Biomedical subjects

L Eckardt

Publications and source records attributed to L Eckardt.

48 records · Page 3Linked to original sources

PubMed1998

Clofilium in the isolated perfused rabbit heart: a new model to study proarrhythmia induced by class III antiarrhythmic drugs.

OBJECTIVE: The clinical usefulness of class III antiarrhythmic drugs for the treatment of tachyarrhythmias is limited by their potential proarrhythmic effects, mainly torsades-depointes (TdP). The goal of this experimental study was to develop an isolated whole-heart model exhibiting typical characteristics of class III drug-induced ventricular arrhythmias. METHODS: Isolated rabbit hearts were perfused with a Krebs-Henseleit buffer containing 10 microM clofilium and then exposed to a modified Krebs-Henseleit buffer with 2.0 mM K+ and 0.5 mM Mg2+. Hearts subjected to either clofilium alone or modified buffer alone were used as controls. RESULTS: Under clofilium the QT interval increased from 187 +/- 16 to 282 +/- 33 ms. Within 8 to 25 s after the change of the perfusate, ventricular arrhythmias developed in all hearts associated with a further QT prolongation to 380 +/- 73 ms when the first ventricular extrasystole occurred. Simultaneously, the monophasic action potential durations increased relatively more during late repolarization; from 99 +/- 21 to 110 +/- 25 ms (+11%) at 50% repolarization, from 143 +/- 24 to 178 +/- 40 ms (+24%) at 70%, and from 200 +/- 30 to 275 +/- 53 ms (+38%) at 90%. The predominant rhythm was polymorphic with either two alternating or multiple QRS morphologies exhibiting the characteristic features of torsades-depointes. All control hearts stayed in normal sinus rhythm. CONCLUSION: Under the conditions selected, the isolated perfused rabbit heart represents a useful experimental approach to study the proarrhythmic effects of class III agents. This model provides a convenient way to manipulate the ionic and pharmacologic milieu in a preparation conserving the functional anatomy of the whole organ without interference by cardiovascular reflexes. It might be useful for analyzing the conditions favoring and preventing drug-induced torsades-depointes.

Animals↗

PubMed1998

Experimental models of torsade de pointes.

Torsade de pointes is a potentially life threatening form of polymorphic ventricular tachycardia typically seen in the setting of congenital and acquired abnormal QT-prolongation. Numerous in vitro studies have investigated basic ionic mechanisms underlying delayed repolarization. The role of different ion channels and the induction of early afterdepolarizations have been studied in various cardiac cells including M cells. In addition, isolated heart models with and without electrical stimulation and/or the use of drugs which prolong repolarization have been developed in recent years. Some of these models have simulated conditions likely to exist in the clinical setting of torsade de pointes, such as bradycardia and hypokalemia. In in vivo canine and rabbit models, torsade-like polymorphic ventricular tachyarrhythmias have been induced by the administration of different agents such as cesium, neurotoxins, e.g., anthopleurin or various class III drugs under conditions designed to mimic the clinical situation. In the context of recent advances in the molecular genetics of long QT syndrome, those models which have used sodium or potassium channel blockers have gained particular interest. Based on all experimental studies it seems probable that the first beats of torsade occur due to early afterdepolarizations and triggered activity. The development of subsequent beats is less clear. Reentry based on inhomogeneity of refractoriness has been suggested as the underlying mechanism.

Animals↗

PubMed1998

Drug-related torsades de pointes in the isolated rabbit heart: comparison of clofilium, d,l-sotalol, and erythromycin.

Torsades de pointes is a potentially life-threatening form of polymorphic ventricular tachyarrhythmia typically seen in the presence of repolarization-prolonging agents. We investigated this particular form of tachyarrhythmia in the isolated, perfused rabbit heart. The experimental model was designed to reproduce conditions that are clinically known to be associated with an increased propensity to the development of torsades de pointes. The class III agent clofilium (1 microM) and d,l-sotalol (10 microM), as well as the antibiotic erythromycin (30-150 microM) were infused in the presence of either normal (5.88 mM) or low (1.5 mM) potassium concentration in sinus-driven or atrioventricular (AV)-blocked hearts. Ventricular tachyarrhythmias spontaneously emerged in the clofilium-, d,l-sotalol-, and erythromycin-treated AV-blocked hearts. The episodes showed typical features of torsades de pointes found in humans. They developed within 4-12 min after the onset of infusion, were normally nonsustained, and only rarely degenerated into ventricular fibrillation. Electrical stimulation at cycle lengths <600 ms and perfusion with MgSO4 suppressed arrhythmic activity. In the d,l-sotalol- and erythromycin-treated hearts, torsades de pointes occurred only in the presence of hypokalemia and bradycardia, whereas, in the presence of clofilium, bradycardia alone caused torsades de pointes. Monophasic action-potential recordings demonstrated early afterdepolarizations in endocardial and epicardial recordings. Thus the isolated AV-blocked rabbit heart represents a model for studying drug-related torsades de pointes and its mechanism.

