PubMed Health⌕ Search

Biomedical subjects

N Taira

Publications and source records attributed to N Taira.

At least 127 records · Page 7Linked to original sources
PubMed1988

The negative inotropic effect of nicorandil is independent of cyclic GMP changes: a comparison with pinacidil and cromakalim in canine atrial muscle.

1. The negative inotropic effects of nicorandil, a nitrate with K-channel opening properties, have been compared with those of pinacidil, cromakalim and nifedipine, in canine right atrial muscle. 2. Cromakalim, pinacidil and nicorandil all produced a negative inotropic effect. However, even at their maximally effective concentrations, the force of contraction remained at about 10% of control levels, whereas contraction was abolished by nifedipine. 3. The pD2 values for the negative inotropic effects of cromakalim, pinacidil and nicorandil were 5.93, 5.37, and 4.35, respectively. 4. The negative inotropic effects of cromakalim (3 x 10(-5)M), pinacidil (3 x 10(-5) M and 3 x 10(-4) M) and nicorandil (3 x 10(-5) M) were not accompanied by changes in cyclic AMP and cyclic GMP levels, whereas that of 3 x 10(-4) M nicorandil was accompanied by an increase in cyclic GMP but not cyclic AMP concentrations. 5. The negative inotropic effect produced by 3 x 10(-4) M nicorandil was greatly reduced by 10(-2) M tetraethylammonium, whereas the increase in cyclic GMP produced by this concentration of nicorandil was not significantly changed. Sodium nitroprusside (10(-3) M) produced a large increase in cyclic GMP concentrations but had no significant negative inotropic effect. 6. It is concluded that the negative inotropic effects of nicorandil like those of cromakalim and pinacidil do not result from an increase in cyclic GMP concentrations. Instead these effects may be due to their action as K-channel openers.

Animals↗
PubMed1988

Voltage- and use-dependent block of the inward calcium current by MCI-176, a new non-dihydropyridine calcium antagonist, in canine ventricular muscles and single ventricular cells of the guinea-pig.

Effects of MCI-176, 2-(2,5-dimethoxyphenylmethyl)-3-(2-dimethylaminoethyl)-6-isopro pox y-4(3H)- quinazolinone hydrochloride, on action potentials of canine ventricular muscles and on membrane currents of single ventricular cells of the guinea-pig heart were studied with the microelectrode and the patch-clamp ("whole-cell recording") methods. In canine ventricular trabeculae, MCI-176 (10(-5)-10(-4) M) decreased the plateau potential, the action potential duration at 30%-repolarization and the maximum rate of rise of the action potential; and it also decreased the amplitude and the duration of the slow response action potential in a concentration-dependent manner. Those effects were much more apparent at higher stimulus frequency. Under voltage clamp condition of single ventricular cells of the guinea-pig heart, MCI-176 (3 x 10(-5) M) decreased the inward calcium current (ICa) by 25-30% when the membrane potential was held at the resting membrane potential, and the drug abolished it when the membrane potential was held at -30 mV. MCI-176 added at rest decreased ICa ("initial block") and reduced it further with repetitive depolarizations in a beat-to-beat fashion. MCI-176 facilitated the reduction of ICa by increasing the clamp pulse frequency. These results indicate that MCI-176 decreases ICa of mammalian ventricular muscles in a voltage- and use-dependent manner.

Action Potentials↗
PubMed1988

Improvement of pentobarbital-induced heart failure by MCI-154, a novel and potent cardiotonic agent, in the dog heart-lung preparation.

The efficacy of MCI-154, a new pyridazinone cardiotonic agent, in improving heart failure was assessed in dog heart-lung preparations in which cardiac function had been severely depressed by pentobarbital. MCI-154 in doses of 10-100 micrograms improved the cardiac function curve and restored it to the control level at 100 micrograms. At this dose, MCI-154 neither produced an increase in heart rate beyond the control value nor induced arrhythmias. The effects of MCI-154 were not affected by atenolol, a cardioselective beta 1-blocker. These results indicate that MCI-154 would be of potential use in the treatment of heart failure.

