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Biomedical subjects

K Landmark

Publications and source records attributed to K Landmark.

At least 37 records · Page 2Linked to original sources

The effect of nifedipine on the monophasic action potential and refractoriness of the right ventricle of the dog heart in situ after beta-adrenergic receptor blockade.

The effect of nifedipine, a calcium-antagonistic drug, was studied on the electrophysiology of the right ventricle in the dog heart in situ. Monophasic action potential recordings were obtained by the suction electrode technique and refractoriness was measured by means of programmed electrical stimulation. Pentobarbital anaesthesia was used. As the basic cardiac effects of nifedipine can be altered by the release of catecholamines from sympathetic nerves of the heart and vessels, the dogs were pretreated with the beta-adrenergic receptor blocking agent acebutolol which increased the action potential duration and the refractoriness. Intravenous injection of nifedipine 30 microgram/kg body weight decreased the times for 50 and 90 per cent repolarization of the monophasic action potential and to a smaller extent the effective and functional refractory period. It is suggested that nifedipine decreases the action potential duration and the refractoriness of the right ventricle of the dog heart in situ due to a direct effect of the drug on the myocardium.

Acebutolol

Ectopic atrial tachycardia on swallowing. Report on favourable effect of verapamil.

A female patient who suffered from atrial tachycardia associated with the ingestion of food or drink was examined in our department. No signs of organic heart disease were discovered, oesophageal motility was normal, but X-ray revealed a small hiatal hernia. The arrhythmia started with an atrial extrasystole arising well outside the functional refractory period of the AV node, and it could be reproduced by inflation of a balloon. It is suggested that the arrhythmia is induced by a mechanical effect of the passage of food on the left atrial wall. Several drugs were tried in order to stop or relieve the complaints. None of them prevented or stopped the atrial tachycardia but verapamil and edrophonium chloride caused 2:1 AV block, and follow-up study has shown that sufficient doses of verapamil are able to relieve the patient's complaints.

Atrioventricular Node

Acebutolol-induced changes in refractoriness and monophastic action potential of the right ventricle of the dog heart in situ.

The effect of acebutolol, a beta-adrenergic receptor blocking agent, on the electrophysiology of the right ventricle was studied in the dog heart in situ. Pentobarbital anaesthesia which is known to increase the sympathetic tone was used. Monophasic action potential recordings were obtained by the suction electode technique and refractoriness was measured by means of programmed electrical stimulation. A stepwise increase in the frequency of stimulation from 170 to 200, 230, and 260 per min caused a progressive decrease in the refractoriness as well as the duration of the monophasic action potential. Intravenous injection of acebutolol 2.0 mg.kg-1 increased the times for 50 and 90% repolarisation of the monophasic action potential. This increase is probably due to beta-adrenergic receptor blockade in the presence of alpha-adrenergic receptor stimulation. The effective and functional refractory periods, however, were increased to an even greater extent than the monophasic action potential duration. It is suggested that this is the result of a blockade of a catecholamine-induced increase in the velocity of the depolarisation.

Acebutolol

Verapamil and pulmonary hypertension.

We report on the effect of verapamil in 12 patients suffering from pulmonary hypertension. The drug caused a slight, but statistically significant decrease in mean pulmonary artery pressure and in the work performance by the right ventricle. The mean pressure of the right atrium, the end-diastolic pressure of the right ventricle, the pulmonary arteriolar resistance, the cardiac index and the stroke volume were not significantly changed, however, and there was a wide spread of the values observed. In some patients the drug exerted a marked negative inotropic effect, with a concomitant increase in the pulmonary arteriolar resistance.

Adult

Serum levels and electrophysiological effects of N-acetlyprocainamide as compared with procainamide in the dog heart in situ.

The electrophysiological effects of procainamide and its major metabolite N-acetylprocainamide were tested and compared on the heart of the anaesthetized dog by means of His bundle electrography and programmed electrical stimulation. Both drugs exerted a negative chromotropic effect. They also increased intra-atrial and intraventricular conduction times; procainamide was, however, the more potent of the two drugs. In contrast to procainamide, N-caetylprocainamide did not increase His-Purkinje and atrioventricular nodal conduction times, and at the lowest dose employed, atrioventricular nodal conduction times were decreased during atrial pacing. Both drugs increased the functional and effective refractory period of the right atrium and ventricle. N-acetylprocainamide increased the functional refractory period of the atrioventricular node, but to a lesser extent than procainamide.

Animals

The effect of nifedipine on the sinus and atrioventricular node of the dog heart after beta-adrenergic receptor blockade.

The effect of nifedipine (BAY 1040), a calcium-antagonistic inhibitor of the electromechanical coupling process was tested on atrioventricular conduction and refractoriness of the dog heart in situ by means of His-bundle electrography and programmed electrical stimulation. The animals were anaesthetized with sodium pentobarbital. As the basic effects of the compound can be altered by release of catecholamines from sympathetic nerves of heart and vessels, the dogs were pretreated with acebutolol, a beta-adrenergic receptor blocking agent, which decreased heart rate and prolonged atrioventricular conduction and refractoriness. Nifedipine 1,6 and particularly 30 microgram/kg body weight increased the heart rate and decreased atrioventricular conduction time during atrial pacing, whereas atrioventricular conduction time during sinus rhythm and atrioventricular refractoriness were only affected by nifedipine 30 microgram/kg. In this respect, nifedipine differs distinctly from another calcium antagonistic compound, verapamil.

Acebutolol

Determination of effective orifice area in mitral stenosis from non-invasive ultrasound Doppler data and mitral flow rate.