Animals↗

PubMed1998

Divergent effect of acute ventricular dilatation on the electrophysiologic characteristics of d,l-sotalol and flecainide in the isolated rabbit heart.

INTRODUCTION: The interaction between acute ventricular dilatation (AVD) as one aspect of ventricular dysfunction and Class I and III antiarrhythmic drugs is uncertain. We therefore investigated the effects of AVD on the electrophysiologic properties of d,l-sotalol and flecainide. METHODS AND RESULTS: The isolated rabbit heart was used as a model of AVD. The ventricular size and, therefore, the diastolic pressure were modified by sudden volume changes of a fluid-filled balloon placed in the left ventricle. Pacing was performed alternately using epi- and endocardial monophasic action potential (MAP)-pacing catheters at cycle lengths from 1,000 to 300 msec. d,l-Sotalol (10 microM) resulted in a significant (P < 0.05) lengthening of refractoriness (+13.5% +/- 3.1%), MAP duration (+14.9% +/- 3.2%), and QT interval (+15.5% +/- 4.1%) (mean +/- SEM at 1,000 msec). These effects had a reverse rate-dependence. AVD to a diastolic pressure of 30 mmHg reduced refractoriness and left ventricular MAP duration. In comparison with the control group with the same extent of AVD, d,l-sotalol still led to a significant prolongation of repolarization for all cycle lengths except 300 msec, so that its effects were not absolutely but relatively preserved. In contrast, flecainide (2 microM) had no significant effects on refractoriness or MAP duration. It led to a significant, rate-dependent increase of pacing thresholds (+47.6% +/- 8.2%), prolongation of QRS (+48.8% +/- 5.6%), and conduction time (+78.6% +/- 8.6%) (mean +/- SEM at 300 msec). In the flecainide group, AVD significantly increased the normal rate-dependent prolongation of QRS (+16.7% +/- 5.5%) and conduction time (+17.1% +/- 4.3%). CONCLUSION: Our data demonstrate that, during AVD, the Class III effect of d,l-sotalol is preserved, whereas flecainide's effect of slowing conduction is exaggerated. This may contribute to flecainide-related proarrhythmia in certain clinical situations.

Action Potentials↗

PubMed1998

[Biomechanical analysis of arch-guided molar distalization with super-elastic nickel-titanium springs].

The typical characteristics of orthodontic devices and their effectiveness during tooth movement are of major importance for the success of orthodontic treatment and the stability of the result. To investigate this situation, two typical tooth movements were simulated experimentally using an Orthodontic Measurement and Simulation System (OMSS). These were Distalisation of an upper last molar and Distalisation of a molar including fixation of the guiding arch to a distal supporting last molar. The movements were simulated by employing various different NiTi coil compression springs and two standard steel guiding arches with the dimensions 0.016" x 0.022" and 0.017" x 0.025". The six NiTi springs differed significantly in shape and force characteristics. The eccentric application of the orthodontic force system relative to the centre of resistance brings about a tilting of the tube and arch via molar rotation. Although the forces developed by the springs are relatively constant, frictional losses result in variations in the effective orthodontic forces. With progressive distalisation, the average frictional losses varied between 50% and 80% of the spring-generated force, and frictional variations increased. Lower frictional losses were seen with a 0.016" x 0.022" guiding arch as compared with one measuring 0.017" x 0.025". In comparison with distalisation of a last molar, fixation of the arch to a third molar was associated with higher frictional losses. The interaction of the springs with the tube-guiding arch system could be so powerful that frictional losses were detected already during the initial phase of movement, and in extreme cases led to cessation of distalisation. The rate of distalisation was not affected by the forces generated by the springs. For physiological reasons, therefore, springs developing smaller forces should be used preferentially.

Biomechanical Phenomena↗

PubMed1997

Drugs versus devices in controlling ventricular tachycardia, ventricular fibrillation, and recurrent cardiac arrest.

