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  • 1
    Electronic Resource
    Electronic Resource
    The acute changes in serum binding of disopyramide and flecainide after myocardial infarction (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 253-255 
    Details
    ISSN: 1432-1041
    Keywords: disopyramide ; flecainide ; myocardial infarction ; drug plasma binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In the serum basic drugs are principally bound to alpha1-acid glycoprotein (AAG). Following acute myocardial infarction it has been shown that the levels of AAG rise. The serum levels of total protein, albumin, AAG and the protein binding of 2 antiarrhythmic drugs which are bases, disopyramide and flecainide, was measured in vitro with blood samples from eleven patients taken over the first 5 days following myocardial infarction. Mean AAG levels significantly increased from 1.04 g/l on Day 1 to 1.80 g/l on Day 5. The binding of disopyramide, which is highly bound, rose from 80% to 87%, representing a 35% decrease in free drug concentration. In contrast the binding of flecainide fell from 61% to 53%, a 20% increase in free drug concentration. These data suggest that although the binding of strongly bound drugs responds appropriately to increases in binding protein after acute myocardial infarction, poorly bound drugs are displaced from binding sites possibly by endogenous substances. Since the pharmacological effects of a drug are related to its free (unbound) concentration, the changes in the proportions of free to bound drug after myocardial infarction may have important clinical implications.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00543319
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  • 2
    Electronic Resource
    Electronic Resource
    Duration of action of tiapamil in stable exercise induced angina (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 339-342 
    Details
    ISSN: 1432-1041
    Keywords: tiapamil ; angina pectoris ; stable exercise ; duration of action
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The duration of action of tiapamil was assessed in ten patients with stable exertional angina. Maximal symptom-limited treadmill exercise electrocardiography was performed before and at 1, 3, 6 and 9 h after therapy. Significant differences were only found at 1 h after tiapamil with increases in mean exercise duration (312 vs 399 s), the time to onset of angina (221 vs 310 s) and exercise work load (5.9 vs 7.3 METS). Tiapamil had no significant effect on the exercise heart rate but increased the resting heart rate by 6 beats/minute. The resting systolic blood pressure fell by 17 mmHg (p〈0.01), and the diastolic blood pressure by 14 mmHg. Exercise systolic and diastolic blood pressures fell by 19 and 17 mmHg respectively. Side-effects were short-lived and attributable to vasodilatation. Tiapamil is effective for the relief of angina with minimal side-effects, but its duration of action is short. For effective chronic oral use, a sustained release preparation is required.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00543965
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Arrhythmogenic mechanisms of non-sedating antihistamines (1999)
    Oxford BSL : Blackwell Science Ltd
    Clinical & experimental allergy 29 (1999), S. 0 
    Details
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Antihistamines (H1-receptor antagonists) are amongst the most frequently prescribed drugs worldwide for the treatment of allergic conditions. Recently, there have been reports that certain non-sedating antihistamines, mainly terfenadine and astemizole, might be associated with the risk of rare but severe arrhythmias, namely torsades de pointes, particularly in overdosage, concomitant ingestion of imidazole or macrolide antibiotics and in patients with underlying cardiac or liver diseases. It has now been shown that the molecular target in human ventricle for the potassium channel blockade of antihistamine is HERG gene located in chromosome 7 that expresses the delayed rectifier IKr and appears to be involved in the congenital long QT syndrome. Mechanistic studies showed that blockade of IKr channels by these drugs leads to prolongation of the monophasic action potential (QT interval on surface electrocardiogram) which may then induce the development of early after-depolarization and dispersion of repolarisation leading to torsades de pointes through re-entry mechanism. There are still many questions that need to be answered such as the roles of other potassium channels (IKs, Ito, and Iped) and the relative expression of various potassium channels in different individuals which may be important in the pathogenesis of torsades de pointes with non-sedating antihistamines. There is also a lack of information on the cardiac actions of newer non-sedating antihistamines. It is hoped that with a better understanding of the arrhythmogenic mechanism of non-sedating antihistamines, one will be able to identify those at risk patients and prevent any cardiac toxicity associated with antihistamines and ultimately death.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2222.1999.0290s3174.x
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  • 4
    Electronic Resource
    Electronic Resource
