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F L Meijler

Publications and source records attributed to F L Meijler.

At least 37 records · Page 2Linked to original sources
PubMed1998

Pharmacological analysis of the activity of the adenosine uptake inhibitor, dipyridamole, on the sinoatrial and atrioventricular nodes of the guinea-pig.

1. Dipyridamole potentiates the effects of adenosine on the heart by inhibiting adenosine uptake. The effects of dipyridamole on both adenosine and N-ethylcarboxamidoadenosine (NECA) concentration-effect (E/[A]) curves were compared on the AV node, in guinea-pig isolated perfused hearts, and on the SA node, in isolated right atria, by measuring dromotropic and chronotropic responses, respectively. In the absence of dipyridamole, adenosine was significantly more potent on the AV node than SA node (AV p[A]5, = 4.95+/-0.10. SA p[A]50=3.62+/-0.10). In contrast, NECA and adenosine in the presence of dipyridamole were approximately equiactive in the two assays (NECA: AV p[A]50=7.07+/-0.07; SA p[A]50=7.30+/-0.08: adenosine: AV p[A]50=6.49+/-0.08; SA p[A]50=6.27+/-0.05). Dipyridamole was significantly more potent in enhancing the effects of adenosine on the SA node than on the AV node (pKi values estimated by Kenakin's method (1981): AV node 8.18+/-0.14; SA node=8.75+/-0.08). 2. The difference in pKi values did not appear to be due to dipyridamole expressing other actions because concentrations of dipyridamole which saturated the adenosine transporter had no effect on the NECA E/[A] curves in either assay. However, the test of another assumption of Kenakin's method, that adenosine taken up into cells is pharmacologically inactive, failed on the AV node assay because a significant potentiating interaction was found between adenosine and NECA. The interaction was concentration-dependent, reciprocal to the extent that pre-incubation with either agonist potentiated the other and was concluded to be due to an intracellular action of adenosine as the potentiation disappeared in the presence of dipyridamole. 3. An explanatory model was developed to account for the data obtained using existing pharmacological concepts of ligand action in isolated tissue bioassays. In the model, adenosine, but not NECA, was assumed to be subject to saturable agonist uptake, an uptake which was competitively blocked by dipyridamole. Adenosine and NECA were assumed to act extracellularly at adenosine A1-receptors. In the AV node, but not the SA node, the adenosine transported into the cells was assumed to potentiate the effects of adenosine A1-receptor activation. For the AV node assay, the model predicted that potentiation of adenosine by uptake blockade is offset by a simultaneous decrease in potentiation due to the intracellular action of adenosine. All of the experimental data obtained in the study could be accounted for by the model including the apparent differences in potency of adenosine in the absence of dipyridamole and the pKi values for dipyridamole.

Adenosine↗
PubMed1997

[Atrioventricular conduction time in premature infants is about half of that in adults].

OBJECTIVE: To determine the atrioventricular (AV) conduction time in prematurely born infants as part of a comparative electrocardiological study of conduction times versus heart size. DESIGN: Recording and analysis of electrocardiograms. SETTING: Department of Neonatology, University Hospital of the Free University of Amsterdam, the Netherlands. METHODS: Using bipolar precordial leads of standard monitoring equipment in 28 babies, born at a gestational age of 26-36 weeks, ECGs were recorded as soon after birth as possible. The ECGs were analysed and relevant conduction times, such as PR intervals and QRS durations, were measured by hand. These data were related to the birth weights of the infants. (The heart weight amounts to approximately 0.6% of body weight.) RESULTS: Average birth weight of the babies was 1374 g (SD: 491), average PR interval 93 ms (9), QRS duration 40 ms (4), and average heart rate 148/min (14). CONCLUSION: Human hearts weighing 6-10 g have conduction times half that of the adult human heart which weighs 50 times as much. The contribution of the AV node to the total AV conduction time increases with diminishing heart size.

Atrioventricular Node↗
PubMed1996

AV nodal function during atrial fibrillation: the role of electrotonic modulation of propagation.

