Biomedical subjects

Y Ogiwara

Publications and source records attributed to Y Ogiwara.

At least 37 records · Page 2Linked to original sources

PubMed1987

Effects of DJ-7141, a new alpha-2 agonist, 2-(2-chloro-6-fluorophenyl)-2,3,5,6-tetra-hydro-1H-imidazo[1,2-a] imidazole hydrochloride, on the isolated atrium, cross-perfused with blood from a support dog.

The effects of DJ-7141, a new alpha-2 agonist, on an isolated atrial preparation cross-perfused with arterial blood from a support dog were investigated. In the isolated atrium, a selective injection of DJ-7141 (1-100 micrograms) into the sinus node artery induced dose-dependent positive chronotropic and inotropic effects. The positive cardiac effects of DJ-7141 were not only inhibited by propranolol and by imipramine, but reversed to negative effects, whereas the positive cardiac effects of norepinephrine were blocked by propranolol and potentiated by imipramine. Tetrodotoxin (TTX) did not modify the cardiac responses to DJ-7141. After propranolol treatment, the negative chronotropic and inotropic responses to DJ-7141 were not influenced by atropine, which completely blocked acetylcholine-induced cardiac responses. When DJ-7141 was injected into the support dog at a dose of 10-300 micrograms/Kg i.v., it induced a brief increase in femoral arterial blood pressure and a long-lasting decrease in heart rate in the support dog and increases in atrial rate and contractile force in the isolated atrium. These results suggest that the new alpha-2 agonist, DJ-7141, induces indirect positive chronotropic and inotropic effects due to a tyramine-like action and direct negative cardiac effects in the isolated dog heart, and that the tyramine-like effect may be partially responsible for the increase in blood pressure seen with DJ-7141 in in situ dogs.

Adrenergic alpha-Agonists↗

PubMed1987

Pharmacological analysis of chrono- and inotropic responses to diazepam in the isolated, blood-perfused canine atrium.

Effects of diazepam on the pacemaker activity and atrial contractility were investigated using the isolated and blood-perfused canine atrium. When diazepam in a dose range of 3-300 micrograms was injected directly into the sinus node artery, biphasic (negative followed by positive) chrono- and inotropic responses were dose-relatedly evoked. These responses were not affected by atropine in a dose which blocked ACh-induced negative ones. Propranolol inhibited positive chrono- and inotropic responses to diazepam, and prolonged the duration of the negative responses. Imipramine, in a dose which blocked tyramine-induced positive responses, significantly augmented the positive inotropic responses to diazepam. From these results, it is suggested that diazepam induces direct negative chrono- and inotropic effects, the mechanism of which remains to be defined, and indirect positive effects by catecholamine release from the sympathetic nerve terminals, though not mediated by a tyramine-like action. Diazepam tended to potentiate negative chrono- and inotropic effects of adenosine but not significantly, suggesting that diazepam plays a minor role as an adenosine potentiator in the dog right atrium.

Acetylcholine↗

PubMed1987

Pharmacologic basis of responses to midazolam in the isolated, cross-perfused, canine right atrium.

The effects of midazolam on atrial rate and contractile force in the isolated canine atrium perfused with donor blood were investigated. When midazolam in a dose range of 100-1000 micrograms was injected directly into the sinus node artery of the isolated atrium, biphasic (negative followed by positive) chronotropic and triphasic (positive, negative followed by positive) inotropic effects were induced. After propranolol or imipramine, the positive chronotropic and the secondary positive inotropic effects were significantly suppressed, but the initial positive inotropic effect was not affected. Tetrodotoxin, atropine, or R05-4864, a selective ligand for peripheral benzodiazepine binding sites, did not modify midazolam-induced effects. When midazolam in a dose of 0.1-1 mg/kg was administered intravenously to the donor dog, monophasic negative chronotropic and inotropic effects in the isolated atrium were observed but were not as prominent. We conclude that midazolam has direct cardiac inhibitory properties including catecholamine release due to a tyramine-like action.

