Biomedical subjects

H Gülker

Publications and source records attributed to H Gülker.

At least 73 records · Page 4Linked to original sources

PubMed1988

[Pneumopyopericardium--a rare complication following surgical correction of an "upside-down stomach"].

The follow-up period after surgery of an upside-down stomach in a 53-year-old patient was complicated by a pneumopyopericardium due to Candida albicans and Enterococcus. Therapy was performed by pericardial drainage. Local instillations of Mezlocillin (100 mg/l) and Amphotericin B (1 mg/l, Candida-MIC = 0.1 mg/l), over a period of 10 days and followed by a systemic antimycosis with 5-Flucytosin (0.14 g/d/kg over 5 days) and Amphotericin B (0.3 mg/d/kg over 11 days) led to recovery. Six months after discharge from the hospital, echocardiography revealed only a thickened pericardium without hemodynamic disorders.

Candidiasis↗

PubMed1988

[Uni- and bipolar 2-chamber stimulation with a DDD system of programmable polarity].

In order to compare bi- (b) and unipolar (u) stimulation, sensing and electrical interference, twelve patients were followed over a period of ten months. The implanted device was the CPI Delta 925, programmable to the bi- and unipolar mode in the atrium (a) as well as in the ventricle (v). A CPI-4266 screw-in lead positioned in the atrium and a CPI-4260 hook lead placed in the ventricle were connected to the pacemaker. Intraoperatively determined were: (1) the threshold at pulse durations of 0.1 ms, of 0.5 ms and of 1.0 ms, (2) the P/QRS-amplitude, (3) the slew-rate and (4) the resistance in both the bi- and unipolar mode. Having programmed the atrial sensitivity to 0.25 mV or to 0.75 mV and the ventricular sensitivity to 0.5 mV or to 1.5 mV, we postoperatively examined and compared in the two modes of polarity the threshold (2.2 V and 5 V), the P/QRS-amplitude and finally the electrical interference triggered with the help of chest wall stimulation. All measurements were performed one day, four weeks and four months after implantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1988

Effect of amrinone in acute severe cardiac failure.

5-Amino-(3,4'-bipyridine)-6(1H)-one (amrinone, WIN-40680, Wincoram) is a potent positive inotropic agent with vasodilator properties. Its positive inotropic effects are unaffected by propranolol and by pre-treatment with reserpine. The effect of intravenous amrinone was studied in 15 patients with acute severe cardiac failure (NYHA class IV) who had failed to respond adequately to treatment with cardiac glycosides, diuretics, vasodilators and catecholamines. Catecholamine dosage was held constant during the period of the study. This is the first report of standardised combination therapy with catecholamines and amrinone. Initially, a mean cumulative dose of 1.6 +/- 0.3 mg/kg of amrinone was administered during the 1st h. This was followed by a long-term infusion of 5-15 micrograms/kg.min. Hemodynamic parameters were monitored by invasive techniques for a minimum of 48 h. At the time of maximal effect, the cardiac index increased from 1.54 +/- 0.35 to 2.8 +/- 0.61 l/min.m2 (p less than 0.001), and the pulmonary arterial capillary pressure decreased from 31 +/- 7.1 to 23 +/- 7.6 mmHg (p less than 0.01). Heart rate and systemic mean arterial blood pressure showed no significant changes during treatment. These results indicate that amrinone may be effective in patients with acute severe cardiac failure refractory to catecholamines.

Acute Disease↗

PubMed1987

Calcium antagonists and acute myocardial ischemia: comparative effects of gallopamil and nifedipine on ischemia-induced and reperfusion-induced ventricular arrhythmias, epicardial conduction times, and ventricular fibrillation thresholds.

