DURING investigations on the upper

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1 The Augmentor Acton of the Sympathetc Cardac Nerves By WALTER C. RANDALL, PH.D., AND WAYNE G. ROHSE, PH.D. An augmentor acton of the cardac sympathetc nerves s demonstrated to elct profound elevatons n systolc blood pressure. Dastolc pressure does not rse n an equvalent amount and sgnfcant ncrease n pulse pressure occurs. Ths perssts for a consderable tme after removal of the stmulaton. Durng stmulaton of the left cardac sympathetc, an augmentor acton s often not accompaned by acceleraton. Stmulaton of the rght cardac sympathetc evokes both effects. The elevaton of blood pressure s chefly produced by augmentaton of ventrcular beats, not by cardac acceleraton. Downloaded from by on December 3, 8 DURING nvestgatons on the upper thoracc sympathetc outflows, electrc stmulaton of the stellate ganglon and assocated nerve pathways elcted profound elevatons n blood pressure whch were unexplaned by conventonal descrptons of the nervous control of the heart. Purely accelerator responses were rare, and pulse pressure changes of 80 to 00 mm. Hg frequently resulted. The Cyon brothers 2 were among the frst to demonstrate acceleraton and elevaton of blood pressure durng nerve stmulaton. Hrthle showed that systole was abbrevated durng the tachycarda nduced by accelerator nerve stmulaton. Hs observatons were confrmed and amplfed by Hunt 4 who dfferentated the acton of these nerves on the perods of systole and dastole, both of whch were sgnfcantly shortened. Wggers and Katz 6 " 7 arrved at essentally smlar conclusons and demonstrated a specfc acton upon ventrcular musculature. None of these reports emphaszed systolc pressure alteratons. Kymographc tracngs*" 0 durng stmulaton of the accelerator nerves or the communcatng ram of the upper thoracc spnal nerves generally show a rse n mean pressure, ncreased heart rate, and an apparent reducton n ampltude of pulse oscllaton. Other workers, " 8 usng more adequate recordng equpment, ob From the Department of Physology, Strtch School of Mcdcno and the Loyola Graduate School, Chcago, III. Receved for publcaton March S, 956. served that faradc stmulaton nfluenced the heart n such a way that ts "vgor of contracton appeared to ncrease greatly." METHOD Usng ether unpolar or bpolar stmulaton techncs and an Amercan Electroncs model 04 square wave generator, controlled stmulatng current pulses were delvered to both rght and left thoracc sympathetc trunks. In ths procedure, sgnfcant and consstent alteratons n patterns of response were nterpreted to ndcate the entrance or ext of sympathetc nerve pathways medatng the recorded responses. Pulses havng a duraton of 0 msecs., ntensty of 0.5 to 5.0 volts, and frequences varyng from 0.5 to /sec. were employed. All stmulatons were montored by a DuMont cathode ray osclloscope connected across the electrodes. oltages reported are those read from the osclloscope durng stmulaton. All experments reported here were carred out n open chest dogs under Nembutal anesthesa. Blood pressure and heart rate were recorded optcally from segment capsules or by a Sanborn electronanometer and Polyvso. RESULTS Analyss of records from optcal tracngs or from the electromanometer revealed sgnfcant and sometmes profound elevatons n systolc pressure durng stmulaton of the stellate ganglon, frequently n the complete absence of acceleraton and wth mnmal changes n dastolc pressure. Exctaton of the rght stellate generally nduced greater acceleraton, but augmentaton was also present. Elevated pulse pressures were sustaned for prolonged perods after cessaton of stmulaton. Comparatve tracngs are shown n fgure. The 470 Crculaton Reteanh, olume I, Jvly lf

