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Biomedical subjects

J G Papp

Publications and source records attributed to J G Papp.

At least 19 recordsLinked to original sources
PubMed1995

Electrophysiological effects of tiracizin and its metabolites in dog cardiac Purkinje fibers.

1. Conventional microelectrode technique was used to study the effects of tiracizin and its two main metabolites on the action potential parameters in dog cardiac Purkinje fibers. 2. Tiracizin induced a use-dependent depression of the maximal rate of depolarization during the upstroke of the action potential (EC50 = 0.323 +/- 0.059 microM, n = 5) and decreased the action potential duration (EC50 = 0.230 +/- 0.024 microM, n = 5). 3. The two main metabolites exerted similar effects, but only at concentrations about one order of magnitude higher than tiracizin. 4. It was concluded that the electrophysiological effects of tiracizin in dog Purkinje fibers correspond to those of Class I antiarrhythmic drugs also in cardiac Purkinje fibers. The main metabolites are less potent than the parent compound, therefore it is likely that their effects play a less important role in the beneficial effect of tiracizin in cardiac arrhythmias.

Action Potentials↗
PubMed1995

Pronounced antiarrhythmic effects of preconditioning in anaesthetized dogs: is adenosine involved?

Although there is good evidence that adenosine contributes to the ability of ischaemic preconditioning to reduce myocardial ischaemic damage (infarct size) there is no evidence that it contributes to the marked antiarrhythmic effects of this endogenous protective mechanism. We have examined this in anaesthetized open-chest mongrel dogs by administering the non-selective adenosine receptor blocking drug 8-sulfophenyltheophylline (8-SPT) (1 mg/kg) given by intracoronary administration 10 min before both 5 min preconditioning coronary artery occlusions and also before the prolonged 25 min LAD occlusion i.e. in a total dose of 3 mg/kg. The only haemodynamic effect of 8-SPT was a reduction in coronary (LAD) blood flow and an increase in cardiovascular resistance. It was difficult to precondition dogs in the presence of 8-SPT; the number of ventricular premature beats was significantly higher (61 +/- 6 v 8 +/- 4; P < 0.01) during the initial preconditioning occlusion and the incidence of ventricular fibrillation during the preconditioning procedure was higher in the presence of the drug (5/11 v 4/20; P < 0.05). Nevertheless, it was still possible to precondition these dogs in the presence of the drug. No VF occurred during the prolonged occlusion (cf. 50% in the controls) and the number of episodes of ventricular tachycardia, and the number of ventricular premature beats in dogs preconditioned in the presence of 8-SPT was similar to those in dogs preconditioned without 8-SPT and significantly (P < 0.01 or P < 0.05) less than in control, non-preconditioned dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1995

Cardiovascular effects of the calcium sensitizer, levosimendan, in heart failure induced by rapid pacing in the presence of aortic constriction.

1. The haemodynamic effects of a novel cardiotonic drug, levosimendan, which has both calcium-sensitizing and phosphodiesterase III (PDE III) inhibitory properties, were studied in conscious dogs in which heart failure had been induced by prolonged cardiac pacing in the presence of aortic constriction. These effects were compared with those in sham-operated dogs with essentially normal cardiac function. 2. Eighteen mongrel dogs were instrumented for the measurement of left ventricular pressure (LVSP, LVEDP) and contractile function (dP/dt; dP/dt/P). In twelve dogs a balloon catheter, positioned in the thoracic aorta, was inflated producing an approximate 60% reduction in effective aortic diameter. Twenty min later rapid ventricular pacing (240 beats mean-1) was commenced and maintained for 48 h by means of a bipolar pacing electrode introduced into the right ventricle. This electrode served also for recording changes in the endocardial electrogram in the absence of pacing. Six of these dogs were used to evaluate the haemodynamic changes of pacing-induced heart failure; a further six of these dogs the haemodynamic changes elicited by levosimendan under these conditions. Six sham-operated dogs (group 2) served as controls. 3. In six dogs (group 1) the haemodynamic alterations were assessed after the development of heart failure. In the presence of aortic constriction, 48 h continuous rapid cardiac pacing resulted in a marked deterioration in left ventricular function which remained stable for at least 48 h after cessation of pacing. Thus, there was a marked reduction in LVSP (15%), +dP/dtmax (35%), -dP/dtmax (36%) and also in dP/dt/P (29%), whereas LVEDP was increased considerably (from 6.4 +/- 1.4 to 20.0 +/- 2.2 mmHg). A marked elevation occurred in endocardial ST-segment (138%), lasting for 20 min.4. Levosimendan was administered intravenously in doses of 0.005, 0.01 and 0.03 micromol kg-1 to 2 groups of conscious dogs. In the sham-operated dogs (group 2), only the higher dose (0.03 micromol kg-1)produced significant increases in LVSP (19%), + dP/dtmax (37%), and in dP/dt/P (32%). In dogs with heart failure (group 3) doses of 0.005, 0.01 and 0.03 micromol kg-1 levosimendan resulted in an improve mentin +dP/dtmax (26%, 38% and 49%), -dP/dtmax (20%, 25% and 38%) and in dP/dt/P (19%, 34%and 50%) and reduction in the elevated LVEDP (from 20 =/- 2.2 mmHg to 16 +/- 1.0, 10 +/- 1.3 and 9 +/- 1.0 mmHg, respectively).5. Levosimendan proved to be a potent cardiotonic drug at the doses used, and was approximately three times more effective under conditions of impaired left ventricular function than in normal hearts.

