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Biomedical subjects

F I Bonke

Publications and source records attributed to F I Bonke.

At least 19 recordsLinked to original sources
PubMed1993

Electrophysiologic effects of ORG 30701 (dopropidil) on rabbit ventricular myocardium.

The electrophysiologic effects of ORG 30701 (1-8 x 10(-6) M) were tested in a thin, two-dimensional sheet of ventricular myocardium. Special attention was paid to a possible promotion of reentrant excitation. The drug did not increase the degree of inhomogeneity of conduction and because of the marked effect on refractoriness prevent fast rates (either spontaneously or driven). If the extracellular potassium concentration was lowered (from 5.6 to 2.0 mM), the enhancement of refractoriness by the drug was more marked. The changes in refractoriness do not appear to be based on lengthening of the repolarization of the action potential, but rather on post-repolarization refractoriness; therefore, the occurrence of triggered activity (early afterdepolarizations) is not anticipated. ORG 30701 is a cardioactive drug that because of its calcium antagonistic action acts as an antianginal drug and, in addition, exhibits antiarrhythmic properties.

Animals↗
PubMed1992

Vulnerability of rabbit atrium to reentry by hypoxia. Role of inhomogeneity in conduction and wavelength.

In isolated superfused left atria of the rabbit, the inducibility of tachyarrhythmias by single early premature stimuli was highly increased by hypoxia. High-resolution mapping showed that these arrhythmias were caused by circus movement around a functional arc of conduction block (leading circle reentry). To determine the electrophysiological changes by hypoxia responsible for the higher vulnerability to intra-atrial reentry, the wavelength of the atrial impulse and spatial inhomogeneities in refractory periods and local conduction delays were measured. Hypoxia caused a transient increase in refractory periods during the first 10-15 min of hypoxia. After this period, refractory periods shortened again to values slightly lower than during control. During the whole period of hypoxia, local differences in refractory periods were enlarged. Conduction velocity was significantly depressed by hypoxia. As a result, the wavelength of the atrial impulse gradually shortened during hypoxia to approximately 80% of control. Inhomogeneity in conduction was quantified by phase maps in which the maximal local delays in conduction are plotted. Hypoxia caused a marked increase in inhomogeneity in conduction both during slow rhythm (inhomogeneity index increased from 2.3 to 3.4) and premature activation (from 3.1 to 4.7). We conclude that the higher vulnerability of the atrium for reentrant arrhythmias by hypoxia is based on a combination of a moderate shortening of the wavelength and an increase in inhomogeneity in conduction of premature wavefronts.

Action Potentials↗
PubMed1989

Effects of verapamil, diltiazem and disopyramide on sinus function: a comparison with bepridil.

Cardiac drugs known to affect sinus function mostly exhibit negative chronotropic activity. However, impulse conduction within the sinus node can also be influenced. Recently we studied the direct effects of bepridil on rabbit sinus function. It appeared that sinoatrial impulse conduction was depressed markedly with drug concentrations that did not affect sinus automaticity. In the present study the direct effects of verapamil, diltiazem and disopyramide on rabbit sinus function and atrial conduction properties were studied. Verapamil (8.8 x 10(-8) M) reduced the sinoatrial impulse conduction velocity by 35% and prolonged sinoatrial refractoriness by 36%. On the other hand, the sinus rate and atrial conduction parameters were hardly affected. Diltiazem (5 x 10(-6) M) exerted similar actions on the sinoatrial impulse conduction velocity and caused a simultaneous reduction in the sinus rate of 48%. Atrial conduction remained unaffected. Disopyramide (5 x 10(-5) M) depressed both the atrial and nodal conduction properties markedly, whereas the sinus rate was reduced moderately, by almost 20%. Thus, verapamil, diltiazem and disopyramide act differently on sinus function and atrial conduction, whereby the predominant effect of verapamil and diltiazem on sinoatrial conduction properties favours the occurrence of a sinus exit block.

Animals↗
PubMed1989

Effects of bepridil on conduction properties of the isolated rabbit sinus node and atrial myocardium.

