On the Cardioinhibitory Reflex Originating from the Superior Laryngeal Nerve

The Japanese Journal of Physiology 18,pp.453-461,1968

ON THE CARDIOINHIBITORY REFLEX ORIGINATING FROM THE SUPERIOR LARYNGEAL NERVE

Juro IRIUCHIJIMAAND Mamoru KUMADA

Institute for Medical Electronics and Department of Physiology, Faculty of Medicine,University of Tokyo

Reflex inhibitory effects on the heart are not confined to the carotid sinus and depressor nerves.Almost all sensory nerves,when stimulated,can induce reflex inhibition of the heart beat under suitable conditions(MCDowALL,1956). The superior laryngeal nerve,containing afferent fibers from the mucous membrane of the upper larynx,is known to induce arrest or slowing of the heart relatively consistently(BRODIE and RUSSELL,1900;TOKITA, 964).Electrical stimulation of this nerve as well as chemical and mechanical stimulation of the laryngeal mucous membrane induces cardiac and respiratory arrest and blood pressure decrease.The recurrent laryngeal nerve produces no such effects.After bilateral vagotomy,electrical stimulation of the superior laryngeal nerve induces cardiac acceleration and elevation of blood pressure(ToKITA, 1964).Since stimulation of the carotid sinus nerve usually induces cardiac deceleration and blood pressure decrease even after vagotomy,the above finding shows that the central mechanism of cardiovascular reflex originating from the superior laryngeal nerve is somewhat different from that of the sinus reflex.The present study was undertaken to examine the difference between the superior laryngeal and carotid sinus nerves in more detail by observing cardiac output and cardiac vagal discharge during the reflexes induced by stimulation of these nerves.

METHODS

Anesthesia.Mongrel dogs of either sex, weighing between 5 and 15kg,were given premedication of morphine hydrochloride(5mg/kg),injected subcutaneously,and an- esthetized one-half hour later with a mixture of alpha chloralose(40mg/kg)and ure- thane(300mg/kg),both dissolved in saline and injected intravenously.The saphenous vein was catheterized for additional injection of anesthetics.

Hemodynamic and respiratory recordings.The trachea was cannulated for artificial ventilation with a positive pressure pump.The chest was opened in the left 4th inter- costal space and the pericardium was slit over the ascending aorta.A KOLIN type

Received for publication September 9,1967 入内島十郎, 熊田衛

453 454 J.IRIUCHIJIMA AND M.KUMADA coreless transducer(KoLIN,1959)was attached around the ascending aorta for the measurement of aortic flow .Then the chest wall was closed around the wires from the transducer.The pneumothorax was reduced ,whereupon the animal breathed normally. The flow signal recorded at the ascending aorta was integrated by a CR circuit with a time constant of 1 sec to obtain a measure of successive changes of cardiac output.Arterial blood pressure was recorded by connecting a cannulation of the femoral or carotid artery to a conventional strain-gauge electric manometer . The respiration of the animal was recorded with a thermistor(BT -15 ,NEC)placed in the tracheal cannula.During expiration , warm air passing by the thermistor diminished its resistance and, during inspiration ,cold room air increased the resistance.The change of resistance of the thermistor with respiration was electrically recorded simul - taneously with blood pressure and cardiac output . Preparation of nerves.The superior laryngeal nerve and the carotid sinus nerve on either side were isolated and severed so that their central ends could be stimulated by a pair o silver-silver chloride electrodes .Rectangular currents isolated from earth were used for stimulation. For observation of action potentials in cardiac vagal fibers ,the right cervical vagus was freed from the surrounding tissues and cut in the midcervical region .A black plate was placed under the central cut end of the vagus,which was desheathed and split into fine strands with watchmaker's forceps under a binocular microscope .A trough formed by tying the edges of the skin wound to a metal ring fixed above the neck was filled with warmed paraffin ,so that the strands of the vagus were completely immrnersed for the prevention of drying .Action potentials from the nerve strands were recorded in the paraffin pool by mounting the strand on a pair of silver-silver chloride electrodes connected to a capacity coupled amplifier with a time constant of 2 msec .The action potentials were displayed on a cathode ray oscilloscope and photographed. In some animals,action potentials were recorded from the intrathoracic cardiac branch of the vagus.The thorax was opened by median sternotomy under positive pressure respiration.Cardiac branches of the right vagosympathetic trunk were sought under the superior caval vein,followed to beneath the auricle ,and cut as distally as possible.The right vagosympathetic trunk was cut at the level of the confluence of the azygos vein to the superior caval vein . All communication of the right vagus with the stellate ganglion and the sympathetic chain were cut and the right vagus with its cardiac branches was freed from the surrounding tissues up to the neck .The recurrent nerve was also severed at its origin from the vagus.The cardiac branches were then brought up to the neck and desheathed.Action potentials therefrom were recorded in a way similar to that for the strands of the cervical vagus.

