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Biomedical subjects

J Brachmann

Publications and source records attributed to J Brachmann.

At least 127 records · Page 7Linked to original sources

Effect of nifedipine and AQ-A 39 on the sinoatrial and atrioventricular nodes of the rabbit and their antiarrhythmic action on atrioventricular nodal reentrant tachycardia.

The effects of two drugs that apparently block slow inward current--nifedipine and the new compound AQ-A 39--were studied on the isolated sinoatrial (SA) and atrioventricular (AV) nodes of the rabbit heart using intracellular microelectrodes. Nifedipine and AQ-A 39 both slowed the sinus rate associated with a decrease in the rate of diastolic depolarisation. Conduction through the AV node was consistently impaired; this effect was enhanced with increasing atrial rates or with decreasing coupling intervals of premature beats. The action potential amplitude was significantly reduced in SA nodal and upper (AN) AV nodal fibres but was not significantly affected in lower (NH) AV nodal and in atrial fibres. The maximum diastolic potential showed little or no alteration. In all fibre types studied, the action potential duration was shortened with nifedipine but was significantly prolonged with AQ-A 39. Prevention of AV nodal reentrant tachycardia by nifedipine was related to an increase in the effective refractory period of the AV node. AQ-A 39 prevented the tachycardia by both slowing of AV nodal conduction and by prolongation of action potential duration in the AV nodal and atrial compartments of the reentrant circuit associated with the appearance of different gap phenomena of the AV conduction. The maximum possible A-H interval was, however, not shortened by either drug and single atrial echo beats could still be initiated. The results suggest that nifedipine and AQ-A 39 both have a direct depressant action on the slow inward current-dependent electrical activity of the SA and AV node but have opposite effects on the repolarisation phase resulting in different antiarrhythmic mechanisms.

Action Potentials↗

Analysis of interectopic activation patterns during sustained ventricular tachycardia.

We analyzed the patterns of interectopic continuous electrical activity recorded within interectopic intervals of sustained ventricular tachycardias. These arrhythmias were induced in dogs that were studied 4 days after left anterior descending coronary artery occlusion. Standard ECG leads and electrograms from the His bundle and left ventricular epicardium, both infarct and normal zone, were recorded. In 19 of 24 dogs with transmural myocardial infarction, one to three ventricular paced beats induced sustained ventricular tachycardia, characterized by continuous electrical activity between the initiating and spontaneous ectopic beat and between successive ectopic beats recorded from the epicardium over the infarct zone but not from the normal epicardium. Continuous activity consisted of discrete potentials that were reproduced in each cardiac cycle, suggesting slow conduction within a reentrant circuit. The interectopic activity was divided into three distinct temporal periods, delineated by potentials occurring at the initial portion, the mid-interectopic portion and terminal portion or exit of the slow conduction segment of the presumed reentrant circuit. In some cases, sustained ventricular tachycardia was induced only if an appropriate initial potential was engaged. Spontaneous termination of the sustained ventricular tachycardia was associated with Wenckebach-like block of conduction in the initial or exit potential. Ventricular pacing caused alteration of the interectopic patterns and resulted in cessation of the arrhythmia. Procainamide produced dose-dependent slowing of the ectopic rate due to depression of conduction in the mid-interectopic portion of the continuous electric activity. Inducibility of the sustained ventricular tachycardia was inhibited by decremental conduction in this compartment of the presumed reentry circuit. The present study uses a preparation showing sustained ventricular tachycardia that is stable and regular. Functional analysis of the various portions of the continuous electrical activity during sustained tachycardias allows further insight into the mechanisms of initiation and termination of sustained ventricular tachycardias. The ability to localize the effect of antiarrhythmic drugs on specific portions of a possible reentrant circuit may provide important correlative data for the analysis and interpretation of detailed epicardial mapping studies.

Animals↗

Bradycardia-dependent triggered activity: relevance to drug-induced multiform ventricular tachycardia.