    The differentiation of propafenone from other class Ic agents, focusing on the effect on ventricular response rate attributable to its beta-blocking action (1996)
    Springer
    European journal of clinical pharmacology 51 (1996), S. 199-208 
    Details
    ISSN: 1432-1041
    Keywords: Key words Propafenone; encainide ; flecainide ; β-adrenoceptor blockade ; ventricular response ; Ic agents ; antiarrhythmic agents
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Propafenone, encainide and flecainide have been categorized as class Ic antiarrhythmic drugs, since they produce similar clinical electrophysiological effects. However, propafenone has also modes of action that differ substantially from pure class Ic activity. The most distinctive electrophysiological difference from other class Ic antiarrhythmic drugs stems from its structural similarity with other beta-adrenoceptor antagonists. The potency of the β-adrenoceptor blocking property of propafenone has been estimated to range from 1/20 to 1/50 that of propranolol on a molar basis. Because the plasma concentrations of propafenone during long-term treatment may be up to 50 or more times that of propranolol, the β-adrenoceptor blocking effect may be clinically relevant. However, although the β-adrenoceptor blocking effects are readily demonstrable in vitro, clinical data are more inconsistent, because the β-adrenoceptor blocking action has been reported as being undetectable to significant. During atrial fibrillation, with or without accessory pathways, propafenone exerts effective and prompt control of the ventricular rate in patients who fail to convert to sinus rhythm. However, compared with other class Ic antiarrhythmic drugs, propafenone has not been proved generally better in controlling the ventricular rate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050184
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  • 5
    Electronic Resource
    Electronic Resource
    Acute electrophysiologic effects of an HT2-serotonin antagonist, ketanserin, in humans (1990)
    Springer
    Cardiovascular drugs and therapy 4 (1990), S. 1157-1160 
    Details
    ISSN: 1573-7241
    Keywords: ketanserin ; serotonin antagonist ; QT interval ; QTc interval
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The acute electrophysiologic effects of an intravenous bolus of ketanserin, a 5HT2 serotonin blocker, were studied in ten patients (four females, six males) during invasive electrophysiology. Following baseline electrophysiologic measurements during sinus rhythm and fixed-rate atrial pacing at 600 ms, a bolus of 0.2 mg/kg ketanserin was given over a 3-minute period. After 30 minutes all measurements were repeated. Systemic blood pressure was measured at regular intervals throughout. During sinus rhythm, there was no significant change in the basic cycle length or in the PA, AH, HV, QRS, QT, and QTc intervals. During atrial pacing there was a nonsignificant increase in the QT interval, from 342±13 ms to 366±16 ms, and a significant increase in the QTc interval, from 422±27 ms to 449±29 ms (p〈0.05). There was no reduction in blood pressure. Thus ketanserin produced a significant prolongation of the QTc interval, in the absence of hypokalemia, in humans.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01856513
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  • 6
    Electronic Resource
    Electronic Resource
    Clinically relevant computer model of cardiac rhythm and pacemaker/heart interaction (1987)
    Springer
    Medical & biological engineering & computing 25 (1987), S. 504-512 
    Details
    ISSN: 1741-0444
    Keywords: Biomedical computation ; Cardiac conduction disorders ; Discrete event simulation ; Heart rate dependence ; Heart rhythm model ; Pacemaker models ; Simulated electrocardiogram ; Simulation process
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract A computer simulation model of cardiac rhythm disturbances and of the heart/pacemaker interaction has been created and implemented on a NORD-100 minicomputer. The model incorporates important properties including cycle length dependence of the refractory periods of different parts of the heart and of the atrioventricular nodal conduction speed. Computational experiments produce an explicit timetable of polarisation changes, a simulated one-channel electrocardiographic record and a pacemaker marker channel. The simulation program is written infortran and uses discrete event simulation techniques. The heart is modelled using instances of nine simulation process prototypes. The paper presents and discusses several examples in the form of simulated electrocardiographic records and the results show that the model is clinically relevant. Included in the examples are the modelling of rhythm disturbances, pacemaker actions, pacing for tachycardia prophylaxis and atrioventricular nodal conduction disorders.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02441742
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  • 7
    Electronic Resource
    Electronic Resource
    Changes in the distribution of ventricular ectopic beats in long-term electrocardiograms (1990)
    Springer
    Medical & biological engineering & computing 28 (1990), S. 423-430 
    Details
    ISSN: 1741-0444
