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Biomedical subjects

T Sada

Publications and source records attributed to T Sada.

At least 37 records · Page 2Linked to original sources
PubMed1990

Hemodynamic changes following long-term administration of CS-905, a novel dihydropyridine calcium blocker, in conscious SHR.

To investigate the central and regional hemodynamics after long-term administration of CS-905, a novel calcium blocker, we administered the agent (1 and 3 mg/kg/day) for 15 weeks in spontaneously hypertensive rats. At the end of the dosing period, hemodynamic changes were examined using the radioactive microsphere technique. CS-905 produced a sustained dose-dependent antihypertensive effect without inducing tolerance during the 15-week dosing period and prevented cardiac hypertrophy. The agent increased cardiac output, decreased blood pressure and thus decreased total peripheral resistance in a dose-related manner. Regional blood flows measured by the microsphere technique were increased in the kidney and brain despite the lowered blood pressure. There was no organ where regional blood flow was decreased. These changes after chronic treatment with CS-905 would be beneficial in the long-term therapy of hypertension.

Animals↗
PubMed1989

Chronic inhibition of angiotensin converting enzyme decreases Ca2+-dependent tone of aorta in hypertensive rats.

Long-term effects of a novel angiotensin converting enzyme (ACE) inhibitor, CS-622, on Ca2+-dependent tone in aortic smooth muscles of spontaneously hypertensive rats (SHR) were examined. CS-622 (3 or 10 mg/kg/day), when orally administered to SHR for 21 weeks, exhibited a dose-dependent antihypertensive action. In Krebs-Henseleit solution, removal of Ca2+ caused much greater relaxation in aortas excised from control SHR than those from SHR treated with CS-622. Restoration of Ca2+ from zero to 2.5 mM elicited a marked contraction in aortas from control SHR but only a small contraction in aortas from both CS-622-treated SHR and normotensive Wistar-Kyoto rats. These findings suggested that myogenic tone that resulted from increased Ca2+ permeability in aortas of SHR was suppressed by long-term treatment with CS-622. The aortic tone from the individual rats correlated well with systolic blood pressure in both CS-622-treated and control SHR. The exaggerated myogenic tone in aortas of SHR was attenuated in the medium containing nicardipine but was not altered in the presence of CS-622 diacid (active form of CS-622) at a concentration high enough to fully inhibit aortic ACE. The myogenic tone in normal Ca2+ concentration was not decreased in aortas excised from SHR treated with hydralazine (5 mg/kg/day) for 21 weeks. We conclude that after prolonged administration CS-622 reduced the high vascular tension resulting from increased Ca2+ permeability of vascular smooth muscle membrane in SHR and that the restoration of normal Ca2+ permeability of vascular smooth muscles may underlie long-term antihypertensive action of ACE inhibitors.

Administration, Oral↗
PubMed1989

Long-term inhibition of angiotensin converting enzyme suppresses calcium channel agonist-induced contraction of aorta in hypertensive rats.

To elucidate functional changes in the vascular smooth muscle of spontaneously hypertensive rats (SHR) after chronic inhibition of angiotensin converting enzyme, we examined the contractile responses to different pharmacological interventions in the isolated aortas from SHR treated with a novel angiotensin converting enzyme inhibitor, CS-622 (10 mg/kg/day) for 20 weeks. In normal K+ medium, a marked contraction was elicited by increasing Ca2+ concentration from 0 to 3 mM in aortas from a control group of SHR, but not in aortas from SHR treated with CS-622. In 60 mM K+ medium, however, the sensitivity of aorta to Ca2+ was almost the same in the two groups. A calcium channel activator, CGP-28392 (10(-7) to 10(-6) M), induced a marked contraction in the aortas from control SHR, but not in the aortas from CS-622-treated SHR. When slightly depolarized in 10 or 12 mM K+ solution, the aortas from CS-622-treated SHR contracted in response to CGP-28392. The aortic sensitivity to KCl contraction was much lower in CS-622-treated SHR than in untreated SHR, whereas the sensitivity to phenylephrine contraction was little different in the two groups. These contractile profiles of aortas from CS-622-treated SHR were very similar to those from normotensive Wistar-Kyoto rats but not to those from hydralazine-treated SHR. These data suggest that contractions due to Ca2+ through voltage-dependent calcium channels are exaggerated in SHR aorta and that long-term treatment with angiotensin converting enzyme inhibitor suppresses the abnormal contractility of SHR vascular smooth muscle, probably through alterations of voltage-related functions of calcium channels.

Animals↗
PubMed1989

Lactone and cyclic ether analogues of platelet-activating factor. Synthesis and biological activities.