RESULTS

Hemodyn,amic study.Arterial blood pressure(P)may be regarded as a monot- onically increasing function of the two variables,cardiac output(I)and peripheral resistance(R): ap aP P=f(I,R); >0, >0. (1) aI aR In total differential form, aP aP dP dI+ dR. (2) al aR LARYNGEAL NERVE REFLEX 455

When the curves of cardiac output and blood pressure are recorded simul- taneously as in FIG.1,the change in peripheral resistance can be estimated by comparing the two curves(IRIUCHIJIMA and OGATA,1964).A parallel change between cardiac output and blood pressure is observed when peripheral resistance is stationary.Under this condition,since the second term of the right hand side of equation(2)is O,a small increment of blood pressure(P) is proportional to that of cardiac output(I).Therefore,changes in peripheral resistance are detected by discrepancies between cardiac output and blood pressure.Thus,in case of the depressor reflex on sinus nerve stimulation (FIG.1,right panel),the initial part of blood pressure decrease was ascribable mainly to a decrease in cardiac output,because of the concomitant decrease of both cardiac output and blood pressure.However,in the latter part of the depressor reflex,a decrease in peripheral resistance was seen from the depression of blood pressure(arrow,FIG.1)which was disproportionately large as compared with that of cardiac output. When the superior laryngeal nerve was stimulated,both cardiac output and blood pressure decreased as in FIG.1,left panel.In contrast to the de-

SUP LARYNG N SINUS N 2V,I MSEC 50/SEC 2V,I MSEC,50/SEC FIG.1. Effect of stimulation of the superior laryngeal nerve(left panel) and the sinus nerve(right panel)on cardiac output,arterial blood pressure and respiration(from top downward,each panel).Blood pressure scale in mm Hg and,in respiratory recording,inspiration upward.Stimulation parameters were 5V,1 msec,and 50/sec for both nerves. pressor effect of the sinus nerve(right panel),cardiac output and blood pressure showed a parallel decrease on stimulation of the laryngeal nerve,indicating that the blood pressure decrease was ascribable solely to a decrease in cardiac output.Comparison of the effects of stimulation of the sinus and laryngeal nerves as in FIG.1 were performed in four dogs and the results were all consistent:a parallel decrease of cardiac output and blood pressure on laryngeal nerve stimulation and a disproportionately prolonged depression of blood pres- 456 J.IRIUCHIJIMA AND M.KUMADA

sure curve on sinus nerve stimulation.In this series of experiments,stimulation parameters were 10-50 cps,1-5 msec,and 2-10V for both nerves.After strong stimulation of the laryngeal nerve a rise of blood pressure was observed when bradycardia had subsided.After bilateral vagotomy,as reported by TOKITA(1964),stimulation of the laryngeal nerve induced a pressor reflex instead of a depressor reflex.These findings indicate that the main cause of the depressor effect on stimulation of the laryngeal nerve is a decrease in cardiac output due to vagal bradycardia. In another series of experiments on three dogs,effects of stimulation of the sinus and laryngeal nerves on heart rate and blood pressure were studied without recording aortic flow.Since thoracotomy was unnecessary in this experiment,cardiovascular effects of both nerves could be compared under more natural conditions.The results were all consistent with those obtained in the above experiments in which cardiac output was measured:On laryngeal nerve stimulation,the decrease in blood pressure was always concomitant with bradycardia(FIG.2A).On stimulation of the sinus nerve,however,blood pressure recovered more slowly than the heart rate. Cardiac vagal discharge is periodically inhibited in the phase of inspiration by a direct inhibitory influence from the respiratory center on the cardiac