The comparative effects of the calcium-antagonists gallopamil and nifedipine on ischemia-induced and reperfusion-induced ventricular arrhythmias, particularly ventricular fibrillation (VF), were assessed in a total of 40 mongrel dogs in two experimental preparations. In part I of the study, changes in the time course of spontaneous ventricular arrhythmias and VF parallel to changes in epicardial conduction following acute coronary artery occlusion lasting 20 minutes and followed by subsequent reperfusion were determined. In part II, repeated coronary artery occlusions (20 min) followed by reperfusion (60 min) were performed, and changes in ventricular fibrillation threshold (VFT) were assessed. Gallopamil proved to be highly effective in preventing ventricular arrhythmias and VF following coronary delay was reduced. The ischemia-induced fall in conduction delay was reduced. The ischemia-induced fall in VFT occurring during the first few minutes after occlusion (phase Ia) was significantly reduced. In contrast, nifedipine failed to influence the incidence of ventricular arrhythmias and VF. Following reperfusion, neither drug reduced the incidence of VF nor the associated fall in VFT at the onset of reperfusion. The time course of recovery of epicardial conduction was not affected by either drug. However, the increase in the VFT during the early postreperfusion period was significantly enhanced by both agents. The effects of gallopamil were more pronounced than those of nifedipine. Delayed reperfusion ventricular arrhythmias arising 5 to 10 minutes after release of coronary artery obstruction were significantly reduced by gallopamil whereas nifedipine proved ineffective. The results show that calcium antagonists display direct antiarrhythmic and cardioprotective actions in acute transient myocardial ischemia. The different effectiveness of gallopamil compared to nifedipine can be explained by differences in electrophysiological properties of the drugs. Enhanced ventricular vulnerability following acute transient coronary artery occlusion and subsequent release of coronary artery obstruction, first described by Tennant and Wiggers, has been extensively investigated over the past decade in a variety of experimental and clinical settings. However, the basic mechanisms underlying ischemia- and reperfusion-induced ventricular arrhythmias and ventricular fibrillation (VF) have not yet been fully elucidated. Furthermore, the results of pharmacological approaches to prevent ventricular arrhythmic activity are conflicting. The present study aimed to evaluate the antiarrhythmic efficacy of calcium antagonists in acute myocardial ischemia and reperfusion. We have examined the effects of gallopamil and nifedipine on the time course of ventricular arrhythmias during the first 20 minutes after acute coronary artery occlusion and subsequent reperfusion. We have studied the underlying mechanisms by mapping epicardial conduction and by assessing the electrically induced ventricular fibrillation threshold (VFT) both within and outside ischemic areas.

Animals↗

PubMed1987

Use of diprafenone, a new potent propafenone-analogue, in acute experimental myocardial ischaemia and infarction.

Diprafenone (D) is a new class I c antiarrhythmic agent, structurally similar to propafenone. We assessed its antiarrhythmic and anti-fibrillatory effects during acute coronary occlusion and reperfusion and the underlying mechanisms of action by epicardial mapping of the conduction delay; also the effects of D on stimulus-induced ventricular tachycardia 18-24 h after permanent coronary occlusion were assessed. Experiments were performed on 32 mongrel dogs with temporary coronary occlusion lasting 20 min and subsequent reperfusion. Control ligations in 16 animals were compared to ligations after pretreatment with D (2 mg kg-1) in 6 dogs. In another 10 dogs a permanent coronary occlusion was performed and the inducibility of ventricular tachycardia was assessed by programmed stimulation before and after D (2.4 mg kg-1). Following D the incidence of ventricular arrhythmias including rapid ventricular tachycardias was not reduced during acute coronary occlusion, but even enhanced in some animals, whereas the frequency of ventricular fibrillation was diminished. No significant difference was observed following reperfusion. Conduction delay in the ischaemic area increased significantly during both phase Ia and Ib following pretreatment with D. During reperfusion conduction delay was significantly prolonged in the D group. At 18-24 h after permanent coronary occlusion the new compound proved to be highly effective in suppressing stimulus-induced ventricular tachycardia. During acute coronary occlusion D diminished the incidence of ventricular fibrillation. D is similar to other class Ic compounds; however, there are some important differences with respect to its additional beta-sympatholytic activity.

Acute Disease↗

PubMed1987

Comparative investigations on the antiarrhythmic and electrophysiological effects of various calcium antagonists (diltiazem, verapamil, gallopamil, nifedipine) following acute transient coronary artery occlusion and reperfusion.

