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Biomedical subjects

C Kawai

Publications and source records attributed to C Kawai.

At least 37 records · Page 2Linked to original sources
PubMed1995

Pravastatin (mevalotin) restenosis trial after percutaneous transluminal coronary angioplasty. Cholesterol reduction rate determines the restenosis rate.

There is no consensus on lipids and restenosis after percutaneous transluminal coronary angioplasty (PTCA). We evaluated whether prevastatin could prevent restenosis after PTCA. In this study, pravastatin therapy was started one month before PTCA. The follow-up angiography was done three months later. Total cholesterol reduction rates [one index of reduction rate is calculated between 1 M (month) before PTCA and at PTCA, and another done between 1 M before PTCA and at follow-up angiography] proved to be good predictors of restenosis rate after PTCA; The greater the cholesterol reduction rate, the lower the rate of restenosis. The residual stenosis after PTCA correlated with the restenosis rate. The restenosis rate in the pravastatin group was lower than that in the control group, but the difference was not statistically significant. However, in the subgroup with pre-PTCA restenosis of 99% or more, the restenosis rate in the pravastatin group was significantly lower than that of the control group. Pravastatin seems to prevent intimal hyperplasia through the reduction of cholesterol level and to reduce restenosis. Many macrophages are present in the highly stenosed or occluded coronary arteries, and the reduction of the number and the activity of macrophages may prevent the restenosis. Pravastatin also has an antithrombotic action. In such regions, the occlusion by the thrombus formation is also considered to play a key role in restenosis in addition to the intimal hyperplasia. Thus, pravastatin may be useful especially for PTCA against highly stenosed or occluded coronary arteries.

Aged↗
PubMed1995

Long-term prognosis after thrombolytic therapy for acute myocardial infarction.

In order to clarify the relationship between the patency of the infarcted arteries and subsequent long-term prognosis after thrombolytic therapy, we evaluated 116 patients with acute myocardial infarction treated with intracoronary (112 patients) or intravenous (four patients) urokinase. Patients treated with angioplasty after thrombolysis were excluded. The infarcted vessel was recanalized in 52 patients (patent group) and was not in the remaining 64 patients (occluded group). Five-year and 8-year follow up was conducted in 91% and 81% of the patients, respectively. The 1-, 5- and 8-year survival rate for the patent and occluded group was 91.8 and 80.9%, 80.8 and 79.2%, and 75.9 and 75.6%, respectively. The survival rate in the patent group tended to be higher than that in the occluded group up to 4 years. However, after 5 years, both groups showed similar survival rates. Therefore, reopening of the infarcted arteries with thrombolysis was not an independent predictor for late cardiac death (Cox regression analysis).

Aged↗
PubMed1995

Gender difference in long-term prognosis after myocardial infarction--clinical characteristics in 1000 patients. The Kyoto and Shiga Myocardial Infarction (KYSMI) Study Group.

To examine gender differences in the long-term prognosis of patients with myocardial infarction, 1000 patients with myocardial infarction were studied after coronary arteriography. Over a follow-up period of 3.3 +/- 2.0 years, 65 patients died from cardiac causes and 301 experienced cardiac events (death, reinfarction and revascularization). Overall, the 5-year cardiac mortality was 8%: that in females (12.4%) was significantly higher than that in males (6.6%) (p = 0.0073). The overall 5-year cardiac event-rate was 35%, with no significant difference between females and males (41.1% vs 33.3%). Univariate analysis revealed that differences in age (57.8 +/- 9.8 years in males vs 64.8 +/- 8.9 years in females, p < 0.0001), presence of smoking habit, obesity, hypercholesterolemia, hypertension, heart failure, right coronary artery disease, nicorandil administration, hypolipidemic, diuretic and anti-hypertensive treatment, and warfarin administration were present between men and women. The mortality rate in elderly females tended to be higher than that in their male counterparts. Multivariate analysis demonstrated that number of diseased vessels, post-infarction angina and left main trunk disease were significant predictors for cardiac death in both sexes, while gender was not. Therefore, gender did not appear to affect the long-term prognosis after age-adjustment among patients with myocardial infarction in the Western part of Japan.

Adult↗
PubMed1995

A novel modified t-PA, E-6010, induces faster recovery of ventricular function after coronary thrombolysis than native t-PA in a canine thrombosis model.