Animals↗
PubMed1988

Are the cardiovascular effects of gentamicin similar to those of calcium antagonists?

Cardiac and coronary vasodilator effects of gentamicin (GM) were investigated in isolated, blood-perfused papillary muscle, sino-atrial (SA) node and atrioventricular (AV) node preparations of dogs. GM (0.3-100 mumol) was injected intraarterially. GM produced an increase in coronary blood flow in all preparations. In paced papillary muscle preparations, GM reduced the force of contraction. In spontaneously beating papillary muscle preparations, GM decreased the rate of automaticity and the force of contraction. In SA node preparations, GM decreased the sinus rate. In AV node preparations, GM injected into the posterior septal artery (which supplies the AV node) increased AV conduction time and in large doses, produced third-degree AV block. In the same preparations, GM in large doses injected into the anterior septal artery (which supplies the His-Purkinje-ventricular system) prolonged AV conduction time (i.e., intraventricular conduction time) and reduced the amplitude of ventricular bipolar electrograms. The order of potencies of GM on the above cardiovascular variables is as follows: Coronary blood flow greater than or equal to ventricular muscle contraction greater than ventricular automaticity greater than SA nodal automaticity greater than AV nodal conduction greater than intraventricular conduction. This cardiovascular profile is different from those of organic calcium-antagonists, but rather similar to that of manganese ions, reflecting its own mechanism of action.

Animals↗
PubMed1988

Isolated dog hearts prepared in cold tyrode solution and reperfused with arterial blood are functionally and ultrastructurally normal.

Isolated dog whole heart preparations run by means of cross-circulation with support dogs were prepared in two different ways. In one way the donors' hearts were quickly removed, and cannulation of their major vessels, insertion of a latex balloon into the left ventricle, etc. were all done in cold Tyrode solution in the condition of heart-anoxia within 30 min and then reperfused with arterial blood of support dogs (Group A). In the other, cannulation of the major vessels of the donors' hearts were done in the state of "beating heart" (Group B). In these two kinds of preparations we compared basal cardio-coronary measurements (coronary blood flow, left ventricular pressure (LVP), its first derivative (LV dP/dt) and myocardial oxygen consumption (MVO2) and ultrastructure of the myocardium at various periods of the experiments. There were no significant differences in these cardio-coronary measurements and ultrastructural findings. Furthermore, Group A preparations kept stable levels of cardio-coronary measurements for 5 hr or more and responded normally to isoproterenol. Therefore, isolated, blood-perfused dog whole hearts prepared in cold Tyrode solution and reperfused by means of the cross-circulation method would be useful for physiological, pharmacological and biochemical studies.

Animals↗
PubMed1988

Cardiovascular profile of AN-132, a new diamine derivative antiarrhythmic agent, revealed in the isolated, blood-perfused dog heart.

The cardiac and coronary effects of AN-132, a new antiarrhythmic agent, were investigated in isolated, blood-perfused atrioventricular (AV) node, sinoatrial (SA) node and papillary muscle preparations of dogs. AN-132 was administered intraarterially. In AV node preparations, whether injected into the anterior septal artery (ASA; supplying the His-Purkinje-ventricular system) or the posterior septal artery (PSA; supplying the AV node), AN-132 prolonged AV conduction time and produced second- or third-degree AV block at large doses in some preparations. Moreover, only when injected into the ASA AN-132 produced a broadening and diminution of amplitude of bipolar electrograms obtained from the right bundle branch and the ventricular septum. In SA node preparations, AN-132 decreased sinus rate and produced atrial standstill at large doses in some preparations. In paced papillary muscle preparations, AN-132 reduced the force of contraction. In spontaneously beating papillary muscle preparations, AN-132 decreased the rate of automaticity and the force of contraction. In all preparations, AN-132 produced a transient increase in blood flow only at large doses. The order of potencies of AN-132 based on the doses that produced 15% suppressions of the above cardiovascular variables was as follows: cardiac muscle contraction greater than ventricular automaticity greater than or equal to intraventricular conduction greater than AV nodal conduction greater than or equal to coronary blood flow greater than SA nodal automaticity.