The effects of various calcium antagonists on ventricular arrhythmias, particularly fibrillation (VF), in relation to epicardial conduction delay during acute myocardial ischaemia and reperfusion were investigated in 40 open-chest anaesthetized dogs. Acute transient coronary artery occlusion lasting 20 min was performed in all animals. Sixteen dogs served as controls; diltiazem (D) (0.5 mg kg-1 iv), verapamil (V) (0.25 mg kg-1 iv), gallopamil (G) (0.13 mg kg-1 iv) and nifedipine (N) (0.04 mg kg-1 iv) were given in six animals each 5 min prior to coronary occlusion. Epicardial conduction delay was assessed by means of an epicardial mapping electrode array consisting of 42 bipolar electrodes. In the control group, conduction delay showed a bimodal time course in the ischaemic area with a maximum of 38 +/- 10 ms 6 min after coronary occlusion followed by partial improvement. After pretreatment with D, V or G the peak in conduction delay as well as the maximum dispersion of conduction times in the ischaemic area were significantly diminished, whereas N failed to improve conduction in the ischaemic area. Correspondingly, ventricular arrhythmias and VF were almost completely suppressed by D, V or G, but not affected by N. Following release of coronary artery occlusion none of the compounds proved to influence the rapid and heterogeneous improvement of conduction immediately after the onset of reperfusion. Correspondingly, none of the drugs diminished the incidence of VF immediately after release. Delayed ventricular reperfusion arrhythmias, arising parallel to complete restoration of conduction, were significantly reduced by D, V and G but not affected by N. Delayed and inhomogeneous activation of the ischaemic myocardium plays an important role in the genesis of ventricular arrhythmias in the early stage of acute myocardial ischaemia; thus a reduction in conduction delay and dispersion of conduction times seems to be a precondition for antiarrhythmic action. The different effects of calcium antagonists type V and type N on ischaemia-induced conduction delay and ventricular arrhythmias can be assumed to result from differences in the electropharmacological properties of the compounds.

Acute Disease↗

PubMed1987

Prophylaxis of exercise-induced ventricular arrhythmias by verapamil.

In this study prophylactic antiarrhythmic effects of verapamil on exercise-induced ventricular arrhythmias are evaluated. Investigations were carried out on a total of 22 patients. All patients showed frequent and/or complex ventricular arrhythmias during repeated exercise tests under control conditions. After two control exercise tests all patients were treated with verapamil 120 mg given every 8 hours orally over 4 days. On the 3rd and 4th day of treatment the exercise tests were repeated. Verapamil caused a significant reduction in the incidence and severity of exercise-induced ventricular arrhythmias in 13 out of 22 patients. In patients with exercise-induced ST-segment depression a prophylactic action could be demonstrated in 9 out of 10 cases. The antiarrhythmic effect was independent of changes in heart rate. A reduction in myocardial oxygen consumption and direct electrophysiological effects (suppression of the 'slow response' and/or an increase in the resting potential of the 'depressed fast response') can be considered, as well as a suppression of 'triggered activity' or a direct inhibition of adrenergic effects. Calcium antagonists (type verapamil) prove to be suitable drugs for the treatment of exercise-induced ventricular arrhythmias in patients with myocardial ischaemia.

Adult↗

PubMed1987

Comparative investigations on the antiarrhythmic and electrophysiologic effects of class I-IV antiarrhythmic agents following acute coronary artery occlusion.

The effects of class I to IV antiarrhythmic drugs on ventricular arrhythmias, particularly ventricular fibrillation, in relation to epicardial conduction delay during acute myocardial ischaemia were investigated in 40 open-chest anaesthetized dogs. In these animals transient coronary artery occlusion lasting 20 minutes was performed. Sixteen dogs served as controls; four groups of 6 dogs each received lidocaine (2 mg kg-1 + 50 micrograms kg-1 over 20 minutes), metoprolol (2 mg kg-1 i.v.), d-sotalol (5 mg kg-1 i.v.) and verapamil (0.25 mg kg-1 i.v.), respectively 5 minutes prior to coronary occlusion. Epicardial conduction delay was assessed by means of an epicardial mapping electrode array consisting of 42 bipolar electrodes. In the control group conduction delay displayed a bimodal time course in the ischaemic area with a maximum of 38 +/- 10 ms 6 minutes after coronary occlusion followed by a partial improvement after 12 to 15 minutes. After pretreatment with lidocaine the peak conduction delay in the ischaemic area was significantly increased (43.2 +/- 12), whereas metropolol (21.5 +/- 1.9), d-sotalol (16.6 +/- 3.7) and verapamil (16.3 +/- 3.1) significantly reduced conduction delay. Correspondingly, ventricular arrhythmias and fibrillation were almost completely prevented by metoprolol, d-sotalol or verapamil, but increased by lidocaine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

A summary of the acute effects of falipamil in man.

