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First published online March 12, 2009
Journal of Experimental Biology 212, 906-913 (2009)
Published by The Company of Biologists 2009
doi: 10.1242/jeb.020529
The basis of vagal efferent control of heart rate in a neotropical fish, the pacu, Piaractus mesopotamicus
1 Department of Physiological Sciences, Federal University of São Carlos
(UFSCar), São Carlos, SP, Brazil
2 School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK
* Author for correspondence (e-mail: e.w.taylor{at}bham.ac.uk)
Accepted 6 January 2009
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Summary |
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 TOP Summary INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Key words: Piaractus mesopotamicus, neuranatomy, neurophysiology, cranial nerves, vagus, cardiorespiratory interactions
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INTRODUCTION |
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TOPSummaryINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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; Taylor,
1992). Predominant among these is tonic inhibitory control imposed
by the parasympathetic division of the autonomic nervous system, via
efferent activity in the vagus nerve
(Taylor et al., 1999). This
inhibitory tonus is abolished by cardiac vagotomy or injection of the
muscarinic cholinoceptor antagonist atropine
(Taylor et al., 1977). An
extensive study of the elasmobranch fish Scyliorhinus canicula (the
dogfish), summarized by Taylor (Taylor,
1992), revealed that the heart operates under an inhibitory vagal
tone that varies with temperature and oxygen supply. Recordings from a cardiac
branch of the vagus in dogfish revealed high levels of spontaneous efferent
activity, which could be attributed to two types of unit
(Taylor and Butler, 1982;
Barrett and Taylor, 1985a).
These units were shown to have separate origins in the CNS
(Barrett and Taylor, 1985a;
Barrett and Taylor, 1985b).
Some units fired sporadically and increased their firing rate during hypoxia.
Consequently, we suggested they may initiate reflex changes in heart rate,
including a hypoxic bradycardia, as well as playing a role in the
determination of the overall level of vagal tone on the heart. Other,
typically larger, units fired in rhythmical bursts which were synchronous with
ventilatory movements. We hypothesized that these units, showing
respiration-related activity, which was unaffected by hypoxia, may serve to
synchronize heartbeat with ventilation
(Taylor, 1992). As activity
was recorded from the central cut end of the cardiac vagus in the
decerebrated, paralysed, force-ventilated dogfish, we reasoned that it must be
centrally generated. Accordingly, cardiorespiratory interactions in dogfish
could be generated primarily by feed-forward control from the central nervous
system (Taylor et al., 1999).
However, in the intact, spontaneously breathing fish, this relationship may be
reinforced by rhythmical stimulation of branchial mechanoreceptors
(Taylor, 1992).
Available evidence suggests that cardiorespiratory interactions in teleost
fish are predominantly under reflex control. When exposed to hypoxia, the
rainbow trout, Oncorhynchus mykiss, showed a developing
hyperventilation and bradycardia. As heart rate (fH) was
higher than ventilation rate (fR) in normoxia, these
changes resulted in convergence to a 1:1 ratio, synchronizing these rhythms.
Both the bradycardia and the cardiorespiratory synchrony were abolished by
atropine injection (Randall and Smith,
1967). These authors also demonstrated 1:1 synchrony between the
heartbeat and pulses of water delivered by forced ventilation of the gills,
independent of the intrinsic respiratory rhythm. This is a phenomenon clearly
generated by reflex pathways. Randall
(Randall, 1966) recorded
bursting activity from the cardiac vagus of Tinca tinca and concluded
that it was the efferent arm of reflex control of heart rate, generating both
a hypoxic bradycardia and synchrony between heartbeat and ventilation. These
results reveal an apparent fundamental dichotomy in our understanding of the
genesis of cardiorespiratory synchrony in fishes. In elasmobranchs it seems to
be generated primarily by central interactions in resting normoxic or
hyperoxic fish, when the overall vagal tone is relatively low. In teleosts the
synchrony occurs in moderate hypoxia and it is apparently generated by reflex
pathways when the vagal tone to the heart is relatively high
(Taylor, 1992;
Taylor et al., 1999). However,
extant studies are limited to very few species and follow up studies are only
available for the elasmobranchs (Taylor et
al., 2006).