Anilides↗
PubMed1988

Hypertensive episodes and circadian fluctuations of blood pressure in patients with phaeochromocytoma: studies by long-term blood pressure monitoring based on a volume-oscillometric method.

A new portable device for the indirect measurement of arterial blood pressure was successfully applied to detect paroxysmal hypertension and circadian fluctuation of blood pressure in patients with phaeochromocytoma. The device utilizes the volume-oscillometric technique, it is equipped with a microprocessor and allows long-term automatic monitoring of indirect blood pressure in the human finger. Compared with conventional fully automated portable devices of the arm-cuff type, our current equipment is lighter, less noisy, and causes less discomfort. With this device repeated measurements can be made without causing stress or discomfort, and without disturbing sleep. The arterial pressure measurement obtained using this device was reliable and reproducible. In some patients certain symptoms, possibly due to phaeochromocytoma, had been observed for several years before the study, although hypertension had not been identified. While these patients had consistently high circulating catecholamine levels, nocturnal falls in blood pressure were clearly documented. This suggests that plasma catecholamines released from the phaeochromocytoma, though excessive, may be of less physiological importance than other regulatory mechanisms concerned with circadian fluctuation of blood pressure, e.g. the sympathetic nervous system and/or hypothalamo-pituitary-adrenal system. This new device has proved to be a reliable means of monitoring long-term blood pressure and is useful in the diagnosis of paroxysmal hypertension in patients with phaeochromocytoma.

Adolescent↗
PubMed1987

Pinacidil increases the background potassium current in single ventricular cells.

Pinacidil, a new antihypertensive agent, increased the background (inward rectifier) potassium current and abolished its negative slope, and did not change the time-dependent component of the outward (delayed outward) current in single ventricular cells isolated from the guinea-pig heart. These effects must be responsible for the negative inotropic action of this drug.

Animals↗
PubMed1987

Differences in cardiovascular profile among calcium antagonists.

Calcium antagonists constitute a group of organic compounds with diverse chemical structures. Although their main pharmacodynamic actions are vasodilatation and myocardial depression, they are not uniform in producing these effects. Based on comparison of the potencies in producing negative inotropic, chronotropic and dromotropic effects to the coronary vasodilator potency of individual calcium antagonists determined by use of isolated, blood-perfused papillary muscle, sinoatrial node and atrioventricular node preparations of dogs, calcium antagonists are classified into 2 major groups. The dihydropyridines, nicardipine, nifedipine, nimodipine, nisoldipine, nitrendipine, PN 200-110 (isradipine) and PY 108-068, are generally far more potent in producing coronary vasodilatation than in producing negative inotropic, chronotropic and dromotropic (first-degree atrioventricular block) effects, although there are minor differences among them. The non-dihydropyridine calcium antagonists, verapamil, diltiazem, KB-944, bepridil and MCI-176, are nearly equipotent in producing coronary vasodilatation and a negative dromotropic effect, although all of them are less potent in producing negative inotropy. The non-dihydropyridine calcium antagonists can be further divided into 2 subgroups. Verapamil, diltiazem and KB-944 are nearly equipotent in producing negative dromotropic and chronotropic effects. Bepridil and MCI-176 are less potent in producing negative chronotropy than in producing negative dromotropy.

Animals↗
PubMed1987

Cardiac and coronary vasodilator profile of pimobendan, a new cardiotonic drug, revealed by use of isolated, blood-perfused dog heart preparations.