We used cesium chloride (CsCl) for electrophysiologic studies in canine hearts in vivo and in vitro to examine the mechanisms underlying ventricular arrhythmias that are related to prolonged repolarization. Cesium is known to depress normal ventricular automaticity and some experimental arrhythmias by blocking delayed outward currents and prolonging action potential duration. In 10 dogs in normal sinus rhythm, 1 to 1.5 mM/kg iv CsCl prolonged the QT (QU) interval and induced ventricular ectopy in all, including multiform ventricular tachycardia. In 12 dogs with atrioventricular block, 1 to 1.5 mM/kg iv CsCl produced marked suppression of idioventricular rates (from 45 +/- 6 to 8 +/- 4 beats/min). These low rates were then associated with bigeminy or bursts of multiform ventricular arrhythmia. Pacing at rates of 60 beats/min or more suppressed these arrhythmias. Low doses of tetrodotoxin (1 microgram/kg) also abolished these bradycardia-dependent arrhythmias without affecting the amplitude of ventricular electrograms. Tissue concentrations of cesium were determined by anatomic absorption spectroscopy in five dogs after injection of 1 mM/kg CsCl. Thirty minutes after the injection, cesium levels in Purkinje fibers were 5.3 +/- 1.0 mM/kg, levels in ventricular muscle were 4.6 +/- 0.9 mM/kg, and levels in atrial muscle were 4.1 +/- 0.8 mM/kg. In eight isolated endocardial preparations from canine ventricles, standard microelectrode techniques were used to study the effects of superfusion with 5 mM cesium. After 30 min, we observed early afterdepolarizations interrupting phase 3 of Purkinje fiber action potentials that already showed prolonged repolarization. Slowing the rate generated single or multiple action potentials arising from partially repolarized levels of membrane potentials (-80 to -65 mV). Pacing rates of 30 to 60 beats/min diminished the afterdepolarizations and suppressed the spontaneous beats. Tetrodotoxin at a concentration of 10(-8) g/ml, which did not affect upstroke velocity, abolished the afterpotentials. We conclude that cesium induced bradycardia-dependent ventricular arrhythmias caused by early afterdepolarizations. These data suggest that an inward current, probably carried by sodium ions, appears to be essential for the occurrence of this phenomenon. The association of delayed repolarization, afterdepolarizations, and triggered activity has similarities to the phenomenon of drug-induced prolongation of the QTU interval associated with multiform ventricular tachycardia in humans, i.e. "torsades de pointes."

Action Potentials↗

Action of sotalol on potential reentrant pathways and ventricular tachyarrhythmias in conscious dogs in the late postmyocardial infarction phase.

Sotalol is a beta-adrenergic blocker that also prolongs action potential duration and myocardial refractoriness over the short term (class III effect). Its short-term antiarrhythmic effects were compared with those of metoprolol, which has neither short-term class III nor membrane-stabilizing action, on reentrant ventricular arrhythmias produced by programmed stimulation in 17 conscious dogs 3 to 8 days after myocardial infarction. Ventricular arrhythmias were prevented or significantly slowed by sotalol in 11 of 19 studies (58%) compared with in one of 14 (7%) studies with metoprolol. Sotalol prolonged refractoriness in the infarct zone, measured from an implanted "composite" electrode, by 41 +/- 45% (mean +/- SD, p less than .01), which was significantly greater than the increases it produced in effective refractory period of the normal ventricle (14.0 +/- 5.5%) or QT interval (12.5 +/- 7.8%). Metoprolol had no effect on infarct-zone refractoriness. Sotalol differentially increases refractoriness in potential reentry circuits in ischemic myocardium. Its antiarrhythmic effect in this model is not due to beta-blockade, and is presumably related to prolongation of action potential duration.

Action Potentials↗

[Comparison of the results of computer tomography and dimer-X ventriculography in the diagnosis of infratentorial processes].

A total of 38 preoperative computer-tomography findings were compared with the results obtained in central dimer-X-ventriculography. CT yields the exact localisation of every tumour. Determination of kind and size of the tumours was possible in about 30 per cent of the cases. No additional information was obtained about the infiltration tendency of the tumour with respect to the rhomboid fossa. The method appears to be insufficient for the appraisal of occlusion of the efferent passage of the cerebrospinal fluid which are not caused by tumours. In 360 f 38 cases, the direct puncture of the third ventricle could be carried out without any complications. In these cases, all tumours as well as the disturbances of the cerebrospinal fluid passage could be diagnosed. An exact tumour localisation, however, was less well possible than it was with CT. Only hemispheral tumours, tumours of the superior vermiform process, tumours of the 3rd ventricle and craniospinal processes could be differentiated. Excellent results were obtained in the diagnosis of stenoses in the region of the aqueduct or malformations. For the above mentioned reasons, we of course give preference to the computer tomography for the diagnosis of infratentorial processes, but we still consider the combination of the two methods to be indispensable because it increases the information value for the planning of the operation.