Evidence that bursts of respiration-related, efferent activity in the
cardiac vagus could entrain the heart was obtained by electrical stimulation
of the peripheral cut end of the cardiac branch of the vagus in S.
canicula (Taylor et al.,
2006). Although continuous stimulation of the cardiac vagus caused
a bradycardia or even cardiac arrest, burst stimulation of the same nerve
entrained the heart rate to imposed rates below or even slightly higher than
the intrinsic fH
(Young et al., 1993b;
Taylor et al., 2006). Similar
data have been obtained from mammals (e.g.
Levy et al., 1969;
Levy et al., 1972; Pokvroskii,
1984), but are lacking for teleost fish.
The neotropical teleost fish the pacu, Piaractus mesopotamicus,
shows episodic breathing while in normoxia. This pattern is characterized by
sequences of ventilatory cycles of varying amplitude separated by respiratory
pauses (Leite et al., 2007).
In normoxia the overall ventilation rate was similar to but slightly lower
than the heart rate. In response to progressive hypoxia pacu showed increases
in the frequency and amplitude of ventilation and a marked bradycardia
(Leite et al., 2007), a
response pattern that is typical for teleosts
(Hughes and Shelton, 1962;
Taylor, 1992). However,
re-examination of the data provided by Leite and colleagues
(Leite et al., 2007) revealed
that before the development of a significant decrease in
fH, at an oxygen tension of 70 mmHg, the relationship
between fH and fR became exactly 1:1,
with very little variability in the data from 12 fish. The development of this
relationship entailed an increase in fH as well as
fR, despite the fact that the typical cardiac chronotropic
response to hypoxia in fish, including pacu, is a developing bradycardia
(Taylor, 1992). A follow-up
study revealed that spontaneous efferent activity recorded from the cardiac
vagus of pacu contained respiration-related activity in moderate hypoxia but
not in normoxia, suggesting that it was generated by reflex pathways
(C.A.C.L., E.W.T. and F.T.R., unpublished observations). These data raise some
interesting questions regarding the nature of cardiac control in this fish.
The aim of this investigation was to clarify the role of the vagus in efferent
control of fH in P. mesopotamicus, as a
contribution to furthering our overall understanding of this relationship in
vertebrates.
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MATERIALS AND METHODS |
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TOPSummaryINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Series 1: neuranatomy
To map the distribution of neurons supplying the heart and respiratory
system, nine fish had the appropriate branches of cranial nerves V, VII, IX
and X injected with a neural tracer. For the injection, the animals were
anaesthetized with benzocaine (0.1 g l–1) and transferred to
a surgical table where they were artificially ventilated with a second aerated
solution of the same anaesthetic (0.05 g l–1). A binocular
operating microscope (Opto SM 2001, Electronic Opto, São Carlos, SP,
Brazil) was used to trace and identify selected branches of cranial nerves
involved in respiratory control. Access to each nerve was as follows. The
mandibular branch of the trigeminal, the Vth cranial nerve that innervates the
jaws, was exposed by an incision (5 mm) at the edge of the ocular orbit,
caudal to the eyeball; the opercular branch of the VIIth cranial nerve was
exposed by an incision on the internal face of the operculum, at its
dorso-rostral insertion on the body wall; the branchial branch of the IXth, as
well as the 1st, 2nd and 3rd branchial branches of the Xth cranial nerves,
which innervate the gill arches, were exposed via an incision at the
point where the first and second gill arches join the roof of the opercular
cavity. An incision made at the caudal edge of the gill chamber along its line
of contact with the operculum, at the level of the medial point of the 4th
branchial arch, exposed the point at which the 4th branch of the vagus divided
into its respiratory and cardiac branches. A local anaesthetic (2% lidocaine;
Pearson, BR, Pilot Point, TX, USA) was injected at each incision site in order
to reduce the post-surgical stress.
