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Biomedical subjects

H Mitsuhashi

Publications and source records attributed to H Mitsuhashi.

At least 73 records · Page 4Linked to original sources
PubMed1989

Antiarrhythmic effect of a new class 1 antiarrhythmic drug, AN-132, on ventricular arrhythmias in beagles.

Using two-stage coronary-ligation-, digitalis- and adrenaline-induced ventricular arrhythmias in beagles, antiarrhythmic effects of AN-132 were examined, and the minimum effective plasma concentration for each arrhythmia model was determined. AN-132 suppressed all the arrhythmias, and the minimum effective plasma concentrations for arrhythmias induced by 24-hour coronary ligation, 48-hour coronary ligation, digitalis, and adrenaline were 3.4-4.6, 1.5-2.3, 0.83, and 9.3 micrograms/ml, respectively. The concentration for adrenaline-induced arrhythmia was significantly higher than that of 24-hour coronary ligation arrhythmia, and it was also higher than that of digitalis arrhythmia. This pharmacologic profile is similar to those of pirmenol and mexiletine. Since AN-132 had no deleterious effects on the hemodynamics and the central nervous system, it may become a clinically useful antiarrhythmic drug.

Anilides↗
PubMed1989

The existence of aldose reductase inhibitors in some kampo medicines (Oriental herb prescriptions).

Traditionally in Japan, some kampo medicines which contain Glycyrrhizae radix (GR) and Paeoniae radix (PR) have long been used for the treatment of diabetic neuropathy. Since we have previously shown that GR und PR have potent aldose reductase inhibitory activities, we further investigated the constituents of these two. The boiled water extract of GR was applied to Sephadex LH-20 column chromatography and 6 fractions (Frs. A, B, Cs, Cp, D, and E) were obtained. Frs. Cp and D were retreated in the same manner and 7 pure compounds (GUs 1-7) were obtained. The boiled water extract of PR was fractionated with ethyl acetate followed by n-butanol and 3 fractions (Frs. 1-3) were collected. Fr. 1 was retreated in the same manner and 2 pure compounds (PRs 1 and 2) were obtained. Among the GU compounds, GU-2 was the most potent inhibitor of rat lens aldose reductase (RLAR) by inhibiting 86% at the concentration of 1.0 microgram/ml. The IC50 of GU-2 was 7.2 x 10(-7) M. Furthermore, GU-2 markedly inhibited sorbitol accumulation in human red blood cells, having an IC50 of 2.9 x 10(-5) M. GU-5 and PR-1 also inhibited RLAR (IC50: 5.6 x 10(-7) M and 6.3 x 10(-7) M, respectively). The structures of GU-2, GU-5, and PR-1 were identified as isoliquiritin, licuraside, and 1, 2, 3, 6-tetra-O-galloyl-beta-D-glucose, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Reductase↗
PubMed1989

Antiarrhythmic effect of a new class 1 antiarrhythmic drug, nicainoprol, on canine ventricular arrhythmias.

Using two-stage coronary ligation-, digitalis- and adrenaline-induced canine ventricular arrhythmias, antiarrhythmic effects of nicainoprol were examined in dogs, and the minimum effective plasma concentration for each arrhythmia model was determined. Nicainoprol suppressed the arrhythmias, and the minimum effective plasma concentrations for arrhythmias induced by 48 hr coronary ligation, digitalis and adrenaline were 8.9 micrograms/ml (by 5 mg/kg, i.v.), 3.0 micrograms/ml (by 3 mg/kg, i.v.) and 2.7 micrograms/ml (by 3 mg/kg, i.v.), respectively. The concentration for coronary ligation arrhythmia was higher than those for the digitalis and adrenaline arrhythmias. This pharmacological profile is similar to those of aprindine and propafenone. Nicainoprol induced some central nervous system effect including vomiting in conscious coronary ligated dogs. Though intravenous nicainoprol (5 mg/kg) was not effective on 24 hr coronary ligation arrhythmia, an oral dose of 30 to 40 mg/kg was effective. These results indicate that it may become a clinically useful antiarrhythmic drug.

Administration, Oral↗
PubMed1989

Endogenous digoxin-like activity of mammalian-lignans and their derivatives.

