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Biomedical subjects

J P Amlie

Publications and source records attributed to J P Amlie.

13 recordsLinked to original sources
PubMed1979

Absolute bioavailability of quinidine in two sustained release preparations.

The bioavailability of quinidine in two sustained release preparations A and B has been compared in three females and three males with i.v. administration of quinidine. The initial rate of oral absorption did not differ between the two drug preparations; the peak concentration was observed after 4 h both for A and B, but was significantly higher after B. A slower decrease in plasma concentration was observed after preparation A than B. Absolute bioavailability did not differ significantly between A (median values 78.4%) and B (median 87.1%). Drug absorption in vivo was in good agreement with the results of in vitro dissolution tests on both preparations. The slower decrease in plasma concentration found for the new sustained release form of quinidine should be of clinical advantage.

Administration, Oral↗
PubMed1979

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↗
PubMed1979

The effect of prolonged pentobarbital anaesthesia on cardiac electrophysiology and inotropy of the dog heart in situ.

The effect of prolonged pentobarbital anaesthesia was tested on the dog heart in situ by means of His bundle electrography and programmed electrical stimulation, monophasic action potential recordings from the right ventricle and measurements of peak dp/dt obtained by Millar tip transducer in the left ventricle. Sixteen dogs were used. Immediately after catheterization during anaesthesia, a slight decreased heart rate, a reduction in the conduction velocity and an increase in the functional refractory period of the atrioventricular node occurred. From 15 to 30 min. after catheterization we observed no change in cardiac electrophysiology during the 8 hrs observation period. A slight decrease in contractility, however, appeared towards the end of the period. We conclude that dogs anaesthetized with pentobarbital could serve as a suitable model for testing drug effect on cardiac electrophysiology and contractility. The limitations of the model area are discussed.

Action Potentials↗
PubMed1978

A study of the labetalol-induced changes in conductivity and refractoriness of the dog heart in situ.

The effect of labetalol, an alpha- and beta- adrenergic receptor blocking agent, on the electrophysiology of the dog heart in situ was studied. Pentobarbital anaesthesia which is known to increase the sympathetic tone was used. Labetalolol in doses of 0.5 to 4.0 mg.kg-1 injected intravenously caused a slight decrease in median heart rate and a slight reduction in the median conduction velocity in the atrioventricular (A-V) node in six dogs. A significant increase in the functional refractory period of the A-V node occurred at doses of 1.0 to 4.0 mg.kg-1. The functional and the effective refractory periods of the right atrium and ventricle were increased by labetalol at all doses tested. The plasma concentrations of labetalol were in the range 0.05 ot 0.8 microgram.cm-3 in five out of six dogs at the three lowest doses tested which is far below the values which could be expected to cause a membrane-stabilising effect. The alpha and beta adrenoreceptor blocking effects of labetalol on cardiac electrophysiology in vivo are discussed.

Acebutolol↗
PubMed1978

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↗
PubMed1978

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↗
PubMed1978

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↗
PubMed1977

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↗
PubMed1976

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↗
PubMed1976

Pure mitral regurgitation. Etiology, pathology and clinical patterns.

The varied etiology of pure mitral regurgitation is demonstrated in this clinicopathological study, comprising 59 surgically treated cases with this condition. One third of the cases was of rheumatic origin, one fifth had ischemic heart disease, another fifth floppy valves and one eighth an isolated rupture of the chordae with necrosis of the chord matrix. To our knowledge the histopathological findings in the last group have not been described before. Congenital mitral regurgitation, bacterial endocarditis and cardiomyopathy were rare causes of mitral regurgitation. Differences between the groups were observed in the sex ratio, duration of history, auscultatory findings ECG signs, compliance of the left ventricle and in the morphological findings.

Adult↗
PubMedDate not supplied

Correlation between pharmacokinetics and intropic and electrophysiologic responses to digitoxin in the intact dog.

We attempted to correlate inotropic and eletrophysilogic digitoxin effects with serum digitoxin concentrations during 8 hr after a single dose. Eight pentobarbital-anesthetized Labrador dogs were given 2.0 mg digitoxin intravenously. Left heart catheterization and His bundle registration were performed. acing and programed electrical stimulation were used to determine heart rate-independant changes in dP/dt, intra-atrial, atrioventricular (AV), His-Purkinje, and intraventricular conduction velocity. The effective (A-ERP) and functional (A-FRP) refractory periods of the atrium and the functional nodal refractory period (AV-FRP) were measured. Serum digitoxin concentrations were determined by radioimmunoassay. Median serum digitoxin half-time was 5.7 hr. The dP/dt increased after digitoxin, with maximum values after 2 hr. Digitoxin concentration correlated with the inotropic response after 4 hr. Heart rate fell significantly within 2 min and remained below control values for the 8 hr observation period concimitant with an increase in AV-nodal conduction time and AV-ERP increased significantly in the late elimination phase, while A-FRP increased slightly initially and remained high. No consistent correlation was found between the electrophysilogic variables and serum concentrations. We conclude that the two main effects of digitoxin, the inotropic and electrophysiologic, are dissociated in the elimination phase after a single dose.

Animals↗