The irregular ventricular rhythm that accompanies atrial fibrillation (AF) has been explained in terms of concealed conduction within the AV node (AVN). However, the cellular basis of concealed conduction in AF remains poorly understood. Our hypothesis is that electrotonic modulation of AVN propagation by atrial impulses blocked repetitively within the AVN is responsible for changes in function that lead to irregular ventricular rhythms in patients with AF. We have tested this idea using two different simplified computer ionic models of the AVN. The first ("black-box") model consisted of three cells: one representing the atrium, another one representing the AVN, and a third one representing the ventricle. The black-box model was used to establish the rules of behavior and predictions to be tested in a second, more elaborate model of the AVN. The latter ("nine-cell" model) incorporated a linear array of nine cells separated into three different regions. The first region of two cells represented the atrium; the second region of five cells represented the AV node; and the third region of two cells represented the ventricle. Cells were connected by appropriate coupling resistances. During regular atrial pacing, both models reproduced very closely the frequency dependence of AV conduction and refractoriness seen in patients and experimental animals. In addition, atrial impulses blocked within the AV node led to electrotonic inhibition or facilitation of propagation of immediately succeeding impulses. During simulated AF, using the nine-cell model, random variations in the atrial (A-A) interval yielded variations in the ventricular (V-V) interval but there was no scaling, i.e., the V-V intervals were not multiples of the A-A intervals. As such, the model simulated the statistical behavior of the ventricles in patients with AF, including: (1) the ventricular rhythm was random; and (2) the coefficient of variation (standard deviation/mean) of the ventricular rhythm was relatively constant at any given mean V-V interval. Analysis of cell responses revealed that repetitive atrial input at random A-A intervals resulted in complex patterns of concealment within the AVN cells. Consequently, the effects of electrotonic modulation were also random, which resulted in a smearing of the AV conduction curve over A-A intervals that were larger than those predicted for 1:1 AV conduction. Hence, during AF, electrotonic modulation acts in concert with the frequency dependence of AVN conduction to result in complex patterns of ventricular activation. Finally, similarly to what was shown in patients, VVI pacing of the ventricle in the nine-cell model at the appropriate frequency led to blockade of nearly all anterograde (i.e., A-V) impulses. The essential feature here was that the retrograde impulse invading the AVN cells was followed by refractoriness with slow recovery of excitability, setting the stage for electrotonic inhibition of anterograde impulses. Overall, the results provide insight into the cellular mechanisms underlying AVN function and irregular ventricular response during AF.

Animals↗
PubMed1995

Left ventricular beat-to-beat performance in atrial fibrillation: contribution of Frank-Starling mechanism after short rather than long RR intervals.

OBJECTIVES: This study sought to evaluate control mechanism of the varying left ventricular performance in atrial fibrillation. BACKGROUND: Atrial fibrillation is characterized by a randomly irregular ventricular response, resulting in continuous variation in left ventricular beat-to-beat mechanical behavior and hemodynamic variables. METHODS: Fourteen patients with chronic nonvalvular atrial fibrillation were studied, using a nonimaging computerized nuclear probe linked to a personal computer. Left ventricular ejection fraction, end-diastolic and end-systolic volume counts, stroke volume counts and filling time were calculated on a beat-to-beat basis during 500 consecutive RR intervals. Multiple regression analysis was used to assess how ejection fraction was predicted by these variables. RESULTS: The preceding RR interval and end-diastolic volume showed a positive relation, and prepreceding interval and end-systolic volume an inverse relation, with ejection fraction (all p < 0.001). Sensitivity analysis suggested that the preceding interval and the end-diastolic volume were equally important in predicting ejection fraction. There was a relatively strong interaction between the preceding interval and end-diastolic volume, indicating that the influence of the end-diastolic volume on ejection fraction was diminished after long intervals. A second interaction showed that the effect of end-diastolic volume on ejection fraction was attenuated after short prepreceding cycles. CONCLUSIONS: Cycle length-dependent contractile mechanisms, including postextrasystolic potentiation and mechanical restitution, determine the varying left ventricular systolic performance during atrial fibrillation over the entire range of intervals. Beat-to-beat changes in preload, consistent with the Frank-Starling mechanism, also play a role, but their influence is diminished after long preceding and short prepreceding intervals.

Aged↗
PubMed1995

Anatomy of the sinus node, AV node, and His bundle of the heart of the sperm whale (Physeter macrocephalus), with a note on the absence of an os cordis.

BACKGROUND: Atrioventricular (AV) conduction time in large whales is only slightly greater than in smaller mammals even though their hearts are enormously larger. Little is known of the detailed histology or cytology of the conduction system of large whales. Such knowledge could be useful in defining the nature of cardiac rhythm and conduction of the whale as well as smaller mammals including humans. METHODS: We studied hearts from seven sperm whales. After fixation in formaldehyde and later dissection, specimens were prepared for histological examination. RESULTS: Cell size, histological organization, and innervation of the sperm whale's sinus node, AV node, and His bundle are similar to most mammalian hearts, except the sinus node is substantially larger. There is no central fibrous body between the atrial and ventricular septa, and the whale has no os cordis. Only the upper quarter of the interventricular septum is fully formed; below that there is only a thin layer of fatty connective tissue between the two ventricles. CONCLUSIONS: Given our morphological findings, we believe that the whale's comparatively short AV conduction time may be best explained by the sinus node and AV node functioning as coupled relaxation oscillators. Absence of an os cordis or central fibrous body or strong attachment between the two ventricles may pose both electrophysiological and hemodynamic hazards when the whale is no longer in its normally buoyant aquatic environment.

Animals↗
PubMed1993

Time course of hemodynamic changes and improvement of exercise tolerance after cardioversion of chronic atrial fibrillation unassociated with cardiac valve disease.