In the isolated rabbit sinus node and right atrial myocardium, the effects of bepridil (1-6 x 10(-6) M) on impulse formation, impulse conduction, and tissue refractoriness were examined. In the sinus node, drug concentrations between 1 and 3 x 10(-6) M were tested. In the border zone of the sinus node, bepridil (3 x 10(-6) M) reduced impulse conduction velocity by 65% and prolonged the effective refractory period by 81% (n = 11). In the center of the sinus node, bepridil in a concentration of 2.5 x 10(-6) M decreased impulse conduction velocity by 78% and prolonged effective refractory period by 77% (n = 9), whereas a drug concentration of 3 x 10(-6) M blocked impulse conduction systematically. Despite these marked effects on nodal conduction properties, only limited effects on sinus rate were found. Conduction properties in the atrium were affected by bepridil as well, but higher concentrations (4-6 x 10(-6) M) were needed. Impulse conduction velocity was decreased by 57%, and the effective refractory period was prolonged by 73% (6 x 10(-6) M; n = 8). At these higher drug concentrations, sinus automaticity decelerated and ceased abruptly, after which only subthreshold oscillations were detectable. From these findings, we concluded that (a) bepridil reduces impulse conduction velocity and prolongs refractoriness in the sinus node, less markedly in the atrial myocardium; (b) bepridil affects nodal impulse conduction prior to nodal impulse formation; and (c) bepridil possesses both "fast channel" and "slow channel" inhibitory properties.

Action Potentials↗
PubMed1988

An easy and direct approach to investigate conduction properties of the rabbit sinus node.

The sinus node is not only important for the generation of the cardiac impulse but also as conductor of this impulse from the site of origin toward the atrium. An easy method to investigate conduction properties of sinus nodal tissue directly is described. The isolated right atrium of the rabbit was divided--via an incision perpendicular to the crista terminalis--into two halves connected only by a bridge of sinus nodal tissue. By means of two atrial surface electrodes conduction through the sinus node bridge was monitored. It appeared that conduction in the sino-atrial border zone is many times slower than in the atrium and refractory period markedly longer. In the center of the sinus node conduction is again slower and refractory period longer than in the border zone. Validity of the method was tested by reconstruction of the conduction route of stimulated impulses using microelectrode recordings. Applications of the method were demonstrated by studying the effects of rate and rhythm, hypothermia, hypoxia, acetylcholine and norepinephrine as well as verapamil. The model is suitable for investigation of the effects of drugs and other interventions on impulse conduction in sinus nodal tissue.

Acetylcholine↗
PubMed1988

Reentrant and focal arrhythmias in low potassium in isolated rabbit atrium.

In isolated superfused left atria of the rabbit, tachyarrhythmias became highly inducible with a decrease of the extracellular potassium concentration to 2.0 mM. The nature of the arrhythmias was determined with a high-resolution mapping system. In several cases, abnormal impulse formation was found, but the majority of arrhythmias (75%) was caused by a circus movement of the impulse. Furthermore, circus-movement tachyarrhythmias often degenerated into fibrillatory activity, and activation maps revealed the presence of multiple wavelets during this chaotic rhythm. The occurrence of reentrant arrhythmias may be caused either by an increase in inhomogeneity in conduction or by a shortening of the wavelength in low potassium. Inhomogeneity in conduction was determined by calculating the difference in activation times between neighboring electrodes. In low potassium, premature activation significantly increased the inhomogeneity index compared with slow rhythm (from 2.2 to 3.9; P less than 0.001) but was not significantly different from the inhomogeneity measured at normal potassium concentrations. Low potassium, however, did shorten significantly the wavelength of the impulse by approximately 40%. The increased inducibility of reentry in low potassium is therefore caused by a reduction of the length of the excitation wave and not by an increase in inhomogeneity in conduction.

Animals↗
PubMed1988

Length of excitation wave and susceptibility to reentrant atrial arrhythmias in normal conscious dogs.

We calculated the wavelength of the atrial impulse in chronically instrumented conscious dogs by measuring both conduction velocity and refractory period: wavelength = refractory period X conduction velocity. Implantation of multiple stimulating and recording electrodes allowed wavelength determination at four different areas: the right and left parts of Bachmann's bundle and the free walls of the right and left atria. During programmed electrical stimulation, three types of arrhythmias were observed: rapid repetitive responses, atrial flutter, and atrial fibrillation. During normal rhythm, the wavelength of the atrial impulse varied between 14 and 18 cm. Premature beats had a shorter wavelength, depending on the degree of prematurity. Premature beats that evoked rapid repetitive responses showed a critical shortening of the wavelength below 12.3 cm. Episodes of atrial flutter were induced at a wavelength below 9.7 cm, while fibrillation occurred at wavelengths shorter than 7.8 cm. We correlated the induction of these arrhythmias with the values of refractory period, conduction velocity, and wavelength during control and during administration of several drugs. Intravenous administration of acetylcholine shortened the wavelength by 30-40%, mainly because of refractory period shortening. Both propafenone and lidocaine had strong but opposite effects on refractoriness and conduction and, consequently, little effect on the wavelength. Quinidine markedly prolonged the refractory period, but prolongation of wavelength was less because of a simultaneous decrease in conduction velocity. d-Sotalol also increased refractory period, but because it had no appreciable effect on conduction velocity, this drug was the most effective in prolongation of wavelength. Linear discriminant analysis of the data showed that the refractory period and the conduction velocity each were poor parameters to predict the occurrence of the different arrhythmias (predictive value 48% and 38%, respectively). The combination of both properties, however, as expressed in the wavelength, was a more reliable index that predicted the induction of the different arrhythmias correctly in 75% of the cases. We conclude that the wavelength is a useful parameter for evaluating antiarrhythmic drugs.