Six-membered lactone and tetrahydropyran analogues of platelet-activating factor (PAF), 4-11, and related antagonistic derivatives 41-46 were synthesized. None of the delta-lactones 4-7 showed PAF-like activities, while the corresponding cyclic ethers 8, 9 and 11 were slightly active. Some of the cyclic antagonists showed more potent inhibitory activities than the open chain antagonist CV-3988 against platelet aggregation (rabbit platelet-rich plasma, IC50) and hypotension (rat, ID50) induced by C16-PAF: e.g. dl-3-[6-[O-(trans-3-heptadecylcarbamoyloxytetrahydropyran-2- yl)methyl]phosphonoxy]hexylthiazolium (inner salt) (41d) (IC50 5.5 x 10(-7) M, ID50 0.046 mg/kg, i.v.); dl-3-[5-[O-(cis-3-heptadecylcarbamoylthiotetrahydropyran-2- yl)methyl]phosphonoxy]pentylthiazolium (inner salt) (43c) (IC50 5.7 x 10(-7) M, ID50 0.076 mg/kg, i.v.).

Animals↗
PubMed1989

Synthesis and antagonistic activities of enantiomers of cyclic platelet-activating factor analogues.

Enantiomers of platelet-activating factor (PAF) antagonists, 3-(6-[O-(trans-3-heptadecylcarbamoyloxytetrahydropyran-2-yl)methyl ] phosphonoxy)hexylthiazolium (inner salt) (3), 3-[5-(trans-3-heptadecylcarbamoyloxytetrahydropyran-2-yl) methoxycarbonylamino]pentylthiazolium bromide (4) and 3-(5-[O-(cis-3-heptadecylcarbamoylthiotetrahydropyran-2-yl) methyl]phosphonoxy)pentylthiazolium (inner salt) (5), were synthesized, starting from (2R,2R)- and (2S,2S)-tartaric acid. Antagonistic activities of these compounds against C16-PAF were measured in vitro (rabbit platelet aggregation, IC50) and in vivo (hypotension in rats, ID50). In these three enantiomeric pairs, the (3S)-(tetrahydropyran numbering) enantiomers were one order more potent than the (3R)-isomers: (2R,3S)-3a (R-74,654), IC50 0.59 microM and ID50 0.054 mg/kg, i.v.; (2S,3R)-3b, IC50 4.7 microM and ID50 0.30 mg/kg, i.v.; (2R,3S)-4a, IC50 0.20 microM and ID50 0.032 mg/kg, i.v.; (2S,3R)-4b, IC50 2.2 microM and IC40 0.21 mg/kg, i.v.; (2R,3R)-5a, IC50 1.1 microM and ID50 0.92 mg/kg, i.v.; (2S,3S)-5b (R-74,717), IC50 0.27 microM and ID50 0.064 mg/kg, i.v.

Chemical Phenomena↗
PubMed1989

Antihypertensive effects of CS-905, a novel dihydropyridine Ca++ channel blocker.

CS-905 is a novel dihydropyridine calcium blocker. A single oral administration of CS-905 or nicardipine at doses of 0.3-3.0 mg/kg produced a dose-dependent reduction of blood pressure in conscious SHR. CS-905, when administered orally in conscious SHR, was more than 3 times as potent as nicardipine. Unlike the hypotensive effect of nicardipine, that of CS-905 has a gradual onset and is long-lasting, with little increase in heart rate. An intravenous administration of CS-905 also produced a hypotension with a slow onset and long duration in SHR, but CS-905 was 3 times less potent than nicardipine by intravenous administration. This difference may be attributed to the first pass effect, which was associated with nicardipine but not with CS-905. The blood pressure lowering effects of CS-905 was most potent in DOCA-salt hypertensive rats, followed by SHR, RHR and normotensive rats, in this order. CS-905 is expected to be an antihypertensive agent that is effective on a once a day regimen in clinical settings.

Anesthesia↗
PubMed1989

Effects of RS-1893, a novel cardiotonic agent, on central and peripheral hemodynamics in anesthetized rats.

After the use of two radionuclides in the tracer microspheres technique in the rat was verified, we examined the central and peripheral hemodynamic effects of RS-1893, an orally active cardiotonic agent. An intravenous infusion of RS-1893 at a dose of 3 micrograms/kg/min gradually decreased blood pressure and increased heart rate and cardiac output. Blood flows in the kidney and stomach were increased. There was no organ in which blood flow was decreased despite the fall in blood pressure. These data suggest that RS-1893 dilates blood vessels in the whole body, especially in the kidney and stomach.

Anesthesia↗
PubMed1989

Risk factors for the complication of cerebral infarction in Japanese patients with acute myocardial infarction.