2 > ' '. * = a! ^ 90 2oor: *I l T? mr " % IE fct s 4 K s T / J s 8 IMK * J! J r s «MC _ I T *? A yd r RANDALL AND ROHSE 47 4f I _. <rr f v Aị. ft J._ ~r T I J ~" A lt, ; _. «J. =4 _J n L.j*.. > rj HIU m m **»'. v «. l^.:. A ' "^ S s. * * A A L A y _j _ r **u N., * j M r SSI! *. 'k.. *t I J. T *», L» JL ^«T ::: IB C. J "MCI ''IG.. Systolc and dastolc pressure responses nduced by electrcal stmulaton (2. volts, 0 msec, duraton, /sec.) of left and rght stellate gangla at slow (top record) and fast speed recordngs. Horzontal bar under each record desgnates the perod of stmulaton. Systolc peaks connected by a contnuous lne n order to clearly outlne the alteraton n pulse pressure. r. Downloaded from by on December 3, 8 top record was made at relatvely slow speed and s characterzed by systolc pressure elevatons n excess of 50 mm Hg whle dastolc pressure actually decreased. Stmulaton was repeated on the left sde and recorded at faster speed. The frst evdence of change n pulse pressure appeared on the sxth cycle followng ntaton of stmulaton, and ths was followed by successve ncrements n pulse pressure to a maxmum of 95 mm Hg. Heart rate remaned unchanged. Stmulaton of the rght stellate ganglon elcted an augmentor response, agan on the sxth cycle, wth a progressve ncrease n pulse pressure. Acceleraton was promnent and was accompaned by a moderate but sustaned elevaton n dastolc pressure. Smlar recordngs at stll faster speeds revealed a much more rapd systolc upstroke concdent wth the ncreased pressure. Table summarzes observatons n 6 anmals whch may be consdered typcal of approxmately 50 anmals studed. Augmentor responses were regularly elcted from stmulaton of both sdes, but were usually more profound on the left. Acceleraton was generally more promnent on the rght, and frequently absent or nsgnfcant on the left. Dfferentaton of fber pathways medatng cardoacceleraton from those medatng augmentaton have not been reported, and ndeed, t s not known whether separate pathways exst. Anatomcal pathways of accelerator nerves pass through communcatng ram of the T2 to T5 segmental nerves. 0 In the present TABLE. Blood Pressure Changes Lett stellate Pulse Press Change n Heart rate S 0 2S 4 S 24 mm. Hg Syst. 52 5S Rght stellate mm Hg Dog. no. Syst. Dnstol. Dastol Pulse Press Change n Heart rate 60 4S 2S 2S 46

3 472 AUGMEXTOR ACTION OF SYMPATHETIC CARDIAC NERES Downloaded from by on December 3, 8 a. 2. Selected records to llustrate varyng blood pressure responses elcted by electrc stmulaton at each segmental level between T2 and Tl. Three upper records at faster speeds than the lower three. Stmulatng current for all stmulatons, 2. volts, 0 msec, /sec. studes, electrodes were placed successvely at each nterganglonc segment from the caudal pole of the stellate (T2 to T0 or Tl), and controlled square wave pulses delvered. Fgure 2 llustrates results of ths procedure. Cardovascular response was prompt and prncpally systolc when the trunk was stmulated at T2 wth progressvely lesser responses as the electrodes were moved caudalward. Lttle or no response was elcted at To. Caudal to ths level, prcssor responses appeared, but were marked by an approxmately equal rse n systolc and dastolc, much as expected durng exctaton of splanchnc constrctor pathways. Ffteen to sec. later, a secondary rse n pressure occurred marked by a relatvely greater change n systolc pressure. The long latency from begnnng of stmulaton to the secondary response, together wth the secondary wdenng of pulse pressure can perhaps be explaned by lberaton of epnephrne or norepnephrne from the adrenal medulla. Thus the pressor responses elcted by stmulaton at T2 to To were dstnctly dfferent from those produced by exctaton of the caudal end of the thoracc trunk. In order to elmnate these splanchnc effects, the trunk was generally sectoned and dssected free mmedately caudal to T5 or T6. To elmnate the possblty of reflex vasoconstrcton medated by afferents ascendng n the vagosympathetc trunk, the vag were cut blaterally just superor to the caudal cervcal ganglon. 4 Combned wth secton of the sympathetc trunk below the stellate, ths operaton served to solate the major efferent sympathetc nnervaton of the heart. At the sgnals (top record, fg. 3), the left and then the

4 RANDALL AXJ) ROHSE 473 Downloaded from by on December 3, 8 Fa. 3. Blood pressure recordngs from n dog durng secton of the vag (top record) and durng electrcal stmulaton (4.8 volts, 0 msec, 0/sec.) of tho left (mddle) and rght (bottom) stellate gangla. Both sympathetc trunks dvded at T4 pror to experment; stmulatons were performed n sequence. rght vag were sectoned. The heart dd not accelerate apprecably followng ether operaton, but a wdened pulse ampltude dd appear. The sgnfcance of ths remans to be nvestgated. It s apparent from fgure 3 that augmentor responses perssted n such neurally solated cardac preparatons. DISCUSSION The early desgnaton of the cardosympathetcs as accelerator nerves was evdently dependent upon two factors: () the use of stmulators wth nadequate current parameters, and (2) the nablty of recorders to follow fathfully rapd changes n pressure. The contnued use of the term perpetuates the concept that acceleraton s the most mportant (or only) functon. The sgnfcance of an augmentor acton seems to have been largely overlooked. The term augmentor was appled by Henderson and Barrnger 5 n 93. In only a few of ther anmals was ncreased ampltude of stroke observed, and then only when the heart was beatng wth "consderably dmnshed vgor and arteral pressure was low." These authors state the augmentor effect never exceeded 30 per cent of the ampltude before stmulaton and concluded the'efore that t represented merely a modfcaton of the acceleraton. The endng of sympathetc fbers on both nodal and muscle tssue of the atra and ventrcles s well known. 8 Whether specfc accelerator pathways may be dfferentated from augmentor s not yet known. At present, t seems probable that regardless of the pre and postganglonc pathways traversed, the mportant determnant of motor response remans the specfc ste of termnaton on the heart. Elevatons n systolc pressure wth lttle or no alteraton n heart rate or dastolc pressure mples an notropc affect, probably medated by lberaton of norepnephrne. Sympathetc endngs upon ventrcular muscle mght be

