Shinichi Kimata

Takayasu's Arteritis Clinical Report of Eighty-four Cases and Immunological Studies of Seven Cases

The manifestations of Takayasus arteritis of the aorta were studied in 84 patients. The extent of the involvement of the aorta was classified on aortographic examination in 54 patients and from the clinical manifestations in 30. Involvement of the aorta was classified as: (1) arch type in 47 cases; (2) extensive type (whole aorta and its branches involved) in 27 cases; and (3) descending thoracic and abdominal type (only descending thoracic and abdominal aortas involved) in 10 cases. The three types resembled one another in clinical manifestations and laboratory findings except for ischemic signs which varied with the type of lesion and a slight difference in the ratio of male to female patients. Generalized, cardiac and pulmonary symptoms were noted by about two thirds of the patients in the early stage. About one third complained of local pain. The erythrocyte sedimentation rate and C-reactive protein were high values during the active stage of this disease. The hemagglutination test using tannic acid-treated erythrocytes was positive in five of seven cases. It is not clear yet that circulating anti-arterial antibodies are the direct cause of Takayasus arteritis.

Atrial natriuretic peptide distribution in fetal and failed adult human hearts.

The distributions of atrial natriuretic peptide (ANP) in human hearts during the developmental stage and in adult pathological states was examined with an antibody specific to human alpha-ANP. With immunoblotting and immunofluorescence methods, we found that a 17-kDa protein, which is a pro ANP, was expressed in human fetal ventricles, in which the numbers of myofibers containing ANP granules were more abundant in the subendocardial region than the subepicardial region. As determined by radioimmunoassay, the content of immunoreactive ANP (per milligram protein) in the developing heart was greatest in the left atrium and occurred decreasingly in the right atrium, right ventricle, and left ventricle, respectively. Because ANP content in the left ventricle declined during the progress of gestation in developing hearts and because it was very low, if ever detectable, in normal adult hearts, ventricular ANP expression appears to be developmentally regulated from the early gestational stage. However, it was reexpressed in the ventricles of patients who had suffered from severe congestive heart failure. In this situation, we found that the ventricular ANP expression was more marked in patients with dilated cardiomyopathy than in patients with severe valvular disease. Interestingly, in the ventricles of patients with dilated cardiomyopathy, ANP contents were higher in the left ventricular free wall than in the right ventricular free wall, although the left ventricular subendocardium contained more ANP than the subepicardium, showing a transmural gradient similar to that expressed in fetal ventricles. Thus, the expression of ANP in human ventricles is developmentally regulated from the early gestational stage, and even adult ventricular myofibers can synthesize ANP during severe congestive heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Endogenous endothelin-1 mediates cardiac hypertrophy and switching of myosin heavy chain gene expression in rat ventricular myocardium.

OBJECTIVES We investigated the role of endogenous endothelin-1 in the development of cardiac hypertrophy in vivo under pressure overload conditions. BACKGROUND Endothelin-1, a potent vasoconstrictor peptide, has recently been shown to act as a growth factor of myocardial cells in culture. METHODS We examined the effect of an endothelin-A receptor antagonist (FR139317) on the development of right ventricular hypertrophy in rats with monocrotaline-induced pulmonary hypertension. Three groups of rats were studied: those given monocrotaline alone or monocrotaline plus FR139317 and those given vehicle alone (control group). RESULTS The ratio of right ventricular systolic pressure to aortic systolic pressure was similarly elevated in rats treated with monocrotaline and monocrotaline plus FR139317. The right ventricular/left ventricular weight ratio was increased in monocrotaline-treated rats but lower in rats treated with monocrotaline plus FR139317 than in those treated with monocrotaline alone (p < 0.01). As a biochemical marker of hypertrophy, the isoform ratio of beta-myosin heavy chain protein was determined for the right ventricular tissue samples. This ratio was increased in all monocrotaline-treated rats but was lower (p < 0.01) in rats given monocrotaline plus FR139317 than in those given monocrotaline alone. The isoform ratio of beta-myosin heavy chain messenger ribonucleic acid quantitated by S1 nuclease mapping also was lower (p < 0.025) in rats receiving monocrotaline plus FR139317 than in those receiving monocrotaline alone. CONCLUSIONS These data suggest that blocking the action of endothelin-1 with a receptor antagonist ameliorates cardiac hypertrophy in this model system, and that this action is not mediated by ameliorating hemodynamic changes.

