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Biomedical subjects

H Refsum

Publications and source records attributed to H Refsum.

At least 217 records · Page 12Linked to original sources
PubMed1984

Effects of thoracic epidural analgesia on cardiovascular function and plasma concentration of free fatty acids and catecholamines in the dog.

Increased plasma levels of free fatty acids (FFA), leading to increases in the myocardial oxygen demand, are seen after, for example, surgical stress, traumas and myocardial infarction. The present study was undertaken to investigate the cardiovascular effects of thoracic epidural analgesia (TEA) and the effect of TEA on the plasma concentration of FFA and catecholamines. In 10 sodium-pentobarbital-anaesthetized dogs the local anaesthetic agent bupivacaine was injected into the thoracic epidural space via a surgically introduced catheter. TEA markedly reduced heart rate, mean aortic blood pressure, left ventricular systolic blood pressure and dP/dtmax. TEA reduced the plasma concentration of FFA. The FFA-lowering effect was greatest when the FFA values were high. The effect of TEA on the plasma concentration of noradrenaline and adrenaline was inconsistent and seemed to be of minor importance for the haemodynamic and FFA effects of TEA. The study indicates that TEA, by its haemodynamic and FFA-lowering effects, may reduce myocardial oxygen demand.

Anesthesia, Epidural↗
PubMed1984

A method for simultaneous epicardial monophasic action potential recordings from the dog heart in situ.

In order to record epicardial monophasic action potentials (MAP) simultaneously from different regions of intact beating hearts, we developed a tripodal suction electrode device (total weight 1.5 g, distance between the flexible silicone legs 25 mm) which we tested in pentobarbital anaesthetized open chest dogs. The device was easy to apply and gave stable and reproducible recordings. Repolarization times for epicardial left ventricular and endocardial right ventricular MAPs correlated well (r = 0.97, P less than 0.001). There was no correlation between MAP amplitude and repolarization times. The beta 1-adrenergic agonist prenalterol decreased MAP duration, while the new class III antiarrhythmic drug melperone increased MAP duration. Mild ischaemia effected MAP prolongation and severe ischaemia MAP shortening, compared to simultaneous recordings from non-ischaemic ventricular regions. We conclude that the new tripodal suction electrode is a simple device for simultaneous recording of multiple MAPs. The method should be suitable for studies of electrophysiological effects of drugs and other interventions in intact beating hearts.

Action Potentials↗
PubMed1984

Comparison of electrophysiological and mechanical effects of droxicainide and lidocaine on heart muscle isolated from rats.

A new antiarrhythmic drug, droxicainide, was compared with lidocaine in order to evaluate droxicainide's effect on heart muscle. Dose-response curves for electrophysiological and mechanical effects of the two drugs on spontaneously beating atria, electrically stimulated atria and papillary muscles isolated from rats were obtained. After increasing doses of both droxicainide and lidocaine sinus node automaticity decreased, atrial and ventricular excitability and contractile force decreased and refractoriness increased. The effects of the two drugs on atrial and ventricular muscle were qualitatively and quantitatively the same, but droxicainide was less potent. The results fit well with the concept that droxicainide is a class 1 anti-arrhythmic drug.

Anilides↗
PubMed1984

Vagus- and post-acetylcholine-induced changes in ventricular electrophysiology of the dog heart with and without beta-blockade.

Electrophysiologic effects of acetylcholine (Ach) injections were compared to those obtained by vagus stimulation with and without beta-adrenoreceptor blockade during right heart catheterization in 12 dogs. Monophasic action potentials were obtained by suction electrode technique, and programmed electrical stimulation was used to determine heart rate independent changes in 50 and 90% repolarization times and the effective (V-FRP) and functional (V-FRP) refractory periods of the right ventricle. Vagus stimulation decreased heart rate with and without beta-blockade, while after Ach injections a marked increase in heart rate was found, which could be eliminated by beta-blockade. Vagus stimulation increased action potential duration and refractoriness at high sympathetic tone induced by pentobarbital anesthesia, mainly by inhibiting the effect of beta-adrenoreceptor stimulation. It is concluded that stimulation of the vagus induces antiarrhythmic effects at high sympathetic activity, while the change in ventricular electrophysiology found after Ach injections in high doses to intact animals is an effect probably induced by stimulation of beta 1-receptors.