    Keywords: Antiarrhythmic drugs ; Definition of proarrhythmia ; Processing of Holter tapes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Only simple methods have been used to assess antiarrhythmic and proarrhythmic effects when comparing baseline and on-therapy Holter recordings taken from the same patient. The paper suggests a new method for definition of these effects based upon comparisons of statistical distributions of ectopic beats. The method is based on multiple random sampling of the recordings and on application of the Smirnov test to compare the samplings. The results of these multiple comparisons are subsequently evaluated using the chi-squared test. An analysis is reported of Holter recordings made on seven patients suffering from ventricular arrhythmia but with anatomically normal heart. In each patient, one baseline recording and one recording on each of three different drugs were made. The results show that the definition of proarrhythmic effects can be partly addressed in a precise mathematical way. The method can also detect a significant change in the character of arrhythmia which can neither be classified as antiarrhythmic nor as proarrhythmic.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02441965
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    Paper (German National Licenses)
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  • 8
    Electronic Resource
    Electronic Resource
    Prognostic value of heart rate variability after myocardial infarction. A comparison of different data-processing methods (1989)
    Springer
    Medical & biological engineering & computing 27 (1989), S. 603-611 
    Details
    ISSN: 1741-0444
    Keywords: Automated filtering of long-term ECG data ; Long-term ECG processing ; Measurement of heart rate variability ; Recognition artefacts
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Reduced heart rate variability (HRV) has been reported as a predictor of mortality in recent myocardial infarction patients. However, its automated assessment in long-term ECG recordings is complicated by recording noise and beat-recognition errors which necessitate filtering of the computer-established sequence of beat-to-beat intervals, and visual checking and manual editing of the long-term recordings, making the whole method operator-dependent. To develop a fully automated method for analysis of HRV from 24 h ECG recordings, five filtering algorithms were combined with three methods of expressing HRV numerically and used to compare two groups of patients undergoing 24 h tape recordings of the ECG within the first two weeks after myocardial infarction. One group comprised 15 patients who later suffered death or ventricular tachycardia, the other group comprised 15 randomly selected uncomplicated cases. Using the same two groups of patients, three different methods of expressing HRV on a beat-to-beat basis were also compared empirically. The results show that alternative, operator-independent methods for establishing HRV from continuous long-term ECG recordings of postmyocardial infarction patients seem to be as effective as previously reported methods which rely on operator-dependent data post-processing techniques.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02441642
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  • 9
    Electronic Resource
    Electronic Resource
    Influence of the recognition artefact in automatic analysis of long-term electrocardiograms on time-domain measurement of heart rate variability (1993)
    Springer
    Medical & biological engineering & computing 31 (1993), S. 539-544 
    Details
    ISSN: 1741-0444
    Keywords: Automatic and manual recognition ; Biological and technical noise ; Long-term electrocardiogram
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02441992
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    Paper (German National Licenses)
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  • 10
    Electronic Resource
    Electronic Resource
    Computer simulation of electronic interactions during excitation and repolarisation of myocardial tissue (1991)
    Springer
    Medical & biological engineering & computing 29 (1991), S. 425-432 
    Details
    ISSN: 1741-0444
    Keywords: Computer model ; ECG ; Electrotonic interactions ; Excitation ; Planning ; Polarisation ; Myocardial tissue ; Simulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract A three-dimensional model of myocardial tissue has been developed which incorporates electrotonic interactions between neighbouring myocytes. The algorithms of the model are based on asynchronous planning of discrete events. Each cellular element is described in a logical way and traces a predefined action potential which is dynamically modified depending on the electrotonic interactions. The model has a low computational complexity and has been implemented on personal workstations even for experiments investigating arrhythmogenic processes and simulating several tens of cycles in blocks composed of several thousand elements. The paper describes the algorithmic implementation of the model and presents three series of experiments examining the dependence of the accuracy of the model on the size of the modelled tissue, changes of the shape of simulated T-waves due to electrotonic interactions and arrhythmogenic processes caused by lowering the threshold of the electric flow which excites individual cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02441665
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