Cardiac and coronary vasodilator effects of pimobendan (UD-CG 115 BS) were assessed in isolated, blood-perfused papillary muscle, sinoatrial (SA) node, and atrioventricular (AV) node preparations of dogs. Pimobendan was administered intra-arterially. In paced papillary muscle preparations, the drug increased the force of contraction in a dose-dependent manner. In SA node preparations, the drug produced an increase in sinus rate. When the drug was injected into the artery supplying the AV node, the drug produced a decrease in AV conduction time by accelerating AV nodal conduction in AV node preparations. In spontaneously beating papillary muscle preparations, the drug increased the rate of ventricular automaticity. No ventricular arrhythmias were produced by the drug. In all preparations, the drug increased (coronary) blood flow. The order of effectiveness of pimobendan on the above cardiovascular variables was as follows: ventricular muscle contraction much greater than coronary blood flow greater than SA nodal automaticity greater than AV nodal conduction greater than ventricular automaticity. The results indicate that pimobendan is relatively specific for force and its cardiovascular profile is very similar to those of phosphodiesterase inhibitors. Therefore, it is likely that this cardiovascular profile would be determined by its inhibitory action on phosphodiesterase.

Animals↗
PubMed1987

Inotropic versus chronotropic, dromotropic, and coronary vasodilator actions of DPI 201-106, a novel positive inotropic agent, in the dog heart.

Inotropic versus chronotropic, dromotropic, and vascular effects of DPI 201-106 were assessed in isolated, blood-perfused papillary muscle, sinoatrial (SA) node, and atrioventricular (AV) node preparations of dogs. DPI 201-106 was administered intraarterially. In paced papillary muscles the drug produced an increase in developed tension. In spontaneously beating papillary muscles the drug slightly decreased the beating rate. In SA node preparations the drug decreased sinus rate, and atrial standstill ensued from the highest dose. In AV node preparations the drug affected AV conduction only when administered into the AV node artery, and in high doses second- or third-degree AV block occurred. In all preparations the drug increased blood flow. DPI 201-106 at the dose that produced a 50% increase in the force of contraction of ventricular muscle increased coronary blood flow by 8.4%, AV conduction time by 7.6%, and decreased sinus rate by 2.6%, indicating its high selectivity for force. When infused into the AV node artery, the drug in high doses produced dose-dependent prolongations of both the AV nodal conduction time and the functional refractory period of the AV node, which were pronounced with elevation of the pacing rate. These effects of DPI 201-106 are very similar to those of calcium channel blockers.

Animals↗
PubMed1987

Coronary vasodilator versus cardiac effects of MCI-176, a novel quinazolinone calcium antagonist, in the dog heart.

We compared the coronary vasodilator and cardiac effects of MCI-176, a novel quinazolinone calcium antagonist, in isolated, blood-perfused sinoatrial (SA) node, atrioventricular (AV) node, and papillary muscle preparations of dogs. The drug was administered intraarterially. In SA node preparations MCI-176 reduced sinus rate and produced atrial standstill in large doses. In AV node preparations MCI-176 prolonged AV conduction time and produced second- or third-degree AV block in large doses only when administered into the artery supplying the AV node, but failed to affect AV conduction when administered into the artery supplying the His-Purkinje-ventricular system. In paced papillary muscle preparations MCI-176 reduced the force of contraction. In spontaneously beating papillary muscles MCI-176 failed to change the beating rate. MCI-176 increased blood flow in all preparations. The dose that doubled blood flow was slightly larger than the dose that produced a 15% increase in AV conduction time, but about one-third the dose that produced a 15% decrease in sinus rate. The dose estimated to reduce the force of contraction by half was more than approximately 10 times the dose that doubled blood flow. The results indicate that MCI-176 can be classified as a nonvasoselective calcium antagonist but that it differs from others.

Animals↗
PubMed1987

Antitachycardiac effect of OPC-8212, a novel cardiotonic agent, on tachycardiac responses of guinea pig isolated right atria to isoproterenol and histamine.

