J. Physiol. (1979), 292, pp. 135-148 With 4 texts-fgure Printed in Great Britain
135
AFFERENT SYMPATHETIC UNMYELINATED FIBRES WITH LEFT VENTRICULAR ENDINGS IN CATS
BY R. CASATI, F. LOMBARDI AND A. MALLIANI From the Istituto di Ricerche Cardiovascolari, University of Milan and Centro Ricerche Cardiovascolari, CNR, Via F. Sforza 35, 20122 Milan, Italy
(Received 14 August 1978) SUMMARY
1. We recorded the electrical impulse activity of thirty-three single afferent fibres with left ventricular endings from the third and fourth left thoracic sympathetic rami communicantes of anaesthetized cats. Their conduction velocity ranged from 0*23 to 0'98 m/sec (group C). 2. The endings of each fibre were localized to the left ventricle by mechanical probing performed at the end of the experiment on the non-beating heart. No fibre had multiple sensory fields. 3. The impulse activity (0.95 + 0-2 impulses/sec) was spontaneous but most often a fixed temporal correlation between impulses and ventricular dynamics was not detectable. It was increased during occlusion of the thoracic aorta, I.v. administration of isoprenaline or infusion of saline. It was unaffected by asphyxia, haemorrhage and i.v. administration of acetylcholine. It was decreased during occlusion of inferior vena cava. Therefore these ventricular receptors appeared to be mainly sensitive to mechanical events. 4. The fibres were excited during the occlusion of the left main coronary artery, after a latency of 14-5 + 1*3 sec. They were also excited during ventricular fibrillation, exhibiting the highest values of impulse activity (2.51 + 0 4 impulses/sec). The increase in impulse activity during ventricular fibrillation was sometimes immediate and extreme, with peak frequencies of about 50 impulses/sec. 5. These spontaneously active ventricular receptors with unmyelinated nerve fibres participate in the transmission of the continuous impulse activity which from the cardiovascular system reaches the spinal cord through the sympathetic nerves and which is likely to contribute to the neural control of circulation. Thus the unmyelinated cardiac sympathetic afferents should not be considered as purely nociceptive in function. INTRODUCTION
Previous workers have described afferent sympathetic myelinated fibres with endings in the heart (Ueda, Uchida & Kamisaka, 1969; Brown & Malliani, 1971; Malliani Recordati & Schwartz, 1973), in the pulmonary artery (Nishi, Sakanashi & Takenaka, 1974) and veins (Lombardi, Malliani & Pagani, 1976) and in the thoracic aorta (Uchida, 1975; Malliani & Pagani, 1976) which were spontaneously active and sensitive to haemodynamic events. Thus we advanced the hypothesis that this afferent channel 0022-3751/79/3940.0685 $01.50 © 1979 The Physiological Society
R. CASATI, F. LOMBARDI AND A. MALLIANI was likely to be tonically involved in the neural regulation of the circulation (Malliani, Lombardi, Pagani, Recordati & Schwartz, 1975). The hypothesis was supported by experiments on chronic spinal animals in which a reflex tachycardia, entirely mediated by afferent sympathetic nerve fibres, was obtained during intravenous infusions of saline (Bishop, Lombardi, Malliani, Pagani & Recordati, 1976). The existence of afferent unmyelinated fibres in the cardiac sympathetic nerves is disputed. Elusive in the early electrophysiological experiments by Brown (1967), their presence was later postulated by Peterson & Brown (1971) and eventually described by Uchida, Kamisaka, Murao & Ueda (1974); on the other hand, a recent anatomical degeneration study (Emmery, Foreman & Coggeshall, 1978) has cast new doubt on their existence. The present paper reports an electrophysiological study of afferent sympathetic unmyelinated fibres with left ventricular endings, spontaneously active and sensitive to haemodynamic events. 136
METHODS
The results were obtained from thirty-three experiments in cats (2.5-4-5 kg), anaesthetized by i.P. injection of pentobarbitone (35 mg/kg). The trachea was cannulated. Polyethylene catheters were inserted into (1) a carotid or femoral artery, (2) the right atrium through the external jugular vein, (3) a femoral vein and (4) the left ventricle through the left atrial appendage and the mitral valve (seven experiments). After a paralyzing dose (2 mg/kg) of gallamine triethiodide (Sincurarina, Farmitalia), all animals were artificially ventilated so as to maintain arterial pH, po, and pco, within physiological limits. The thorax was opened through the fourth left interspace. The fifth and sixth ribs on the left side were removed. In sixteen experiments, the pericardium was left intact until nervous activity was recorded or, in seven additional experiments, until the animal was killed and the heart opened. Threads were loosely passed around the distal portion of the