After positive identification each nerve branch was cleared of connective tissue and then injected with 2–6µl of a neural tracer (Fluorogold or True Blue, Sigma, St Louis, MO, USA) as a solution in deionized water, delivered from a Hamilton syringe with the needle point inserted through the nerve sheath. The nerve was then pinched with fine forceps at the injection site to damage axons, as this promotes uptake of the tracer. The nerves, however, were not sectioned. Tracers were injected into branches of two nerves on different sides of each fish, which was then fitted with an identifying tag and recovered by irrigation of the gills with aerated water before placement in a holding tank. After recovery for 3 weeks at 25°C to enable transport of the tracer to the cell bodies of neurons supplying the injected nerve branch, each fish was terminally anaesthetized and the ventral aorta was perfused with heparinized 0.9% saline then with a 4% solution of formaldehyde in saline, buffered to pH 7.3. The brain was removed and stored in buffered fixative for 3 days before being placed in a 20% solution of sucrose in buffered saline overnight. Each brain was then frozen and sectioned (transverse sections of 40µm) on a cryostat (Microm/Zeiss HM 505 E, Germany). The serial sections were mounted on gelatine-coated slides and cover-slipped in a solution of glycerine. Sections were examined under a photomicroscope (Olympus BX50 illuminator UV U-ULH, Tokyo, Japan) equipped with UV epi-illumination and a video camera attached to an image analysis system (Image-Pro Plus, Bethesda, MD, USA), enabling the images of fluorescing neuron cell bodies to be captured.
Cell bodies of labelled neurons were counted and mapped according to their proximity to the 4th ventricle and their rostro-caudal distance from obex. As there is no interneuronal transport of these tracers the technique enables identification of the cell bodies of neurons supplying axons directly to the site of labelling on the selected nerves. The proportion of axons taking up tracer is unknown so the technique enables the location of groups of cell bodies in discrete areas of the CNS but only gives approximate estimates of their relative numbers. The specific pattern of labelling for each nerve was similar in all cases and data are presented from fish that showed the largest number of labelled cells.
Series 2: electrophysiology
For measurement of respiratory and cardiac variables, each fish
(N=20) was first anaesthetized by immersion in a solution of
benzocaine (0.1 g l–1) until righting responses were
abolished, when it was laid on its left side on the operating table. It was
supported by strips of plastic sponge, so that the operculum on the underside
was free to move. The fish was then supplied with a continuous flow of aerated
water containing anaesthetic diluted to a concentration (approximately 0.04 g
l–1) at which the animal commenced spontaneous respiratory
activity, consisting of rapid shallow movements of the jaw and opercula.
The opercular movements were recorded by attaching to the edge of the right
operculum a length of suture thread that led to a force transducer (Myograph
F-2000, Odense, Denmark) inputting to a physiograph (MK-III-S, Narco
Biosystems, Austin, TX, USA). A cannula (PE 50), filled with saline solution
(0.9%, NaCl plus 100 IU ml–1 heparin), was inserted into the
caudal artery to record heart rate as blood pressure, using a standard
procedure (Perry et al.,
2004). The cannula was connected to a Baxter Edward pressure
transducer (model PX600; Irvine, CA, USA) and the signals were amplified using
a preamplifier built in-house at the University of Aarhus, Denmark. The
outputs from all measuring devices were taken to a data acquisition system
(either Dataq DI-194, Akron, OH, USA, during the nerve stimulation
experiments, or AcqKnowledge–Biopac system, Goleta, CA, USA, during the
nerve recordings).
The central cut end of the respiratory branches of the Vth, VIIth, IXth or Xth cranial nerves and either the central or peripheral cut ends of the cardiac branch of the Xth were exposed using the same operative routes described in series 1. Each branch was dissected, sectioned and placed on a pair of platinum electrodes positioned by a mechanical manipulator (Prior Scientific, Cambridge, UK), in order to either record from or electrically stimulate the nerve. The fish was then supplied with a continuous flow of aerated water containing anaesthetic, diluted until the animal commenced spontaneous respiratory activity, consisting of rapid, shallow movements of the jaw and opercula (approximately 0.04 g l–1).
