Search PubMed⌕ Search

Biomedical subjects

H Kotake

Publications and source records attributed to H Kotake.

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

Plasma concentrations and coronary vasodilation after sublingual and intracoronary administration of isosorbide dinitrate.

To investigate the relationship between plasma levels and coronary vasodilation after administration of isosorbide dinitrate (ISDN), the plasma concentration and diameters of six segments of the left coronary artery were measured before and after sublingual (SL) ISDN (5 mg) and left intracoronary (IC) administration of ISDN (3 mg) in 12 patients. After SL-ISDN, the systolic aortic pressure decreased with no significant concomitant changes in heart rate or diastolic aortic pressure. After IC-ISDN, all hemodynamic parameters showed significant changes, and these were greater after IC-ISDN than those after SL-ISDN. The individual mean vasodilation of six segments induced by SL- and IC-ISDN, were 23 +/- 9 and 35 +/- 11% (p < 0.01), respectively. Before SL-ISDN, ISDN was not detected in plasma. After SL- and IC-ISDN, however, the plasma values of the ISDN were 36.1 +/- 53.3 and 101.5 +/- 90.0 ng/ml (p < 0.01), respectively. Thus, both coronary vasodilative responses and plasma ISDN levels after IC-ISDN were significantly greater than those after SL-ISDN. However, neither the individual mean coronary vasodilation nor the hemodynamic changes correlated significantly with plasma ISDN levels. Consequently, with administration of the same dose, the coronary vasodilative response to ISDN did not correlate with plasma levels. Furthermore, IC-ISDN dilutes coronary arteries more effectively than SL-ISDN.

Administration, Sublingual↗
PubMed1995

Quinidine enhances intracellular Ca2+ accumulation during rapid stimulation.

1. The quinidine-induced modification of intracellular Ca2+ concentration ([Ca2+]i) was studied in guinea-pig myocardium using fura-2. Quinidine reduced the systolic fluorescence signal level for [Ca2+]i and enhanced the end-diastolic signal level during a stimulation train. 2. The diastolic decay of [Ca2+]i fitted 2 exponential curves. Quinidine distorted the stimulation frequency-dependent acceleration of rapid [Ca2+]i decay, and prolonged the mean time constant of rapid decay after 2 Hz stimulation, from 154.4 to 205.3 msec (20 microM), and to 259.7 msec (60 microM quinidine). The time constant of slow recovery from [Ca2+]i accumulation after the stimulation train was not affected by stimulation frequency, or by quinidine, or caffeine. 3. These results suggest that quinidine modulates [Ca2+]i via a balance between the slowing of rapid [Ca2+]i decay and the reduction of the systolic [Ca2+]i. This effect may contribute to the anti-arrhythmic and pro-arrhythmic effects exerted by quinidine in some conditions.

Animals↗
PubMed1995

Mechanism of inhibition of the sodium current by bepridil in guinea-pig isolated ventricular cells.

1. Effects of bepridil, a sodium-, calcium-, and potassium-antagonistic agent, on the Na+ current were studied by the whole cell voltage clamp technique (tip resistance = 0.5 MOhm, [Na]i and [Na]o 10 mmol l-1 at 20 degrees C). 2. Bepridil produced tonic block (Kdrest = 295.44 mumol l-1, Kdi = 1.41 mumol l-1; n = 4). 3. Bepridil (100 mumol l-1) shifted the inactivation curve in the hyperpolarization direction by 13.4 +/- 2.7 mV (n = 4) without change in the slope factor. 4. In the presence of 50 mumol l-1 bepridil, bepridil showed use-dependent block at 2 Hz, whereas changes in pulse duration did not significantly effect this use-dependent block (81% +/- 2% at 10 ms, 84% +/- 3% at 30 ms, 86% +/- 3% at 100 ms; n = 4). 5. After removal of fast inactivation of the Na+ current by 3 mmol l-1 tosylchloramide sodium, bepridil (50 mumol l-1) still showed use-dependent block which was independent of the holding potential. 6. The recovery time constant from the bepridil-induced use-dependent block was 0.48 s at holding potential of -100 mV and 0.51 s at holding potential of -140 mV. 7. These results indicate that bepridil could bind to the receptor in the sodium channel through the hydrophobic and the hydrophilic pathway and leave the receptor through the hydrophobic pathway in the lipid bilayer. The binding and dissociation kinetics of this drug were shown to be fast, and the accumulation of the drug in the sodium channel appeared to be small. Bepridil is presumed to be safe in terms of adverse effects that result from drug-accumulation in the sodium channel.

