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Biomedical subjects

C Kawai

Publications and source records attributed to C Kawai.

At least 271 records · Page 15Linked to original sources

[Advances in intracoronary thrombolysis treatment].

Based on the results of intracoronary thrombolysis in 30 patients with initial onset of anterior myocardial infarction, we concluded that: (1) left ventricular function and clinical features are markedly improved when reperfusion is accomplished within four hours after coronary artery occlusion; and (2) intracoronary thrombolysis therapy should be considered possible up to 10 hours after the onset of myocardial infarction to prevent expansion of infarct sizes and to preserve ventricular functions. Not infrequently, there is a significant stenosis at the site of initial occlusion after thrombolytic therapy, which results in an immediate reocclusion. Consequently, percutaneous transluminal coronary angioplasty (PTCA) is now widely performed after thrombolytic treatment to achieve more definite revascularization. Our early experiences showed that PTCA following thrombolytic treatment has an increased potential for reinfarction rather than added benefits for left ventricular functions. More recently, however, since our PTCA technique has been improved so as to achieve sufficient dilatation of the stenosed coronary artery, there has been less tendency to immediate reinfarction after the procedure for acute myocardial infarction. Whether PTCA should be added to thrombolytic therapy during the acute phase of myocardial infarction is controversial. The alternative is to wait until it can be performed on an elective basis. It is obvious that early revascularization is essential for preserving left ventricular functions after acute myocardial infarction. For this reason, thrombolytic agents such as tissue plasminogen activator and plasminogen proactivator, which can be administered intravenously, are being intensively sought using molecular biological techniques. The ideal thrombolytic agents should have more fibrin-specific properties with longer half-lives than currently-available substances. However, so far none of these novel agents, have been studied in patients.

Angioplasty, Balloon, Coronary↗

Regulation of angiotensin converting enzyme activity in cultured human vascular endothelial cells.

Angiotensin converting enzyme (ACE) of vascular endothelial cells is suggested to control vascular wall tonus through the conversion of angiotensin I (AI) to angiotensin II (AII) and the degradation of bradykinin. To obtain more insight into the pathophysiological significance of ACE of vascular endothelial cells, we studied the regulation of ACE produced by cultured human umbilical vein endothelial cells (EC). Phorbol 12-myristate 13-acetate (PMA) increased the cellular and medium ACE activity, accompanied by a marked morphological change in EC. N'-O'-dibutylyladenosine 3';5'-cyclic monophosphate (db-cAMP) increased only the cellular ACE activity and not the medium ACE activity. The effect of isoproterenol with 0.1mM theophylline mimicked that of db-cAMP. These findings suggest that PMA and cAMP-related agents participate in the control of vascular wall tonus through the positive regulation of ACE produced by vascular endothelial cells.

Bucladesine↗

Early estimation of acute myocardial infarct size soon after coronary reperfusion using emission computed tomography with technetium-99m pyrophosphate.

Early appearance of positive findings on a technetium-99m pyrophosphate scan has been shown to be associated with the presence of a reperfused acute myocardial infarction (AMI). Early technetium-99m pyrophosphate imaging was performed by emission computed tomography to evaluate reperfusion and to test the feasibility of estimating infarct size soon after coronary reperfusion based on acute positive tomographic findings. Twenty-seven patients with transmural AMI who were treated with intracoronary urokinase infusion followed by percutaneous transluminal coronary angioplasty underwent pyrophosphate imaging 8.7 +/- 2.1 hours after the onset of AMI. None of the 8 patients in whom reperfusion was unsuccessful had acute positive findings. Of 19 patients in whom reperfusion was successful, 17 had acute positive findings (p less than 0.001). In these 17, tomographic infarct volumes were determined from reconstructed transaxial images. The threshold for areas of increased pyrophosphate uptake within the infarct was set at 60% of peak activity by the computerized edge-detection algorithm. The total number of pixels in all transaxial sections showing increased tracer uptake were added and multiplied by a size factor and 1.05 g/cm3 muscle to determine infarct volume. The correlations of tomographic infarct volumes with peak serum creatine kinase (CK) levels (r = 0.82) and with cumulative release of CK-MB isoenzyme (r = 0.89) were good. Moreover, the time to positive imaging was significantly shorter than that to peak CK level (8.5 +/- 2.3 vs 10.4 +/- 2.2 hours, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Regulated expression of human atrial natriuretic polypeptide gene in mouse L cells.

To investigate whether the human atrial natriuretic polypeptide (hANP) gene is responsive to glucocorticoid, we co-introduced the hANP gene (with SV40 enhancer) with HSV-tk gene into mouse tk- L cells. The transformants with hANP gene with SV40 enhancer expressed hANP specific RNAs. The administration of 1 microM dexamethasone reduced the expressed hANP specific RNAs, especially those that had a physiological initiation site. These results suggest that the hANP gene is really a glucocorticoid responsive gene and may be negatively regulated by glucocorticoid.