Series 2.1: activity in the cardiac and respiratory nerves
Recordings of nervous activity were obtained from the central cut ends of
respiratory and cardiac nerves in eight fish with the input to the electrodes
led to a purpose-built preamplifier and then to an AC amplifier (Digitimer,
Neurolog NL105, Welwyn Garden City, Herts, UK), a filter (NL 125) and an
audio-amplifier (NL 120). These electrical recordings were performed inside a
screened metal `Faraday' cage to reduce electrical interference with recorded
signals. Recordings of spontaneous activity were obtained from all nerves in
normoxic fish supplied with aerated water (oxygen tension in the water,
PwO2=140 mmHg) and in the case of activity in
cardiac nerves from fish in which the flow rate of water was halved to induce
systemic hypoxia (C.A.C.L., E.W.T. and F.T.R., unpublished). To observe the
phase relationships between the bursts of respiration-related activity
recorded from respiratory and cardiac nerves, the delay between both the onset
and the peak of each burst and the peak of the resulting respiratory cycle,
represented by opercular movements, was recorded. The onset of nervous
activity was identified from integrated bursts as the time at which the
waveform rose to 15% above baseline. All data were displayed and stored on a
computer and are illustrated by representative traces and by data from six
fish, combined to illustrate phase relationships.
Series 2.2: electrical stimulation of respiratory and cardiac nerves
To study the role of the cardiac vagus in the efferent control of heart
rate and the role of reflexes originating in the respiratory system in
modulating heart rate, the peripheral cut end of the cardiac branch of the
vagus and the central cut ends of the mandibular branch of the Vth, opercular
branch of the VIIth, branchial branch of the IXth and the 1st, 2nd, 3rd and
4th branchial branches of the Xth cranial nerves were exposed for electrical
stimulation in 12 fish. Each nerve was accessed as described in series 1 and
placed on platinum electrodes. It was then stimulated with pulses of varying
voltage and frequency using a physiological stimulator (Farnell Instruments,
Leeds, UK). Initially the nerve was tonically stimulated with square-wave
pulses of 1–2 ms duration, at 10–40 Hz and increasing voltages
from 3 to 15 V, until the applied stimulus caused the heart to stop. The same
settings were then used to deliver bursts of stimuli of 200–300 ms
duration. The nerve was then stimulated at a range of bursting frequencies
both faster and slower than the intrinsic heart rate. Heart rate was obtained
from blood pressure pulse rate. Data are illustrated by representative traces
and by the measured ranges over which the heart was recruited by the bursts of
stimuli in all fish.
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RESULTS |
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TOPSummaryINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Central stimulation of respiratory nerves
Continuous electrical stimulation of the central cut end of the respiratory
branches of the VIIth, IXth and Xth cranial nerves caused cardiac arrest (e.g.
Fig. 4A). When the stimuli were
delivered in bursts the heart was entrained by the bursts over a wide range of
frequencies lower than the pre-stimulation fH
(Fig. 4D,E). At higher bursting
frequencies the heart was entrained to alternate bursts or other fixed ratios
with the stimuli (e.g. 3:1, Fig.
4C). Uniquely, there was no effect on heart rate of central
stimulation of the mandibular branch of cranial nerve V even at higher rates
and voltages of stimulation than routinely applied
(Fig. 4F). Injection of
atropine abolished all effects on the heart of central stimulation of the
respiratory nerves (data not shown).
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Peripheral stimulation of cardiac nerve
Peripheral stimulation of a cardiac branch of the vagus with a continuous
train of stimuli slowed or stopped the heart
(Fig. 5A). When the same
stimuli were delivered in bursts the heart was entrained over a wide range of
burst frequencies. In all fish it was possible to entrain
fH to the frequency of stimulation over a range of
frequencies lower than the intrinsic fH
(Fig. 5B), although at lower
rates (e.g. at 42 bursts min–1) the heart often beat more
than once for each burst of stimuli. At stimulation rates higher than the
intrinsic fH the heart was entrained either 1:1 (up to 120
bursts min–1) or by a fixed fraction of the burst frequency,
from 1:2 to 1:6 up to 180 bursts min–1 (see
Fig. 5C,D). The relationships
between stimulation frequency and heart rate are plotted for four fish in
Fig. 6. All four fish showed
recruitment of the heart by rates of stimulation below the pre-stimulation
heart rate. One fish (P2) showed recruitment by rates of stimulation well
above the pre-stimulation heart rate while two fish (P3 and P4) showed
recruitment by a whole number ratio of the stimulation frequency (1:2 to 1:6).
The range of stimuli entraining the heart on central stimulation of the
respiratory nerves is compared with the effects of peripheral stimulation of
the cardiac nerve in Fig. 7.
This shows that responses to peripheral stimulation of the cardiac nerve were
over a wider range of frequencies than responses to central stimulation of
respiratory nerves.