FIG.2.Effect of tetanic stimulation of the superior laryngeal nerve (5V,1 msec,50/sec)on heart rate and blood pressure during spontaneous breathing(A)and during positive pressure artificial respiration(B). In both A and B,from top downward,heart rate,blood pressure and respiration(inspiration upward). LARYNGEAL NERVE REFLEX 457 vagal center(HEYMANS,1929;ANREP et al.,1935;KOEPCHEN et al.,1961; IRIUCHIJIMA and KUMADA,1964).On laryngeal nerve stimulation,since the respiratory center is inhibited(BRODIE and RUSSELL,1900),the cardiac vagal center is released from this periodical inhibition.The bradycardia on laryngeal nerve stimulation may be partly attributed to this secondary effect of respiratory arrest.However,during artificial respiration when spontaneous respiration of the animal was suppressed,laryngeal nerve stimulation still induced bradycardia,though diminished in extent(FIG.2B). Not infrequently,in a given animal,bradycardia was more intense on laryngeal nerve stimulation than on sinus nerve stimulation.However,during artificial respiration, the response to laryngeal nerve stimulation was greatly diminished.Artificial respiration had less effect on the response to sinus nerve stimulation.

Observations of cardiac vagal discharge at the cervical vagus.As reported earlier(IRIUCHIJIMA and KUMADA,1964),in the cervical vagus,there are fibers responding to single pulse stimulation of the carotid sinus nerve with a latent period of 50-100 msec.As shown in FIG.3A,upper record,the latent period fluCtUated abOUt 10mSeC Or mOre Onrepeated Stim UlatiOn.SUCh fiberS may De regarded as cardiac vagal fibers for the following reasons:1)A similar response to sinus nerve stimulation can be obtained in the intrathoracic cardiac branches of the vagus(IRIucHIJIMA and KUMADA,1963).2)Spontaneous impulses in such fibers were diminished by occlusion of the common carotid arteries.3)The spontaneous activity is inhibited during inspiration,when the heart rate is accelerated in respiratory arrhythmia.These kinds of fibers ‘seem to be identical with Type I fibers reported by JEWETT(1964),though he did not try sinus nerve stimulation when recording from these fibers. It was expected that the cardiac vagal fibers,responding to sinus nerve stimulation,were also excitable by stimulating the laryngeal nerve,because both nerves induced reflex vagal bradycardia of comparable magnitude.In seven dogs,the cardiac vagal fibers identified by sinus nerve stimulation were tested to determine whether they also responded to stimulation of the laryngeal nerve.Contrary to expectation,the majority of the fibers did not respond to laryngeal nerve stimulation as shown in FIG.3A,lower record.Even tetanic stimulation of frequencies up to 100 cps failed to induce any appreciable reflexive impulsesin such fibers.Only 5 of 31 fibers,responding to sillus nerve stimulation,appeared to respond also to single pulse stimulation of the laryngeal nerve with a shorter latent period than in response to sinus nerve stimulation. However, the response was uncertain, mingled with spontaneous impulses of the same fiber. In another series of experiments on four more dogs,nerve strands of the cervical vagus were searched for fibers responding to stimulation of the superior 458 J.IRIUCHIJIMA AND M.KUMADA

A D

FIG.3. From A to E,each pair,the upper record was taken on stimulating the sinus nerve with a single pulse and the lower record on stimulating the superior laryngeal nerve with a single pulse.Each record was a superposition of 20 successive sweeps at 2/sec.A:A fiber in the cervical vagus responding to sinus nerve stimulation only .B:A fiber in the cervical vagus responding to both sinus and laryngeal nerve stimulations.C:Recording at an intrathoracic cardiac branch of the vagus.D:A fiber in the cervical vagus responding to laryngeal nerve stimulation but not to sinus nerve stimulation.E:Recording at the recurrent nerve,on stimulation of the ipsilateral sinus and laryngeal nerves.Time scales:each 50msec. laryngeal nerve.These kinds of fibers were then tested with sinus nerve stimulation.Of 20 fibers responding to laryngeal nerve stimulation ,12 fibers were found responding also to sinus nerve stimulation;one example of such fibers is shown in FIG.3 B.Though the latent periods for both response fluctuated considerably,for a given fiber,the mean latent period was always shorter for laryngeal nerve stimulation than for sinus nerve stimulation(36•}

8msec against 69•}7msec,means of 11 fibers with standard deviation) .The remaining 8 fibers did not respond to sinus nerve stimulation as in FIG.3 D. LARYNGEAL NERVE REFLEX 459

The latent period of the response to laryngeal nerve stimulation was shorter in such fibers than in those responding to both nerves(23•}10msec against 36•}8msec,means of 8 and 11 fibers,respectively,with standard deviation).