Using the centerline method in a canine model, we compared left ventricular function after coronary thrombolysis induced by a novel modified recombinant tissue plasminogen activator (rt-PA) (E6010: 84Cys-->84Ser) to that induced by rt-PA or urokinase. Thirty minutes after occlusion, a bolus injection of E6010 (0.2 mg/kg) or a continuous infusion of either rt-PA (0.6 mg/kg over 1 h) or urokinase (0.38 mg/kg over 1 h) was administered intravenously. Animals with sustained copper coil-occlusion served as non-reperfused controls. Left ventricular ejection fraction and regional wall motion (expressed as the infarction chord number; ie, the number of chords < -2SD among chords 12-66) were 42 +/- 5%** and 5 +/- 3,** respectively, in the E6010 group, 31 +/- 8% and 16 +/- 12 in the rt-PA group, and 31 +/- 2% and 32 +/- 13 in the urokinase group 1 h after reperfusion, indicating earlier recovery of left ventricular function after thrombolysis in the E6010 group than in the rt-PA and urokinase groups (**p < 0.01 vs control). Coronary reperfusion with E6010 induced earlier recovery of left ventricular function than reperfusion with rt-PA or urokinase. These results suggest that E6010 may be of clinical value in the treatment of coronary occlusion.

Animals↗
PubMed1995

A novel modified tissue-type plasminogen activator (t-PA), E6010, reduces reperfusion arrhythmias induced after coronary thrombolysis--comparison of native t-PA and urokinase.

The aim of this study was to compare the effects of a novel modified tissue-type plasminogen activator (t-PA), E6010, to those of native t-PA and urokinase on reperfusion arrhythmias (premature ventricular complexes: PVC) and the mortality rate after coronary thrombolysis. The frequency of PVC and the mortality rate were evaluated in anesthetized dogs which had 1-, 3- or 6-h-old thrombi induced by a copper coil in the coronary artery. Thrombolytic treatment with a bolus intravenous (iv) injection of E6010 was compared with the continuous iv administration of native t-PA or urokinase. The frequency of PVC was significantly lower in the E6010 group than in the native t-PA and urokinase groups (P < 0.05). The mortality rate in the E6010 group (0.0%) tended to be lower than those in the native t-PA group (10.7%) and the urokinase group (7.1%). These results indicate that the bolus iv injection of E6010 reduced both PVC and the mortality rate, compared with the continuous iv administration of native t-PA or urokinase for coronary thrombolysis; Therefore, E6010 may have beneficial effects in prehospital thrombolysis.

Analysis of Variance↗
PubMed1995

[Cytokines in laboratory medicine].

A cytokine was first recognized in 1965, and many kinds of cytokines have been found since then. Cytokines are the biologically active substances which are produced in immuno-competent cells, macrophages and monocytes, excluding immunoglobulins. They form complex networks among themselves, and mainly act locally. A single cytokine may have physiological actions to many different cells, while a certain physiological action may be shared by many different cytokines. Some of them could be now quantitated immunochemically by using highly sensitive immunoassays. Therefore, immunoassay of some cytokines may become very important in laboratory medicine.

Cytokines↗
PubMed1995

[Sudden death among 1,000 patients with myocardial infarction: incidence and contributory factors. KYSMI Study Group].

Clinical indicators and the incidence of sudden death among 1,000 consecutive patients (816 males and 184 females) with myocardial infarction were investigated between 1983 and 1987 after coronary arteriography. Twenty-four patients died suddenly during a study period of 3.3 +/- 2.0 yrs. The yearly incidence of sudden death calculated by the Kaplan-Meier method was 0.7%, nearly half of the incidence of cardiac death (1.5%/yr). Univariate analysis demonstrated statistically significant differences in the number of cases with coronary thrombolysis in the acute phase, degree of coronary artery stenosis, the frequency and degree of congestive heart failure and angina in the acute and chronic phase, the presence of serious post-infarction arrhythmia, ejection fraction, recurrent myocardial infarction, and administration of digitalis and diuretics. between the sudden-death group and the cardiac and other patient groups. There was also a tendency to higher frequency of history of diabetes mellitus, presence of acute mitral regurgitation, nitrates and nicorandil treatment, and coronary artery bypass graft in the sudden-death group. Multivariate analysis revealed that digitalis and nitrates treatment and left anterior descending artery involvement were major contributing factors. Re-infarction, left ventricular ejection fraction, and nicorandil therapy were not significant and minor contributing factors. The incidence of sudden death increased with digitalis therapy (Odds' ratio of 9.59), and left anterior descending artery disease, and decreased with nitrates (0.34).

Adult↗
PubMed1994

Preferential inhibition of inducible nitric oxide synthase by ebselen.