5 474 AUGMEXTOR ACTION OF SYMPATHETIC CARDIAC NERES Downloaded from by on December 3, 8 expected to nduce more powerful or augmented contractons. Fbers endng on or near nodal tssue mght be expected to nduce acceleraton. Augmented contractons would ncrease systolc ejecton and the ventrcle must then functon wth smaller resdual volume untl normal endsystolc volume s restored. Such changes n contractle force have been demonstrated recently by Cotten. 7 We would lke to suggest the possble mportance of these phenomena n the neural control of blood pressure and cardac output durng exercse, durng actvaton of barostatc reflexes and n emotonal or neurogenc hypertenson. One fnal pont deserves emphass. Independent of heart rate and venous return or atral pressure, another mportant mechansm has been shown to be concerned n cardac output. An mmedate myocardal response to nerve stmulaton wthout prelmnary ncrease n presystolc fber length best explans the prompt pulse pressure change. Apparent volaton of the "all or none law" need not be troublesome because as Wggers 8 ponted out, the magntude of response depends upon the physologcal state of myocardal reactvty. Mnute quanttes of epnephrne produce ncreased systolc ejecton wth unchangng rght atral rllng pressure or heart rate. 9 Ths s n accord wth Wggers' ' 2 observatons, that adrenalne causes a more vgorous and more rapd ventrcular contracton together wth more complete relaxaton n dastole. The data are compatble wth the concept of Hamlton and Kemngton 25 that changes n resstance to ejecton and n myocardal stmulaton are more mportant than change n dastolc sze (fllng pressure) n the regulaton of stroke volume. It also provdes the neural mechansm to account for cardac adjustments observed 2 * n ntact, unanesthetzed dogs durng exerton. SUMMARY Drect electrcal stmulaton of the left sympathetc nerves of the heart generally caused pronounced elevaton of systolc arteral pressure wthout changes n heart rate. Stmulaton of the rght cardac sympathetc nerves caused both acceleraton and augmentaton. Snce cardoacceleraton was frequently absent durng stmulaton t contrbuted relatvely lttle to the elevated mean pressures. Pulse pressure remaned elevated for prolonged perods followng cessaton of stmulaton. The neural acton may represent an mportant mechansm for the mmedate alteraton n stroke volume, ndependent of venous return or presystolc fber length. SUMMARIO IX IMTERLlNGUA Le drecte electrostmulaton del nervos snstrosympathetc del corde causava generalmente un pronuncate elevaton del systolc presson arteral non accompanate de alteratones del frequenta cardac. Stmulaton del nervos dexterosympathc del corde causava e acceleraton e augmentaton. Porque cardoacceleraton esseva frequentemente absentc durante le stmulaton, llo contrbueva relatvemente pauco al elevate pressones medan. Le presson pulsatl remaneva elevate durante prolongate perodos de tempore post le cessaton del stmulaton. Le acton neural pote representar un mportante mechansmo pro le mmedate alteraton del volumne per pulso, sn dependenta del retorno venose o del longor presystolc del fbras. REFERENCES ROHSE, W. G., AND RANDALL, W. C: Functonal analyss of sympathetc nnervaton of the heart. Feel. Proc. 4: 23, 955. CYON, M., AND CYON, E.: Ueber, de Innervaton des Herzens von Ruchenmerke aus. Arch. f. Anat., Physol., u. wssensch. Med. 403, HORTHLE, K.: Betrage zur Hmodynamk. Arch, f. d. ge3. Physol. 49: 29, 89. * HUNT, R.: Drect and reflex acceleraton of the mammalan heart wth some observatons on the relatons of the nhbtory and accelerator nerves. Am. J. Physol. 2: 395, 899. 'KATZ, L. N.: Factors modfyng the duraton of ventrcular systole. J. Lab. Cln. Med. 6: 29, WIGGERS, C. J., AND : The specfc nfluence of the accelerator nerves on the duraton of ventrcular systole. Am. J. Physol. 53: 49, 9. 7, AND : The selectve effect of the accelerator nerves on ventrcular systole. Proc. Soc. Exp. Bol. & Med. 7: 94, 9. 8 LIDDELL, E. G. T., AND SHERRINQTON, C.: Mammalan Physology. A Course of Practcal Ex

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