Analysis of Variance↗
PubMed1995

Effects of Levosimendan, a cardiotonic agent targeted to troponin C, on cardiac function and on phosphorylation and Ca2+ sensitivity of cardiac myofibrils and sarcoplasmic reticulum in guinea pig heart.

A new cardiotonic agent, (R)-[[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)-phenyl] hydrazono]propanedinitrile (Levosimendan), has been developed and screened for its ability to bind to cardiac troponin C. In perfused hearts, low concentrations of 0.03 or 0.1 mumol/L Levosimendan increased +dP/dt, but did not affect the speed of relaxation and produced only a slight increase in spontaneous heart rate in the hearts perfused with 0.1 mumol/L of the drug. In these same hearts, perfusion with 0.03 mumol/L Levosimendan did not alter the 32P incorporation into troponin I or C protein, whereas a slight but significant increase was noted for phospholamban, with no detectable change in tissue cAMP levels. Administration of 0.1 or 0.3 mumol/L Levosimendan significantly increased myocardial cAMP levels as well as the phosphorylation of phospholamban, troponin I, and C protein. Levosimendan (0.03 to 10 mumol/L) reversibly increased force generated by detergent-extracted fiber bundles over a range of submaximally activating free Ca2+ concentrations with no significant effect on maximum force or on Ca2+ binding to myofilament troponin C. There was no direct effect of Levosimendan on Ca2+ uptake by vesicles of sarcoplasmic reticulum (SR). In contrast, under conditions optimal for cAMP-dependent phosphorylation, Levosimendan slightly but significantly lowered the concentration of Ca2+, yielding half-maximal uptake rates by the SR vesicles. Our results indicate that at low concentrations Levosimendan acts preferably as a Ca2+ sensitizer, whereas at higher concentrations its action as a phosphodiesterase inhibitor contributes to the positive inotropic effect.

Analysis of Variance↗
PubMed1995

Left ventricular dysfunction induced by occlusion of coronary arteries in conscious dogs.

The aim of the present study was to investigate stable left ventricular dysfunction resulting from severe myocardial ischemia in conscious dogs, in order to evaluate the action of cardiotonic agents under pathological conditions mimicking moderate cardiac failure. Mongrel dogs with a catheter implanted in the left ventricle were trained on a treadmill and subjected to a standardized exercise before and after a Harris-type ligation of the anterior descending branch of the left coronary artery in two stages. Two weeks later the lower third of the left circumflex coronary branch was also occluded, and the exercise test repeated for at least two additional weeks to evaluate the changes in the left ventricular function indicated by left ventricular systolic pressure, end-diastolic pressure, heart rate, positive and negative dP/dtmax and dP/dt/P. Noninvasive radionuclide investigations of the left ventricular function and myocardial perfusion were done before and after the development of cardiac failure. Following occlusion of the anterior descending and circumflex coronary arteries, the baseline end-diastolic pressure increased from 7.6 +/- 2.3 mmHg to 23.3 +/- 3.0 mmHg (p < 0.05) and increased even further during exercise (to 49.2 +/- 3.5 mmHg, p < 0.05). After the development of cardiac failure, no substantial change occurred in the end-diastolic pressure, either during rest or repeated exercise tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Electrophysiologic effects of detajmium on isolated dog cardiac ventricular and Purkinje fibers.