Animals↗
PubMed1995

Exercise-induced ST-segment elevation--role of left ventricular wall motion abnormalities and coronary artery narrowing.

We studied the causes of exercise-induced ST-segment elevation. Group I consisted of 15 patients with anterior myocardial infarction in the absence of a coronary artery luminal narrowing of 75% or more. Group II consisted of 36 patients with predominantly exertional angina and a luminal narrowing of 90% or more in the left anterior descending coronary artery in the absence of previous myocardial infarction. In group I, exercise-induced ST-segment elevation occurred frequently during treadmill exercise (15/15, 100%). None of the patients showed 201Tl redistribution. The standard deviation of the phase in radionuclide ventriculography increased during bicycle exercise. Of group II patients, only those with 99% narrowing and poor collaterals showed exercise-induced ST-segment elevation (13/14, 93%), whereas none of those with complete occlusion or 99% narrowing and good collaterals, or 90% narrowing showed ST-segment elevation. In group II, patients with exercise-induced ST-segment elevation showed lower 201Tl uptake during exercise and washout in the territory of the diseased vessel than those without exercise-induced ST-segment elevation. In conclusion, wall motion abnormalities may cause exercise-induced ST-segment elevation independently of myocardial ischemia. In patients with predominantly exertional angina, exercise-induced ST-segment elevation may be a marker for 99% narrowing with poor collaterals and severe myocardial ischemia.

Adult↗
PubMed1995

Neurohumoral factor responses to mental (arithmetic) stress and dynamic exercise in normal subjects.

We examined the responses of plasma catecholamine and plasma renin activity (PRA) during mental (arithmetic) stress and dynamic exercise in 15 normal subjects. Compared to rest values, there was a significant increase in the plasma epinephrine concentration (E), but not in the plasma norepinephrine concentration (NE) or PRA during mental arithmetic. During dynamic exercise, there were significant increases in both NE and E and in PRA. The ratio of E to NE was significantly higher during mental arithmetic than during dynamic exercise. NE was significantly correlated with PRA at rest, during mental arithmetic and dynamic exercise. No significant correlations were observed between E and PRA. Dynamic exercise primarily induces a sympathetic nervous response, and mental (arithmetic) stress mainly induces an adrenal response. The renin-angiotensin-aldosterone system response may in part be regulated by sympathetic nervous activity during both mental (arithmetic) stress and dynamic exercise.

Adult↗
PubMed1995

Antiarrhythmic drugs inhibit the G-protein and K+ channels in the cultured thyroid cell line.

We examined the effects of antiarrhythmic drugs on the induction of cAMP by TSH (thyroid-stimulating hormone), using continuously cultured FRTL-5 rat thyroid cells. Group Ia antiarrhythmic drugs had no effect, but Group Ib antiarrhythmic drugs suppressed cAMP induction by TSH. These drugs suppressed cAMP induction in response to cholera toxin but did not inhibit TSH receptor binding or cAMP induction by forskolin. These results indicate that Group Ib antiarrhythmic drugs inhibit thyroid G-protein, resulting in a decrease in cAMP induction by TSH. We also examined the effect of antiarrhythmic drugs on K+ channels. Group Ia antiarrhythmic drugs had no effect on K+ channel activation by TSH and cAMP. On the other hand, Group Ib antiarrhythmic drugs suppressed K+ channel activation by TSH and cAMP. This indicates that the mechanism of suppression is not inhibition of TSH receptors or G-proteins but the direct suppression of K+ channels. Group Ib antiarrhythmic drugs inhibited thyroid Gs-protein and thyroid K+ channels. Considering the close relationship between G-protein and ion channels in the cardiac cell membrane, these different effects of Group Ia and Group Ib antiarrhythmic drugs on G-proteins and K+ channels are of interest. Further investigation is necessary to clarify the relationship between thyroid G-proteins and thyroid K+ channels.

Animals↗
PubMed1995

Effects of ET antagonists (PD143296 and PD145065) on contractions in guinea pig hilar bronchus induced by endothelin-1 and its related peptide.

