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Biomedical subjects

H Heuer

Publications and source records attributed to H Heuer.

At least 109 records · Page 6Linked to original sources

[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↗

[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↗

[Method for the direct comparison of the frequency behavior in QT- and activity-controlled pacemaker systems].

A non-invasive method of testing the suitability of an activity-controlled pacemaker system in patients with VVT-programmable systems is presented. The QT-time controlled TX-pacemaker of a 36-year-old patient was programmed into the VVT-mode. Then the activity-controlled pacemaker (Activitrax) was fixed epicutaneously above the pectoral muscles and two stimulation electrodes were applied above the implanted pacer and the tip of the implanted probe. Thus the external could be made to trigger the implanted system. The frequency profile was recorded with identical loads with QT and/or activity control. For both the frequency-adapted pacemaker systems, the direct comparison yields characteristic frequency profiles: a quick frequency increase and decrease of both Activitrax and load, but a delayed frequency profile of the QT-controlled pacer. Different frequency maxima are rendered by the two pacemakers as a function of the load.

Adult↗

[The usefulness of a model of acute hypoxia for the testing of cerebroprotective drugs].

The aim of this study was to find out whether the mouse in acute normobaric hypoxia (3.5% O2) may be appropriate as a screening model for testing cerebroprotective drugs. The survival time of the mice in hypoxia was used to determine drug effects. 39 agents with various pharmacological and toxicological properties were investigated. Cerebroprotective, centrally depressant and stimulating as well as cardiovascular drugs were included. Only 6 out of 16 cerebroprotective drugs used therapeutically prolonged the survival time of mice in acute hypoxia. However, a positive effect was demonstrable especially for those cerebroprotective drugs (extractum Ginkgo bilobae, meclofenoxate, naftidrofuryl, pentoxifylline and pyritinol), which are generally accepted to be active. On the other hand, 12 out of 23 drugs which are therapeutically used as cardiovascular drugs, central stimulants or depressants or have known toxicological effects also prolonged the survival time of mice in hypoxia. Thus, it became clear that the result of this hypoxia test may be influenced by various pharmacological actions. Especially drugs stimulating the cardiovascular system or depressing CNS activity could prolong the survival time of mice in hypoxia, whereas drugs with vasodilating effects could even shorten it. Opposite effects could superpose or neutralize each other. Therefore, the mouse in acute hypoxia seems to be of limited value as a screening model for testing cerebroprotective drugs.

Animals↗

[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↗

Intermanual interactions during simultaneous execution and programming of finger movements.

In bimanual movements, some differences between the movements performed by the two hands cause interference, while others do not. Similarly, in choice between responses with the left and right hand some differences between the two movements increase RT, while others do not. It is suggested that both kinds of effects are, at least in part, due to the incompatibility between processes that determine characteristics of movements jointly for both hands and that are present during preparation as well as during execution. This hypothesis implies that during execution of one movement, programming of a different movement to be performed with the other hand should be impaired, as compared to a condition in which the successive movements of both hands are the same. this expectation was confirmed for finger movements of different forms where an effect on choice RT had been shown previously. On the other hand, interference between execution and programming is not to be expected when successive movements differ in characteristics that are likely to be specified separately for each hand, as indicated by a lacking effect in choice experiments. This expectation was confirmed for successive movements performed with different fingers of either hand as compared to movements performed with the same fingers.

Journal Article↗

Assessment of the antiarrhythmic profile of the new class I agent diprafenone.