Acetylcholine↗
PubMed1984

Cardiac electrophysiological and hemodynamic effects of beta-adrenoceptor blockade and thoracic epidural analgesia in the dog.

To investigate whether thoracic epidural analgesia (TEA) has additional cardiac electrophysiological and hemodynamic effects when induced after beta-adrenergic blockade, bupivacaine (0.7-1.2 mg/kg) was injected into the epidural space at T2-3 after intravenous injection of atenolol (1.0 mg/kg) in anesthetized dogs. Cardiac electrophysiology was studied by His bundle electrography, programmed electrical stimulation, and monophasic action potential recordings. Atenolol reduced heart rate, prolonged atrio-ventricular (AV) nodal impulse conduction time and refractoriness, prolonged ventricular refractoriness and action potential duration, and decreased left ventricular (LV) dP/dt max. Addition of TEA further reduced heart rate, prolonged AV nodal conduction time and refractoriness, decreased LV dP/dt max and arterial blood pressure, but had no effect on atrial and ventricular electrophysiology. Induction of TEA during beta-blockade may thus have additive depressive effects on sinoatrial and AV nodal functions, as well as on left ventricular inotropy. The study indicates that the cardiac electrophysiological effects induced by TEA are mainly caused by decreased beta-receptor stimulation, but increased vagal activity may also contribute.

Anesthesia, Epidural↗
PubMed1983

Electrophysiological effects of thoracic epidural analgesia in the dog heart in situ.

To investigate cardiac electrophysiological effects of thoracic epidural analgesia, a local anaesthetic solution, 0.5% bupivacaine, was administered into the thoracic epidural space in twelve pentobarbital anaesthetised dogs. Intracardiac conduction times were measured by His bundle electrography and refractoriness was determined by programmed electrical stimulation. Monophasic action potentials were recorded from the right ventricle by a suction electrode technique. Thoracic epidural analgesia increased the ventricular effective and functional refractory period, as well as the duration of the monophasic action potential. The intra-atrial and His-Purkinje conduction times and the QRS-width were not significantly influenced. AV nodal conduction time and AV nodal functional refractory period were markedly prolonged by thoracic epidural analgesia. Thoracic epidural analgesia induced AV block of the second degree in most experiments after a second dose of bupivacaine during pacing at higher frequencies. We conclude that thoracic epidural analgesia has significant cardiac electrophysiological effects which may be both antiarrhythmic and arrhythmogenic. Thoracic epidural analgesia should be used with care in patients with atrioventricular conduction disturbances.

Action Potentials↗
PubMed1982

Plasma levels and cardiac electrophysiological effects of melperone in the dog.

The butyrophenone neuroleptic melperone has recently been shown to possess antiarrhythmic properties in man and animals. We studied the correlation between plasma concentration of melperone and the electrophysiological and blood pressure effects of the drug in 20 pentobarbital-anaesthetized dogs. Linear correlations were found between the log melperone plasma concentration and decreases in mean aortic blood pressure and heart rate, and increases in atrial and AV nodal refractoriness. The correlations were better after pretreatment with the beta 1-blocker atenolol. There was a linear correlation between log melperone plasma concentration and increases in ventricular refractoriness only after atenolol. No correlation was found between log melperone plasma concentration and decreases in AV nodal conduction time. Apart from the effect on AV nodal conduction time, the relationship between plasma concentration of melperone and the electrophysiological and blood pressure effects after beta 1-blockade fits well into an overall log concentration-effect relationship. The poorer correlation without beta 1-blockade was probably due to a combination of direct and indirect effects of the drug.

Animals↗
PubMed1982

Pentobarbital plasma concentrations and cardiac electrophysiology during prolonged pentobarbital infusion anaesthesia in the dog.

