[Educational inspection of medicine and health sciences; a glimpse of the final report].
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Certification↗
Biomedical subjects
L N Bouman
Publications and source records attributed to L N Bouman.
Spatial and functional relationship between myocytes and fibroblasts in the rabbit sinoatrial node.
In an attempt to understand better the directional differences in conduction velocity in the rabbit sinoatrial node, a possible conductive role of the abundant connective tissue surrounding the myocytes has been investigated. In particular, starting from the finding of communicating junctions between heart muscle cells and fibroblasts in tissue culture, heterologous gap junctions were searched for in thin sections of the rabbit sinoatrial node. Within and at the edge of nodal cell clusters, fibroblasts often show thin sheet-like extensions parallel to the surface of myocytes. In contrast to the intimately contacting myocytes, fibroblast extensions are kept separated from the myocytes by the basement membrane of the latter. Besides some rare undefined membrane appositions a single tiny gap junction-like structure was found between a fibroblast and a myocyte in a tissue area in which the calculated number of gap junctions between myocytes amounts from 1.10(4) to 3.10(4). Yet, fibroblasts are linked together regularly by small gap junctions containing a wider gap than the junctions between the myocytes (1.4 +/- 0.4 nm vs. 1.0 +/- 0.4 nm, resp., P less than 0.05). As an alternative to direct electrical coupling, the possibility of interaction between fibroblasts and nodal cells by capacitive coupling has been considered. Model calculations based on the reconstruction of some fibroblast extensions parallel to nodal cells show that the current which can be transmitted from discharging nodal cells to fibroblasts is negligible. It is concluded that fibroblasts do not participate in the impulse conduction within the sinoatrial node. The origin of the directional differences in conduction velocity in the sinoatrial node must be found in the spatial arrangement of the myocytes and the distribution of the gap junctions between these cells only.
Animals↗
Effect of transmural vagal stimulation on electrotonic current spread in the rabbit sinoatrial node.
OBJECTIVE: The effect of vagal stimulation on the decay of electrotonic potential caused by intracellular current injection and on input resistance was measured in the sinoatrial node of isolated rabbit right atria. METHODS: Studies were performed on New Zealand White rabbits weighing approximately 2-3 kg. Vagal stimulation was achieved by transmural stimulation of intramural nerve fibres in the presence of propranolol. A K+ perfused suction electrode was used to inject hyperpolarising current pulses; input resistance was measured by means of a double barrel microelectrode. RESULTS: Vagal stimulation which caused a 14-20% increase of cycle length diminished electronic potential significantly by a decrease of membrane resistance. The input resistance of the sinoatrial node was not affected. Space constant values calculated by using either a one or a two dimensional model of electrotonic current spread were decreased on average by 13% and 14% respectively. CONCLUSIONS: The results from this study show that vagal stimulation which gave rise to a moderate negative chronotropic effect and marked changes in action potential configuration of nodal fibres affects the electrotonic interaction within the sinoatrial node. This may have consequences for the electrical activity and synchronisation of the sinoatrial nodal fibres.
Action Potentials↗
[Clinical education for basic physicians].
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Clinical Medicine↗
The cellular basis of intrinsic sinus node recovery time.
STUDY OBJECTIVE: The aim was to investigate the mechanism of the intrinsic sinus node recovery time. DESIGN: The effect of 2 min periods of 20% and 50% overdrive on the electrical activity of fibres in the sinoatrial node was studied in isolated atria of rabbits under complete autonomic blockade (atropine 3 x 10(-6) M and propranolol 3 x 10(-7) M). EXPERIMENTAL MATERIAL: Rabbits (New Zealand white) of either sex up to 3 kg weight were used. MEASUREMENTS AND MAIN RESULTS: The first returning cycle after overdrive is prolonged not only by the time needed for retrograde plus antegrade conduction but also by a delay in impulse formation (overdrive suppression). During pacing, action potential duration, amplitude, maximum diastolic potential (only in primary pacemaker fibres), and diastolic depolarisation rate were all decreased. Action potential duration, amplitude and maximum diastolic potential returned to control value during the first cycle following a period of overdrive, but diastolic depolarisation remained depressed during many consecutive cycles. In primary pacemaker fibres, diastolic depolarisation appeared to be depressed throughout diastole. In latent pacemaker fibres diastolic depolarisation was depressed only in the second part of the diastole. CONCLUSIONS: Sinus node recovery time has two components: (1) a conduction component of both retrograde and antegrade conduction, and (2) a depression of the automaticity (= overdrive suppression), which is only due to a slowing of diastolic depolarisation.