Accelerated purine nucleotide degradation by anaerobic but not by aerobic ergometer muscle exercise

The exact conditions under which exercise causes purine nucleotide degradation are not well understood. We determined plasma hypoxanthine and uric acid levels serially in eight individuals during ergometer muscle exercise. When the load was increased gradually by 15 W/min, plasma hypoxanthine was elevated only after the status exceeded the anaerobic threshold (AT), as determined by analysis of expired gas. Nonstrenuous ergometer exercise, which kept the status continuously below the AT, induced neither blood lactic acid nor plasma hypoxanthine elevation. These results suggest that the AT is also the threshold for the acceleration of purine nucleotide degradation. Muscle exercise to a degree that does not exceed the AT does not cause major purine nucleotide degradation, and, therefore, is expected to be beneficial for patients with gout and/or hyperuricemia.

A Prospective, Randomized, Double-Blind Multicenter Trial of a Single Bolus Injection of the Novel Modified t-PA E6010 in the Treatment of Acute Myocardial Infarction: Comparison With Native t-PA

Abstract Objectives. This prospective, randomized, double-blind multicenter trial evaluated the efficacy and safety of a single bolus injection of the novel modified tissue-type plasminogen activator (t-PA) E6010 in the treatment of acute myocardial infarction compared with that of native t-PA. Background. E6010 is a novel modified t-PA with a prolonged half-life (t1/2alpha ≥23 min) compared with native t-PA (t1/2alpha = 4 min). E6010 can be administered in patients as a single intravenous bolus injection, and early recanalization can be expected. Methods. The efficacy of E6010 was compared with that of native t-PA in 199 patients with acute myocardial infarction who were treated within 6 h of onset in a prospective, randomized, double-blind multicenter trial. Patients were given either 0.22 mg/kg body weight of E6010 intravenously over 2 min or native t-PA (tisokinase) 28.8 mg or 14.4 million IU (10% of the total dose over 1 to 2 min, the remainder infused over 60 min). Results. The primary end point was the recanalization rate of the infarct-related coronary artery at 60 min after the start of treatment. Time to reperfusion was shorter in the E6010 group than in the native t-PA group. Thrombolysis in Myocardial Infarction flow grade 2 or 3 recanalization at 15, 30, 45 and 60 min after administration was observed in 37%, 62%, 74% and 79% (95% confidence interval [CI] 70% to 87%) of the E6010-treated patients and in 14%, 32%, 50% and 65% (95% CI 55% to 74%) of native t-PA-treated patients, respectively (p = 0.032 at 60 min). Conclusions. The present study indicates that, compared with native t-PA, a single bolus injection of E6010 over 2 min produces a higher rate of early recanalization of the infarct-related coronary artery without fatal bleeding complications. (J Am Coll Cardiol 1997;29:1447–53)

Microanalysis of free fatty acids in plasma of experimental animals and humans by high-performance liquid chromatography

A high-performance liquid chromatographic (HPLC) method was developed for microanalysis of thirteen free fatty acids using 200 microliter of plasma. Fatty acids were derivatized with 9-anthryldiazomethane for HPLC analysis. Use of an ODS minicolumn for pretreatment of plasma gave a more accurate determination of free fatty acids in plasma than by chloroform extraction. Using this method, thirteen free fatty acids in the plasma of normal human, dog, rabbit, guinea pig and rat were determined.