The verapamil analog falipamil is a new compound with specific bradycardic action on the sinus node. It differs from verapamil with respect to its electrophysiological and haemodynamic actions. Falipamil causes a slight prolongation of intraatrial and intraventricular conduction, whereas sinuatrial and AV-node conduction is enhanced. The refractory periods of atrial and ventricular myocardium and ventricular repolarization are significantly prolonged, whereas the refractory period of the AV-node is shortened. Falipamil fails to influence any haemodynamic parameter significantly at rest, if heart rate is kept constant. In exercise-induced myocardial ischaemia, changes in haemodynamics reflect changes in heart rate. Increased sinus rate at rest is significantly reduced by falipamil 15%-25%. Around 150 mg falipamil prove aequieffective to about 40 micrograms pindolol. Atropine-induced and catecholamine-induced sinus tachycardia is also significantly diminished. Increased sinus rate during exercise is lowered by about 10%. Through reduction of heart rate, falipamil proves capable of significantly diminishing or even preventing ischaemic ST-segment depression and ischaemia induced increase in pulmonary capillary pressure. Thus falipamil can be used to normalize sinus rate in patients with sinus tachycardia of various origin, particularly in intensive care, in acute ischaemic heart disease, in anaesthesia and in surgery cases.

Anti-Arrhythmia Agents↗

PubMed1987

Electrophysiologic effects of asocainol, a new antiarrhythmic agent with predominant class I action.

In experiments on 6 mongrel dogs the electrophysiologic effects of the new antiarrhythmic compound (+/-)-6,7,8,9-tetrahydro-2,12-dimethoxy-7-methyl-6-phenethyl-5H- dibenz[d,f]azonin-1-ol (asocainol) were examined in the non-ischemic heart. The PR interval increased significantly following doses of 5 mg/kg caused by a conduction delay in the His-Purkinje system. At high doses (10 mg/kg) the QRS duration was also prolonged. Atrial and ventricular effective refractory periods were only slightly increased. Asocainol significantly increased the atrial fibrillation threshold, whereas the ventricular fibrillation threshold was not altered. Hemodynamics were not changed except for a slight increase in heart rate after 10 mg/kg asocainol. Thus asocainol predominantly exhibited class Ia antiarrhythmic properties, whereas calcium antagonistic actions could not be established in this intact dog heart model.

Animals↗

PubMed1987

[Prevention of effort-induced ventricular arrhythmia using verapamil].

In this study prophylactic antiarrhythmic effects of verapamil on exercise-induced ventricular arrhythmias were evaluated in a total of 22 patients. All patients displayed frequent and/or complex ventricular arrhythmias during repeated exercise tests under control conditions. After two control exercise tests, all patients were treated with 120 mg verapamil given every 8 h orally for 4 days. On the 3rd and 4th day of treatment the exercise tests were repeated. The results were that verapamil caused a significant reduction in the incidence and severity of exercise-induced ventricular arrhythmias in 13 out of 22 patients. In patients with concomitant significant ST-segment depression, a prophylactic action could be demonstrated in nine out of ten cases. The antiarrhythmic effect was independent of changes in heart rate. In patients with myocardial ischaemia, a reduction in myocardial oxygen consumption and direct electrophysiological effects (suppression of the "slow response" and/or an increase in the resting potential of the "depressed fast response") can be discussed as mechanisms of action. Also, a suppression of "triggered activity" or a direct inhibition of adrenergic effects must be considered. According to our results and the literature, calcium antagonists (verapamil type) proved to be suitable drugs for the treatment of exercise-induced ventricular arrhythmias, particularly in patients with concomitant myocardial ischaemia.

Arrhythmias, Cardiac↗

PubMed1987

[Electrophysiologic and hemodynamic effects of the new anti-arrhythmia agent diprafenone].

Diprafenone is a new antiarrhythmic agent currently under clinical investigation, with close chemical similarity to propafenone. In this study, the electrophysiological and haemodynamic effects of the compound were investigated both in animals, by experiment, and in man. Diprafenone produces a dose-dependent prolongation of conduction in all parts of the conducting system. Lengthening of PQ-time is more pronounced than prolongation of QRS. The atrial and ventricular refractory periods are also significantly prolonged. There are no significant changes in the QT-time. Heart rate and aortic pressure are slightly decreased. The electrophysiological and haemodynamic profile of Diprafenone is similar to propafenone with respect to a dominant local anaesthetic activity and an additional beta-sympatholytic effect. However, with respect to the dose needed, the efficacy of the new drug appears to be significantly stronger. Diprafenone can be considered an effective antiarrhythmic drug for the treatment of supraventricular and ventricular tachyarrhythmias.

Animals↗

PubMed1987

[Treatment of chronic ventricular arrhythmias with the new class Ic anti-arrhythmia agent diprafenon--results of long-term therapy].