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DISCUSSION |
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TOPSummaryINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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;
Reid and Perry, 2003).
However, in a comparative study of three tropical teleosts Perry and
colleagues (Perry et al.,
2004) showed that pacu did not respond to hypoxia or injection of
nicotine with a significant increase in circulating catecholamines, while the
other two species showed marked increases. They interpreted this as evidence
for an inoperative or absent humoral adrenergic response in this species. In
addition, studies on mammals, reptiles and fish have revealed that sympathetic
control of heart rate is generally associated with long latency control of
blood pressure and changes in levels of disturbance, while tonic and rapid
phasic control of the heart, which is likely to generate cardiorespiratory
interactions, is predominantly parasympathetic
(Bootsma et al., 1994;
Taylor et al., 1999;
Le Mevel et al., 2002;
Campbell et al., 2004;
Campbell et al., 2006).
In the elasmobranch fish Scyliorhinus canicula, the motor areas of
the respiratory branches of cranial nerves VII, IX and X and the CVPN
supplying the cardiac vagi occur in a rostro-caudal sequential series with
some degree of overlap between each sequential motor group. This pattern of
distribution continues rostrally with the trigeminal motor area of cranial
nerve V but with no superposition
(Withington-Wray et al., 1987;
Taylor, 1992). Piaractus
mesopotamicus presents a similar distribution of motoneurons but with an
even higher degree of overlap between RVPN and CVPN. Each motor nucleus
overlies several others and the CVPN overlap all of them except the trigeminal
motor neurons, which occur in a topographically separate, more rostral
position.
Barrett and Taylor (Barrett and Taylor,
1985a) showed that respiratory branches of cranial nerves V, VII,
IX and X in S. canicula fire in a temporal sequence according to the
rostro-caudal distribution of their motoneurons in the brainstem. Similar
patterns of sequential firing were recorded from pacu. In both fish this
respiration-related efferent activity was also recorded from the cardiac vagi.
However, in dogfish this activity was recorded from normoxic animals that were
pharmacologically paralysed (Barrett and
Taylor, 1985a) suggesting that it was generated by central
interactions between the RVMN and CVPN that are sited together in the dorsal
vagal nucleus (DVN). In contrast, bursting efferent activity was only recorded
from the cardiac vagus of pacu during periods of increased ventilatory effort
in fish exposed to moderate hypoxia (C.A.C.L., E.W.T. and F.T.R.,
unpublished), suggesting that it may be generated by reflexes derived from
branchial receptors. Previous work on pacu
(Leite et al., 2007) revealed
that mean heart rate increased from 63±6 beats min–1
in intact fish to 82±3 beats min–1 following
denervation of the gill arches supplied by the IXth and Xth cranial nerves.
This suggests that an important element of vagal tone on the heart of pacu is
generated reflexly, possibly by stimulation of branchial receptors.
Central stimulation of the respiratory branches of cranial nerves VII, IX
and X with bursts of stimuli that may simulate stimulation of mechanoreceptors
recruited the heart in pacu (Fig.
4). This supports the possibility of a role for afferent activity
derived from branchial receptors in recruiting the heart. Phasic central
stimulation of a respiratory branch of the vagus in the dogfish induced bursts
of efferent activity in the cardiac vagus
(Young et al., 1993a;
Taylor, 1992) and this is
likely to be the case in pacu. So, an increase in ventilatory effort during
hypoxia, by stimulating branchial mechanoreceptors, may generate
respiration-related activity in cardiac nerves that can cause the heart to
beat at a rate corresponding to the ventilation rate. This is in accordance
with the recruitment of the heart by imposed pulses of water flow, described
for the trout (Randall and Smith,
1967). This model is clearly based on reflex feedback control of
cardiorespiratory interactions. So, the current study provides support for the
generation of cardiorespiratory interactions by a reflex route. However, there
is also the possibility that during the current experiments RVMN were
stimulated antidromically by electrical impulses during central stimulation of
their efferent fibres and that direct interactions between these neurones and
CVPN in the DVN led to induced activity in the cardiac nerves and subsequent
cardiac recruitment. These putative relationships were summarized for dogfish
in a schematic diagram (Taylor,
1992).