We studied the electrophysiologic effects of the antiarrhythmic compound detajmium (Tachmalcor) on isolated dog and rabbit cardiac preparations, applying the conventional intracellular microelectrode techniques. In dog ventricular muscle fibers (37 degrees C, stimulation frequency 1 Hz), 1 microM detajmium did not change resting potential (RP), action potential amplitude (APA), AP duration measured at 90% of repolarization (APD90), or effective refractory period (ERP) significantly, but reduced maximum rate of depolarization (Vmax) significantly from 236.7 +/- 28.9 to 177.3 +/- 22.5 V/s (n = 6, p < 0.01). In dog Purkinje fibers (37 degrees C, stimulation frequency 1 Hz), 1 microM detajmium significantly decreased APA from 111.1 +/- 12.3 to 100.0 +/- 2.5 mV (n = 8, p < 0.003), APD90 from 359.0 +/- 17.5 to 262.1 +/- 12.3 ms (n = 8, p < 0.001) and Vmax from 687.5 +/- 57.2 to 523.7 +/- 58.2 V/s (n = 8, p < 0.001) without changing maximal diastolic potential or ERP/APD ratio significantly. The effect of detajmium on Vmax in both dog ventricular muscle and Purkinje fibers was frequency dependent. Fractional Vmax block was 0.185 +/- 0.008 1/AP. The recovery kinetics of Vmax (offset kinetics) was extremely slow (time constant = 348.16 +/- 57.43 s) considerably slower than most of those of other antiarrhythmic drugs yet reported. Detajmium in concentration < 32 microM did not influence the beta-adrenoceptors or slow response APs in dog ventricular tissue significantly. On the basis of its electrophysiologic effects, detajmium, like prajmaline, encainide, or flecainide, can be best classified as a class I/C antiarrhythmic drug according to the Vaughan Williams' classification scheme.

Action Potentials↗
PubMed1994

Effect of moxonidine on arrhythmias induced by coronary artery occlusion and reperfusion.

The aim of the present study was to investigate the influence of moxonidine, a representative of I1-imidazoline-receptor agonist, on arrhythmias induced by myocardial ischemia or reperfusion. Acute myocardial infarction was produced by tightening a previously placed loose silk loop around the coronary artery in conscious rats. Moxonidine (0.01, 0.03, or 0.10 mg/kg i.v., 10 min before coronary ligation) significantly decreased the incidence of ventricular tachycardia during the first 15 min of infarction (70 versus 100% in controls), and the number of animals that survived without developing any arrhythmia was increased (15, 20, and 25%, respectively, versus 0%). Reperfusion-induced arrhythmias were produced by releasing a snare after 6 min of myocardial ischemia in anesthetized, artificially ventilated rats. Reperfusion rapidly induced severe dysrhythmias in all of the control animals. Moxonidine pretreatment (0.03 and 0.10 mg/kg) decreased the incidence of ventricular fibrillation (25 and 30% versus 64%) and increased the number of animals that survived without developing any arrhythmia (20 and 25% versus 0%). We conclude that moxonidine offers significant protection against the development of arrhythmias induced by acute regional myocardial ischemia in conscious rats. Moxonidine pretreatment also provides a beneficial effect during reperfusion-induced arrhythmias that appear after a brief period of myocardial ischemia.

Analysis of Variance↗
PubMed1994

Prevention by dexamethasone of the marked antiarrhythmic effects of preconditioning induced 20 h after rapid cardiac pacing.

Dogs were paced, via a pacing electrode in the right ventricle, for four 5 min periods at a rate of 220 beats min-1. On the following day they were reanaesthetized, thoracotomized and the left anterior descending coronary artery occluded for 25 min. Pacing markedly reduced the severity of ischaemia-induced arrhythmias (e.g. reduction in VF from 45% in unpaced dogs to 10% in paced dogs; P < 0.05), an effect reversed by dexamethasone (4 mg kg-1 i.v., 45 min prior to pacing). This protection may be due to the induction of nitric oxide synthase or cyclo-oxygenase.

Animals↗
PubMed1994

Attenuation of the antiarrhythmic effects of ischaemic preconditioning by blockade of bradykinin B2 receptors.