Ebselen, 2-phenyl-1,2-benzisoselenazole-3(2H)-one can preferentially inhibit the activity of inducible nitric oxide (NO) synthase with little inhibition of endothelial constitutive NO synthase within a certain concentration range. This suggests that ebselen deserves further in vivo studies to examine its possible application to the therapy of septic shock where inducible NO synthase is responsible for vasodilation.

Amino Acid Oxidoreductases↗
PubMed1994

Structure and function of nitric oxide synthases.

Nitric oxide (NO), which accounts for the biological activity of endothelium-derived relaxing factor, is now thought to play a variety of roles in the nervous system and in immunologic reactions. NO is synthesized from L-arginine by nitric oxide synthase (NOS). There are three isoforms of NOS; type I (neuronal), type II (inducible), and type III (endothelial). The fundamental structure of the three isoforms, which contain calmodulin-, FMN-, FAD-, and NADPH-binding domains, is the same. Calmodulin is already bound to inducible NOS without requiring Ca2+, while the others are Ca2+/calmodulin-dependent. Endothelial NOS is bound to membranes by N-myristoylation, while the other isoforms are soluble. The human endothelial NOS gene has been cloned. It has several highly repetitive regions which could provide potential sites for DNA polymorphism. It might be of interest to examine the relationship between such polymorphism and cardiovascular disorders.

Amino Acid Oxidoreductases↗
PubMed1994

Pathogenesis of acute myocardial infarction. Novel regulatory systems of bioactive substances in the vessel wall.

Rupture of the lipid-rich atheromatous plaque, intraplaque hemorrhage, and intraluminal thrombus are three pathological hallmarks most commonly recognized in the infarct-related coronary artery at the site of acute myocardial infarction. Rupture of the atheromatous plaque is closely related to but does not fully explain the genesis of occlusive intracoronary thrombus formation and thus the development of acute myocardial infarction. Besides a variety of hematologic disorders, one should emphasize the role of the platelet-derived mediators that promote an environment where thrombosis and vasoconstriction occur, including TXA2, serotonin, ADP, platelet-derived growth factor, tissue factor, and the diminished availability of those natural endogenous substances that inhibit platelet aggregation, such as EDRF, tissue plasminogen activator, and PGI2. PGI2 released from vascular endothelial cells is extremely unstable. Our group provided the first evidence that HDL stabilizes PGI2 through the newly discovered function of Apo A-I, which is associated with the surface of HDL particles and identified as PGI2 stabilizing factor. Decrease in HDL-associated Apo A-I in patients with unstable angina and during the acute phase of myocardial infarction indicates that HDL plays an important role in preventing coronary atherosclerosis and intracoronary thrombus formation by stabilizing PGI2 in addition to the generally accepted biochemical property of HDL to prevent the accumulation of cholesterol by mobilizing free cholesterol from tissues or macrophages. There is also a PGI2 synthesis-stimulating factor in serum that has not yet been identified chemically. EDRF or nitric oxide provides another important regulating system in the vessel wall. Lipoproteins are inhibitors of endothelium-dependent relaxation of rabbit aorta.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Detection of exercise-induced silent ischemia and the sequence of ischemic events in coronary artery disease by radionuclide ambulatory ventricular function monitoring.

Twenty-seven patients with stable coronary artery disease were continuously monitored with an ambulatory radionuclide ventricular function monitor (VEST) during exercise to determine the prevalence of silent ischemia and the temporal sequence of events during ischemic episodes. Exercise-induced ejection fraction abnormality was considered a < 6% increase in the control value lasting for more than 60 sec. Patients performed exercise for 424 +/- 111 sec during VEST recording. Seventeen exercise-induced ejection fraction abnormalities were observed in 17 patients, of which eight (47%) were silent electrocardiographically and 12 (71%) were silent symptomatically. In all of the patients, exercise-induced ischemia occurred in a temporal sequence of ejection fraction abnormalities, ST depressions and then symptoms. In nine patients with ejection fraction and ST abnormalities, ejection fraction abnormalities occurred earlier (199 +/- 87 sec) than ST depressions (321 +/- 117 sec; p < 0.01). In five patients with symptoms (399 +/- 151 sec), the sequence was ejection fraction abnormalities (205 +/- 64 sec; P < 0.05) followed by ST depressions (266 +/- 101 sec; P < 0.05) and symptoms (399 +/- 151 sec; P < 0.01). After termination of exercise, ejection fraction (49 +/- 12 sec) recovered sooner than symptoms (102 +/- 27 sec; p < 0.01) or ST abnormalities (191 +/- 96 sec; p < 0.01). Thus, hemodynamic monitoring by VEST may be helpful in detecting ischemic episodes in coronary artery disease which remain electrocardiographically or symptomatically silent. Furthermore, exercise-stress induces a cascade of temporal changes in ischemic events which may be helpful in understanding the pathophysiology of ischemia.

