Cryostat sections of endomyocardial biopsies from 53 patients (mean age 41 +/- 5 years, 38 male and 15 female) clinically indicated to suffer from myocarditis were stained using monoclonal antibodies against subpopulations of T-lymphocytes and macrophages and with polyclonal rabbit-anti-human sera marking two calcium-binding proteins expressed by monocytes and macrophages appearing in inflammatory sites only. No inflammatory infiltrate cells were found in 13 cases (25%). Mononuclear cell infiltrates were present in 40 cases (75%). Ten biopsies showed a predominance of macrophages bearing the marker 27E10, characteristic for an early acute inflammation and 18 biopsies contained 25F9 positive macrophages, characteristic for a late stage of inflammation. An intermediate type of inflammation with both macrophage types present was found in 12 patients. Patients with immunohistologically confirmed myocarditis had atrial, ventricular or combined forms of arrhythmias (78%), scars in the vectorcardiogram (100%) and radiological evidence of cardiomegaly (36%). In conclusion, typing and endomyocardial biopsies for macrophage subpopulations is a sensitive new approach to assess the diagnosis of myocarditis.

To examine the value of the combined approach of transthoracic and transesophageal 2D-echocardiography in diagnosis of heart tumors this study was performed on 30 patients (11 males, 19 females, age 15 to 82 years) with atrial (n = 17) and pericardial (n = 13) tumors. Echocardiography was performed using an electronic sector scanner (Varian 3400 R) and a 2.25 MHz transducer for the transthoracic approach and a 3.5 MHz transducer at the tip of a 9 mm gastroscope for examination from the esophagus. In 9 of 11 patients with atrial myxoma diagnosis was established by transthoracic echocardiography, whereas in 2 cases with reduced image quality at the conventional approach the tumor was identified by the transesophageal technique. In one of 5 patients with atrial thrombi acoustic properties and mobility could be better judged by transesophageal echocardiography. In 7 of 13 cases with pericardial tumors diagnosis was established by transthoracic echocardiography, whereas in 6 cases diagnosis was achieved by the transesophageal approach only. Thus, transesophageal echocardiography is suggested a decisive additional tool in diagnosis of heart tumors.

Die klinische Anwendung von Kalziumantagonisten bei Patienten mit koronarer Herzkrankheit führt über Veränderungen des hämodynamischen Systems und des myokardialen Stoffwechsels in vielen Fällen zu einer Abnahme der Symptome (6, 7, 11). Gerade bei einer eingeschränkten linksventrikulären Funktion dieser Patienten ist die Bilanz der Wirkungen auf das Koronarsystem, die Pumpfunktion und den Sauerstoffverbrauch entscheidend. Eine Herzinsuffizienz bei koronarer Herzkrankheit gilt daher auch grundsätzlich als Kontraindikation. In der Klinik stellen diese Patienten mit stark eingeschränkter Ventrikelfunktion jedoch häufig eine Problemgruppe dar; einerseits ist eine weitere Verminderung der linksventrikulären Leistung durch eine negativ-inotrope Komponente bei Medikamenten nicht tolerabel, andererseits sind die Wirkungen der Kalziumantagonisten auf das Koronarsystem und zum Teil auch auf Chronotropie und Afterload therapeutisch erwünscht. Es wurde daher in der folgenden Untersuchung geprüft, zu welcher Bilanz die Anwendung von Gallopamil bei dieser Patientengruppe führt.

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.

Die Bedeutung ventrikulärer Reperfusionsarrhythmien als Ursache des plötzlichen Herztodes des Menschen ist bislang ungeklärt. Lediglich bei 30% der Patienten mit plötzlichem Herztod sind postmortal frische Myokardnekrosen bzw. akute Koronarthrombosen nachweisbar (12, 33). In den übrigen Fällen könnten Spasmen normaler oder stenosierter Koronararterien bzw. eine spontane Lyse von Koronarthromben an der Auslösung der lebenbedrohlichen Arrhythmien beteiligt sein. Im Tierexperiment führt eine abrupte Wiederfreigabe der Durchblutung passager okkludierter Koronargefäße in Abhängigkeit von der Verschlußdauer (4; Tabelle 1) sowie von der Gefäße des ischämiegefährdeten Myokardareals (1, 45) zu morphologisch, pathogenetisch und prognostisch differenten Formen ventrikulärer Rhythmusstörungen. Innerhalb der ersten 30 Minuten nach Koronarverschluß nimmt die Häufigkeit von initialem Kammerflimmern nach Reperfusion (Abb. 1) mit der Dauer der Ischämie signifikant zu (siehe Tabelle 1). Bei längeren Verschlußzeiten ist sie anschließend parallel zur Entwicklung irreversibler Zellschädigungen mit Abnahme der Erregbarkeit (12, 29) deutlich rückläufig.

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.

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.

Der akute einzeitige Verschluß eines koronaren Hauptstammes führt im Tierexperiment und ebenso häufig beim Menschen innerhalb der ersten 20–30 Minuten zu charakteristischen zeitlichen Änderungen der ventrikulären Vulnerabilität mit einer zweigipfligen Häufigkeitsverteilung der Arrhythmien, insbesondere von Kammerflimmern (33).

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.

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.