1. The possibility that bradykinin is involved in the pronounced antiarrhythmic effects of ischaemic preconditioning in anaesthetized mongrel dogs was examined with the use of the selective B2 antagonist, icatibant (Hoe-140). 2. Preconditioning, achieved by two 5 min occlusions of the left anterior descending coronary artery, followed 20 min later by a 25 min occlusion of the same artery resulted, during this prolonged occlusion, in less severe arrhythmias (VF 0% versus 47% in control non-preconditioned dogs), reductions in the incidence and number of episodes of ventricular tachycardia (VT) and in the number of ventricular premature beats and increased survival following reperfusion (50% versus 0% in the controls). 3. Hoe-140 was given in a dose of 300 micrograms kg-1 either before the preconditioning procedure or after preconditioning but before the prolonged occlusion. This dose of Hoe-140 had insignificant haemodynamic effects and failed to modify the increase in coronary blood flow that occurred in the circumflex coronary artery when the anterior descending branch was occluded. 4. It was difficult to precondition dogs in the presence of Hoe-140. There were more ventricular arrhythmias during the initial 5 min occlusion (44 +/- 12 versus 10 +/- 3) and a higher incidence of ventricular fibrillation (50% versus 21%) during the preconditioning procedure. There was also a more pronounced ST-elevation (recorded from epicardial electrodes) during the preconditioning occlusions in those dogs given Hoe-140. 5. In those dogs that survived to the long (25 min) occlusion, Hoe-140 prevented the antiarrhythmic effects of preconditioning (reduction in ventricular premature beats and in VT) although all the dogs survived the occlusion period. However on reperfusion, survival in the preconditioned dogs given Hoe-140 was less than in those dogs preconditioned without the B2 antagonist.6. Changes in the degree of inhomogeneity of conduction within the ischaemic area, which were markedly suppressed by preconditioning, were attenuated in those dogs preconditioned in the presence of Hoe-140.7. These results suggest that bradykinin acts as both a 'trigger' for preconditioning and as one of the mediator protective (antiarrhythmic) substances generated by the myocardium under these conditions.Since the protection afforded both by preconditioning and by local intracoronary infusions of bradykinin is markedly attenuated by an inhibitor of the L-arginine nitric oxide pathway, we suggest that much of the protection afforded by ischaemic preconditioning results from the generation of nitricoxide, and that bradykinin, released early during ischaemia, acts as a stimulant for this generation.

Animals↗
PubMed1993

Moderate stress by cardiac pacing may induce both short term and long term cardioprotection.

OBJECTIVE: The aim was to investigate whether moderate ischaemic stress induced by brief periods of cardiac pacing to twice the normal heart rate protects the heart from the electrophysiological and haemodynamic consequences of subsequent periods of rapid pacing. METHODS: Conscious rabbits with implanted right ventricular electrodes and a permanent catheter in the left ventricular cavity were studied. Hearts were paced at a rate of 500.min-1 for 5 min. The resulting transient ST segment elevation in intracavital electrogram, the ventricular effective refractory period, and the left ventricular end diastolic pressure were measured. RESULTS: After discontinuation of pacing, a shortlasting ST segment elevation appeared in the endocardial electrogram, together with a transient rise in left ventricular end diastolic pressure. These changes were significantly reduced after a second pacing, provided that this was applied not later than 30 min after the first pacing; maximum protection occurred when there was a 5 min interval between these pacing periods. Serial stimulation (10 pacing periods with a 5 min interval between each) gave a similar protection to that resulting from a single pacing period. The protection was lost after 1 h; however, 24 h and 48 h (but not 72 h) after the end of serial stimulation there was again a reduction in postpacing ST segment and left ventricular end diastolic pressure elevation. At these times the ventricular effective refractory period was prolonged. The cyclo-oxygenase inhibitor sodium meclofenamate (1-2 mg.kg-1) prevented the early protection. CONCLUSIONS: The results suggest that brief periods of rapid pacing induce both short term and long term cardioprotection, as shown by reduced electrophysiological and haemodynamic consequences of subsequent pacing periods. Endogenous prostanoids might play a role in the short term cardioprotection.

Animals↗
PubMed1993

Are ATP sensitive potassium channels involved in the pronounced antiarrhythmic effects of preconditioning?