Aged↗
PubMed1994

A novel modified tissue-type plasminogen activator (t-PA), E6010, gradually increases coronary blood flow after thrombolysis compared with native t-PA, urokinase and balloon catheter occlusion-reperfusion.

In a canine copper coil-induced coronary thrombosis model, the differences in frequency of reperfusion arrhythmias (premature ventricular complexes: PVC) and mortality rate after thrombolysis by intravenous bolus injection of a novel modified tissue-type plasminogen activator (t-PA), E6010, and by continuous intravenous infusion of native t-PA or urokinase were evaluated. Rapid coronary occlusion and reperfusion were produced with a balloon catheter in another group of dogs, and the findings were compared with those in the thrombolysis groups. Reperfusion occurred gradually after the administration of E6010, but was significantly more rapid after administration of native t-PA and urokinase (P < 0.05). PVC were observed more frequently in native t-PA, urokinase and balloon occlusion-reperfusion groups than in the E6010 group. The mortality rate due to ventricular fibrillation was 0.0% in the E6010 group, 50.0% in the native t-PA and balloon occlusion-reperfusion groups, and 33.3% in the urokinase group. These results suggest that the more gradual reperfusion of the coronary artery at an earlier period after drug administration led to the lower frequency of reperfusion arrhythmias and low mortality rate in the E6010 group than in the native t-PA, urokinase and balloon occlusion-reperfusion groups.

Animals↗
PubMed1994

[Large scale multicenter cooperative study for cardiovascular therapy (Japan Multicenter Investigation for Cardiovascular Drugs/Therapies, J-MIC)--results and perspectives].

With rapidly progressing therapeutic methods in the cardiovascular medicine, scientific evaluations for newly developed cardiovascular drugs and therapies have become mandatory. We have launched five large scale multicenter cooperative studies, namely, Japan Multicenter Investigation for Cardiovascular Drugs/Therapies, J-MIC (I), (B), (M), (S), and (K). The aims of studies include to investigate: the best therapeutic approach in patients with acute myocardial infarction who underwent thrombolytic therapy with or without any adjunctive treatment (I), the long-term comparative study (3 years) of nifedipine (extended release tablet) with ACE inhibitor in patients with essential hypertension and ischemic heart disease (B), the long-term effect (3 years) of trapidil and/or ethyl icosapentate in patients with ischemic heart disease with or without arteriosclerotic obstructive disease in terms of progression or regression of atherosclerotic changes in coronary as well as peripheral arteries (M), the efficacy and safety of pravastatin to prevent post-PTCA restenosis (S), and regression of atherosclerotic lesion of coronary arteries in patients with familial hypercholesterolemia by LDL apheresis (K).

Cardiovascular Agents↗
PubMed1993

Long-term prognosis after myocardial infarction: univariate and multivariate analysis of clinical characteristics in 1,000 patients. Kyoto and Shiga Myocardial Infarction (KYSMI) Study Group.

To examine the clinical outcome for patients with myocardial infarction and to analyze clinical predictors for long-term prognosis, 1,000 patients were studied retrospectively. Between January 1983 and December 1987, 1,002 consecutive patients with myocardial infarction, who resided in the Kyoto and Shiga districts, were reviewed after coronary arteriography, but in two patients medical records were not located. During 3.3 +/- 2.0 years, 75 patients died of cardiac causes and 301 experienced cardiac events (death, reinfarction, and revascularization). Overall 5-year cardiac mortality was 8% and cardiac event rate was 35%. Among determinants of age, smoking, hypertension, diabetes mellitus, heart failure, postinfarction angina, serious arrhythmia, mitral regurgitation, digitalis and diuretics administration, ejection fraction (EF), left main trunk disease, and number of diseased coronary arteries selected by univariate analysis, multivariate analysis revealed that heart failure, EF, number of coronary vessel disease, diabetes, and mitral regurgitation were the important predictors of cardiac death. For cardiac events, multivariate analysis demonstrated that the number of diseased coronaries, postinfarction angina, and left main trunk disease were significant predictors. Therefore, impaired left ventricular function and myocardial ischemia appear to be important markers for cardiac death, but impaired left ventricular function does not appear to be a predictor for cardiac events. The data obtained in this study will be useful in the assessment of patients with myocardial infarction and will be of clinical significance in predicting mortality and cardiac events.

Adult↗