There is need for a prolonged stable level of anaesthesia, and we therefore investigated the cardiac electrophysiological effects of continuous pentobarbital infusion after initial pentobarbital injection to induce anaesthesia in dogs. Plasma concentrations of pentobarbital were measured by gas-liquid chromatography. Heart rate, atrial, atrioventricular (AV) nodal and His-Purkinje conduction times were measured by His bundle electrography, and atrial, AV nodal and ventricular refractoriness by programmed electrical stimulation. Over a 5-h observation period, continuous infusion of pentobarbital 3.5 mg X kg-1 X h-1 after an initial pentobarbital injection of 25 mg X kg-1 intravenously gave stable mean plasma concentrations of 140-135 mumol X 1(-1). The cardiac electrophysiological variables studied did not change significantly during this period. We conclude that a stable experimental model for cardiac electrophysiological studies can be obtained for several hours by continuous pentobarbital infusion.

Anesthesia, Intravenous↗
PubMed1982

Effect of hyaluronidase on substrate exchange and blood flow in the ischaemic myocardium of the dog.

The mechanism for reduced myocardial ischaemic injury by hyaluronidase was studied in open chest anaesthetized dogs. Repeated coronary artery occlusions were performed and the effect of hyaluronidase (225 NF units per kg) was studied during infusion of noradrenaline 0.125 mg/kg . min. Ischaemic injury was measured as the sum of ST-segment elevations (sigma ST) at 10-15 sites. Regional myocardial blood flow was determined by tracer microspheres. Blood for metabolic studies was sampled from a local coronary vein draining ischaemic tissue and from the coronary sinus draining predominantly non-ischaemic tissue. Hyaluronidase reduced sigma ST and increased subepicardial and transmural blood flow in ischaemic myocardium, but flow was not significantly changed in the ischaemic subendocardium or in non-ischaemic myocardium. Hyaluronidase had no significant effect on arterio-local venous differences of oxygen, glucose, lactate or free fatty acids across the ischaemic myocardium. In conclusion, reduction of myocardial ischaemic injury by hyaluronidase can be explained by increased collateral blood flow and not by an effect on fluxes of substrates across the ischaemic myocardium.

Animals↗
PubMed1982

Electrophysiological and mechanical effects of sulphinpyrazone on isolated rat atria.

Clinical trials suggest that sulphinpyrazone reduces the incidence of sudden death in patients having suffered a myocardial infarction. To investigate possible direct antiarrhythmic properties of sulphinpyrazone, we carried out experiments on spontaneously beating and electrically stimulated isolated rat atrial preparations. Dose-response curves for electrophysiological and mechanical effects of sulphinpyrazone were obtained. Increasing doses of sulphinpyrazone decreased the spontaneous atrial frequency, prolonged the sinus node recovery time after overdrive pacing, slightly increased the electrical threshold for excitation and decreased the contractile force. Although the mechanism by which sulphinpyrazone may reduce the incidence of sudden cardiac death is still not settled, the present study demonstrates direct electrophysiological and mechanical effects of the drug at high concentrations.

Animals↗
PubMed1982

The mode of antiarrhythmic action of melperone.

We studied the mode of antiarrhythmic action of melperone by His bundle electrography combined with programmed electrical stimulation in 21 pentobarbital anaesthetized dogs. Melperone alone (0.5 to 12.5 mg/kg) as well as melperone after sympathetic and parasympathetic blockade caused a dose-dependent increase in the ventricular and, even more, the atrial effective refractory period without affecting atrial and ventricular conduction times. Melperone shortened the atrioventricular nodal conduction time regardless of sympathetic and parasympathetic blockade. We conclude that the antiarrhythmic effect of melperone in most likely primarily due to a direct class III antiarrhythmic action.

Action Potentials↗
PubMed1982

Comparative force-velocity relation and analyses of myosin of dog atria and ventricles.

The isolated muscle and purified myofibrillar proteins of canine atria and ventricles were compared relative to force-velocity relations and rate of adenosine 5'-triphosphatase (ATPase) activity as a function of calcium concentrations. The maximal stress development of isolated trabeculae of canine atria was similar to that of canine right ventricular papillary muscles when analyzed at saturating calcium concentrations (7.5 mM); however, stress was less in the atria when studied at normal calcium concentrations (2.5 mM). The maximal velocity of shortening of atrial trabeculae was about 2.3 times higher than that of ventricular muscle. Regulated actomyosin characterized from the myofibrillar proteins of the two tissues gave directionally similar calcium sensitivity. The maximum velocity of shortening for actin-activated atrial myosin of the dog was approximately 1.8 times higher when the latter was analyzed as a function of actin concentration. Both maximal tension of isolated muscle and regulated actomyosin ATPase activity were dependent on calcium concentration.