The alternative possibility that cardiorespiratory interactions may be generated centrally in the brainstem is supported by the apparent concurrence of bursting activity in the cardiac nerve with activity in the Vth cranial nerve (Figs 2 and 3). In contrast to the other respiratory nerves, central electrical stimulation of the Vth was without effect on heart rate (Fig. 4) and the motor neurones supplying the Vth cranial nerve do not overlap with the CVPN (Fig. 1). Accordingly, the concurrence of activity between the Vth and cardiac nerves is likely to be generated centrally, possibly by inputs to both groups of neurons from a central respiratory pattern generator when respiratory drive is high, as in hypoxia. Consequently, it is still not possible, on the basis of the present data, to determine how much of the efferent activity delivered by the cardiac vagus originates reflexly from stimulation of branchial chemo- and/or mechanoreceptors and how much comes from central interactions between respiratory and cardiac motor areas or a central respiratory rhythm generator. There is evidence for both sources of interaction and their relative importance may vary with the level of central respiratory drive.
Tonic peripheral electrical stimulation of the cardiac vagus in pacu caused
cardiac arrest but when the stimuli were delivered in bursts they were shown
to recruit the heart over a wide range of frequencies. This entrainment was
apparently a form of cardiac pacing, with the heart caused to contract by each
burst of electrical stimuli rather than the bursts increasing the duration of
each cardiac interval by phasic inhibition of the pacemaker. This relationship
is suggested by examination of Fig.
5C, which shows the heart being driven faster than its intrinsic
rate, and more particularly by Fig.
5D, which shows the heart responding to every 4th burst of
stimuli. Fig. 6 shows examples
of whole number ratios between stimulation and heart rates varying from 2:1 in
fish P4 to 6:1 in fish P3. The range of frequencies over which central
stimulation of respiratory nerves recruited the heart was narrower than
reported here for direct peripheral stimulation of the cardiac vagus (see
Fig. 7). Unlike central
stimulation of respiratory nerves, recruitment by peripheral stimulation of a
cardiac nerve could sometimes be to rates higher as well as lower than the
intrinsic heart rate. The potential cardio-acceleration resulting from phasic
efferent stimulation of the cardiac vagus was impressive, with the heart
driven to beat at almost twice its intrinsic rate. This requires a drastic
reinterpretation of the role of the cardiac vagus in determining heart rate in
fish, which has historically been described as tonic inhibition
(Taylor, 1992).
A central question raised by these data is how cardiac contractions can be
driven by bursts of efferent activity derived from peripheral electrical
stimulation of the cardiac vagus when its role is primarily inhibitory, due to
the release of acetylcholine onto muscarinic receptors on the heart. If the
inhibitory effect of the vagus related directly to the intensity of its
efferent output then increased rates of bursting should slow the heart rather
than recruiting it to a faster rate. Bursts of stimuli delivered at rates
considerably faster than the intrinsic fH (higher than 120
bursts min–1) did indeed have an overall inhibitory effect
(i.e. caused the heart to slow) but again there was evidence of cardiac
pacing, because the heart was observed to beat at fixed whole number ratios of
the applied stimulus (see Fig.
5D), implying that it was being paced by the imposed stimulus,
even though not by each individual burst. A partial answer to this apparent
paradox was provided by Thompson and O'Shea
(Thompson and O'Shea, 1997).
They showed that in an elasmobranch fish, acetylcholine had an atypical
excitatory effect on cardiac ventricular muscle that was blocked by atropine.
However, their data implied that the effect was of long latency and probably
mediated by indirect effects on the release of catecholamines so it is
unlikely to play a role in the rapid beat-to-beat control exhibited in the
present investigation.
A direct relationship between efferent vagal activity and heartbeats has
been reported in mammals (Levy et al.,
1969; Levy et al.,
1972). The pattern of the vagal electrical activity to the heart
has been described as non-constant, having pulses or bursts of activity
occurring with variable frequencies
(Jewett, 1964;
Katona et al., 1970;
Kunze, 1972;
Taylor et al., 1999). The
effects of bursts of efferent vagal activity on the heart have been
investigated in several groups of mammals. In all of them it was possible to
pace the heart with burst activity over a range of stimulation frequencies
lower than the intrinsic fH (e.g.