Ten patients with mitral stenosis, but without mitral insufficiency, have been studied during cardiac catheterization. The mitral orifice blood velocities, the mitral pressure gradient, and the mitral flow rate were determined with ultrasound, manometry, and the direct Fick method, respectively. The effective orifice area was calculated from the ultrasound data and the mitral flow rate. The geometric orifice area was calculated from the pressure gradient and the mitral flow rate, using a revised Gorlin formula. A comparison of the two methods showed a correlation coefficient of 0.975. The investigation demonstrated that the ultrasound method represents an alternative to the conventional catheterization methods used for the quantification of mitral flow obstruction.

Blood Flow Velocity

A comparison of the effects of ouabain, noradrenaline and nifedipine on the contractile force of the isolated rat atrium at different calcium levels.

The effects of ouabain 5 x 10-5 M, noradrenaline 10-7 M and nifedipine 100 mug/1 on the contractile force of the isolated rat left atrium were tested and compared at varying concentrations of calcium in the Ringer solution. The effect of ouabain was small, developed slowly and almost independently of the calcium concentration. Noradrenaline, which increases Ca++ influx during excitation, caused an increase in the contractile force which was complete within 2 min. The percentage as well as the absolute increase in contractile force was pronounced at lower, but small at higher calcium concentrations. Nifedipine, which reduces Ca++ influx during excitation, caused a decrease in contractile force which was complete within 2-4 min. The nifedipine-induced depression in contractile force decreased with a rise in the calcium concentration. It is assumed that the ouabain-induced increase in contractile force in the rat, is not mediated by an increase in the magnitude of the inward calcium current, and other modes of action for the inotropic effect of glycosides are discussed.

Animals

Plasma levels and electrophysiological effects of acebutolol (M & B 17.803) in the dog heart in situ.

The effect of acebutolol a beta-adrenergic receptor blocking agent was tested on the dog heart in situ. The drug decreased heart rate, and caused a reduction in the conduction velocity and a significant increase in the functional refractory period of the atrioventricular node. The functional and the effective refractory period of the right atrium was increased by acebutolol. During sinus rhythm, the drug did not affect conduction velocity in the rest of the conduction pathway. During atrial pacing, however, the intra-atrial and His-Purkinje conduction times were slightly increased. The plasma concentrations of acebutolol were in the range between 0.09 and 0.5 mug/ml, which is far below those values expected to cause a membrane-stabilizing or quinidine-like effect. The clinical applications of the results are discussed.

Acebutolol

The effect of calcium and beat interval on the contractile force and refractoriness of the isolated rat atrium in the absence and presence of nifedipine: a possible mechanism for the negative staircase phenomenon.

An increase in the calcium concentration of the Ringer solution increased the contractile force and reduced the effective refractory period of the isolated rat left atrium paced at a frequency of 60 per min. An increase in the frequency of stimulation decreased the contractile force (negative staircase) and reduced the effective refractory period; these effects being most pronounced at the highest calcium levels. A calcium-antagonistic drug, nifedipine, decreased the contractile force and the effective refractory period. The effect of an increased frequency of stimulation on the contractile force at different calcium levels in the absence and presence of nifedipine paralleled its effect on the effective refractory period. This observation suggests that both these phenomena are caused by a decreased quantity of inflowing calcium ions during the period of exciation, and thus might explain the absence of positive staircase in the rat myocardium.

Action Potentials

Determination of pressure gradient in mitral stenosis with a non-invasive ultrasound Doppler technique.

A 2 MHz continuous waveform non-invasive ultrasound doppler system has been used in the present investigation. With the aid of the audio signals of the frequency shifts, the ultrasound probe was positioned on the external chest so that the axis of the incident ultrasonic beam coincided with the direction of the maximum velocity vectors of the mitral jet. The frequency shifts due to the mitral jet were frequency analyzed and the time course of the maximum frequency shift was determined. The time course of the maximum mitral jet velocity was then determined from the doppler equation and the time course of the mitral pressure gradient from an orifice equation. The usefulness of the technique was evaluated by studying 25 patients with mitral stenosis and 10 without heart disease. The patients with mitral stenosis were studied during cardiac catheterization and the ultrasound data, the pulmonary artery wedge pressure, and the left ventricular pressure were recorded simultaneously. A table is presented where the gradient determined with the ultrasound technique, deltaPU, is compared with the gradient determined from the pressure tracing, deltaPM. Averaged over the 25 patients studied, deltaPU was 1.7 mmHg smaller than deltaPM at 0.08 sec diastolic time and 1.8 mmHg smaller at 0.25 sec diastolic time. The findings in the patients without heart disease differed distinctly from those in the patients with mitral stenosis. The investigation demonstrated that the non-invasive ultrasound technique can be used with confidence to gain an impression of the magnitude of the mitral pressure gradient. The findings also suggest that deltaPU represents the actual pressure gradient more accurately than deltaPM. Another investigation is proposed to assess the accuracy of the technique more completely.

Adult

A study of the verapamil-induced changes in conductivity and refractoriness and monophasic action potentials of the dog heart in situ.

In the dog heart in situ, verapamil 0.30 mg/kg injected intravenously did not impair intraatrial, His--Purkinje and intraventricular conduction. The monophasic action potential (MAP) derived from the right atrium and ventricle was not altered by the drug. The functional refractory period (FRP) and the effective refractory period (ERP) of the atrium was not changed by verapamil. However, the drug caused a small but statistically significant decrease in the ratio between 50 and 90% repolarization, respectively, and the ERP of the right atrium, i.e. the ERP of the atrium increased in relation to the MAP duration. Verapamil used a marked reduction of the conduction velocity within and a pronounced increase of the AV nodal FRP and ERP. These changes were reversed by a rapid injection of calcium gluconate 40 mg/kg. The sinus node automaticity was not influenced by verapamil.

Action Potentials