Acetylcholine↗
PubMed1987

Impulse propagation from the SA-node to the ventricles.

Normally the pacemaker of the mammalian heart is located in the sinus node. In the rabbit the sinus node can be subdivided into two regions, the center of the node where the impulse originates and the border zone through which the impulse is conducted towards the atrium. Conduction properties of both regions were investigated. It appeared that conduction velocity increases and refractoriness decreases when one goes from the nodal center towards the atrium. The tissue mass of the atrium is large in comparison to the sinus node and normally the resting membrane potential of atrial fibers is more negative than that of nodal fibers; consequently, a potential difference exists causing a current flow between both areas. Evidently this hyperpolarizing current flow depresses impulse formation in the border zone fibers which have better intrinsic pacemaker properties than fibers in the nodal center. If the impulse has reached the atrium it is conducted with a relatively high safety factor and will reach the AV node in principle without difficulty. The AV node, if deprived of sinus nodal dominance, develops spontaneous activity originating from the lower nodal fibers. Also in this structure, electrotonic depression by surrounding tissue causes deceleration of the pacemaker.

Action Potentials↗
PubMed1987

The influence of the atrial myocardium on impulse formation in the rabbit sinus node.

In the isolated right atrium of the rabbit heart the influence of the atrial myocardium on impulse formation in the sinus node was investigated. Under normal conditions the pacemaker (earliest activation) was located in the center of the node where fibers with the highest rate of diastolic depolarization were found. After disconnection of the atrium from the sinus node spontaneous cycle length decreased from a mean of 348 ms to a mean of 288 ms (-18%) in all experiments (n = 15). This was accompanied by a shift of the pacemaker from the nodal center towards the border zone. By means of multiple microelectrode impalements changes in action potential configuration were studied. After disconnection of atrium and sinus node the rate of diastolic depolarization of fibers in the border zone was increased from a mean of 26 mV/s to a mean of 78 mV/s, whereas in the center of the sinus node no increase was found (mean: 52 mV/s). It was concluded that the fibers in the border zone of the sinus node are better pacemaker fibers than in the nodal center. However under normal conditions the intrinsic pacemaker properties of the border zone fibers are electronically depressed by the connected atrial myocardium.

Action Potentials↗
PubMed1986

The wavelength of the cardiac impulse and reentrant arrhythmias in isolated rabbit atrium. The role of heart rate, autonomic transmitters, temperature, and potassium.

We measured the wavelength of the cardiac impulse, defined as the distance traveled by the depolarization wave during the functional refractory period, in isolated narrow strips of rabbit atrium. During control, wavelength was 42 mm during pacing with 2 Hz, and was 28 mm at the maximum pacing rate; early premature beats had a wavelength as short as 23 mm. Administration of carbamylcholine (4 X 10(-7) g/ml) shortened the wavelength to 21 mm during 2 Hz, 18 mm at the maximum pacing rate Fmax, and 16 mm during an early premature impulse, respectively. The effects of epinephrine (6 X 10(-7) M) were strongly rate dependent. At slow heart rates, epinephrine clearly prolonged the wavelength (58 mm), whereas, during maximum pacing, wavelength remained unchanged (28 mm). Hypokalemia (2 mM) decreased the length of the impulse at all stimulation frequencies. Moderate hyperkalemia (5.6 and 7.0 mM) did not modify wavelength because refractoriness and conduction velocity were affected proportionally. Above 7.0 mM potassium, the wavelength became progressively prolonged because of the development of post-repolarization refractoriness. Cooling to 27 degrees C resulted in a slight lengthening of the impulse. At lower temperatures, however, wavelength prolonged significantly because of a relatively strong prolongation of the refractory period. In separate experiments in 15 X 20 mm segments of atrium, reentrant tachyarrhythmias were induced and the circuit size compared with the wavelength. The size of intraatrial circuits was similar to the magnitude of the measured wavelength during maximum pacing. Carbamylcholine and hypokalemia, both of which shorten the impulse length, also clearly decreased the size of reentrant circuits. Cooling to 27 degrees C, which affects both refractoriness and conduction velocity, only slightly prolonged the wavelength; accordingly, the size of reentrant circuits at 27 degrees C was only slightly longer than at 37 degrees C. These experiments emphasize the importance of the wavelength of the cardiac impulse in relation to the occurrence of intramyocardial reentry.