Diprafenone is a new antiarrhythmic drug with a dominant local anaesthetic action and an additional beta-sympathicolytic activity. In this study, the results of long-term treatment (8 months on average) obtained from 27 patients with chronic ventricular arrhythmias are reported. Before diprafenone, all patients were treated unsuccessfully with flecainide, propafenone, sotalol, combined sotalol/flecainide and sotalol/propafenone, and another two to six antiarrhythmic agents. Following diprafenone (300-600 mg/24 h), a substantial reduction in arrhythmic activity (greater than or equal to 80%; Lown classification less than or equal to II) was achieved in 21 cases. In 12 patients, side effects (fatigue, headache, blurred vision, dizziness and heartburn) were apparent. Diprafenone had to be discontinued in five patients, because of these side effects. At dosages greater than or equal to 450 mg/24 h, the PQ interval was significantly lengthened, and QRS duration prolonged. In one patient, an AV block III degree developed. In another case, SGOT and SGPT increased significantly; this increase was reversed after the drug was discontinued. Despite these side effects, further clinical evaluation of the compound seems promising, as the antiarrhythmic potency of diprafenone is very strong and superior to that of propafenone with respect to the required doses.

Adult↗

PubMed1987

Assessment of the electrophysiologic, antiarrhythmic and haemodynamic profile of a new isoquinolinedione derivative.

The electrophysiological, antiarrhythmic and haemodynamic profile of a new isoquinolinedione derivative, 2,2'-[iminobis(trimethylene)]-di(4,4-dimethyl-1,3-(2H,4H)-isoqu inolinedione) hydrochloride (AR-03 Cl) was evaluated using dog models relevant to conditions in humans. In 16 animals dose-related effects on intercardiac conduction, ventricular refractoriness and on haemodynamic parameters were determined. In another 7 dogs antiarrhythmic actions of AR-03 Cl on delayed reperfusion arrhythmias following release of coronary artery occlusion after 2 h of obstruction were investigated. The results show: AR-03 Cl causes a significant prolongation in conduction through all parts of the conducting system. The AH-interval, HV-interval and QRS-duration are significantly lengthened. Ventricular repolarization is only slightly changed. There are no significant changes in heart rate, systolic and diastolic aortic pressure up to doses of 2 mg/kg b.w. However, left ventricular (dp/dtmax) and cardiac output are significantly reduced, and left ventricular enddiastolic pressure is increased. In acute myocardial necrosis delayed reperfusion arrhythmias are almost completely abolished, the effective dose is lower than that required with any other antiarrhythmic drug investigated so far in this particular experimental set-up. Further experimental and clinical testing of the new compound seems to be promising because of its strong dose-related antiarrhythmic potency. However, there is a need for further analysis of potential haemodynamic side effects of the new compound to establish the clinical significance of negative inotropic actions at therapeutic doses.

Animals↗

PubMed1986

Antiarrhythmic and antifibrillatory action of diltiazem on early and late phase ventricular arrhythmias following coronary artery occlusion and on reperfusion ventricular arrhythmias.

The effects of diltiazem on ventricular arrhythmias and ventricular vulnerability for fibrillation, both in the very beginning of myocardial ischemia and in the early stage of myocardial necrosis, were evaluated in 13 mongrel dogs. In part I of the study, repeated coronary occlusions were performed. Time course and extent of ventricular ectopy were continuously recorded, and changes in ventricular fibrillation threshold were assessed, both after coronary artery occlusion and release. In part II, a permanent coronary artery occlusion was performed, and the changes in frequency of ventricular arrhythmias were assessed. Diltiazem displayed strong antiarrhythmic and antifibrillatory effects on early ventricular occlusion arrhythmias. The drop in ventricular fibrillation threshold 5 min after coronary occlusion was significantly attenuated. Following the release of coronary artery obstruction, diltiazem failed to reduce the frequency of ventricular fibrillation immediately after the onset of reperfusion. However, during the early postreperfusion period, the drug was able to accelerate significantly the increase in the ventricular fibrillation threshold. Late phase ventricular arrhythmias were not influenced by the drug even when high doses were applied. The different antiarrhythmic actions of diltiazem on early and late phase ventricular arrhythmias can be assumed to be due to differences in the arrhythmogenesis at the very onset of myocardial ischemia compared to the stage of myocardial necrosis.

Animals↗

PubMed1986

[Dynamic 2-chamber overdrive stimulation with an implantable pacemaker system as a method for terminating slow ventricular tachycardias].