thoracic aorta and the inferior vena cava and the ends of these ligatures were pulled through rigid polyethylene tubes whenever the vessels had to be occluded. In ten experiments the pericardium was opened, the main left coronary artery was dissected from the surrounding tissues without any damage to the pericoronary nerve (Brown, 1967) and a thread was loosely passed around it. In seven of these animals a catheter was introduced into the left ventricle (see above). The heads of the second and third rib were removed retropleurally on the left side to expose the stellate ganglion and its branches. The ganglion was covered by a pool of mineral oil maintained at body temperature by thermal radiation. Variables recorded. Afferent nervous impulse activity was recorded from filaments isolated under a dissecting microscope from the cut peripheral end of the third and fourth (T3, T4) left thoracic sympathetic rami communicants. Filaments were split until discharges from a single active fibre were present; in some experiments from two to four fibres were simultaneously active in the same filament, however the constant shape and amplitude of their action potentials made identifiable the impulses of the unmyelinated fibre which was under study. The details for recording nervous activity have been previously published (Malliani et al. 1973; Malliani & Pagani, 1976). Arterial and atrial pressures were measured with Statham P 23 De strain gauges. The cathetermanometer systems had a flat ( ± 5 %) frequency response of 30 Hz as calculated by their responses to step increases in pressure (Fry, 1960). Left ventricular pressure was measured with a Statham P 23 De strain gauge connected to a specially built, high-frequency d.c. operational bridge amplifier that was linear (-3 db) up to 15 kHz. The measured flat ( ± 5%) frequency response of the left ventricular cather-manometer system was 30 Hz. We also recorded the e.c.g. and the respiratory movements, all details having been already reported (Lioy, Malliani, Pagani, Recordati & Schwartz, 1974).
Measurement of conduction velocitie8 of afferent fibres. In most of the experiments, the left inferior cardiac nerve was isolated from the surrounding tissues above the aortic arch. This por-
VENTRICULAR SYMPATHETIC AFFERENTS
137
tion of the nerve was stimulated via platinum electrodes (interelectrode distance of 5 mm; cathode proximal) with a Grass S4 stimulator through an isolation unit. Pulses were monophasic, 0 1-1-5 msec duration, 10-15 V. Conduction distance was measured from the proximal stimulating electrode to the closest recording electrode (Malliani et al. 1973). In some experiments the left inferior cardiac nerve was not isolated and the electrical stimulation was applied along its course to the adjacent connective tissues; this procedure was adopted in order to verify that slowly conducting fibres could also be obtained in absence of any dissection performed along their path. To ascertain that all nervous impulses elicited by electrical or mechanical stimuli as well as those occurring spontaneously originated from the same fibre we analysed their configuration on photographic records with expanded time base. Constancy of amplitude and shape of action potentials as well as absence, in most experiments, of other impulses was considered a safe criterion. The same stimulating apparatus was also used to induce ventricular fibrillation: in this case trains of impulses (15-3 msec, 20 V, 200 Hz) were delivered for about 1 sec. Ventricular fibrillation was usually induced by electrically stimulating one site of the right ventricle located distally from the receptive field of the fibre which was under study. In a few cases, however, ventricular fibrillation could be obtained by applying for the duration of a few cardiac cycles a light mechanical pressure on some part of the ventricular surface. Finally, spontaneous episodes of ventricular fibrillation could be observed. Episodes of fibrillation often subsided spontaneously; if this had not occurred, a gentle cardiac massage was often capable of restoring a normal rhythm. Repeated observations could then be made on the activity of the same fibre during several episodes of ventricular fibrillation. Location of receptor ending. The left ventricular location of the sensory endings of each single fibre displaying a spontaneous impulse activity was tested by very gentle probing performed through the intact pericardium with a blunt instrument. In some cases a light pressure exerted by a finger was an appropriate manoeuvre. In sixteen experiments the pericardium was later opened during the experiment and the light probing was repeated directly on the surface of the left ventricle. However in several cases no excitations of impulse activity could be obtained during