The antiarrhythmic profile of the new compound diprafenone was evaluated using various dog models relevant to conditions in humans. In 8 animals, dose related effects on intracardiac conduction, atrial and ventricular refractoriness, fibrillation thresholds and on hemodynamics were determined. In this part of the study also the comparative actions of propafenone were assessed (8 animals). IN another 28 dogs the antiarrhythmic and antifibrillatory actions of diprafenone following short-term coronary occlusion and subsequent release were established. In additional 16 animals the effects of diprafenone on "delayed" reperfusion arrhythmias following release of coronary artery occlusion after 2 h and on stimulus-induced ventricular tachycardia in acute myocardial infarction were investigated. The results show: Diprafenone slows conduction through all parts of the AV-conduction system. The AH-interval is significantly prolonged, QRS-duration and ventricular repolarization are slightly lengthened, and both the atrial and ventricular refractory periods and fibrillation thresholds are markedly increased. Heart rate is slowed, aortic pressure and cardiac output are not significantly changed. Following acute short-term coronary artery occlusion, the incidence of ventricular fibrillation is reduced, and the drop in the ventricular fibrillation threshold is diminished. By contrast, the frequency of ventricular fibrillation after release of short-term occlusion is not influenced. "Delayed" reperfusion arrhythmias, however, are completely abolished, and initiation of ventricular tachycardia in myocardial infarction can be easily prevented. With a predominant local anesthetic mechanism of action and a potential additional beta-sympatholytic activity, the new compound displays close similarities to propafenone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Is temazepam an accumulating hypnotic?

Ten healthy volunteers aged 22 to 30 years received a single 20-mg oral dose of temazepam. Serum temazepam concentrations were measured by gas chromatography at multiple times during the next 48 hours. Mean kinetic variables were: volume of distribution, 1.45 liter/kg; elimination half-life, 8.6 hours; total clearance, 2.33 ml/min/kg. The subjects then received 20 mg temazepam once daily for seven consecutive days. Serum concentrations were measured just prior to each dose and at multiple time points after the last dose. Predose serum levels increased during the first three days of dosage, then increased no further. Mean values measured 24 hours after doses 1 through 6, respectively, were 33, 43, 55, 47, 53, and 51 ng/ml. Based on the area under the serum concentration curve after the last dose compared with that after the first dose, the mean accumulation ratio was 1.32, which was significantly greater than unity. The extent of accumulation was consistent with that predicted from the single-dose study. Postdosage washout half-life averaged 10.2 hours. Thus, temazepam has a pharmacokinetic profile of an intermediate half-life benzodiazepine that produces an intermediate degree of accumulation with multiple dosage.

Absorption↗

Antiarrhythmic effects of stirocainide in acute myocardial infarction.

Ventricular arrhythmias, especially ventricular fibrillation, are assumed to be a main cause of sudden death during the first 24 h of acute myocardial infarction. Effective prophylaxis and acute suppression of these life-threatening rhythm disturbances are a major therapeutic problem. The present study was undertaken to investigate the efficacy of the new antiarrhythmic compound stirocainide (2-(1-benzylidene)cycloheptenimino-oxyethyl-diisopropylamine -2-butenedionate, Th 494) in suppressing "2nd phase arrhythmias" arising from large anteroseptal myocardial infarctions using a standardized experimental canine preparation. Our results demonstrate that "2nd phase arrhythmias"--i.e. frequent ventricular ectopics, tachycardias, salvos, and R-on-T phenomena--are reduced by 80-90% (sometimes even completely abolished) by stirocainide (dose: 4 mg/kg within 3 min, followed by 300 micrograms/kg X min over a 20-min period). The administration of the drug at the dose used does not produce severe cardiodepression, but intraventricular conduction time is significantly prolonged. Thus, Th 494 is a highly effective antiarrhythmic agent in acute myocardial infarction, and further experimental and clinical investigations on its antiarrhythmic and antifibrillatory properties may lead to beneficial therapeutic results.

Animals↗

Aftereffects of sustained convergence: some implications of the eye muscle potentiation hypothesis.

Aftereffects of sustained convergence are generally explained as the result of eye muscle potentiation (EMP). Three implications of this hypothesis for aftereffects in distance perception were tested: (i) According to the EMP hypothesis the aftereffects are based on oculomotor distance cues only. The addition of secondary cues during the test period should therefore reduce or eliminate the aftereffects. This expectation was confirmed. (ii) According to the EMP hypothesis the critical variable determining the aftereffect should be the distance of the inspection stimulus from the observer but not from the test stimulus. In confirmation of the expectation the aftereffects of certain inspection stimuli were of the same direction for test stimuli which bounded the range of inspection distances on both sides. (iii) When the aftereffects are based on oculomotor distance cues only, the effect of secondary cues during the test period should remain unchanged when they are present during the inspection period as well. Contrary to this expectation the aftereffects did not depend on the cues available during the test. This suggests that they are based on secondary cues, too, provided they are present during the inspection period.