Action Potentials↗
Structure and function of the simian sinoatrial node (Macaca fascicularis).
In isolated preparations of the simian (Macaca fascicularis) heart, we studied the activation pattern within the sinoatrial node, using the conventional microelectrode technique. After electrophysiological experiments we subjected three preparations to a correlative light microscopical and two to an electron microscopical investigation. The sinoatrial node of the Macaca fascicularis is characterized by unifocal impulse generation. The impulse is propagated preferentially in an oblique direction towards the inferior vena cava, which is a unique direction compared to all other mammals studied so far. Possible consequences for A-V nodal input are discussed. Conduction block was seen in an oblique superior direction towards the atrial septum. In this small zone of blocked conduction double component action potentials could be recorded. The morphology of the sinoatrial node of the Macaca fascicularis is essentially the same as found in other mammals.
Animals↗
Phase dependency of electrotonic spread of hyperpolarizing current pulses in the rabbit sinoatrial node.
Electrotonic current spread in the SA node of the rabbit was measured by means of hyperpolarizing current pulses (1 to 10 microA, 60 ms), which were injected intracellularly through a K(+)-perfused suction electrode. The pulses were applied at the beginning, middle or end of the diastolic depolarization phase. The resulting membrane potential change of nodal fibers was measured with microelectrodes. Space constants were calculated by fitting single exponential curves to the data. The input resistance (Rin) of fibers at different sites in the SA node was measured by means of a double barrel microelectrode (current pulses 5.5 to 11 nA, 60 ms) to detect a change in the internal resistance during the diastolic depolarization phase. During diastole the average electrotonic potential increased by 30% (P less than 0.001), the increase of the space constant ranged from 9 to 183% (P less than 0.05). Rin however, did not change during diastole. It is concluded that the electrotonic spread increased phase dependently, due to an increase of membrane resistance; the internal resistance was not phase dependent.
Animals↗
Anisotropy of electrotonus in the sinoatrial node of the rabbit heart.
In fibers of the sinoatrial node of isolated right atria of rabbits the decay of the electrotonic potential caused by intracellular current injection was measured in two directions: parallel to the crista terminalis and perpendicular to it. A K+-perfused extracellular suction electrode was used to apply current pulses (10(-5) A, 60 ms) to fibers located in the primary center of the SA node every fourth cardiac cycle at a fixed moment during diastole. The decay of the electrotonic spread was measured in a series of impalements on a straight line from the current source. Space constants were calculated by fitting single exponential curves to the data. Considerable regional differences in space constant values were found in either direction. Parallel to the crista terminalis the mean value was 529 +/- 446 microns (S.D., n = 7), perpendicular to it 306 +/- 295 microns (n = 12); the difference was not significant (P less than 0.2). However, a significant anisotropy (P less than 0.05) of the electrotonic spread was found when measurements were taken from small areas of the node. Large abrupt changes in the electrotonic potential within 200 microns were observed in the center of the node. These data indicate a non-uniformity of electrotonic spread in this part of the SA node.
Animals↗
Mechanisms of impulse generation in isolated cells from the rabbit sinoatrial node.