the experiment by local mechanical stimuli. In these cases the left ventricular location of the endings was inferred on the basis of the pattern of their impulse activity in relation to various haemodynamic stimuli. The endings of each fibre were however definitely localized to the left ventricle by mechanical probing repeated after the animal had been killed and the heart opened (Coleridge, Hemingway, Holmes & Linden, 1957). All fibres during mechanical probing, exhibited typical after-discharges at the end of the stimulus (Fig. 3E) (Burgess & Perl, 1973; Iggo & Kornhuber, 1977). The destruction of the left ventricular receptive field always produced the disappearance of impulses in the studied fibre, confirming that no additional active fields were present (Coleridge, Kidd Coleridge & Banzett, 1975; Malliani & Pagani, 1976). The fibres which were erroneously considered, in the course of the experiment, possessing ventricular endings and instead innervating other structures, e.g. the aorta or the left atrium, were not included in this report. We also discarded those fibres whose impulse activity seemed to be permanently modified by the preliminary mechanical manoeuvres performed in order to assess their location. Signs of injury typically consisted in erratic bursts of action potentials. Statistical analy8is. The paired t test was used to evaluate the significance of the changes induced by the experimental interventions on the impulse activity within the same fibres and on the haemodynamic variables within the same animals. The grouped t test was used to compare the impulse activity and the haemodynamic conditions between the group of animals in which the pericardium was open and a catheter was positioned into the left ventricle and those in which the pericardium was intact (Armitage, 1971).
RESULTS
We studied the impulse activity of thirty-three afferent sympathetic unmyelinated fibres the endings of which were excited by direct mechanical probing of the nonbeating, opened left ventricle. Some endings were activated by light probing over the external or internal surface of the left ventricle (respectively seventeen and six
-~ ~ I - ;
R. CASATI, F. LOMBARDI AND A. MALLIANI fibres), while others (ten fibres) could only be excited with mechanical stimuli deforming the depth of the ventricular muscle, e.g. punctures with penetrating needles. Of the external receptive fields, seven were located in proximity of the left anterior descending coronary artery, five around the left circumflex ramus and five on the lateral portion of the left ventricle. This last part of the ventricle contained seven out of ten deep receptive fields. The fields on the internal surface appeared to be sparsely distributed without preferential sites. The dimensions of each receptive field were often difficult to establish, especially in the depth of the ventricular wall; however, the superficial ones appeared to be no smaller than 2-3 mm2 and no larger than 1 cm2. No fibre showed functional evidence of multiple sensory areas within the ventricle. 138
A
8
r ~~~~~~~200 xmmnHg
r
200
-mmHg
0 5 sec
Fig. 1. Impulse activity of an afferent sympathetic unmyelinated nerve fibre (group C) with its receptive field in the left ventricle. Tracings represent from top to bottom, the e.c.g., the systemic arterial pressure, the left ventricular pressure (polygraph recordings) and neural activity (cathode-ray oscilloscope recording). A, spontaneous activity; B, during occlusion of the aorta. The fibre conduction velocity was 0-87 m/sec; the measured conduction distance from the receptive field to the recording electrode was 9-6 cm. Dots indicate the approximate relation between impulses and cardiac cycles, taking into account a conduction time of 110 msec.
Spontaneous impulse activity of afferent sympathetic unmyelinated fibres with left ventricular endings. In twenty-three animals with intact pericardium the spontaneous impulse activity was 0-94 + 0-2 (s.E.) impulses/sec at an arterial systolic pressure of 138 + 4 mmHg, right atrial pressure of 6-8 + 1 -0 cm H20, heart rate of 187 + 5 beats/min. In seven animals with the pericardium opened and a left veiitricular catheter (see Methods), the spontaneous impulse activity and haemodynamic conditions were not statistically different (nervous activity 1-0+ 0-2 impulses/sec; arterial systolic pressure 141 + 5 mmHg; right atrial pressure 6-4 + 0-4 cm H20; heart rate 192 + 7 beats/min). Henceforth the two groups of animals will be combined (see Table 1 and Fig. 2). The spontaneous impulse activity of the thirty-three fibres was 0-95 + 0-2 (range 0-10-2-90) impulses/sec. This discharge consisted of not more than a single action potential per cardiac cycle but each cardiac cycle was not necessarily accompanied by a nervous impulse.