ETs-induced contractions were resistant to ET(A)-selective antagonists and believed to be mediated by activation of ETB receptors in guinea pig bronchus. In the present study, the effects of the ET antagonists, PD143296 (Ac-D-Phe-L-Leu-L-Phe-L-Ile-L-Ile-L-Trp.2Na) and PD145065 (Ac-[(R)-2-10, 11-dihydro-5H-dibenzo[a, d]cyclohepten-5-yl]Gly)-L-Leu-L-Asp-L-Ile-L-Ile- L-Trp.2Na), on contractions induced by ET-1, ET-3, sarafotoxin S6c (STXc), and IRL1620 in the isolated hilar bronchus of the guinea pig were investigated. An ETA/B nonselective antagonist, PD145065 antagonized contractions induced by ET-1, ET-3, STXc, and IRL1620. Its antagonistic activity against ET-1, with pKB of 5.77 +/- 0.02 (n = 16, 3-10 microM), was significantly lower than that against ET-3, with pKB of 6.18 +/- 0.02 (n = 12, 3-10 microM), STXc, with pKB of 5.97 +/- 0.01 (n = 14, 3-10 microM), and IRL1620, with pKB of 6.80 +/- 0.04 (n = 14, 0.3-1 microM). Conversely, although a putative ETB-selective antagonist, PD143296 (10 microM) slightly but significantly antagonized the concentration-response curve of IRL1620 (pKB = 5.28 +/- 0.14, n = 6), it had no effect on ET-1-,ET-3-, or STXc-induced contractions. These results suggest that ETs possibly activate ETB2 or an atypical ETB receptor subtype in guinea pig hilar bronchus.

Animals↗
PubMed1994

Biliary lipid composition in heterozygous familial hypercholesterolemia and influence of treatment with probucol.

The lipid composition of fasting duodenal bile was determined in 11 healthy subjects with normolipidemia and 15 patients with heterozygous familial hypercholesterolemia (FH) (12 with type IIa, three with type IIb). The age distribution among the groups of subjects was similar. In the patients with heterozygous FH type IIa, the mean value for molar percentage of cholesterol and lithogenic index (LI) of bile were significantly higher than those of controls (8.4 +/- 1.0%, 1.47 +/- 0.18 calculated by Hegard, Dam, and Holzbach vs 4.3 +/- 0.4%, 0.81 +/- 0.07, respectively). The value of LI in the patients with FH type IIb was also found to be significantly higher than that of the controls. In the patients with heterozygous FH type IIa, we observed both a significant decrease in the molar percentages of glycochenodeoxycholic acid, glycoursodeoxycholic acid, and glycolithocholic acid, and a significant increase of taurochenodeoxycholic acid compared to the corresponding values in the controls. Bile analysis of six patients was reexamined during probucol treatment after 16 weeks. Probucol significantly lowered serum cholesterol levels. However, biliary lipid composition and individual bile acid proportions was not altered by the treatment. The results suggest that most of the patients with heterozygous FH have supersaturated bile and are predisposed to cholesterol gallstone formation. In addition, the mechanism by which probucol lowers serum cholesterol appears to be independent of any change in the metabolism of biliary lipid.

Adult↗
PubMed1994

Changes of QRS axis in transient myocardial ischaemia induced by percutaneous transluminal coronary angioplasty.

The QRS axis of 130 consecutive patients with coronary artery disease undergoing percutaneous transluminal coronary angioplasty (PTCA) were measured before balloon inflation and just before balloon deflation. Patients were divided into two groups. Group A (103) had angina pectoris and/or non-transmural old myocardial infarction with no abnormal Q waves; group B (27) had an old transmural myocardial infarction with abnormal Q waves. In group A, the QRS axis had significantly shifted to the left in patients with left anterior descending artery (LAD) occlusion (from 68.0 +/- 42.7 degrees to 40.2 +/- 44.6 degrees, P < 0.001); however in those patients without involvement of the major septal branch, significant axis changes were not observed (from 53.6 +/- 34.1 degrees to 49.8 +/- 33.1 degrees). When the right coronary artery (RCA) was occluded in group A, the QRS axis shifted to the right significantly (from 63.2 +/- 40.0 degrees to 89.8 +/- 30.1 degrees. P < 0.01); during left circumflex artery (LCX) occlusion, no significant axis shift was observed. In group B, no significant axis shift was observed either in patients with occlusion of the LAD or the RCA. It is concluded that transient left axis deviation reflects an obstructive lesion of the proximal portion of the LAD with involvement of the major septal branch, and transient right axis deviation reflects an obstructive lesion of the RCA.

Angioplasty, Balloon, Coronary↗
PubMed1994

Perfusion reserve of coronary collateral circulation and its significance in the development of exercise-induced ischemia in patients with multivessel disease.