The contribution to spontaneous activity of three currents INa, If, and Isi was investigated in isolated spontaneously active SA nodal cells. It was demonstrated that isolated cells have electrophysiological properties similar to those of cells in the intact node. Evidence for the contributory role of INa to the upstroke of the action potential was obtained from membrane responsiveness curves and from the observation that Vmax was strongly reduced after the addition of 9 microM TTX to the bathing solution. The relative role of If and Isi as depolarizing diastolic membrane currents was investigated by relating the maximal density of each of these currents to the corresponding DDR during spontaneous activity. Both currents If and Isi-peak appear to be linearly related to DDR, indicating their contributory role to diastolic depolarization. Although the cells studied were heterogeneous with regard to the density of If and Isi we found no evidence for their separation into distinct groups of pacemaker cell types.
Action Potentials↗
Functional morphology of the pig sinoatrial node.
The porcine sinoatrial node in an isolated right atrium preparation is characterized by unifocal impulse generation. It has a rather elongated shape and the larger part of its volume is taken up by collagen and fibroblasts. The impulse appears to emerge from a site where the percentage of myofilaments is relatively low. The impulse is propagated faster towards the crista terminalis than to the interatrial septum with preference for the oblique-upward direction. A very large zone of cells with low excitability is located at the interatrial septal side of the node.
Actin Cytoskeleton↗
The intrinsic cycle length in small pieces isolated from the rabbit sinoatrial node.
In this study we show that small pieces of tissue cut from the intact sinoatrial node beat faster, but with the same regularity as the intact sinoatrial node. The pieces with highest diastolic depolarization rate are not isolated from the primary pacemaker area, but from sites closer to the crista terminalis. In pieces cut from the primary pacemaker area, changes in the action potential configuration are restricted to the action potential duration, whereas in pieces cut from sites closer to the crista terminalis, not only the action potential duration has decreased, but also the diastolic depolarization rate has increased. Under the influence of adrenaline or acetylcholine, quiescent pieces are able to generate spontaneous activity.
Acetylcholine↗
Alinidine as a model of the mode of action of specific bradycardic agents on SA node activity.
Three different bradycardic agents, alinidine, AQ-A39 and UL-FS49 increase the intrinsic cycle length of the isolated SA node preparation of the rabbit. This increase is mainly caused by a decrease in rate of diastolic depolarization. One of these agents, alinidine, was used to study the underlying ionic mechanism of the decrease in the diastolic depolarization rate in isolated cells and small cell clusters of the rabbit SA node. In these preparations alinidine slowed down the rate of spontaneous activity at higher concentrations (80 microM). At lower concentrations (10 microM) the decrease in rate of spontaneous activity was variable, but injection of a hyperpolarizing current slowed the spontaneous rate more in the presence of alinidine, indicating an increase in membrane resistance. In voltage clamp experiments we found that the main effect of alinidine was a block of the hyperpolarization activated current if. The block was potential dependent and was maximal in the potential range in which diastolic depolarization occurs. These results are discussed in relation to previous findings of others.
Animals↗
Functional morphology of the mammalian sinuatrial node.
The primary pacemaker area is located at the site with lowest percentage of myofilaments and the highest rate of diastolic depolarization in rabbit, guinea-pig, cat and pig. All investigated sinuatrial nodes contained large amounts, 45% or more, of collagen. There was, however, substantially more collagen in the sinuatrial nodes of the cat and the pig than in the rabbit and the guinea-pig. This had, however, no consequences for the sinuatrial conduction time and the regularity of the beat-to-beat cycle length in the different species, because the rabbit and cat had comparable sinuatrial conduction times, although their nodal collagen content was very different and the beat-to-beat cycle length showed a comparable variability in the different species. We conclude that extensive proliferation of collagen and fibroblasts does not necessarily impair intercellular coupling in the sinuatrial node.
Actin Cytoskeleton↗
Functional and morphological organization of the cat sinoatrial node.