VENTRICULAR SYMPATHETIC AFFERENTS *
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135
AFFERENT SYMPATHETIC UNMYELINATED FIBRES WITH LEFT VENTRICULAR ENDINGS IN CATS
BY R. CASATI, F. LOMBARDI AND A. MALLIANI From the Istituto di Ricerche Cardiovascolari, University of Milan and Centro Ricerche Cardiovascolari, CNR, Via F. Sforza 35, 20122 Milan, Italy
(Received 14 August 1978) SUMMARY
1. We recorded the electrical impulse activity of thirty-three single afferent fibres with left ventricular endings from the third and fourth left thoracic sympathetic rami communicantes of anaesthetized cats. Their conduction velocity ranged from 0*23 to 0'98 m/sec (group C). 2. The endings of each fibre were localized to the left ventricle by mechanical probing performed at the end of the experiment on the non-beating heart. No fibre had multiple sensory fields. 3. The impulse activity (0.95 + 0-2 impulses/sec) was spontaneous but most often a fixed temporal correlation between impulses and ventricular dynamics was not detectable. It was increased during occlusion of the thoracic aorta, I.v. administration of isoprenaline or infusion of saline. It was unaffected by asphyxia, haemorrhage and i.v. administration of acetylcholine. It was decreased during occlusion of inferior vena cava. Therefore these ventricular receptors appeared to be mainly sensitive to mechanical events. 4. The fibres were excited during the occlusion of the left main coronary artery, after a latency of 14-5 + 1*3 sec. They were also excited during ventricular fibrillation, exhibiting the highest values of impulse activity (2.51 + 0 4 impulses/sec). The increase in impulse activity during ventricular fibrillation was sometimes immediate and extreme, with peak frequencies of about 50 impulses/sec. 5. These spontaneously active ventricular receptors with unmyelinated nerve fibres participate in the transmission of the continuous impulse activity which from the cardiovascular system reaches the spinal cord through the sympathetic nerves and which is likely to contribute to the neural control of circulation. Thus the unmyelinated cardiac sympathetic afferents should not be considered as purely nociceptive in function. INTRODUCTION
Previous workers have described afferent sympathetic myelinated fibres with endings in the heart (Ueda, Uchida & Kamisaka, 1969; Brown & Malliani, 1971; Malliani Recordati & Schwartz, 1973), in the pulmonary artery (Nishi, Sakanashi & Takenaka, 1974) and veins (Lombardi, Malliani & Pagani, 1976) and in the thoracic aorta (Uchida, 1975; Malliani & Pagani, 1976) which were spontaneously active and sensitive to haemodynamic events. Thus we advanced the hypothesis that this afferent channel 0022-3751/79/3940.0685 $01.50 © 1979 The Physiological Society
R. CASATI, F. LOMBARDI AND A. MALLIANI was likely to be tonically involved in the neural regulation of the circulation (Malliani, Lombardi, Pagani, Recordati & Schwartz, 1975). The hypothesis was supported by experiments on chronic spinal animals in which a reflex tachycardia, entirely mediated by afferent sympathetic nerve fibres, was obtained during intravenous infusions of saline (Bishop, Lombardi, Malliani, Pagani & Recordati, 1976). The existence of afferent unmyelinated fibres in the cardiac sympathetic nerves is disputed. Elusive in the early electrophysiological experiments by Brown (1967), their presence was later postulated by Peterson & Brown (1971) and eventually described by Uchida, Kamisaka, Murao & Ueda (1974); on the other hand, a recent anatomical degeneration study (Emmery, Foreman & Coggeshall, 1978) has cast new doubt on their existence. The present paper reports an electrophysiological study of afferent sympathetic unmyelinated fibres with left ventricular endings, spontaneously active and sensitive to haemodynamic events. 136
METHODS
The results were obtained from thirty-three experiments in cats (2.5-4-5 kg), anaesthetized by i.P. injection of pentobarbitone (35 mg/kg). The trachea was cannulated. Polyethylene catheters were inserted into (1) a carotid or femoral artery, (2) the right atrium through the external jugular vein, (3) a femoral vein and (4) the left ventricle through the left atrial appendage and the mitral valve (seven experiments). After a paralyzing dose (2 mg/kg) of gallamine triethiodide (Sincurarina, Farmitalia), all animals were artificially ventilated so as to maintain arterial pH, po, and pco, within physiological limits. The thorax was opened through the fourth left interspace. The fifth and sixth ribs on the left side were removed. In sixteen experiments, the pericardium was left intact until nervous activity was recorded or, in seven additional experiments, until the animal was killed and the heart opened. Threads were loosely passed around the distal portion of the thoracic aorta and the