Adolescent↗

[Divergent time courses of ventricular vulnerability of the heart to ventricular tachycardias and ventricular fibrillation in the early necrosis stage of acute experimental myocardial infarct].

UNLABELLED: Early necrosis in acute experimental myocardial infarction is characterized by severe ventricular dysrhythmias beginning approx. 6 hours after coronary artery occlusion and persisting for 2-5 days. It was the aim of this study to investigate the comparative changes in ventricular vulnerability to spontaneous and stimulus-induced tachycardia and fibrillation during early necrosis 6-18 hours following acute coronary artery occlusion. RESULTS: 1) The thresholds for repetitive extrasystoles and for ventricular fibrillation determined via electrodes placed on to the endocardium of the right and left ventricle outside of the ischemic area are within the normal range of the non-ischemic heart. 2) Both stimulation thresholds increase significantly within the area of infarction and in many cases are not inducible any more after 18 hours of ischemia, whatever amount of current is applied. 3) Sustained ventricular tachycardia can be induced in about 30% of cases after an occlusion lasting approx. 6 hours and in about 80% after an occlusion period of 18 hours. 4) Electrically induced ventricular tachycardias differ from spontaneously occurring VT in so far as the former appear to be due to a reentry mechanism, whereas the latter seem to be "accelerated ventricular rhythms" and thus of focal origin. Our results demonstrate that enhanced ventricular vulnerability during early necrosis in acute myocardial infarction is predominantly due to ventricular tachycardia rather than to ventricular fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of flecainide on atrial and ventricular stimulation thresholds to repetitive extrasystoles and fibrillation and on "2nd Phase" ventricular arrhythmias in dogs.

Repetitive extrasystole and fibrillation thresholds were assessed by various methods of programmed atrial and ventricular stimulation using intracavitary bipolar electrode catheters and a microcomputer based 3-channel stimulator as previously described. "2nd Phase" ventricular arrhythmias were produced by ligation of the left descending coronary artery. 2,5-Bis-(2,2,2-trifluoroethoxy)-N-(2-piperidylmethyl)benzamide acetate (flecainide, R 818, Tambocor) caused a significant increase of the atrial and ventricular fibrillation thresholds. The antifibrillatory action was similar in atrial and ventricular tissues. "2nd Phase" ventricular arrhythmias were dose-dependently reduced or abolished completely. Similar doses were required to suppress spontaneous arrhythmic activity and to increase the fibrillation thresholds. Thus, flecainide proved to be a powerful antiarrhythmic agent with strong antifibrillatory properties in therapeutic doses. It may be a promising drug for the treatment of atrial and ventricular reentrant arrhythmias.

Animals↗

Effects of diltiazem on vulnerability to atrial and ventricular reentrant arrhythmias in the normal and ischemic heart.

In experiments on 20 artificially ventilated anaesthetized dogs, the effects of the new calcium antagonist diltiazem on the stimulation thresholds to repetitive extrasystoles and fibrillation of the atria and the ventricles, respectively, and on ventricular dysrhythmias 6-24 h after acute coronary occlusion were investigated. The electrophysiological studies were performed using different methods of programmed stimulation of the heart. The results show that therapeutic doses of diltiazem provide no protection against stimulus-induced supraventricular reentrant arrhythmias with the AV-node not involved in the reentrant circus, and have no antifibrillatory efficacy in electrically induced ventricular arrhythmias in the non-ischemic heart. In acute myocardial infarction there is no antiarrhythmic effect either. Our results can be explained by the fact that diltiazem is a specific calcium antagonist and that the slow response plays only a minor role in the arrhythmias investigated.

Animals↗