OBJECTIVE: The aim was to determine whether the antiarrhythmic effects of preconditioning are modified by blockade of K+ATP channels with glibenclamide in a model (anaesthetised dogs) in which this procedure has previously been shown to prevent the effects of preconditioning in reducing myocardial infarct size. METHODS: 10 mongrel dogs were preconditioned by two 5 min occlusions of the left anterior descending coronary artery, separated by a 20 min reperfusion period, and then subjected, 20 min later, to a prolonged (25 min) occlusion and to subsequent reperfusion. In another 10 dogs glibenclamide (300 micrograms.kg-1) was given by intravenous injection both after the first preconditioning stimulus and before the prolonged occlusion. Control dogs (25) were subjected to a 25 min occlusion followed by reperfusion; five of these dogs also received glibenclamide. RESULTS: Preconditioning reduced the severity of ventricular arrhythmias, epicardial ST segment elevation, and the degree of inhomogeneity of conduction. The antiarrhythmic effect of preconditioning was attenuated by glibenclamide (twice as many ventricular premature beats and more episodes of ventricular tachycardia) but there was no modification of preconditioning induced reduction in ventricular fibrillation either during ischaemia or during reperfusion, or on survival (0% in controls; 50% in preconditioned dogs with or without glibenclamide). Glibenclamide did, however, prevent the effects of preconditioning on the inhomogeneity of conduction and, less markedly, on epicardial ST segment elevation. CONCLUSIONS: In a similar model to that in which it has previously been shown that glibenclamide prevents the effect of preconditioning in reducing myocardial infarct size (suggesting involvement of K+ATP channels), the most pronounced antiarrhythmic effects of preconditioning (reduction in ventricular fibrillation; increase in survival) were not modified by glibenclamide. This, and other evidence, suggests that the mechanisms of the protective effect of preconditioning in reducing the severity of arrhythmias and on infarct size are not the same.

Adenosine Triphosphate↗
PubMed1993

Caffeine-induced decreases in the inward rectifier potassium and the inward calcium currents in rat ventricular myocytes.

The effects of high (20 mM) concentrations of caffeine were studied on the transmembrane voltage and currents in rat single ventricular myocytes by the whole cell configuration of the patch clamp technique. Rapid application of caffeine released Ca2+ from the sarcoplasmic reticulum and induced a Ni(2+)-sensitive transient inward current with concomitant change of the transmembrane voltage from -72.6 +/- 0.4 to -68.0 +/- 0.6 mV (n = 4). Maintained application of caffeine lengthened the action potential duration (APD90) from 66.7 +/- 16.9 to 135.1 +/- 34.1 ms (n = 4) and depressed the amplitude of both the inward rectifier potassium and the inward calcium currents. It is concluded that these effects of caffeine should be recognized when it is used as a tool to study electromechanical coupling.

Action Potentials↗
PubMed1993

Prevention by an inhibitor of the L-arginine-nitric oxide pathway of the antiarrhythmic effects of bradykinin in anaesthetized dogs.

The intracoronary administration of bradykinin (25 ng kg-1 min-1) markedly reduces the severity of arrhythmias that occur during a 25 min occlusion of the left anterior descending coronary artery in chloralose, urethane anaesthetized dogs. This protection was abolished by the prior administration, by the same route, of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of the L-arginine-nitric oxide pathway. The protective effect of bradykinin on reperfusion-induced VF was not affected by L-NAME. These results strongly suggest that the antiarrhythmic effect of bradykinin in this model is mediated by nitric oxide release. It also supports the concept that bradykinin might be a 'primary mediator' of the protective, antiarrhythmic effects of ischemic preconditioning.

Anesthesia↗
PubMed1992

The local intracoronary administration of methylene blue prevents the pronounced antiarrhythmic effect of ischaemic preconditioning.

Short periods of coronary artery occlusion (2 x 5 min) markedly reduce the severity of arrhythmias and the changes in ST-segment elevation and in the degree of inhomogeneity of conduction during a subsequent 25 min occlusion of the left anterior descending coronary artery in anaesthetized dogs. These changes were completely reversed if methylene blue (5 mg min-1) was infused into a side branch of the coronary artery throughout both the preconditioning and prolonged occlusions. These results suggest that the pronounced antiarrhythmic effects of preconditioning result from activation of guanylyl cyclase and result in increased levels of guanosine 3':5'-cyclic monophosphate.

Animals↗
PubMed1992

Electrophysiological changes induced by lysophosphatidylcholine, an ischaemic phospholipid catabolite, in rabbit atrial and ventricular cardiac cells.