inferior vena cava and the ends of these ligatures were pulled through rigid polyethylene tubes whenever the vessels had to be occluded. In ten experiments the pericardium was opened, the main left coronary artery was dissected from the surrounding tissues without any damage to the pericoronary nerve (Brown, 1967) and a thread was loosely passed around it. In seven of these animals a catheter was introduced into the left ventricle (see above). The heads of the second and third rib were removed retropleurally on the left side to expose the stellate ganglion and its branches. The ganglion was covered by a pool of mineral oil maintained at body temperature by thermal radiation. Variables recorded. Afferent nervous impulse activity was recorded from filaments isolated under a dissecting microscope from the cut peripheral end of the third and fourth (T3, T4) left thoracic sympathetic rami communicants. Filaments were split until discharges from a single active fibre were present; in some experiments from two to four fibres were simultaneously active in the same filament, however the constant shape and amplitude of their action potentials made identifiable the impulses of the unmyelinated fibre which was under study. The details for recording nervous activity have been previously published (Malliani et al. 1973; Malliani & Pagani, 1976). Arterial and atrial pressures were measured with Statham P 23 De strain gauges. The cathetermanometer systems had a flat ( ± 5 %) frequency response of 30 Hz as calculated by their responses to step increases in pressure (Fry, 1960). Left ventricular pressure was measured with a Statham P 23 De strain gauge connected to a specially built, high-frequency d.c. operational bridge amplifier that was linear (-3 db) up to 15 kHz. The measured flat ( ± 5%) frequency response of the left ventricular cather-manometer system was 30 Hz. We also recorded the e.c.g. and the respiratory movements, all details having been already reported (Lioy, Malliani, Pagani, Recordati & Schwartz, 1974).
Measurement of conduction velocitie8 of afferent fibres. In most of the experiments, the left inferior cardiac nerve was isolated from the surrounding tissues above the aortic arch. This por-
VENTRICULAR SYMPATHETIC AFFERENTS
137
tion of the nerve was stimulated via platinum electrodes (interelectrode distance of 5 mm; cathode proximal) with a Grass S4 stimulator through an isolation unit. Pulses were monophasic, 0 1-1-5 msec duration, 10-15 V. Conduction distance was measured from the proximal stimulating electrode to the closest recording electrode (Malliani et al. 1973). In some experiments the left inferior cardiac nerve was not isolated and the electrical stimulation was applied along its course to the adjacent connective tissues; this procedure was adopted in order to verify that slowly conducting fibres could also be obtained in absence of any dissection performed along their path. To ascertain that all nervous impulses elicited by electrical or mechanical stimuli as well as those occurring spontaneously originated from the same fibre we analysed their configuration on photographic records with expanded time base. Constancy of amplitude and shape of action potentials as well as absence, in most experiments, of other impulses was considered a safe criterion. The same stimulating apparatus was also used to induce ventricular fibrillation: in this case trains of impulses (15-3 msec, 20 V, 200 Hz) were delivered for about 1 sec. Ventricular fibrillation was usually induced by electrically stimulating one site of the right ventricle located distally from the receptive field of the fibre which was under study. In a few cases, however, ventricular fibrillation could be obtained by applying for the duration of a few cardiac cycles a light mechanical pressure on some part of the ventricular surface. Finally, spontaneous episodes of ventricular fibrillation could be observed. Episodes of fibrillation often subsided spontaneously; if this had not occurred, a gentle cardiac massage was often capable of restoring a normal rhythm. Repeated observations could then be made on the activity of the same fibre during several episodes of ventricular fibrillation. Location of receptor ending. The left ventricular location of the sensory endings of each single fibre displaying a spontaneous impulse activity was tested by very gentle probing performed through the intact pericardium with a blunt instrument. In some cases a light pressure exerted by a finger was an appropriate manoeuvre. In sixteen experiments the pericardium was later opened during the experiment and the light probing was repeated directly on the surface of the left ventricle. However in several cases no excitations of impulse activity could be obtained during the experiment by local mechanical stimuli. In these