The feline sinoatrial node has a unifocal impulse generation as previously described for rodents. Its main component is collagen. The primary pacemaker consists of at most 2000 cells, but appears to function normally with less than 500 cells. Primary pacemaker cells are found in the area where empty cells are predominant. A negative correlation between myofilament density and diastolic depolarization rate, known to exist in the rabbit and guinea-pig, is absent in the cat. Gap junctions are seen in the center and in the periphery of the nodal region, but they are extremely rare. The electrophysiological characteristics of the primary pacemaker of the cat are quite similar to those of the rabbit, although the nodal morphology is very different. Abrupt transitions from one cell type into another are observed in the feline sinoatrial node. From this morphological point of view the feline sinoatrial node resembles the canine and human sinoatrial nodes more than the lapine sinoatrial node.
Animals↗
Electrophysiological effects of alinidine (ST 567) on sinoatrial node fibres in the rabbit heart.
In a study of the electrophysiological effects of alinidine a concentration of 0.7-14.3 mumol X litre-1 decreased the rate of diastolic depolarisation and prolonged especially the terminal part of the action potential in the rabbit sinoatrial node. It did not induce pacemaker shifts since the effects were not restricted to the primary pacemaker or the central nodal area but were evident in the more peripheral nodal region. The substitution of chlorine ions by other anions did not prevent the decrease in the rate of diastolic depolarisation due to alinidine but did prevent the effect on the action potential duration. The decreased chronotropic action of alinidine in low chlorine Tyrode solution was, however, caused by a shift of pacemaker dominance towards an atrial pacemaker. This pacemaker shift concealed the response of the primary pacemaker to alinidine in low chlorine Tyrode. Blockade of the pacemaker current of if by caesium prevented neither the alinidine effect on the diastolic depolarisation completely nor its effect on the action potential duration, but blockade of if probably was one of the determinants of the action of alinidine. It cannot be excluded that alinidine interferes with still another current than if. Alinidine decreased the chronotropic responses to adrenaline and to acetylcholine and also prevented pacemaker shifts due to these substances.
Acetylcholine↗
Structure and function of the sino-atrial node: a review.
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Adolescent↗
Functional and morphological organization of the guinea-pig sinoatrial node compared with the rabbit sinoatrial node.
The primary pacemaker, i.e. the group of pacemaker cells discharging the sinoatrial node comprises less than 1000 cells in the guinea-pig and about 5000 cells in the rabbit. These primary pacemaker cells are described as 'central nodal' cells in light microscopy and as 'typical nodal' cells in electron microscopy. The action potential of the leading cells has a higher upstroke velocity in the guinea-pig than in the rabbit (6.2 v. 1.9 V/s). Gap junctions have been observed even in the very center of the node in both species. A zone of double-component action potentials at the septal margin of the node was observed in the rabbit, but not in the guinea-pig. Evidence is presented for abrupt transitions in electrophysiological as well as in ultrastructural characteristics in the guinea-pig sinoatrial node. The differences in intrinsic cycle length between both species but also between individuals of the same species are discussed.
Action Potentials↗
Short-latency tachycardia evoked by stimulation of muscle and cutaneous afferents.
The short-latency effect on heart rate of peripheral nerve stimulation was studied in decerebrate cats. Selective activation (17-40 microA, 100 Hz, 1 s long) of low-threshold fibers in the nerves to the triceps surae muscle yielded isometric contractions of maximal force that were accompanied by a cardiac cycle length shortening within 0.4 s from the start of stimulation. This effect was abolished by pharmacologically induced neuromuscular blockade. The cardiac cycle length shortening during paralysis reappeared after a 6- to 10-fold increase of the stimulation strength. Cutaneous (sural) nerve stimulation (15-25 microA, 100 Hz, 1 s long) elicited reflex contractions in the stimulated limb, which were also accompanied by a cardiac acceleration with similar latency. Paralysis prevented the reflex contractions and reduced the cardiac response in some cats and abolished it in others. The response reappeared in either case after a 5- to 10-fold increase of the stimulus strength. It is concluded that muscle nerve and cutaneous nerve activity both cause a similar cardiac acceleration with a latency of less than 0.4 s. The response to muscle nerve stimulation is elicited by activity in group III afferents. It is excluded that the cardiac response to nerve stimulation is secondary to a change in the respiratory pattern.
Afferent Pathways↗