The effects of palmitoyl-lysophosphatidylcholine (LPC) were studied on the cellular electrical activity of rabbit heart preparations. LPC (100 mumol/l) caused a considerable enhancement of the automaticity of the SA nodal and Purkinje fibers and frequently induced irregular firing in both supraventricular (SA node, atrium, AV junction) and ventricular (Purkinje fibers, papillary muscle) myocardial regions. The 'automatotropic' and arrhythmogenic effects of LPC were accompanied by a lengthening of the atrioventricular conduction time. In ventricular muscle fibers LPC (100 mumol/l) decreased the resting potential (RP), the maximum rate of depolarization (Vmax) and the amplitude (APA) and duration (APD) of the action potential, and often evoked action potentials of 'slow response' type. In atrial muscle cells, 100 mumol/l LPC was capable of inducing hyperpolarization, with concomitant increases in RP, Vmax, APA and APD; higher concentrations (300 and 600 mumol/l) of LPC resulted in decreases in RP, Vmax, APA and APD, i.e. phenomena similar to those observed with 100 mumol/l LPC in the ventricular myocardium. The results seem to support the assumption that lysolipids accumulating in the ischaemic myocardium may play a pathogenetic role in the development of both supraventricular and ventricular dysrhythmias accompanying coronary artery occlusion.

Animals↗
PubMed1992

The impact of single cell voltage clamp on the understanding of the cardiac ventricular action potential.

In this article we review results obtained during the last decade by the single cell voltage clamp technique on cardiac ventricular myocytes, and we re-evaluate the major ionic currents underlying the cardiac action potential. Since its introduction into cardiac electrophysiology in the late seventies this technique has greatly contributed to our knowledge about the role of the transmembrane ionic currents in the heart. Recent findings gained with this method have confirmed that the inward sodium current is responsible not only for the fast depolarization, but, in part, also for the maintenance of the plateau phase of the action potential. The kinetics of the inward calcium current measured by the single cell voltage clamp technique proved to be much faster than was previously thought. In addition, two types of the inward calcium current with different physiological roles have recently been identified. The L-type calcium current plays an important part in maintaining the plateau phase of the action potential and may cause depolarization at less negative potentials. Although the physiological significance of the T-type calcium current is less clear, it appears to be involved in the pacemaker function of cardiac tissues. Single cell voltage clamp experiments have shown that the inward rectifier potassium current is not independent of time, as described earlier, but it helps to terminate the final phase of repolarization, and presumably controls the resting membrane potential. Recent studies with the single cell voltage clamp method have revealed that the delayed rectifier potassium current has, most probably, more than one component and is extensively modulated by neurotransmitters. Its main role is to initiate and terminate cardiac repolarization. This current is of particular importance in regulating rate-dependent repolarizations. The transient outward current, which rapidly activates and inactivates after depolarization, initiates early fast repolarization and may also take part in rate-dependent repolarization. The ionic carriers of this current are most likely potassium and chloride. The use of the single cell voltage clamp technique has led to the discovery of formerly unrecognized currents, like the ATP-dependent potassium current, the sodium activated potassium current and the chloride currents. The application of the new technique has made it possible to focus more attention on currents which were difficult to study previously, such as Na/K pump and Na/Ca exchanger currents.

Action Potentials↗
PubMed1991

Effects of simulated ischaemia on the electrical activity of ventricular myocardium in the presence of antiarrhythmic drugs.

The effects of a nutrient solution simulating the 'ischaemic milieu' (combined hyperkalaemia, hypoxia and acidosis) on the electrical activity of rabbit isolated ventricular myocardium were examined in the absence and presence of antiarrhythmic drugs. In such a simulated ischaemia the resting membrane potential, the rate of depolarization (Vmax) and the action potential duration (APD) were all diminished with a resultant decrease in conduction and a shortening of the effective refractory period (ERP). Sotalol, a Class 3 antiarrhythmic drug (5 x 10(-6)-10(-5) M/l) afforded a marked protection against the "ischaemic" abbreviation of the ERP and APD. To a much lesser extent, the same applied to propafenone, a predominantly Class 1C antidysrhythmic agent (1.65-3.3 x 10(-6) M/l). The 'ischaemia'-induced depression of Vmax was increased considerably by propafenone and diminished slightly by sotalol. The results are in keeping with the efficacy of propafenone and sotalol in ventricular arrhythmias of ischaemic origin and also with the proposal that the major mechanism by which propafenone inhibits postinfarction ventricular arrhythmias is a further depression of ischaemic myocardial cells resulting in conduction block of the reentrant wave front.

Action Potentials↗