The incidence and risk factors for cerebral infarction in Japanese patients with acute myocardial infarction were evaluated. Seven (5.0%) of 140 patients with acute myocardial infarction suffered from cerebral infarction during their initial hospitalization. The incidence was slightly higher than those reported in Western countries. Anterior wall myocardial infarction and a past history of cerebrovascular disease were considered to be probable risk factors for the complication. A beneficial effect of anticoagulant therapy in preventing cerebral infarction in cases of acute myocardial infarction with those risk factors is suggested.

Aged↗
PubMed1988

Effects of chronic treatment with a novel angiotensin converting enzyme inhibitor, CS622, and a vasodilator, hydralazine, on atrial natriuretic factor (ANF) in spontaneously hypertensive rats (SHR).

We studied the effects of chronic treatment with a novel angiotensin converting enzyme inhibitor, alpha-[(2S,6R)-6-[(1S)-1-ethoxycarbonyl-3-phenylpropyl]amino-5-oxo-2- (2-thienyl)perhydro-1,4-thiazepin-4-yl]acetic acid.HCl (CS622), and a vasodilator, hydralazine, on plasma atrial natriuretic factor (ANF) levels and kidney ANF receptors in spontaneously hypertensive rats (SHR). Plasma ANF level was decreased and cardiac hypertrophy reduced in CS622 treated SHR, but not in hydralazine treated SHR, although blood pressure was lowered similarly in both SHR groups. The binding capacity of kidney ANF receptors increased and the affinity decreased in CS622 treated SHR compared to untreated SHR. These results suggest that decrease of plasma ANF results from decreased cardiac load but not from lowered blood pressure, and that changes in ANF receptors result from increased plasma ANF.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Pharmacological profiles of CS-622, a novel angiotensin converting enzyme inhibitor.

CS-622 is a prodrug type ACE inhibitor with a thiazepin ring. Its active form, CS-622 diacid, was slightly more potent than enalaprilat in inhibiting ACE isolated from rabbit lung. The inhibitory potency of CS-622 diacid on isolated rat aorta was 3 times that of enalaprilat. The inhibitory action of enalaprilat was abolished quickly by washing the aortic strip with drug-free solution, whereas that of CS-622 diacid was abolished only slowly. This difference suggests that CS-622 diacid binds to vascular ACE more firmly than enalaprilat. By oral administration, CS-622 was 3 times more potent than enalapril, and its onset of action was faster than that of enalapril, suggesting that the conversion of CS-622 to its active diacid occurs faster than the conversion of enalapril. Although CS-622 diacid was only slightly more potent than enalaprilat by intravenous administration, it had a longer duration than enalaprilat. Elimination of renal excretory function potentiated the action of captopril but not that of CS-622, suggesting that unlike captopril, only a small portion of CS-622 is excreted through the kidney.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1985

Ambulatory electrocardiograms obtained by Holter monitoring system in patients with permanent demand pacemakers.

Ventricular inhibited demand pacemakers (VVI) were implanted in 27 patients with complete A-V block and pacemaker arrhythmias were analyzed by Holter system ambulatory electrocardiograms and conventional electrocardiograms. With Holter ECG, 13 patients showed myopotential inhibition, 5 patients had sensing failure and premature ventricular contractions (PVC) were observed in all patients. On the contrary, myopotential inhibition and sensing failure were not detected by conventional ECG and the detection rate of PVC was only 30%. The transient recovery of A-V conduction was observed in 14 of 27 patients with Holter ECG, but was not detected by conventional ECG. The Holter system ambulatory electrocardiogram clearly demonstrated the complex cardiac arrhythmias. Therefore, it is useful for monitoring arrhythmias caused by VVI pacemakers.

Adult↗
PubMed1984

[Mitral valve prolapse in patients with anorexia nervosa].

Mitral valve prolapse (MVP) is frequently observed in patients with low body weight and/or skeletal abnormalities such as pectus excavatum and straight spines. There may be a variety of associated autonomic dysfunctions. Whether MVP is a complication of anorexia nervosa which has similar clinical features, including weight loss, skeletal abnormalities and autonomic dysfunctions, has not been reported. The present study was an investigation of the incidence of MVP and cardiac function in anorexia nervosa by echocardiography. Two-dimensional and M-mode echocardiography, and systolic time intervals were evaluated for 19 women with anorexia nervosa, from 13 to 25 years of age and having a mean age of 18.2 years. Their body weights ranged from 23.9 to 43 kg with a mean of 33.5 kg, and were at least 25% less than their ideal body weights (ranges were from 25 to 52%). The same studies were performed for 19 women with MVP diagnosed echocardiographically and without anorexia nervosa as controls. Their ages ranged from 14 to 26 years. Results were as follows: MVP was observed in 74% of patients with anorexia nervosa. The mean heart rates were 51.7 and 70.5/min in the anorexia nervosa and control groups, respectively. A significant difference (p less than 0.001) was observed between the two groups. The mean heart rate of patients with anorexia nervosa having MVP of both leaflets and no MVP were 45.8 and 59.0/min, respectively. The difference between these two sub-groups was statistically significant (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1983

Continuous axillary brachial plexus block.