Patients with symptomatic ventricular tachycardia, ventricular fibrillation, or aborted sudden cardiac death remain at high risk for arrhythmia recurrence. In recent years, strategies to treat these patients have changed. Concerns about the proarrhythmia risk and uncertain efficacy of class I agents have resulted in a shift in interest to non-class I antiarrhythmic drugs such as sotalol and amiodarone. Both drugs have class III antiarrhythmic properties (i.e., both lengthen repolarization and refractoriness); however, each also has its own additional electrophysiologic effects. Prospectively designed, randomized studies have shown that both sotalol and amiodarone have more potent antiarrhythmic actions than class I agents. However, even as the advantages of sotalol and amiodarone have been recognized, enthusiasm for nonpharmacologic modes of treatment, particularly the implantable cardioverter-defibrillator (ICD), has also markedly increased. The ICD has been shown to decrease dramatically the incidence of sudden death, which may lead to the reduction of total mortality. Whether patients with life-threatening ventricular tachyarrhythmias should be treated first with antiarrhythmic agents or with an ICD is an important question. The results of recent studies suggest that treatment with an ICD is more effective than electrophysiologically guided treatment with class I agents. However, results of prospectively designed randomized studies comparing the efficacy of the ICD with that of sotalol and amiodarone must become available before definitive recommendations can be made concerning the use of the ICD as first-line therapy in patients with ventricular tachycardia/ventricular fibrillation or aborted sudden cardiac death. In addition, there may be a significant role for the use of antiarrhythmic drugs in conjunction with ICDs.

Amiodarone↗

PubMed1997

Comparative study of excitation patterns in the masseter muscle before and after orthognathic surgery.

This study was designed to inquire into changes occurring in the electromyographic activity throughout the masseter muscle after orthognathic surgical treatment of various bite anomalies. A total of 32 adult patients showing distinct class II (n = 15) or class III malocclusions (n = 17) were entered into the investigation. All patients had monopolar surface electromyograms of the masseter muscle taken prior to presurgical orthodontic treatment and after removal of their orthodontic appliances after surgery. Twenty eugnathic adult patients served as controls. Unlike bipolar lead readings, simultaneous sampling from 16 electrodes permits the registration of the overall excitation pattern in the entire muscle. Recordings were taken during clenching, chewing and protrusion of the lower jaw against a defined force. Comparison with preoperative EMGs proved postsurgical distribution of excitation in class 11 patients to approximate the excitation pattern of eugnathic patients. By contrast, correction in class III malocclusions produced a shift in excitation maxima in the sense of a cranial advance. Harmonization, as evident in class II patients, did not occur. The postoperative discords in masseter excitation patterns, as observed after correction of class III anomalies, are indicative of the risk of relapse and the prolonged phase of retention associated with these conditions.

Adult↗

PubMed1996

Indications for compensatory extractions in orthodontic space closure in the frontal segments.

This follow-up study presents patients who underwent orthodontic space closure in the maxilla after traumatic loss of frontal teeth or aplasia of a lateral incisor. Comparison covers findings obtained from casts and cephalograms in 24 patients with or without compensatory extraction. The findings indicate that acceptable results regarding axial tooth positioning and profile can be obtained without compensatory extraction. Prerequisites are distal occlusion of the first molars by one premolar width and continuous monitoring for regular overbite and uncrowded lower incisors. If orthodontic space closure can be achieved only by compensatory extraction, the indication for this space closure procedure calls for even more critical judgement.

Bicuspid↗

PubMed1996

Facial structure and functional findings in patients with progressive muscular dystrophy (Duchenne).

The investigation of 15 patients who have a progressive muscular dystrophy of the Duchenne type (PMD) shows the affection of various groups of muscles of the stomatognathic system, studied by means of electromyography and mechanical force measurements. We observed the following deviations in patients with PMD; transversal overdevelopment and sagittal shortening of the dental arch; reduction of overbite and overjet; sagittal underdevelopment of the cranial, maxillary and mandibular base; retrusion of incisors; concave profile; increase in bizygomatic width; and a difference in time between the attack on the musculi orbicularis oris and that on masticatory muscles. In our study, the activity of the jaw muscles diminished 2 years earlier compared with the perioral muscles. This, and also the enlargement of the hypotonic tongue, causes a transversal expansion of skull and dental arches. This expansion was strongly pronounced in the lower jaw; we invariably observed a posterior crossbite. In contrast to the transversal overdevelopment, we observed a sagittal underdevelopment of skeletal and dental parameters, as well as a retrusion of the incisors. The results of surface electromyography showed the affection of the masseter muscle in patients who had PMD. By means of the Fast-Fourier transformation, we observed a displacement of the median frequency as compared with the lower frequency range.