To assess the perfusion reserve of coronary collateral circulation, we analyzed exercise-stress tomographic thallium-201 myocardial images in 12 patients who had total occlusion in the right coronary artery (RCA) or left circumflex coronary artery (LCX) with well-developed collateral circulation and 90% stenosis in the left anterior descending coronary artery (LAD). In 6 of the 12 patients, the collateral circulation was non-jeopardized (group A). In the remaining 6 patients, the collateral circulation was jeopardized (group B). All 6 of the patients in group A had an exercise-induced decrease in thallium uptake in the segments supplied by the occluded RCA or LCX with collateral circulation, and 3 (50%) of these 6 also showed a decrease in thallium uptake in the segments supplied by the LAD. All 6 of the patients in group B also had an exercise-induced decrease in thallium uptake in the segments supplied by the occluded RCA or LCX with collateral circulation, but none showed a decrease in thallium uptake in the segments supplied by the LAD. In conclusion, the perfusion reserve of collateral circulation is equal to or less than 90% stenosis and myocardial ischemia occurs first in the collateralized segments during exercise in patients with jeopardized collateral circulation.

Adult↗
PubMed1994

Characteristics of ventricular premature contractions and their clinical course.

One hundred patients with frequent (> 1,000 beats/day) ventricular premature contractions (VPCs) were followed for 4 years. All of the patients, except those with non-cardiac death (n = 8), were classified into 3 groups based on their outcome. Group A consisted of 29 patients with idiopathic VPCs who survived the study period. Group B consisted of 49 patients with underlying diseases who survived the study period. Group C consisted of 14 patients who suffered cardiac death. There was no significant difference in the daily number of VPCs. However, groups B and C had more patients with Lown grade 4a or 4b VPCs than group A. The mean coupling interval was significantly longer in group C than in group A, and the standard deviation of the coupling interval was significantly larger in group C than in group A. Forty patients underwent serial Holter monitorings to assess changes in the number of VPCs. VPCs spontaneously decreased in 13 patients, while the other 27 patients continued to have frequent VPCs. Most of these 13 patients were classified as Lown grade 2. The results suggest that in patients with frequent VPCs, longer and more varied coupling intervals may predict a poor prognosis, and Lown grade 2 may predict a spontaneous regression.

Adult↗
PubMed1994

Coronary artery ectasia with annuloaortic ectasia.

A 50-year-old Japanese woman with annuloaortic ectasia was found to have total coronary artery ectasia without evident atherosclerosis. The coronary ectasia may have been secondary to or of similar etiology to the annuloaortic ectasia. There was neither stigmata of Marfan's syndrome nor any sign of dissection of the ascending aorta or coronary arteries. Furthermore, the patient was not elderly, and had no hyperlipidemia, diabetes mellitus, or history of smoking. There was a marked blood pressure difference between the arms, and linear calcification was present in the aortic wall. A stenotic lesion was present in the right mid-subclavian artery. Although it is impossible to rule out atherosclerosis as the etiology of these findings, the possibility that they may be a manifestation of Takayasu's arteritis is discussed.

Angiography↗
PubMed1994

Evaluation of negative inotropic and antiarrhythmic effects of class 1 antiarrhythmic drugs.

The effects of 6 class 1 antiarrhythmic drugs (aprindine, cibenzoline, disopyramide, lidocaine, pirmenol, and quinidine) on myocardial action potential, its maximal upstroke velocity (Vmax) and isometric contractile force were evaluated by electrophysiological techniques. All the class 1 antiarrhythmic drugs examined had dose-dependent negative inotropic effects. The inhibitory effects on contractile force (Fc) was compared with the inhibitory effects on sodium channels under fast response. This ratio was indicated by IC50 Vmax/IC50Fc, and when evaluated and arranged in order of descending magnitude, these were the results: pirmenol, disopyramide, lidocaine, quinidine, cibenzoline and aprindine. The negative inotropic effects and the effects on action potential duration induced by these antiarrhythmic drugs were independent of each other; it had been found that classification of the drugs according to their effects on action potential duration did not provide sufficient information about negative inotropic effects. Class 1 antiarrhythmic drugs can be divided into 3 groups depending on the regression pattern of myocardial contractile force and the Vmax of action potentials under fast response and slow response. Drugs, whose inhibitory effects on sodium channels, are the main cause of negative inotropic effects. Drugs, whose inhibitory effects on calcium channels, are the main cause of negative inotropic effects. Drugs for which it is difficult to determine whether sodium channel or calcium channel blockade contributes more to their negative inotropic effects.

Action Potentials↗
PubMed1993

The TSH-dependent potassium channel in a cloned rat thyroid cell line.