Animals↗

Expression of human atrial natriuretic polypeptide gene in Cos 7 cells.

Cos 7 cells transfected with human atrial natriuretic polypeptide (hANP) gene with SV40 enhancer and replication origin sequences expressed hANP gene. The expressed RNA was indistinguishable from native hANP mRNA and the transcribed protein seemed to be properly processed to alpha-hANP and beta-hANP. This system provides a useful approach to investigate the processing of hANPs and the structure-function relationship of amino acid sequences of hANPs.

Animals↗

Kinetics of ajmaline disposition and pharmacologic response in beagle dogs.

Pharmacokinetics and pharmacodynamics of ajmaline were studied in four healthy dogs after intravenous administration of the drug at the infusion rate of 1.0 mg/min for 45 min. Ajmaline exhibited a saturable binding to plasma protein. One kind of binding site was found in the range of observed drug concentrations and its binding capacity showed nearly threefold interindividual difference. The time course of ajmaline concentration in whole blood Cb could be described by the two-compartment open model and the unbound concentration of ajmaline in plasma Pf was estimated from Cb by using the hematocrit value and the parameters of plasma protein binding and erythrocyte partitioning. The pharmacologic responses to ajmaline were assessed by recording ECG, and the changes in PQ and QRS interval were studied in relation to ajmaline disposition. When ECG changes were related to the ajmaline concentration, a significant degree of hysteresis was observed. The relationship between the unbound drug concentration and the pharmacologic effect was analyzed by a combined pharmacokinetic-pharmacodynamic model, where the hypothetical effect compartment is connected to the Pf in the central compartment by a first-order process. This model allows estimation of the changes in PQ and QRS intervals after intravenous administration of ajmaline. By comparing the drug effect on PQ and QRS intervals, it was suggested that ajmaline distributes to the atrial and the ventricular tissue in a similar degree and causes a reduction in the conduction rate in both sites with similar activity.

Ajmaline↗

Interventricular septal motion in acute myocardial infarction with proximal and distal left anterior descending coronary lesions.

To evaluate the ability of echocardiography to detect and localize lesions of the proximal and distal left anterior descending (LAD) coronary arteries, the systolic excursion of the left side of the septum and the ratio of septal to posterior wall excursion (IVS/PW) were measured in 26 patients with acute myocardial infarction (AMI) and nine normal control subjects. The patients with proximal LAD lesions had septal wall excursions of less than 3 mm, whereas in those with distal LAD lesions septal wall excursions were more than 3 mm. All patients with proximal LAD lesions showed an IVS/PW ratio of less than 0.4, but in those with distal LAD lesions the ratio was 0.4 or greater. We conclude that reduced or absent interventricular septal motion in anterior AMI suggests an LAD lesion, and a septal excursion of less than 3 mm suggests involvement of the proximal LAD artery, whereas septal excursion of 3 mm or more indicates involvement of the distal LAD artery.

Adult↗

Clonotypic comparison of IgG anti-DNA antibodies of healthy subjects and systemic lupus erythematosus patients: studies on heterogeneity and avidity.

Qualitative characteristics of IgG anti-ssDNA antibodies were studied and compared by isoelectric focusing (IEF) and enzyme-linked immunosorbent assay (ELISA) between normal human sera (NHS) and systemic lupus erythematosus (SLE) sera. In NHS, IgG anti-ssDNA spectrotypes were observed in a high alkaline pH range (7.5 to 8.5) at physiological NaCl concentrations (0.15 M). In SLE sera the spectrotypes were found to a more intensified extent in the alkaline pH range as compared to those in NHS. With regard to avidity, analyzed by salt-dependent changes of anti-ssDNA activities, NHS showed strong ssDNA-binding bands in a wide range of pH 7.0-8.5 comparable to those in SLE sera. However, these bands became extremely weak and/or faint in pH 7.5-8.5 as the NaCl concentration was raised to 0.15 M and 0.20 M. On the other hand, SLE sera still exhibited thick binding bands at higher NaCl concentrations. This salt-dependency of these antibodies was-also demonstrated by ELISA of serum samples adjusted to contain comparable antibody levels. These findings suggest that clonotypes of IgG anti-ssDNA antibodies both in NHS and in SLE sera are essentially oligoclonal and highly cationic, and that the distinctive characteristics of these antibodies in NHS may be of low avidity, in contrast to SLE sera which exhibit high avidity.

Adult↗

Probucol prevents the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbit, an animal model for familial hypercholesterolemia.