Adolescent↗

PubMed1995

[The dental and skeletal changes in early Class II treatment with a Klammt open activator].

In order to evaluate the initiation of treatment of Angle class II malocclusion at an early age, seventy-six patients, 34 girls aged on average 10.1 years and 42 boys, average age 11.3 years, were selected for the study. For the treatment we used the Klammt open activator. For evaluation purposes we used casts and cephalograms taken before and after treatment. The results showed distinctive differences between Angle class II/1 and II/2. The sagittal correction in class II/1 was a result of the reduction of the SNA angle, the mandibular protrusion, and the retrusion of the upper incisors. The face high index was normalized. No labial inclination of the lower incisors was registered. In the Angle class II/2 cases the SNA angle was unchanged. The sagittal correction was brought about exclusively through mandibular translation. The deep bite and the retrusion of the upper incisors weren't markedly improved. The lower incisors showed a labial tip. The incisor angle was unchanged. Our study showed that the ANB reduction on an annual basis is highest, when treatment is initiated at an age of 10 to 11 years for girls and 12 years for boys. On the growth curve this is a point in time below the accelerated growth phase of puberty.

Activator Appliances↗

PubMed1995

[The relationships between the EMG excitation pattern of the masseter muscle and the facial skeletal morphology].

The purpose of this study was to investigate the correlations between malocclusions and the electromyographic activity of the orofacial muscles as this activity reveals itself through multi-channel, simultaneous recording of surface potentials from the masseter muscle. Thirty adults with class II or class III malocclusion formed the study's patient base. Surgical correction of the anomaly was planned for all patients. Ten patients served as the control group. In addition to the standard diagnosis, EMG were recorded during various stress situations such as maximal intercuspidations, chewing, swallowing, and mandible protrusion. We obtained a so-called "myomap" by means of the simultaneous multi-channel recording of the surface potential of the right masseter. Comparison of the EMG revealed a higher activity from the masticatory muscles in the class II cases than in the class III cases. The analysis of the masseter excitation pattern brought to light interesting differences. A higher activity on the lower margin of mandible in the area of the superficial part of masseter was found in the class II cases, whereas contrary to this an increase in EMG activity was found above the deep part of masseter in class III cases. The differing distribution of excitation of the 2 parts of the muscle in class II and class III malocclusions confirms the correlation between muscle function and morphology.

Adolescent↗

PubMedDate not supplied

Simultaneous in utero assessment of AV nodal and ventricular electrophysiologic parameters in the fetal sheep heart.

BACKGROUND: Fetal tachyarrhythmias are usually of supraventricular origin. To investigate whether specific electrophysiologic properties of the fetal heart contribute to this preponderance by either favoring supraventricular tachycardias or by rendering ventricular tachycardias unlikely, we measured fetal electrophysiologic parameters in utero using transuterine fetal transesophageal electrocardiograms in fetal sheep. Since overdrive pacing may help to establish the mechanism of an arrhythmia and may be used to treat fetal tachycardias, different modes of transesophageal pacing in utero were also assessed. METHODS AND RESULTS: Decapolar electrophysiology catheters were fetoscopically inserted into the esophagus of 9 fetal sheep (pregnancy duration 94- 105 days, term = 145 days). Electrocardiograms were recorded simultaneously from all adjacent bipoles and from two pacing wires sutured onto the fetal shoulders. Pacing was attempted either via two adjacent electrodes of the intraesophageal catheter or via the most distal and most proximal electrode. Fetal cycle length, PQ, and QT intervals were close to (approx. 75 %), but fetal QRS duration was < 20 % of maternal values, thus shifting the relation between activation and repolarization towards longer excitation wave lengths. Fetal QT dispersion was small (< or = 10 ms). Atrial pacing was achieved in all fetuses using distant electrodes, and with lower thresholds when compared to closely spaced bipolar electrodes (p < 0.05). CONCLUSIONS: (I) An altered relation between ventricular activation and repolarization and a low dispersion of ventricular repolarization may protect the fetal heart against ventricular reentrant tachycardias. (II) Relatively normal fetal AV nodal conduction delay already provides one of the prerequisites for supraventricular reentrant tachycardias involving the AV node at this stage of fetal development. (III) High-rate esophageal pacing of the fetal atria is best achieved using widely spaced bipolar pacing electrodes.

Animals↗