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Biomedical subjects

F Bender

Publications and source records attributed to F Bender.

At least 19 recordsLinked to original sources

Phenotyping of macrophages with monoclonal antibodies in endomyocardial biopsies as a new approach to diagnosis of myocarditis.

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.

Adult

[Diagnosis of intra- and pericardial tumor with transthoracic and transesophageal 2D echocardiography].

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.

Adolescent

[Combination therapy with slow release isosorbide nitrate and diltiazem in silent myocardial ischemia].

In 11 patients (2 female, 9 male) suffering from angiographically proven CHD (age 45-60 years; 54.3 years on an average) the efficacy of a once-daily oral medication with 120 mg ISDN/50 mg ISMN and diltiazem (D) each in a long-acting preparation was examined in a placebo-controlled study. Each period lasted for 3 days; 2 capsules were given at 0700 a.m. one capsule at 5 p.m. Long-term ECG-recordings for 24 hrs (Tracker recorder, Pathfinder III) were performed twice under placebo and once during the third day of ISDN or ISMN, ISDN/ISMN + D in the morning and JSDN or ISMN in the morning and D in the afternoon. The rate of ischemic events declined from 10.4 to 4.7, 3.3 and 2.2; the duration of ischemia in 24 hours declined from 128 min to 43 min, 44 min and 34 min. The product of ST-depression (mV) and time of duration (min) showed an equivalent course. A more than 80% reduction of ischemia (duration and frequency) was achieved by a combination therapy in 72% of the patients. Minimal increase of heart rate at the beginning of ST-depression increased significantly during all periods of therapy, maximal increase of heart rate at that time showed a decrease only during combination therapy with D, the mean value did not change significantly. The once-daily application of ISDN/ISMN (50 mg) in a long-acting preparation (120 mg) led to a significant reduction of silent myocardial ischemia. The efficacy of ISDN/ISMN can be improved by D (120 mg, long acting preparation) up to a greater than 80% reduction in frequency and duration of ischemic events.

Adult

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

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

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

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

[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

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

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

[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

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

[Diagnosis of thoracic aortic aneurysms by combined transthoracic and transesophageal 2D echocardiography].

Transthoracic (tth) and transesophageal (TEE) 2D-echocardiography (E) were performed in 20 consecutively examined patients (17 males, 3 females, age 18 to 76 years, mean age 48.6 +/- 18.9 years) with dissecting (n = 11) and nondissecting thoracic aortic aneurysms confirmed by angiography or surgery. In 7 out of 9 cases, nondissecting aneurysms were detected by 2-DE, whereas in 2 patients diagnosis was established only by TEE. Three out of 6 type I dissections and 1 type II dissection could be diagnosed by tth 2-DE. But in 3 type I dissections and in all cases with type III aneurysms (n = 4) the intimal flaps and the DeBakey type of classification were identified only by TEE. In 1 patient with an extensive aneurysm of the ascending aorta and severe aortic insufficiency, a dissection was erroneously diagnosed by TEE, but not confirmed by surgery. In 1 case with type I dissection, spontaneous echo contrast within the false lumen was revealed by TEE. Complications due to TEE were not observed. Thus, in the diagnosis of thoracic aortic aneurysms and dissections the combination of tth 2-DE and TEE is superior to only tth 2-DE.

Adolescent

[Electrophysiologic and hemodynamic effects of the new bradycardia-inducing substance AQ-A 39].

AQ-A 39 is a new agent with specific bradycardic action on the sinus node. In this study the electrophysiologic and hemodynamic effects of this compound were investigated in 24 patients with various cardiac diseases. The results show: AQ-A 39 causes a significant decrease in enhanced sinus rate. The bradycardic action is more profound at higher sinus rates. In sinus rhythm of normal frequency or, in sinus bradycardia, sinus rate remains unchanged or increases even in the case of sick sinus node syndrome. Conductivity of the AV-node is significantly improved. QT- and QTc-interval increase dose dependently. Other cardiac conduction times and refractory intervals are not significantly changed. In exercise-induced myocardial ischemia increased left ventricular filling pressures are diminished. The extent of this decrease parallels the reduction in heart rate. AQ-A 39 appears to be suitable to reduce inadaequate increases in sinus rate, and seems to be of particular interest in surgical cases or intensive care emergencies as well as in acute ischemic heart disease.

Electrocardiography

[Diagnosis of extensive dissections of the thoracic aorta by 2-D echography].

Dissecting aortic aneurysms require immediate diagnosis and accurate knowledge of extension. In two patients with dissecting aortic aneurysms the extension of the dissection could be evaluated by the noninvasive method of 2-D-echography. All aortic regions could be visualized in both cases, The diagnosis of dissection was established by visualization of intimal flaps in short and long exis views.

Adult