In this study, we questioned whether in vivo probucol could prevent the progression of atherosclerosis in homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model for familial hypercholesterolemia. At 2 months of age, eight WHHL rabbits were divided into two groups. Group A (n = 4) was fed standard rabbit chow for 6 months. Group B (n = 4) was fed standard rabbit chow containing 1% probucol for 6 months. At the end of the experiments, average plasma concentrations of cholesterol were 704 +/- 121 mg/dl in group A and 584 +/- 61 mg/dl in group B, respectively. The percentage of surface area of total thoracic aorta with visible plaques in group A versus group B was 54.2% +/- 18.8% versus 7.0% +/- 6.3%, respectively. What was noteworthy was that the percentage of plaque in the descending thoracic aorta was almost negligible (0.2% +/- 0.2%) in group B rabbits compared to that in group A rabbits (41.1% +/- 20.2%). Low density lipoproteins (LDL) isolated from WHHL rabbits under treatment with probucol (group B) were shown to be highly resistant to oxidative modification by cupric ion and to be minimally recognized by macrophages. On the contrary, LDL from group A rabbits incubated with cupric ion showed a 7.4-fold increase in peroxides (thiobarbituric acid-reactive substances) and a 4.3-fold increase in the synthesis of cholesteryl ester in macrophages compared to those of LDL from group B rabbits. Thus, probucol could definitely prevent the progression of atherosclerosis in homozygous WHHL rabbits in vivo by limiting oxidative LDL modification and foam cell transformation of macrophages.

Animals↗

Thromboxane A2 analogue induced coronary artery vasoconstriction in the rabbit.

Diffuse coronary artery vasoconstriction was provoked in the rabbit by a stable thromboxane A2 analogue, STA2 (9,11-epithio-11,12-methano thromboxane A2). Injection of 25 micrograms.kg-1 STA2 into the left main trunk caused complete occlusion of the left anterior descending artery and narrowing of the left circumflex artery. Two minutes after injection, however, the diameter of the coronary artery returned to the control value (n = 10). The right coronary artery was also temporarily occluded by an injection of 25 micrograms.kg-1 STA2. Left ventricular end diastolic pressure increased significantly, and ST segment elevation of the electrocardiogram occurred during vasoconstriction. The angiographic findings showed that the vasoconstriction in the coronary artery induced by STA2 was similar to the diffuse vasoconstriction seen clinically. Induction of the vasoconstriction by STA2 was prevented by the preadministration of 25 micrograms.kg-1 of either a calcium antagonist, diltiazem, or a thromboxane A2 receptor antagonist, ONO 3708 (n = 10). The relation of the calcium movement to this vasoconstriction was studied in vitro using the isolated left circumflex artery in the rabbit. STA2 (50 micrograms.litre-1 to 0.5 mg.litre-1) produced a concentration dependent contraction of helical strips of left circumflex artery. Diltiazem (50-100 g.litre-1) suppressed this contraction dose dependently. ONO 3708 (10 micrograms.litre-1 to 1 mg.litre-1) caused a significant rightward and downward shift of the dose-response curve.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Myocarditis and dilated cardiomyopathy.

The recent developments in the study of myocarditis and dilated cardiomyopathy are reviewed here, with the primary emphasis on the issue of myocarditis as a precursor to dilated cardiomyopathy. Advances in immunologic approaches have expanded our knowledge of the course of myocarditis, experimentally as well as clinically. Although further investigations are necessary to prove the direct link between acute myocarditis and some cases of dilated cardiomyopathy, clinical trials of immunosuppressive agents, virus-specific vaccine, and antiviral agents such as ribavirin and interferon appear warranted, with the hope of potential benefits in the treatment of myocarditis and, therefore, in some forms of dilated cardiomyopathy.

Adolescent↗

Measurement of aortic blood flow with MR imaging: comparative study with Doppler US.

An innovative magnetic resonance imaging technique was applied to the measurement of blood flow in the abdominal aorta. The technique combines selective excitation and visualization from an orthogonal view. The distance that fluid has moved is directly visualized. The blood flow velocity at every 50 msec throughout the cardiac cycle was measured in a short time (about 4 minutes) using electrocardiographic gating and repeated excitations in each cycle. Measurements were compared with those obtained by Doppler ultrasound (US) as a reference. The pulsatile change of flow velocity in the cycle correlated well with the Doppler US recording. Two flow velocity indexes, peak flow velocity and the velocity integral, also showed good correlation (r = .98 for both). This method is applicable for clinical use and is useful for measurement of high flow rates, as found in arteries.

Adult↗

Quantitative analysis of contraction band and coagulation necrosis after ischemia and reperfusion in the porcine heart.