Animals↗

PubMed1987

Blocking effects of alinidine on negative chronotropic and inotropic responses to vagal stimulation and injected acetylcholine and carbachol in dogs.

The effects of alinidine on negative chrono- and inotropic responses to cholinergic interventions, i.e., intramural vagal nerve stimulation and an injection of acetylcholine (ACh) or carbachol, were investigated in isolated, blood-perfused canine atrial preparations perfused by arterial blood from donor dogs. Vagal nerve stimulation (5, 10 or 30 Hz) and an injection of ACh (0.17-1.65 nmol) or carbachol (0.05-0.55 nmol) induced frequency-dependent and dose-dependent negative chrono- and inotropic responses, respectively. These responses were reproducible in the same preparation. During the negative chrono- and inotropic responses to alinidine (85-854 nmol), cardiac responses to cholinergic interventions were depressed dose-dependently. The depressive effects of alinidine on the negative chronotropic responses were significantly (P less than .05) greater than those on the negative inotropic ones. However, alinidine did not affect adenosine-induced negative cardiac responses. Atropine (0.43-4.32 nmol) uniformly blocked responses to cholinergic intervention dose-dependently. The potency of the antimuscarinic effect of alinidine was approximately 1/200 to 1/500 of the potency of atropine at the 50% inhibition dose for responses to vagal stimulation, carbachol and ACh. Intravenous administration of alinidine (1 mg/kg) to the donor dog also suppressed cardiac responses to choline esters and vagal stimulation in the isolated atrium perfused by the donor's blood. These results suggest that alinidine has suppressive effects on the negative chrono- and inotropic responses to exogenous choline esters and endogenous ACh from parasympathetic nerve terminals at the post-junctional cholinergic muscarinic receptors in the dog heart.

Acetylcholine↗

PubMed1986

Different effectiveness of glucagon on the pacemaker activity and contractility in intact dog hearts and in isolated perfused right atria.

In an isolated right atrial preparation, which was cross-perfused with heparinized arterial blood from a support dog, we investigated the effects of glucagon on heart rate and systemic arterial blood pressure of the support dog and on atrial rate and contractile force of the isolated perfused atrium when glucagon was injected into the external jugular vein of the support dog or into the sinus node artery of the isolated atrial preparation. Glucagon (0.3 to 3 micrograms/Kg i.v.) to the support dog dose-dependently induced a prominent increase in heart rate and a small increase in systemic arterial blood pressure. In the isolated, perfused atrium, marked positive chronotropic and slight, but significant, positive inotropic effects were evoked dose-dependently 1.5 min after intravenous injection of glucagon. These positive effects were not altered significantly by propranolol (1 mg/Kg i.v.). Direct injection of glucagon into the sinus node artery of isolated atria also induced marked positive chronotropic and small positive inotropic effects dose-dependently. CF/HR ratios, inotropic effect per chronotropic effect in isolated atria, of glucagon injected intravenously or intraarterially were less than 0.7 and they were much less than those of norepinephrine (more than 3.6). These results confirm that glucagon injected intravenously or regionally produces a prominent positive chronotropic effect and a small positive inotropic effect and suggest that glucagon may be less effective as a cardiotonic agent.

Animals↗

PubMed1986

Inotropic and chronotropic activity of a new cardiotonic agent, DM 9278 (1,2,3,4,8,9,10,12-octahydro[2,1-b]pyrido[2,3-f]quinazolin-9-one ), on isolated dog atrial and ventricular muscles.

The cardiac effects of DM9278 were studied in isolated and blood-perfused atrial and ventricular preparations from mongrel dogs. In spontaneously beating isolated right atria, DM9278 caused positive chronotropic and inotropic responses in a dose-related manner (1-100 micrograms). DM9278 produced relatively larger positive inotropic than positive chronotropic effects as compared with effects of aminophylline or papaverine. DM9278 increased the developed tension in left ventricles electrically driven at 1.5-2.0 Hz. Positive inotropic and chronotropic responses to DM9278 in both atrial and ventricular preparations were suppressed slightly but not significantly by 1-3 micrograms of propranolol, which completely blocked the positive chronotropic and inotropic effects of norepinephrine (0.01-0.1 micrograms). From these results, it is concluded that DM9278 has direct cardiotonic properties in isolated dog heart tissues, showing relatively selective positive inotropic activity.