A comparative study was made on the endogenous digoxin-like activity of sixteen mammalian-type lignan derivatives including enterolactone and enterodiol. Cross-reactivity to antidigoxin antibody, inhibition of dog kidney Na+,K+-ATPase, and ouabain displacing activity against [3H]ouabain binding to human erythrocytes on the part of these derivatives were examined and compared in all cases with that of ouabain. meso-2,3-Dibenzylbutane-1,4-diol (meso-HA-1) was found to possess the most potent cross-reactivity to antidigoxin antibody. Several lignans, particularly HA-1 (either meso or dl), dl-2,3-bis(3-methoxybenzyl)butane-1,4-diol(HA-4), dl-2,3-bis(3,4-dimethoxybenzyl)butane-1,4-diol(HA-10), dl-2,3-bis(3,4-dimethoxybenzyl)-1,4-dimethoxybutane(HA-11), and trans-2,3-bis(3,4-dimethoxybenzyl)-gamma-butyrolactone(HA-14) were capable of inhibiting Na+,K+-ATPase activity with IC50 at a concentration less than 5 x 10(-4) M. Meso-HA-1, HA-11 and HA-14 also showed [3H]ouabain displacement activity with IC50 at a concentration of 10(-4)-10(-3) M. These determinations of activity were made at doses 100-1000 times those of ouabain. The synthetic lignans are considered to derive in vivo from plant material usually present in fibrous food. Based on the data obtained, some lignans may possibly be endogenous digitalis-like substances.

Animals↗
PubMed1989

Immunosuppressive principles of Rehmannia glutinosa var. hueichingensis.

Separation of the immunosuppressive principles from Rehmanniae radix was done by monitoring hemolytic plaque-forming cells (HPFC) inhibitory activity to give two new phenethyl alcohol glycosides: jionosides A1 (4) and B1 (5), along with six known compounds: acetoside, isoacteoside, purpureaside C, echinacoside, and cistanosides A and F.

Animals↗
PubMed1988

Antiarrhythmic profile of a new class 1 drug, AHR 10718, on canine atrial and ventricular arrhythmia models.

Antiarrhythmic effects of AHR 10718 were examined using two-stage coronary ligation, digitalis and adrenaline-induced canine ventricular arrhythmias and aconitine-induced canine atrial arrhythmia. The minimum effective plasma concentration for each arrhythmia model was determined for quantitative analysis of the antiarrhythmic effects. AHR 10718 suppressed the above arrhythmias except for adrenaline-induced arrhythmia. The minimum effective plasma concentrations for arrhythmias induced by 24 hr coronary ligation, 48 hr coronary ligation and digitalis were 8.1 +/- 0.7 (by 10 mg/kg, i.v.), 2.9 +/- 0.9 (by 5 mg/kg, i.v.) and 2.8 +/- 0.6 (by 5 mg/kg, i.v.) microgram/ml, respectively (mean +/- S.D., n = 6). The correlation coefficients between the antiarrhythmic effects of AHR 10718 and its plasma concentrations were not high. This pharmacological profile is characteristic of class 1 Na channel blockers, and in particular, it is similar to those of disopyramide, procainamide and SUN 1165 from our previous studies. AHR 10718 is expected to become a clinically useful antiarrhythmic drug.

Aconitine↗
PubMed1987

Antiarrhythmic plasma concentrations of cibenzoline on canine ventricular arrhythmias.

Using two-stage coronary ligation-, digitalis-, and adrenaline-induced canine ventricular arrhythmias, antiarrhythmic effects of cibenzoline were examined and the minimum effective plasma concentration for each arrhythmia model was determined. Cibenzoline suppressed all the arrhythmias, and the minimum effective plasma concentrations for arrhythmias induced by 24-h coronary ligation, 48-h coronary ligation, digitalis, and adrenaline were 1.9 +/- 0.9 (by 8 mg/kg i.v.), 1.6 +/- 0.5 (by 8 mg/kg i.v.), 0.6 +/- 0.2 (by 2 mg/kg i.v.), and 3.5 +/- 1.3 (by 5 mg/kg i.v.) micrograms/ml, respectively (mean +/- SDM, n = 6-7). The concentration for adrenaline-induced arrhythmia was significantly higher than those for the other types of arrhythmias. This pharmacological profile is similar to those of mexiletine and tocainide, and all three drugs have central nervous system (CNS) stimulant action. Because cibenzoline had only weak hypotensive and sinus node depressive effects and was found to be orally active when given to coronary ligation arrhythmia dogs, its clinical usefulness is expected.

Animals↗
PubMed1987

Do antiarrhythmic drugs act on the site of abnormal impulse generation or act on the normal myocardium?