Brain Neoplasms↗

[Tumors of the 4th ventricle and the craniospinal transitional zone. Review of patients of the Neurosurgical Clinic of the Department of Medicine of the Karl Marx University].

From a total of 1,028 infratentorial tumours operated on at the Neurosurgical Hospital of the Section Medicine of the Karl-Marx University Leipzig in the last 30 years, 167 tumours in the region of the 4th ventrical have been selected. Their statistical processing was carried out with respect to specific localisation, average age, kind of tumour, sex, clinical findings, duration of case history, application of instrumental diagnostic procedures and radicality of operation, success and failure. Some fundamental conclussions are drawn. A subdivision in detail will be contained in the following articles based on this material.

Adolescent↗

[Special diagnostic and surgical problems in tumors of the 4th ventricle in adulthood].

Within 30 years, 1028 operations because of cerebellar tumours have been carried out at the Neurosurgical University Hospital in Leipzig. Of these, 167 were related to tumours within the 4th ventricle or encroaching a little outside of it. In the group of the adults (from the 18th year), 54 observations were made. These patients are subdivided according to histology (ependymomas in the first place), according to clinical findings (high values of cerebral pressure symptoms), according to the duration of the case history in dependence upon histology (long duration of angioblastomas and ependymomas), according to the possibilities of radicality (somewhat below the values in child age), the condition at discharge (better than in child age) and the cause of death (absolute predominance of central causes). A comparison is made with the results obtained with the studied patients in child age. Subsequently, the operation tactics of the Leipzig hospital is dealt with and the respective value of microneurosurgery carried out 10 years before is emphasised. A striking improvement for benign tumours can now only be achieved by a considerably improved early diagnosis.

Adolescent↗

[Special diagnostic and surgical problems in tumors of the 4th ventricle in childhood].

A report is given on 113 tumours of the 4th ventricle in children (up to the age of 18 years) observed among a total of 1028 cerebellar operations. Of these, 87 (= 77%) tumours were exclusively tumours of the 4th ventricle, in 26 cases the tumour also encroached on adjacent structures (cerebellar hemisphere and vermis, pons and Medulla oblongata). Medulloblastomas were predominant (55%), they mainly occurred in school age. Leading clinical symptom of the tumours of the 4th ventricle - especially in child age - is the increase in intracranial pressure which can often be demonstrated radiologically in this age group. Besides there are coordination disturbances and disturbances of the cerebral nerves; relatively frequently one sees a "vermis syndrome". The initial symptoms, which are in most cases non-characteristic (nausea, headache, also ataxia), are more often than not misinterpreted. Surgically treatment aims at a radical removal of the tumour whenever of possible, which is frequently problematic in children, and the restoration of the pathways the cerebrospinal fluid. Microsurgical techniques clearly contributed to a decrease in the mortality rate which, however, still is very high. This stresses the importance of an improvement of early recognition of these tumours.

Adolescent↗

[Special problems in the diagnosis and therapy of craniospinal tumors].

Tumours in the region of the Foramen magnum are rare (34 cases among more than 1000 infratentorial and 400 spinal tumours). The clinical symptoms can be guiding but they sometimes involve differential-diagnostic difficulties. In dependence upon the starting point and the direction of the development, cerebellar signs or transverse paralysis in the cervical region of the medulla are in the fore. In most cases, supplementary examinations are indispensable (X-ray examinations of the skull and the cervical vertebral column, ventriculography and CT). Angiography is of lesser importance. The anatomical relations of the tumour to its environment not only form the clinical picture, but also bring about therapeutical problems. The use of microsurgical methods has improved the prognosis a little, but nevertheless these disease pictures should be considered to be very serious.

Adult↗

Electrophysiological effects of glucose-insulin-potassium on sinus node function in patients with and without sinus node dysfunction.