This study prospectively assessed the time course, magnitude and mechanism of the hemodynamic changes after restoration of sinus rhythm in patients with chronic atrial fibrillation (AF) unassociated with valvular disease. Severe cardiac dysfunction may occur after chronic supraventricular tachycardia in patients with and without underlying cardiac disease. Improvement may follow abolishment of the arrhythmia or adequate slowing of the ventricular rate. Eight patients were studied with a mean previous duration of AF of 10 +/- 9 months. Ejection fraction, exercise capacity and the atrial contribution to the left ventricular filling (only during sinus rhythm) were studied before cardioversion, after cardioversion and 1 week, 1 month and 6 months thereafter. A significant improvement in ejection fraction from 36 +/- 13 to 53 +/- 8% (p < 0.05) occurred at 1 month after cardioversion. Concomitantly, peak oxygen consumption had increased at 1 month, from 20.1 +/- 7 to 25.2 +/- 6 ml/min/kg (p < 0.05). Thereafter, no further improvement in hemodynamic parameters occurred. The atrial systole improved already at 1 week (from 3 +/- 5 to 16 +/- 11%, p < 0.05) and remained unchanged thereafter. Thus, restoration of sinus rhythm was associated with a delayed improvement in ejection fraction and maximal exercise capacity, preceded by an early restoration of atrial contractility and an acute slowing of the heart rate. The discrepancy in time course of restoration of atrial and ventricular function parameters suggests that an intrinsic left ventricular cardiomyopathy is present in patients with AF.

Aged↗
PubMed1992

Electrocardiogram of the humpback whale (Megaptera novaeangliae), with specific reference to atrioventricular transmission and ventricular excitation.

OBJECTIVES: The objective of the study was to record the electrocardiogram (ECG) of a large whale to obtain crucial data for comparative electrophysiologic analysis. BACKGROUND: The data were needed to establish the mismatch between heart size and PR interval and QRS duration in mammals. METHODS: In the waters off the coast of Newfoundland, in two humpback whales (Megaptera novaeangliae) with an estimated weight of 30,000 kg a 1-lead ECG was recorded, enabling reliable assessment of P waves and QRS complexes. RESULTS: It was found that both the PR interval (atrioventricular [AV] transmission time) and QRS duration (ventricular excitation) are extremely short for animals of this size. These findings are difficult, if not impossible, to explain on the basis of currently accepted electrophysiologic theories. However, the narrow QRS complex may be due to a very dense His-Purkinje network in the ventricular wall of whales. Alternative mechanisms that can explain the function of the mammalian AV node need to be considered and explored. CONCLUSIONS: The results of the study may be of value for the understanding of the ECG in humans.

Animals↗
PubMed1990

Post-extrasystolic potentiation without a compensatory pause in normal and diseased hearts.

Variables derived from left ventricular volume were used to study post-extrasystolic potentiation. Left ventriculograms were obtained from 11 healthy individuals and 49 patients with coronary heart disease (30 with a previous myocardial infarction and 19 without any signs of myocardial damage). Post-extrasystolic potentiation was induced by a regularly driven right atrial rhythm that was interrupted by one atrial extrasystole in such a way that the post-extrasystolic RR interval was kept equal to the basic RR interval. The left ventricular end diastolic volumes of the pre-extrasystolic and post-extrasystolic beats were equal. In all groups there was evidence of post-extrasystolic potentiation in one or more of the indices of left ventricular function (ejection fraction, mean normalised systolic ejection rate, and systolic volume, and stroke volume). Potentiation was especially evident in patients with left ventricular damage; this suggests that a compensating mechanism is an intrinsic property of the myocardium. The Frank-Starling mechanism does not contribute to the increased performance of the post-extrasystolic beat in normal individuals or in patients with coronary artery disease.

Action Potentials↗
PubMed1990

[Comparative pathophysiology of the atrioventricular node].

The apparent mismatch between size and electrical function of the mammalian heart can be exemplified by the relation between ventricular rate during atrial fibrillation in dog, human, and horse, and bodyweight. The same is true for the relation between atrioventricular transmission time and heart size. While heart size may increase with a factor of 10(8), PR interval (on the surface ECG) will only increase with a factor 30. The curve of the PR interval versus the third root of heart weight has an S-shape. This form of relation cannot easily be explained on the basis of current electrophysiological theories. The contribution of the AV nodal delay to AV transmission time probably diminishes with increasing heart size. The mechanism of AV nodal delay is therefore not clear. Right ventricular pacing with intervals twice as long as the shortest PR-intervals in patients with atrial fibrillation results in complete block of anterograde conduction. The AV node as an unprotected pacemaker, entrained during sinus rhythm and electrotonically modulated during atrial fibrillation, rather than a cable with conduction properties, may offer an explanation for the non-linear and non-conductive behaviour of the AV node. This may well have consequences for the treatment of patients with atrial fibrillation.

Animals↗