The fibers responding solely to stimulation of the superior laryngeal nerve were not regarded as cardiac fibers.Since stimulation of the superior laryngeal nerve induced reflex action potentials in a considerable number of fibers in the recurrent nerve with similar latent periods as shown in FIG.3 E,lower record, the majority of such fibers were considered supplying the laryngeal muscles via the recurrent nerve,but not the heart.These kinds of fibers were already described in the cat by EYZAGUIRRE and TAYLOR(1963).

Observations of action potentials at intrathoracic cardiac branches of the vagus.

In still another group of six dogs,action potentials were observed at the cardiac branches of the vagus in open chest dogs under positive pressure respiration.In five of the six dogs sinus nerve stimulation induced reflexive discharge in the cardiac branch as reported earlier(IRI UCHIJIMA and KUMADA,

1963).However,stimulation of the superior laryngeal nerve induced reflexive discharge only in two of the five dogs.This may be ascribable to the more labile nature of the laryngeal nerve reflex than the sinus nerve reflex under artificial respiration and other experimental interventions.Even in the two dogs,the response to laryngeal nerve stimulation was less marked than that to sinus nerve stimulation.Comparison of the effects of the two nerves was presented in FIG.3 C and FIG.4.As seen in FIG.3 C,on single pulse stimulation,the mean latent period was shorter on laryngeal nerve stimulation than on sinus nerve stimulation.

FIG.4. Induced impulses in an intrathoracic cardiac branch of the vagus on tetanic stimulation of the sinus nerve(A)and the superior laryngeal nerve(B)at 10V,1msec and 50/sec for the underlined periods.Each record from top downward,neurogram,electro-cardiogram and respiration(inspiration upward).Time scale:1sec. 460 J.IRIUCHIJIMA AND M.KUMADA

DISCUSSION

While the depressor reflex from the sinus nerve is ascribable to decreases in cardiac output and peripheral resistance due to vagal excitation and sympathetic inhibition,the depressor reflex from the laryngeal nerve is ascribable solely to a decrease in cardiac output due to vagal bradycardia.The absence of inhibition of the sympathetic activity seems to be the most conspicuous difference between the laryngeal nerve depressor reflex and the sinus nerve reflex. The functional significance of the reflex inhibition of respiration and heart beat on superior laryngeal nerve stimulation is obscure.As propounded by BRODIE and RUSSELL(1900),it is tempting to conclude that,when an irritant is applied to the mucous membrane of the air way,the respiratory arrest at once stops further entrance of the irritant and the circulatory disturbance tends to impede its absorption from the surface. Only a small fraction of the cardiac vagal fibers,identified in the cervical vagus by sinus nerve stimulation,responded to laryngeal nerve stimulation, On the other hand,not infrequently,laryngeal nerve stimulation induced more intense bradycardia than sinus nerve stimulation.From these facts it is con- ceivable that stimulation of the laryngeal nerve excites,in addition to the fibers responding to both nerves,the cardiac vagal fibers which are not excitable by sinus nerve stimulation.However,at presen, there is no way to, discriminate such cardiac fibers from the motor fibers supplying the laryngeal muscles via the recurrent nerve,since the latter fibers also respond to laryngeal. nerve stimulation(FIG.3 E).Nevertheless,it may be concluded that the efferent pathway for bradycardia on laryngeal nerve stimulation does not. coincide with that on sinus nerve stimulation,though there are some fibers which are common to both pathways.

SUMMARY

1. Cardiovascular effects of stimulation of the superior laryngeal nerve were studied in the dog by observing cardiac output and blood pressure as well as, efferent discharges in the vagus nerve. 2. The blood pressure decrease on stimulation of the superior laryngeal nerve was ascribable mostly to a decrease in cardiac output due to vagal bradycardia. No decrease in peripheral resistance was observed. 3. Only a fraction of the cardiac vagal fibers,responding to sinus nerve stimulation,were reflexly excitable on stimulation of the superior laryngeal nerve. 4. It is concluded that laryngeal nerve stimulation excites the cardiac vagal center without reciprocal inhibition of the sympathetic cardiovascular center LARYNGEAL NERVE REFLEX 461 and that the group of the cardiac vagal fibers which is excitable on laryngeal nerve stimulation is not identical with that of the fibers excitable on sinus nerve stimulation,though there is some overlapping between them.

The authors'thanks are due to Profs.Koijro MATSUDA and Masamitsu OSWHIMAfor their advice and encouragement throughout this study.The expense for this work was partly defrayed by a research grant from the Ministry of Education to Prof.MATSUDA.

REFERENCES

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