The electrophysiological effects of glucose (100 g)-insulin (20 U)-potassium (10 mmol X litre-1) infusion (GIK) on three parameters of sinus node function were studied in 14 control subjects (mean age 53 +/- 14 yr) and 11 patients (mean age 50 +/- 17 yr) with sinus node dysfunction (SND). In a first series of experiments the response to GIK was examined in nine control and 11 SND patients. Following GIK, the mean spontaneous cycle length decreased by 17% (671 to 560 ms; P less than 0.01) in the control group and by 33% (1066 to 715 ms; P less than 0.001) in the SND patients; this difference between both groups was statistically significant (P less than 0.01). In the control group mean corrected sinus node recovery time (CRST) and calculated sinoatrial conduction time (SACT; n = 6) were not significantly altered after GIK. In SND patients GIK decreased the mean value of CSRT by 40% (693 to 416 ms; P less than 0.05) and of calculated SACT (n = 6) by 27% (130 to 95 ms; P less than 0.05); prolonged secondary pauses following termination of rapid atrial pacing in SND patients were also shortened. In a second series of experiments, mannitol (100 g, iv) was administered in five control patients but had no significant effect on the electrophysiological parameters tested. Plasma levels of glucose were significantly increased, by 500% (P less than 0.01), after GIK; plasma potassium and sodium concentrations decreased by 7 and 5% (P less than 0.05). The results indicate that GIK had a beneficial effect on sinus node dysfunction.

Adult↗

Arrhythmogenic effects of toxic concentrations of the antiarrhythmic drug lorcainide on the isolated canine ventricle.

The effect of the new antiarrhythmic drug lorcainide was studied on the specialized conducting system of isolated canine ventricle. Transmembrane action potentials were recorded simultaneously from three subendocardial sites within the ventricular basis, free wall and apex. At concentrations of 3 x 10(-6) and 2.4 x 10(-5) M, lorcainide caused a dose-dependent decrease in maximum rates of rise and in amplitude of the action potential; 0.6 x 10(-6) M had no significant effect, resting potential and action potential duration remained unchanged with 0.6 x 10(-6) M and 3 x 10(-6) M. The most prominent effect of 2.4 x 10(-6) M lorcainide was the appearance of an increasing notch resulting in clear separation of the action potential in an initial short spike depolarization (50-120 msec) with or without a subsequent plateau depolarization 280-370 msec). Both components demonstrated an independent and inhomogeneous conduction through functionally different pathways. Changes in stimulation rate or premature stimuli resulted in nonstimulated reexcitations resembling bigemini, ventricular tachycardia or regional ventricular fibrillation. The results indicate that dissociation of the action potential in two components is due to toxic alterations of ionic channels of the fiber membrane and that nonstimulated reexcitations are due to reentry via functionally fast and slow pathways.

Action Potentials↗

[Clinical aspects and differential diagnosis of occipital bone processes].

Tumours and tumour-like processes of the cranial bones do not occur very frequently; 2.5 per cent of all bone tumours are found in the calotte. On the other hand, the pre-operative and operative error possibilities regarding these processes are considerable, leaving multiple bone metastases out of consideration. The situation is complicated by many processes in the vicinity of the bone which affect or alterate the bone secondarily. On the basis of two better known tumours, the giant cell tumour and the aneurysmatic bone cyst, the diagnostic possibilities and difficulties are discussed in greater detail. The value of computer tomography mainly consists in the exact localisation in the bone and the surrounding tissues. Scintigraphy, too, can yield valuable information. Since in these processes as well as some other tumours no advantages can be derived from an irradiation therapy, but induced malignisations are even possible after several years, radical surgery is the only therapy of choice that is left. Considerable difficulties may arise in this connection due to narrow relations to vessels and blood paths. Finally, the problems of a prognostic statement is dealt with because histologic examinations, for instance in case of giant cell tumours, cannot yield precise information either with respect to dignity. Some authors, therefore, classify the latter as potentially malignant tumours.

Adolescent↗

Function of the sarcoplasmic reticulum (SR) in hypophosphatemic myopathy.

Lipid composition and Ca2+ transport properties were examined in the isolated sarcoplasmic reticulum of non-exercised muscles of markedly phosphorus depleted rats. Phosphorous depletion with a fall of plasma Pi from 8.04 +/- 0.85 to 2.56 +/- 0.48 mg/dl was accompanied by a decrease in muscle Pi and ATP content and by a significant decrease in the phospholipid/protein ratio of sarcoplasmic reticulum. The phosphatidyl -choline/phosphatidyl-ethanolamine ration in sarcoplasmic membranes was increased. Storing capacity for Ca2+ was significantly diminished. In contrast, there was no significant change of kinetic parameters of Ca2+ transport, i.e. of the initial rate of uptake and concentrating ability. These findings do not necessarily exclude changes of cytosolic Ca2+ concentration in phosphate depletion, but they exclude alterations of intrinsic kinetic properties of the sarcoplasmic reticulum as a cause of any such potential changes.

Animals↗