on acute viral myocarditis, which was induced with encephalomyocarditis virus, was investigated in 4-week-old male BALB/c mice. In vitro, peritoneal exudate cells and spleen cells from mice that were pretreated with a synthetic immunoactivating peptide, FK565 (heptanoyl-gamma-D-glutamyl-(L)-meso-diaminopimelyl-(D)-alan ine), significantly inhibited the multiplication of encephalomyocarditis virus in BALB/c 3T3 cells compared with peritoneal exudate cells and spleen cells from untreated mice (6.14 +/- 0.21 log10 plaque-forming units (pfu) per milliliter, control: 6.59 +/- 0.03, p less than 0.05; 3.55 +/- 0.23, control: 5.64 +/- 0.09, p less than 0.01, respectively), although FK565 did not inhibit viral replication directly. The mice were inoculated intraperitoneally with 100 pfu of encephalomyocarditis virus. FK565 (1 mg/kg/day), which was administered 1 day before or simultaneously with virus inoculation, effectively inhibited myocardial viral replication (2.77 +/- 0.17 log10 pfu/mg, 2.46 +/- 0.35, log10 pfu/mg, respectively, control: 3.33 +/- 0.26, p less than 0.025) and increased survival (70% and 60%, respectively, control: 20%, p less than 0.01). Histopathologic findings were scored on a scale of 0 to 4. Treatment with 1 mg/kg/day of FK565 that was started 1 day before virus inoculation was most effective in reducing the inflammatory response (1.2 +/- 0.63, control: 2.0 +/- 0.81, p less than 0.05) and myocardial necrosis (1.2 +/- 0.42, control: 2.0 +/- 1.00, p less than 0.025). The present study suggests that immunostimulant therapy improves the course of viral myocarditis during the virus-mediated phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