Animals↗

PubMed1986

Cardiovascular effects of budralazine in the dog.

Cardiovascular effects of budralazine were investigated in isolated and cross-circulated dog atrial preparations. When budralazine was injected into the jugular vein of the donor dog, a hypotension was produced with slight tachycardia in a dose-related manner. At the same time, slight positive chronotropic and biphasic inotropic effects were induced in the isolated atrium perfused with donor's arterial blood. When budralazine was injected into the cannulated sinus node artery of the isolated atrial preparation, it produced only slight negative chronotropic and inotropic responses, occasionally followed by positive responses. Vehicle injections induced monophasic negative chronotropic and inotropic effects. It is concluded that budralazine has a potent vasodilator action, a reflex-induced sympathomimetic action, but no direct cardiac stimulating properties. Moreover, a direct catecholamine releasing action of budralazine does not appear to be prominent.

Animals↗

PubMed1986

Cardiovascular effects of ZSY-27 [5-methyl-6-(4-pyridinyl)-2H-1,4-thiazine-3(4H)-one X hydrochloride] in the dog cross-circulated atrial preparation.

A new cardiotonic compound, 5-methyl-6-(4-pyridinyl)-2H-1,4-thiazine-3(4H)-one X hydrochloride (ZSY-27), was investigated in cross-circulated dog atrial muscle preparations. When ZSY-27 was intravenously administered to the donor dog, a dose-dependent depressor effect with slight sinus tachycardia was induced in the donor dog. At the same time, a significant dose-dependent increase in developed tension was usually observed in an isolated atrium perfused with donor's arterial blood, but there were no significant changes in sinus cycle length and sinoatrial conduction time. The ZSY-27-induced positive inotropic effect was not significantly influenced by treatment with propranolol in doses which completely inhibited norepinephrine-induced positive chronotropic and inotropic effects. When ZSY-27 was injected into the cannulated sinus node artery of the isolated atrium, dose dependent positive chronotropic and inotropic effects were induced. The dominant increases in developed tension by ZSY-27 were similar to effects of other phosphodiesterase inhibitors, such as papaverine and aminophylline. From these results, it is concluded that ZSY-27 has non-adrenergic, cardiotonic properties with a depressor effect.

Aminophylline↗

PubMed1986

Effects of calcium channel blockers on sinoatrial conduction in the isolated and blood-perfused dog atrium.

Our previous study demonstrated that class I antiarrhythmics (fast sodium channel blockers) increased sinoatrial conduction time (SACT) in a dose-related fashion, indicating that a fast sodium current might play an important role in sinoatrial conduction. To assess a role of a slow calcium current in sinoatrial conduction, we examined effects of calcium channel blockers (diltiazem, verapamil, AQ-A 39, dilazep and bepridil) on SACT estimated by the constant atrial pacing in addition to on sinus cycle length (SCL) and on atrial developed tension (DT), using the isolated and blood-perfused dog right atrium. These calcium entry blockers except for bepridil were administered into the cannulated sinus node artery at an infusion rate of 0.2, 0.4 and 1.0 micrograms/min and bepridil at a rate of 0.6, 1.2 and 3.0 micrograms/min. The calcium antagonistic agents produced a dose-dependent decrease in DT and increase in SCL. The observed order of depression of inotropism was verapamil greater than diltiazem greater than bepridil = dilazep greater than AQ-A 39, while the order of negative chronotropism was diltiazem greater than verapamil greater than AQ-A 39 greater than dilazep greater than bepridil. However, as to dromotropism none of the five drugs exerted significant influences on SACT. From the previous and present results it is concluded that the fast sodium current may be predominantly important in sinoatrial conduction.

Animals↗

PubMed1972