Locally-induced digitalis arrhythmia was produced to study whether antiarrhythmic drugs suppress arrhythmia by directly acting on the abnormal impulse generation or by suppressing Na channels of normal myocardium to make it unresponsive to abnormal impulses. Dogs were thoractomized and the anterior descending artery (ADA) was isolated and autoperfused with arterial blood from the carotid artery. Forty micrograms and an additional 10 micrograms every 20 min of ouabain was injected directly into the ADA produced ventricular tachycardia originating from the digitalis intoxication. Locally injected class 1 antiarrhythmic drugs, including tetrodotoxin, were effective in suppressing this arrhythmia. However, when intravenously applied lidocaine was prevented from reaching the ADA area, lidocaine was not effective in suppressing this arrhythmia. We conclude that class 1 drugs produce antiarrhythmic effect by directly suppressing the digitalis toxicated area, not by suppressing the normal myocardium.

Animals↗
PubMed1987

Effects of betaxolol, a new beta 1 selective blocker, on canine ventricular arrhythmias.

Antiarrhythmic effects of a new beta 1 selective adrenoceptor blocker, betaxolol, were examined in comparison with those of atenolol using two canine ventricular arrhythmia models (adrenaline arrhythmia and digitalis arrhythmia). Both betaxolol and atenolol suppressed adrenaline arrhythmia, and the minimum effective plasma concentration of betaxolol for this arrhythmia model was determined to be less than 10 ng/ml. However, on digitalis arrhythmia, both beta blockers were ineffective, even though the high doses used in these experiments, 3 mg/kg for betaxolol and 5 mg/kg for atenolol, showed significant hypotensive effects. The present results suggest that betaxolol and atenolol may be expected to be clinically effective on arrhythmias related to increased sympathetic tone.

Adrenergic beta-Antagonists↗
PubMed1987

Antiarrhythmic effects of a new drug, E-0747, on canine ventricular arrhythmia models.

Antiarrhythmic effects of a new antiarrhythmic drug, E-0747, were examined using four canine ventricular arrhythmia models: digitalis-, adrenaline- and two-stage coronary ligation-induced arrhythmias and a newly developed locally-induced digitalis arrhythmia. The minimum effective plasma concentration of E-0747 was determined for the first three arrhythmia models. E-0747 suppressed those arrhythmias, and the minimum effective plasma concentrations for arrhythmias induced by digitalis, adrenaline, 24 hr coronary ligation, and 48 hr coronary ligation were 1.4 +/- 0.6, 1.8 +/- 0.4, 1.6 +/- 0.4 and 2.2 +/- 0.2 micrograms/ml, respectively (mean +/- S.D., n = 5-10). The aforementioned minimum effective plasma concentrations of E-0747 for these arrhythmias were almost equal to the reported concentration in vitro to suppress the Na channels of isolated canine ventricular tissues. The class 1 property of E-0747 was also shown in a newly developed locally-induced digitalis arrhythmia. Thus E-0747 suppresses arrhythmia by inhibiting Na channels of cardiac cells and is expected to become a clinically useful antiarrhythmic drug.

Animals↗
PubMed1987

Immunopotentiating activity of a nucleotide derivative, heptaminol AMP amidate (HAA) in mice and spontaneously hypertensive rats (SHR).

The immunopotentiating activity of heptaminol AMP amidate (HAA), a new derivative of 5'-AMP, was examined in experimental animals. Anti-SRBC PFC activity and antibody titer values augmented for both of single and 4 days consecutive administrations in ICR male mice. The dose of 10 mg/kg was found to cause the maximum enhancement. In spontaneously hypertensive rats, with a state of immunosuppression, 10 days consecutive administrations of HAA at the dose of 10 mg/kg was found to increase significantly the anti-SRBC PFC and antibody titer values. From these results, it is tempting to suggest that HAA may possess an immunopotentiating activity.

Adenosine Monophosphate↗
PubMed1986

Effects of OPC-8212, a new positive inotropic agent, on canine ventricular arrhythmias.

OPC-8212, a positive inotropic agent that increases intracellular cyclic AMP and stimulates the Ca current, was compared with amrinone and AR-L 115 in their effects on canine ventricular arrhythmias. OPC-8212, up to 3 mg kg-1, did not worsen 24 h coronary ligation arrhythmias, while it aggravated ventricular arrhythmias seen 48 h after coronary ligation. However, OPC-8212 did not at any time induce ventricular fibrillation in dogs subjected to coronary ligation. OPC-8212, up to 3 mg kg-1, had no arrhythmogenic or antiarrhythmic effect on digitalis-induced arrhythmias, while amrinone and AR-L 115 showed antiarrhythmic effects. With adrenaline-induced arrhythmias, the three drugs aggravated ventricular tachycardia to produce ventricular fibrillation. The absence of a worsening effect of the new positive inotropic agents on digitalis arrhythmia may be helpful in clinical setting of combined therapy of these new drugs with digitalis.

Animals↗