To assess the importance of contraction band necrosis (CBN) in reperfusion, CBN, coagulation necrosis (CN), and infarct size, expressed as CBN + CN, were quantitatively analyzed in 25 porcine hearts without collateral circulation. The left anterior descending coronary artery was ligated for 20, 30, 60, and 120 min and then reperfused for 8 hr (groups 1 to 4, respectively). Five hearts were not reperfused (group 5). The areas of CBN and CN were traced at a magnification of X 100 under an inverted microscope and quantified with use of an image analyzer. There was no change in hemodynamics with either occlusion or reperfusion. Regional myocardial blood flow, measured by the generated hydrogen gas clearance method, decreased to almost zero after occlusion but recovered during reperfusion. Percent of risk area infarcted in groups 1 to 4 was 0 +/- 0%, 11 +/- 7%, 80 +/- 9%, and 96 +/- 2%, respectively, and the percent of risk area infarcted in group 4 was the same as that in hearts subjected to permanent occlusion (95 +/- 3%). The percent area of CBN was 100 +/- 0% in group 2, 68 +/- 11% in group 3, 2 +/- 1% in group 4, and 2 +/- 2% in group 5. In group 3, the inner third of the ischemic left ventricular wall showed CN and the middle and outer third CBN. These findings show that in pig hearts without collateral circulation, the transmural infarct, two-thirds of which is occupied by CBN, is evident even when reperfusion is achieved after 1 hr occlusion. Therefore, protection against CBN might reduce infarct size after reperfusion.

Animals↗

Quantitative analysis of narrowings of intramyocardial small arteries in normal hearts, hypertensive hearts, and hearts with hypertrophic cardiomyopathy.

To clarify the pathophysiologic role of intramyocardial small artery (IMSA) diseases in hypertrophied hearts, narrowings of the IMSA were quantitatively evaluated in 39 autopsied hearts, 10 from patients with typical hypertrophic cardiomyopathy (HCM), four from patients with HCM showing features mimicking dilated cardiomyopathy (DCM-like HCM), 10 from patients with hypertension, and 15 from normal adults. The relations of narrowings of the IMSA to myocytic hypertrophy, myocardial fiber disarray, and fibrosis were also examined. The external caliber and the ratio of the luminal area to the total vascular area (percent luminal area, % lumen) were calculated by an image analyzer in 85 to 203 IMSAs from each patient. The external calibers of the IMSAs were similar among groups of hearts with HCM, hypertensive hearts, and normal hearts but were greater in those with DCM-like HCM. The mean % lumen of the IMSAs was similarly reduced in the hearts with HCM (29 +/- 5% in the ventricular septum and 31 +/- 5% in the left ventricular free wall) and in hypertensive hearts (30 +/- 8% and 31 +/- 7%) compared with that in normal hearts (40 +/- 5% and 38 +/- 5%) and was the lowest in the ventricular septum of hearts with DCM-like HCM (17 +/- 3%). The mean % lumen of the IMSA was inversely correlated with heart weight (r = -.59), the mean size of myocytes (r = -.66 in the ventricular septum, r = -.63 in the free wall), and percent fibrotic area in the septum (r = -.68). The mean % lumen values of the IMSAs in the tissues with and without disarray in the hearts with HCM were similar. Thus IMSA disease is of pathophysiologic importance in patients with HCM, DCM-like HCM in particular, or with hypertension.

Adult↗

Quantitative analysis of infarct size, contraction band necrosis, and coagulation necrosis in human autopsied hearts with acute myocardial infarction after treatment with selective intracoronary thrombolysis.

To assess the importance of contraction band necrosis (CBN) in patients with acute myocardial infarction (AMI) treated with selective intracoronary thrombolysis, CBN, coagulation necrosis, and infarct size (expressed as CBN + coagulation necrosis) were analyzed quantitatively in 16 autopsied hearts. Intracoronary thrombolysis was performed from 2 to 6 hr after the onset of AMI, and the time from the onset of AMI to death was 7 to 168 hr. Cineangiography revealed no evidence of good collateral circulation in any of the patients. The 16 patients were classified into three groups: six patients with successful thrombolysis (100% to 99% stenosis, group I), five patients with unsuccessful thrombolysis (100% to 100%, group II), and five patients with 99% stenosis before thrombolysis (group III). Among the three groups, there were no significant differences in the time from the onset of AMI to thrombolysis, the time from the onset of AMI to death, the cause of death, or the degree of collateral circulation. The percentage of the risk area involved by the infarct in group I (82 +/- 6%) was similar to that in group II (80 +/- 11%). Infarct size was not reduced in group I because collateral circulation was not good and because the degree of recanalization after thrombolysis was 1%. However, the percentage of the infarct area with CBN was significantly higher in group I (20 +/- 9%) then in group II (3 +/- 3%). This finding shows that diffuse CBN occurred after reperfusion in patients with AMI treated with thrombolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