Long-term prognosis of medically treated patients with acute myocardial infarction and one-vessel coronary artery disease

Long-term prognosis was studied in 156 patients with acute myocardial infarction (AMI) with 1-vessel coronary artery disease (CAD). During a mean follow-up period of 110 months, 19 patients (14%) had reinfarction, 15 (9.6%) died (including 7 deaths of cardiac origin) and 15 (9.6%) were hospitalized for worsening of angina. A coronary arteriogram was obtained twice in 54 patients. The coronary arteriogram revealed multivessel CAD in all cases with reinfarction (n = 14). Ten percent of the patients with multivessel disease experienced a reinfarction during the initial 3 years after the onset of the first AMI. The recurrence rate of AMI in patients with 1-vessel disease increased gradually from the third year after the onset of their first AMI, reaching 10% in 6.7 years. The recurrence of AMI at the same region as the original infarction was detected in only 1 patient. Six of 19 patients (32%) with recurrence of AMI died and 13 survived after the reinfarction. It was difficult to predict future progression from the outcome of the comparison between the first and second coronary arteriograms. Thus, in patients with uncomplicated AMI with 1-vessel CAD, the prognosis is relatively good and the frequency of reinfarction is very low with conservative treatment.

The Feasibility of Beat-to-Beat Detection of His-Purkinje Activity by Finite Element Method

A noninvasive method has been applied on human and canine subjects to observe beat‐to‐beat activity of the His‐Purkinje system without using signal averaging. Recordings were performed with multiple Ag/AgCI electrodes, very low noise, high gain amplifiers and by analog filtering. The subjects were in a supine position during the recording. In order to reduce random noise inherent in the high‐gain body surface recording, a finite element method (FEM) was applied to calculate His‐Purkinje activity. The dimensional relationship between electrode sites, necessary for the calculation, was pre‐estimated by x‐ray computed tomographs of the subject. A prominent waveform was observed between the atrial and ventricular complexes and corresponded to His bundle activity which was simultaneously recorded by an intracardiac electrode (on every beat). It was, however, difficult to recognize the His‐Purkinje activity during inhalation due to the thoracic electromyogram on some human subjects. This interference could theoretically be reduced by increasing the number of body surface electrodes used for this technique.

Hemodynamic Effects and Variations in Plasma Renin Activity after Single Oral Administration of Oxprenolol

In 5 healthy young males who received 40 mg oxprenolol given orally in a single dose, the hemodynamic effects, plasma renin activity and blood level of oxprenolol were investigated. One hour after adm

Hemodynamic and clinical effects of a new inotropic agent TA-064 in patients with refractory heart failure due to cardiomyopathy with special reference to dose-response effects.

SummaryA new hydroxybenzyl alcohol derivative TA-064 exerts a positive inotropic action in experimental preparations. To assess the acute effects in man, we made a cardiac catheterization study of the hemodynamic responses to TA-064 (20 mg and/or 40 mg given orally) in eleven patients with refractory heart failure due to cardiomyopathy (nine patients with dilated cardiomyopathy and one with amyloidosis). All patients were already receiving full digitalis and diuretics therapy. The following statistically significant (P<0.05–0.01) effects were noted: Upon administration of 20 mg of the drug, the cardiac index (CI) increased from a mean ±1 SD of 1.6±0.4 to 2.1±0.6 1/min/m2; pulmonary capillary wedge pressure (PCW) fell from 25±5 to 21±5 mm Hg; right atrial pressure (RA) fell from 12±3 to 10±4 mm Hg. In contrast, when 40 mg TA-064 were administered orally, the CI increased from 1.7±0.4 to 2.4±0.9 1/min/m2; PCW fell from 25±8 to 20±6 mm Hg; pulmonary arterial mean pressure fell from 35±11 to 29±9 mm Hg. Neither systemic arterial mean pressure nor heart rate increased. No toxicity was observed. The plasma concentration of TA-064 increased dose-dependently and reached a peak value 0.5–1.5 h after oral administration. Plasma catecholamine levels revealed no significant changes before and after use of the drug; therefore, the mechanism of action may not have been mediated by catecholamine.