A case report is given on a new method for treatment of drug-resistant slow ventricular tachycardias by automatic dynamic overdrive stimulation, using an implantable pacemaker system. In a 60-year-old patient with coronary heart disease and ventricular tachycardia refractory to drug therapy, an antitachycardia Medtronic pacemaker (type SP 0501) was implanted in October 1984 and used successfully in 65 attacks during 13 months. However, when trying to terminate the tachycardia by means of programmed stimulation, acceleration of the ectopic ventricular rate occurred at 8 occasions. The administration of the experimental antiarrhythmic drug diprafenone (Class Ic) resulted in a reduction of the ventricular frequency but not of the rate of attacks. Then the Vitatron Quintech DDD pacemaker was implanted, providing the chance of terminating the now reduced ventricular rate by the dynamic overdrive mode.

Cardiac Complexes, Premature↗

PubMed1986

Effects of the new vagolytic compound ciclotropium bromide on heart rate and atrial vulnerability.

The effects of the new vagolytic compound alpha-phenylcyclopentane-acetic acid-N-isopropyl-nortropine ester methobromide (ciclotropium bromide) on heart rate and atrial vulnerability were assessed in the animal experiment. Therefore, the comparative effects of atropine (A) and ciclotropium bromide (C) on heart rate (HR) and electrical stimulation thresholds for repetitive atrial extrasystoles (RET) and fibrillation (AFT) were established in 14 mongrel dogs (BW 20-30 kg, artificial ventilation, piritramide-N2O anaesthesia). AFT and RET were determined using trains of rectangular current pulses (13 single pulses, 2 ms, 200 Hz) applied to the right atrial endocardium via bipolar platinum electrodes during the vulnerable period of atrial excitation, which was determined by scanning of the relative refractory period in steps of 10 ms. A (0.025 mg/kg) caused a small transient increase in the AFT; HR rose from 82 +/- 7 to 138 +/- 10/min. Control values were regained after 30 min. RET did not show any significant change. C (0.25 mg/kg) effected a significant increase in the AFT from 7.7 +/- 2 to 34 +/- 6 mA and in HR from 93 +/- 5 to 148 +/- 6/min. The effects lasted about 2 h. RET was not altered.

Animals↗

PubMed1986

[Ischemic disorders of cardiac rhythm: effects of the autonomic nervous system on electrophysiologic findings and pharmacotherapy].

The time course and frequency of ventricular arrhythmias in myocardial ischemia and myocardial necrosis are influenced by a great number of different factors. The most important are: size and localization of the ischemic area, mode of coronary artery occlusion (one stage occlusion, phasic, protracted or gradual occlusion), intermittent reperfusions, and influence of the autonomic nervous system. Autonomic factors influence both the mechanisms of arrhythmias and the results of pharmacological interventions. An increased sympathetic tone causes both in reversible myocardial ischemia and in partially irreversible myocardial necrosis a significant increase in incidence and severity of arrhythmias. The underlying mechanism of action is complex and includes enhanced automaticity, an increase in ischaemia-induced prolongation of conduction while the frequency of bidirectional conduction blockades is reduced, and an increase in dispersion of repolarization. Due to these various factors the preconditions for reentry are favourable. Vagal effects consist in an increase or decrease of frequency-related arrhythmias. Furthermore, indirect antifibrillatory effects are apparent due to an antagonism of sympathetic actions. The significance of autonomic factors for arrhythmogenesis following "early" reperfusion (i.e. arrhythmias occurring immediately after release of short-term coronary artery obstruction) has not yet been established. Reports in the literature suggesting antifibrillatory actions of sympathicolytics have not yet been confirmed. The results of antiarrhythmic pharmacotherapy are also influenced by autonomic factors, particularly increased sympathetic activity. At the very onset of acute myocardial ischemia, when sympathetic tone is markedly increased in most patients, class I antiarrhythmic agents, particularly those which cause a significant conduction delay display only weak antiarrhythmic effects or even no effectiveness at all. The frequency of ventricular fibrillation is not diminished. Various agents even produce significant arrhythmogenic effects. The electrophysiological mechanism of action is based on a further increase in ischemia-induced prolongation of conduction and in dispersion of conduction times. By contrast, beta-sympathicolytics, class III antiarrhythmic agents (d-Sotalol type) and calcium antagonists (Verapamil type) (the latter only at high doses) cause a decrease in ischemia-induced prolongation of conduction and in dispersion of conduction times thereby reducing the incidence of early ventricular fibrillation. In the stage of manifest necrosis the order of relative potency is reversed if the sympathetic tone is low.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Arrhythmia Agents↗