cases the left ventricular location of the endings was inferred on the basis of the pattern of their impulse activity in relation to various haemodynamic stimuli. The endings of each fibre were however definitely localized to the left ventricle by mechanical probing repeated after the animal had been killed and the heart opened (Coleridge, Hemingway, Holmes & Linden, 1957). All fibres during mechanical probing, exhibited typical after-discharges at the end of the stimulus (Fig. 3E) (Burgess & Perl, 1973; Iggo & Kornhuber, 1977). The destruction of the left ventricular receptive field always produced the disappearance of impulses in the studied fibre, confirming that no additional active fields were present (Coleridge, Kidd Coleridge & Banzett, 1975; Malliani & Pagani, 1976). The fibres which were erroneously considered, in the course of the experiment, possessing ventricular endings and instead innervating other structures, e.g. the aorta or the left atrium, were not included in this report. We also discarded those fibres whose impulse activity seemed to be permanently modified by the preliminary mechanical manoeuvres performed in order to assess their location. Signs of injury typically consisted in erratic bursts of action potentials. Statistical analy8is. The paired t test was used to evaluate the significance of the changes induced by the experimental interventions on the impulse activity within the same fibres and on the haemodynamic variables within the same animals. The grouped t test was used to compare the impulse activity and the haemodynamic conditions between the group of animals in which the pericardium was open and a catheter was positioned into the left ventricle and those in which the pericardium was intact (Armitage, 1971).
RESULTS
We studied the impulse activity of thirty-three afferent sympathetic unmyelinated fibres the endings of which were excited by direct mechanical probing of the nonbeating, opened left ventricle. Some endings were activated by light probing over the external or internal surface of the left ventricle (respectively seventeen and six
-~ ~ I - ;
R. CASATI, F. LOMBARDI AND A. MALLIANI fibres), while others (ten fibres) could only be excited with mechanical stimuli deforming the depth of the ventricular muscle, e.g. punctures with penetrating needles. Of the external receptive fields, seven were located in proximity of the left anterior descending coronary artery, five around the left circumflex ramus and five on the lateral portion of the left ventricle. This last part of the ventricle contained seven out of ten deep receptive fields. The fields on the internal surface appeared to be sparsely distributed without preferential sites. The dimensions of each receptive field were often difficult to establish, especially in the depth of the ventricular wall; however, the superficial ones appeared to be no smaller than 2-3 mm2 and no larger than 1 cm2. No fibre showed functional evidence of multiple sensory areas within the ventricle. 138
A
8
r ~~~~~~~200 xmmnHg
r
200
-mmHg
0 5 sec
Fig. 1. Impulse activity of an afferent sympathetic unmyelinated nerve fibre (group C) with its receptive field in the left ventricle. Tracings represent from top to bottom, the e.c.g., the systemic arterial pressure, the left ventricular pressure (polygraph recordings) and neural activity (cathode-ray oscilloscope recording). A, spontaneous activity; B, during occlusion of the aorta. The fibre conduction velocity was 0-87 m/sec; the measured conduction distance from the receptive field to the recording electrode was 9-6 cm. Dots indicate the approximate relation between impulses and cardiac cycles, taking into account a conduction time of 110 msec.
Spontaneous impulse activity of afferent sympathetic unmyelinated fibres with left ventricular endings. In twenty-three animals with intact pericardium the spontaneous impulse activity was 0-94 + 0-2 (s.E.) impulses/sec at an arterial systolic pressure of 138 + 4 mmHg, right atrial pressure of 6-8 + 1 -0 cm H20, heart rate of 187 + 5 beats/min. In seven animals with the pericardium opened and a left veiitricular catheter (see Methods), the spontaneous impulse activity and haemodynamic conditions were not statistically different (nervous activity 1-0+ 0-2 impulses/sec; arterial systolic pressure 141 + 5 mmHg; right atrial pressure 6-4 + 0-4 cm H20; heart rate 192 + 7 beats/min). Henceforth the two groups of animals will be combined (see Table 1 and Fig. 2). The spontaneous impulse activity of the thirty-three fibres was 0-95 + 0-2 (range 0-10-2-90) impulses/sec. This discharge consisted of not more than a single action potential per cardiac cycle but each cardiac cycle was not necessarily accompanied by a nervous impulse.
VENTRICULAR SYMPATHETIC AFFERENTS *
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