Continuous axillary brachial plexus block was performed in 597 patients undergoing prolonged operations on the hand. The technique required placement of a 5 cm 23 gauge teflon intravenous catheter in the axillary perivascular sheath. Lidocaine 1.5 per cent or mepivicaine 1.5 per cent (20-40 ml) were used for the initial block dose. Surgery was completed in 77.2 per cent of patients (460) with the axillary block alone while in 19.1 per cent of patients (114) supplementary narcotic administration or additional regional blocks were required. In 3.7 per cent of patients (22) the technique was considered a complete failure. Complications included local anaesthetic toxic reactions (2.85 per cent, 17 cases), nerve injury (0.50 per cent, three cases) and one case of major haematoma formation. The advantages of this technique and the possible complications are discussed.

Adult↗
PubMed1983

R wave changes in patients with myocardial infarction during treadmill stress testing.

A graded multistage treadmill exercise test was performed on 78 patients with myocardial infarction (65 males and 13 females, ranging in age from 30 to 76). The amplitude of the R wave in CC5 was measured at rest and during the periods of peak exercise. The exercise-induced R wave changes were classified into 3 groups: increased, 39.1%; no changes, 39.7% and decreased, 22.2%. Acute attacks of myocardial infarction were more severe in the patients whose R wave decreased during exercise than in those whose R wave increased. Heart rate, blood pressure and pressure rate products were not different among the groups. However, oxygen consumption was greater in the R-increased group than in the R-decreased group. Therefore, an increase in R wave amplitude during exercise in post-myocardial infarction patients indicates a good efficiency of the myocardium and skeletal muscles. Exercise-induced changes of the mean electrical axes of the transverse plane were significantly related to changes of the R wave amplitude in CC5 (r = 0.50, p less than 0.001). Therefore, change in the transverse plane axis is one of the important determinants of exercise-induced R wave changes.

Adult↗
PubMed1983

Medical treatment of infective endocarditis and its limitations.

In an attempt to establish an appropriate management program for patients with active infective endocarditis, 30 patients treated during the past 20 years were studied retrospectively. Microorganisms were confirmed in 27 of the 30 patients (90%) (86.7% by culture and 3.3% at surgery). Among these 27 patients, viridans streptococci were confirmed in 23 (85.2%), aureus staphylococci in 2 (7.4%), epidermidis staphylococci in one (3.7%) and candida albicans in one (3.7%). Twenty of the 23 patients (87%) with viridans streptococcal endocarditis were treated medically with good success, but 2 patients (8.7%), who developed severe congestive heart failure (NYHA 3-4 degrees), underwent emergency surgery, and one of them (4.3%) died from severe heart failure. The synergistic effects of the combined antibiotic therapy were not ascertained in the present series. It was noteworthy that a bolus intravenous administration of penicillin was more effective than its continuous drip infusion. Both patients with aureus staphylococcal endocarditis died before surgery. One patient with prosthetic valve endocarditis due to candida died after a second operation. It is concluded that most patients with active infective endocarditis can be medically treated successfully, but surgery should be performed urgently for patients with severe heart failure, poor response to antibiotics, aureus staphylococcal and candida endocarditis and prosthetic valve endocarditis.

Adolescent↗
PubMed1983

Exercise capacity of the patients with myocardial infarction.

This study was conducted to investigate the functional capacity in postmyocardial infarction. Eighty-four multistage treadmill exercise tests were performed on 60 patients, none of whom had had any formal rehabilitation or regular exercise. There were 50 men and 10 women, ranging in age from 30 to 81 with an average age of 60. The time interval between the acute attack and the exercise test ranged from one month to 9 years. Even though severe infarction affects the exercise capacity for a long time after an acute attack, its effect on cardiac function was more obvious than that on physical capacity. Age was the most important determinant of physical capacity, and the slope of decreasing physical capacity with age in patients with infarct was the same as that in normal subjects. Cardiac function also decreased with age. However, during the early recovery phase, cardiac function was influenced by the severity of infarction and the influence of age could not be established. There was no significant correlation between early ambulation and physical capacity. The beneficial effects of early ambulation may be lost if physical activity is discontinued for some time after the acute attack. The physical capacity increased 2-3 years after the acute attack, but myocardial function did not change significantly.

Adult↗