Animals↗
PubMed1982

Electrophysiologic mapping to determine the mechanism of experimental ventricular tachycardia initiated by premature impulses. Experimental approach and initial results demonstrating reentrant excitation.

Epicardial activation patterns were determined during repetitive responses and nonsustained and sustained ventricular tachycardias induced by premature impulses in infarcted canine hearts. A multiplexing system enabled recordings to be obtained from up to 192 electrodes simultaneously either from the entire epicardial surface with a sock electrode array or only from the sheet of epicardial muscle that survives over the infarcts, with a plaque electrode array. In hearts with an infarct caused by permanent occlusion of the left anterior descending coronary artery, the earliest epicardial excitation during nonsustained tachycardias occurred on the anterior left ventricle at the border of the infarcted region and in epicardial muscle surviving over the infarcted region. Circuitous conduction patterns leading to reentry occurred in the epicardial muscle over the infarct and probably caused the arrhythmias. During sustained tachycardia in hearts with an infarct caused either by permanent or temporary occlusion of the left anterior descending coronary artery, the earliest epicardial excitation also occurred at the border of the infarcted region, but there was no evidence of reentry in the surviving epicardial muscle.

Animals↗
PubMed1980

The effect of ouabain on the isolated sinus node preparation of the rabbit studied with microelectrodes.

In 30 isolated, spontaneously beating right atrial preparations of the rabbit, the arrhythmogenic actions of ouabain were studied with microelectrodes. Ouabain (10(-6) M) uniformly produced the following events: (1) a gradual increase in sinus rate with periods of alternation of beta-to-beat atrial intervals, (2) a rapid rate and regular rhythm, (3) severe irregularity of rhythm, (4) total atrial arrest. Cycle length decreased from 394 msec +/- 43 (mean +/- SD) during control to 229 msec +/- 26 during the period of rapid rate and regular rhythm (P less than 0.001). Pretreatment with atropine or propranolol did not abolish this positive chronotropic action of ouabain. Maps of the spread of activation in the area of the sinus node in eight experiments revealed that the speeding up of rate is accompanied by a shift of dominant pacemaker site toward the sinoatrial border. In explanation, it is shown that sinoatrial border fibers develop strong diastolic depolarization, whereas dominant pacemaker fibers do so to a lesser extent or not at all. The atrial arrhythmias--best to be described as "digitalis-induced sinus tachycardia"--may represent the experimental counterpart of the so-called "paroxysmal atrial tachycardia with block" described as a common manifestation of digitalis intoxication in man.

Action Potentials↗
PubMed1978

Sinus node response to premature atrial stimulation in the rabbit studied with multiple microelectrode impalements.

In this study we investigated the response of the isolated rabbit sinus node to ectopic atrial premature beats elicited late in the atrial cycle. In three experiments the response of at least 45 different fibers of the sinus node was recorded, whereas, in other experiments, investigation was less extensive. In this way the spread of activation of the total pacemaker area could be mapped accurately both during spontaneous beating and the induction of ectopic atrial beats of different degrees of prematurity. We found that: (1) The conduction of an impulse from the dominant pacemaker area to the atrium during spontaneous rhythm (antegrade conduction) is slower than the conduction of an ectopic atrial impulse towards the center of the sinus node (retrograde conduction). (2) The action potential of the dominant pacemaker fibers in the sinus node is shortened because of premature activation caused by an ectopic impulse from the atrium. Late premature beats had no effect on diastolic depolarization. If the retrograde activation wave did not reach the area of the dominant pacemaker before the spontaneous discharge of these fibers, there was electrotonic influence demonstrable over a distance of about 0.5 mm. (3) Comparison of the true sinoatrial conduction time with the estimated sinoatrial conduction calculated indirectly from the length of the postextrasystolic atrial cycle revealed that, in the isolated rabbit heart, the calculated value is a serious underestimation of the true antegrade sinoatrial conduction time.

Action Potentials↗