Adenosine Triphosphatases↗
PubMed1981

Haemodynamic and metabolic effects of the antiarrhythmic drug melperone during acute left ventricular failure in dogs.

Haemodynamic and metabolic effects of the new antiarrhythmic drug melperone were studied during acute ischaemic left ventricular failure in closed-chest anaesthetized dogs. Embolisation of the left main coronary artery with 50 micrometer plastic microspheres induced severe depression of left ventricular performance as evidenced by a marked increase in left ventricular end-diastolic pressure and a marked reduction in the maximum rate of left ventricular pressure rise (LVdP/dtmax), cardiac output, and stroke volume. Six dogs received intravenous melperone 1.0 and 2.5 mg . kg-1 (cumulative dose) 90 and 115 min after the embolisation, respectively. Six other dogs received no treatment and served as controls. Melperone effected a marked reduction in left ventricular end-diastolic pressure, a slight but transient increase in LVdP/dtmax, a moderate reduction in heart rate, a moderate reduction in mean aortic blood pressure and total peripheral resistance and a moderate increase in stroke volume. Melperone moderately decreased myocardial O2-consumption, while myocardial lactate uptake remained unchanged. In conclusion, in contrast to commonly used antiarrhythmic drugs which may all induce cardiodepression, melperone improved left ventricular function in dogs with acute ischaemic left ventricular failure.

Acute Disease↗
PubMed1981

Electrophysiological effects of melperone in the dog heart in situ - a new antiarrhythmic drug.

In pentobarbital anaesthetised dogs, melperone (a neuroleptic butyrophenone) reduced mean aortic blood pressure and at lower doses (0.5 and 2.5 mg . kg-1) increased the heart rate. By means of His bundle electrography and programmed electrical stimulation, conduction velocity and refractoriness were measured at different frequencies of stimulation (170, 200, 230 and 260 beats.min-1). Melperone 0.5 and 2.5 mg.kg-1 decreased the atrioventricular nodal conduction time and refractoriness. Melperone (0.5 to 12.5 mg.kg-1) did not affect the intra-atrial or His-Purkinje conduction times or the QRS width. However, melperone increased the functional and effective refractory period of the right atrium and ventricle dose-dependently at all frequencies studied. This suggests that melperone may be a valuable drug in treating selected cardiac arrhythmias.

Animals↗
PubMed1981

Influence of beta-adrenergic and cholinergic blockade on the electrophysiological effects of melperone in the dog heart in situ.

Melperone (0.5 to 12.5 mg.kg-1) reduced mean aortic blood pressure in pentobarbital anaesthetised dogs to a greater extent after beta1-adrenergic receptor blockade with atenolol than after cholinergic blockade with atropine. Electrophysiological studies demonstrated that increased heart rate and decreased atrioventricular nodal refractoriness after lower doses of melperone (0.5 to 2.5 mg.kg-1), could be prevented by pretreatment with atenolol. The melperone-induced decrease in atrioventricular nodal conduction time was, however, not affected by pretreatment with atenolol or atropine. Intra-atrial and His-Purkinje conduction times and QRS width were not affected by atenolol or atropine plus melperone. Melperone caused a dose-dependent and very pronounced increase in ventricular and, even more, atrial refractoriness after atenolol. The ventricular and atrial refractoriness increased less after pretreatment with atropine. Some of the cardiac electrophysiological effects of melperone thus depend on the degree of beta-adrenergic stimulation. The overall cardiac electrophysiological effects of melperone results from a combination of direct and indirect actions of the drug.

Animals↗
PubMed1981

Classification of cardioactive drugs in vivo by using programmed electrical stimulation in combination with monophasic action potential recordings at different pacing rates.

The effect of antiarrhythmic drugs on myocardial refractoriness may be due to changes either in Vmax of phase 0 or the phase of repolarization of the AP or both. By using programmed electrical stimulation in combination with MAP recordings at different pacing rates in the intact dog heart, it was possible to classify and to a certain extent to elucidate the mode of action of various cardioactive drugs in vivo.

Acebutolol↗