In isolated right atria of guinea pigs, OPC-8212 produced a concentration-dependent decrease in spontaneous beating rate that had previously been elevated by isoproterenol or histamine in the presence of nadolol. OPC-8212 scarcely affected the baseline rate, however, OPC-8212 depressed the maximum increase in right atrial rate induced by isoproterenol or histamine in the presence of nadolol. These effects of OPC-8212 were discernible from the effects of its solvent sulfolane. We propose the term "antitachycardiac" to describe such effects of OPC-8212 to distinguish it from those of bradycardic agents. When the concentration-response curves of isoproterenol or histamine for positive chronotropy were normalized, these curves were shifted in a parallel way to the left with OPC-8212, indicating that OPC-8212 retains activity as a cyclic AMP phosphodiesterase inhibitor. The virtual absence of the chronotropic effect of OPC-8212 on the baseline rate and the antitachycardiac effect are discussed in terms of the opposing effects in increasing the inward calcium current on one hand and in decreasing the outward potassium and the inward current activated by hyperpolarization on the other.

Animals↗
PubMed1987

Effect of DHP-218, a novel dihydropyridine phosphonate, on atrioventricular nodal conductivity compared with its vascular effect in dogs.

The effect of DHP-218, a dihydropyridine phosphonate Ca2+ channel blocker, on atrioventricular (AV) nodal conductivity was compared with its vascular effect in dogs. In isolated, blood-perfused AV node preparations, a long-lasting increase in AV conduction time which culminated in second- or third-degree AV block at large doses occurred when DHP-218 was injected into the AV node artery, but not when injected into the artery that supplies the His-Purkinje-ventricular system. However, with DHP-218, a far longer-lasting increase in blood flow through both arteries occurred, and at smaller doses it occurred with little effect on AV conduction. In anesthetized, open-chest dogs of which heart rate was controlled at 150 beats/min, intravenous DHP-218 produced an initially rather quick and later very slowly developing and long-lasting fall in blood pressure. AV conduction time was prolonged only after the largest dose. The functional refractory period of the AV conduction system was rather shortened in all doses examined except for the largest dose. A marked increase in AV conduction time which culminated in third-degree AV block was seen in one of six dogs, only under conditions in which the heart was deprived of central neural control. These results indicate appreciable selectivity of DHP-218 for vasculature versus the AV node.

Animals↗
PubMed1987

Cardiac and coronary vasodilator effects of the novel cardiotonic agent, MCI-154, assessed in isolated, blood-perfused dog heart preparations.

MCI-154 is a potent nonglycoside and non-sympathomimetic cardiotonic agent with a pyridazinone structure. We assessed its cardiac and coronary vasodilator effects by use of isolated, blood-perfused papillary muscle, sinoatrial (SA) node, and atrioventricular (AV) node preparations of dogs. The drug (1-100 nmol) was injected intraarterially. MCI-154 increased the force of contraction of paced and unpaced papillary muscles but failed to affect the rate of automaticity of the latter. It increased sinus rate and shortened AV conduction time by accelerating AV nodal conduction, but in all doses examined it produced no arrhythmias. In all preparations, it increased blood flow. All the effects were long-lasting (1-2 h). MCI-154, however, was not homogeneously effective on these cardiovascular variables. The drug was nearly equieffective in producing a positive inotropic effect and coronary vasodilatation, but less effective in producing positive chronotropic and dromotropic effects. In having such a cardiovascular profile, MCI-154 most resembles milrinone among new cardiotonic agents, although unlike milrinone, its main mechanism of cardiotonic action is believed to be the sensitization of the contractile proteins to Ca2+. Whatever mechanisms are involved, the revealed cardiovascular profile of MCI-154 justifies its clinical trial in the treatment of heart failure.

Animals↗
PubMed1987

Differential effects of isoproterenol on the canine atrial action potential in the presence of carbachol or nicorandil.

In canine atrial muscles, carbachol and nicorandil hyperpolarized the resting membrane potential and shortened the action potential duration. In the presence of carbachol or nicorandil, isoproterenol further hyperpolarized the resting membrane potential and shortened the action potential duration. Isoproterenol significantly increased the plateau duration in the presence of nicorandil, but further abbreviated it in the presence of carbachol. This increase in the plateau duration by isoproterenol in the presence of nicorandil probably reflects the increase in the slow inward current.

Action Potentials↗