We found a TSH-dependent K+ channel in the membrane of a rat thyroid cell line (FRTL-5 cell). This K+ channel is activated by extracellular application of the thyroid stimulating hormone (TSH). Treatment of dibutyryladenosine cyclic monophosphate (Bt2 cAMP) also activated the TSH-dependent K+ channel. Intracellular application of protein kinase A activates this K+ channel without the presence of free Ca2+. These findings indicate that the thyroid K+ channel is activated through the TSH-cAMP-protein kinase A system. This is the first report of a polypeptide hormone activated K+ channel and it should be useful for examining the effects of this K+ channel on thyroid cell functions.

Amino Acid Sequence↗
PubMed1993

Effects of hypoxia on the use-dependent inhibition of conduction velocity induced by cibenzoline in guinea pig ventricular myocardium.

The use-dependent effects of cibenzoline, a new anti-arrhythmic drug, on the maximal rate of rise (Vmax) of the action potential and on conduction velocity, and their corresponding recovery kinetics were studied in isolated papillary muscles of guinea pigs under normal and hypoxic conditions. Standard microelectrode techniques were applied to monitor the action potential of the muscles and their conduction. Under control conditions, the amount of use-dependent block of Vmax, conduction velocity, and square of conduction velocity, induced by 10 mumol/L cibenzoline were 26.5 +/- 3.9, 13.8 +/- 1.4, and 25.6 +/- 2.4%, respectively; under hypoxic conditions, these values increased to 32.3 +/- 4.8, 19.7 +/- 1.2, and 35.5 +/- 2.0%, respectively. In the presence of 10 mumol/L cibenzoline, the mean values of time constants for the onset of the use-dependent inhibition of Vmax, conduction velocity, and the square of conduction velocity, during a 2-Hz stimulation, were 3.65 +/- 0.27, 2.77 +/- 0.33, and 2.56 +/- 0.26 seconds, respectively. Under hypoxic conditions, these values changed to 5.10 +/- 0.96, 3.05 +/- 0.44, and 2.84 +/- 0.39 seconds, respectively. The recovery time constants averaged 14.72 +/- 4.08 seconds (for Vmax), 22.23 +/- 3.78 seconds (for conduction velocity), and 23.17 +/- 13.38 seconds (for the square of conduction velocity) in the presence of 10 mumol/L cibenzoline, and 17.19 +/- 8.59 seconds (for Vmax), 15.77 +/- 2.37 seconds (for conduction velocity), and 16.82 +/- 2.61 seconds (for the square of conduction velocity) under hypoxic conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Facilitation of beta-adrenoceptor-mediated slow channel responses by hypoxia in guinea pig ventricular myocardium.

The effects of hypoxia on the beta-adrenoceptor-mediated slow channel responses of guinea pig ventricular muscle in a potassium-rich (27 mM) solution containing Ba2+ were examined using microelectrode techniques. Isoproterenol produced a small depolarization of the resting membrane and also induced repetitive discharges of action potentials at higher concentrations, mainly due to a beta-adrenoceptor-mediated increase in the slow channel conductance. Two different threshold concentrations of isoproterenol, one for inducing depolarization and one for inducing automatic activity, were measured to assess myocardial responsiveness to catecholamines. During hypoxia, the electrically triggered slow upstroke action potentials of muscle were gradually depressed and catecholamine-induced membrane responses mediated by the beta-adrenoceptor/slow channel system were enhanced. The enhancement of the catecholamine effects was accelerated by acidosis and reversed by reoxygenation. Methyl xanthine-induced responses, similar to those induced by catecholamines, were also enhanced during hypoxia. It is suggested that not only changes of catecholamine-beta-adrenoceptor interaction, but also changes of intracellular metabolic processes, may be responsible, at least in part, for the enhancement of abnormal automatic activity mediated by the myocardial beta-adrenoceptor/slow channel system under hypoxic conditions.

Action Potentials↗
PubMed1993

Acute hemodynamic effects of bunazosin in congestive heart failure--differing responses according to degree of cardiac dysfunction.

1. Hemodynamic responses to Bunazosin (BZN) in congestive heart failure (CHF) were evaluated for 6 hours (hr) in 30 patients (A, normal cardiac function; B, mild cardiac dysfunction; C, severe cardiac dysfunction). 2. For 6 hr after BZN, the increments of cardiac index (delta CI) and stroke volume index (delta SVI) with BZN were higher in groups A and B than in group C. 3. A significant positive correlation was observed between ejection fraction and maximum delta CI and SVI, and between % fractional shortening and maximum delta CI and SVI. 4. These data showed that BZN improved the hemodynamics of CHF patients and that patients in groups A and B responded well to this vasodilator, however, patients in group C did not.

Adrenergic alpha-Antagonists↗