Pokrovskii, 1984;
Pace et al., 1984) and in some
species at rates higher than the intrinsic fH
(Brown and Eccles, 1934;
Levy et al., 1981). The
neurological basis of recruitment of the heart at rates higher than its
intrinsic rate by bursts of electrical stimuli delivered peripherally down the
cardiac vagus has long been of interest to mammalian physiologists. Pokrovskii
(Pokrovskii, 1984;
Pokrovskii, 2003;
Pokrovskii, 2006) reported
that increasing the intra-burst frequency improved the effectiveness of the
stimulation in pacing the heart. This implies that as more acetylcholine is
delivered to efferent vagal synapses the heart is driven to beat rather than
inhibited. Brown and Eccles (Brown and
Eccles, 1934) described a complex relationship between the
chronotropic effect of efferent stimulation of the cardiac nerve and the phase
of the cardiac cycle in which stimuli were delivered. Levy and colleagues
(Levy et al., 1972) and Spear
and colleagues (Spear et al.,
1979) confirmed that a pulse of stimulation could be effective in
causing two inhibitory phases separated by a brief phase of
cardio-acceleration, depending on the phase of the cardiac cycle in which it
was delivered. Martin (Martin,
1977) noted that atrio-ventricular conduction time in the heart of
the dog could be shorter in the presence of vagal stimulation. Similar complex
relationships were reviewed by Levy and colleagues
(Levy et al., 1981). Pace and
colleagues (Pace et al., 1984)
noted that the maximum R–R intervals were triggered when the efferent
stimulus was delivered to the post-ganglionic terminal of the vagus, on the
sino-atrial node, during the phase of slow depolarization of the pacemaker
cells, while minimum R–R intervals occurred when the stimulus was
delivered before this phase.
These observations imply that the effect of each burst depends on the phase of the cardiac cycle at which it is applied. Thus, the vagal effect on the heart cannot be measured merely in terms of the amount of acetylcholine delivered per unit time. The overall effect of vagal stimulation will be related to the summation of the effects of stimuli delivered in the inhibitory and stimulatory phases. Similar detailed information is not yet available for fish but the present study does provide clear evidence that the cardiac vagus imposes beat-to-beat control of heart rate in fish rather than merely imposing an inhibitory tone.
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Footnotes |
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References |
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TOPSummaryINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Axelsson, M., Ehrenstrom, F. and Nilsson, S. (1987). Cholinergic and adrenergic influence on the teleost heart in vivo. Exp. Biol. 46,179 -186.[Medline]
Barrett, D. J. and Taylor, E. W. (1985a).
Spontaneous efferent activity in branches of the vagus nerve controlling heart
rate and ventilation in the dogfish. J. Exp. Biol.
117,433
-448.
Barrett, D. J. and Taylor, E. W. (1985b). The
characteristics of cardiac vagal preganglionic motoneurones in the dogfish.
J. Exp. Biol. 117,459
-470.
Bootsma, M., Swenne, C. A., Vanbolhuis, H. H., Chang, P. C., Cats, V. M. and Bruschke, A. V. G. (1994). Heart-rate and heart-rate-variability as indexes of sympathovagal balance. Am. J. Physiol. 266,H1565 -H1571.[Medline]
Brown, G. L. and Eccles, J. C. (1934). The
action of a single vagal volley on the rhythm of the heart beat. J.
Physiol. 82,211
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Campbell, H. A., Taylor, E. W. and Egginton, S.
(2004). The use of power spectral analysis to determine
cardio-respiratory control in the short-horned sculpin Myoxocephalus
scorpius. J. Exp. Biol. 207,1969
-1976.
Campbell, H. A., Leite, C. A. C., Wang, T., Skals, M., Abe, A.
S., Egginton, S., Rantin, F. T., Bishop, C. M. and Taylor, E. W.
(2006). Evidence for a respiratory component, similar to
mammalian respiratory sinus arrhythmia, in the heart rate variability signal
from the rattlesnake, Crotalus durissus terrificus. J. Exp.
Biol. 209,2628
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Hughes, G. M. and Shelton, G. (1962). Respiratory mechanisms and their nervous control in fish. Adv. Comp. Physiol Biochem. 1,275 -364.[Medline]
Jewett, D. L. (1964). Activity of single
efferent fibres in the cervical vagus nerve of the dog, with special reference
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