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Adrenaline noradrenaline-investigation


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Adrenaline noradrenaline-investigation

  1. 1. Studies of the Arterial Pulse Wave ARTHUR W. FEINBERG, HENRY LAX and William Urban Circulation 1958;18;1125-1130Circulation is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX 72514 Copyright © 1958 American Heart Association. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539 The online version of this article, along with updated information and services, is located on the World Wide Web at: Subscriptions: Information about subscribing to Circulation is online at Permissions: Permissions & Rights Desk, Lippincott Williams & Wilkins, a division of Wolters Kluwer Health, 351 West Camden Street, Baltimore, MD 21202-2436. Phone: 410-528-4050. Fax: 410-528-8550. E-mail: Reprints: Information about reprints can be found online at Downloaded from by on October 13, 2010
  2. 2. Studies of the Arterial Pulse Wave ARTHUR W. FEINBERG, M.D. AND HENRY LAX, M.D. With the technical assistance of William Urban Previous studies have shown abnormalities of the arterial pulse wave in hypertensive subjects of all age groups. The major change has been diminution to disappearance of the dicrotic wave. The pharmacologic differences between epinephrine and norepi- nephrine offer a means of studying the mechanism of this change in the dicrotic wave. In the present study, normotensive subjects have had transient hypertension induced by the infusion of epinephrine and norepinephrine. The different effects of these drugs on their arterial pulse waves have been recorded.I N A previous report, describing observa- The pharmacologic studies of Goldenberg tions on the arterial pulse wave in human and his group8 have shown that although bothsubjects, a new technic was introduced for epinephrine and norepinephrine produce com-recording the pulse wave without intra-arte- parable degrees of hypertension, they do so inrial puncture. The method has been shown to different ways. The hypertensive action ofbe sensitive and to give reproducible results. epinephrine in man is due primarily to aThe accuracy of the recordings has been dem- large increase in cardiac output that over-onstrated by the similarity of simultaneous balances a decrease in total peripheral resist-intra-arterial and extra-arterial tracings. ance. On the other hand, hypertension Figures 1 and 2 show typical instances of induced by norepinephrine is produced innormal and abnormal arterial pulse waves as man by a striking increase in peripheral re-recorded by this technic. The major difference sistance with little or no change in the cardiacin the abnormal cases appears to be diminu-tion to disappearance of the dicrotic wave.These changes in the dicrotic segment of thearterial pulse wave have been found in hyper-tensive subjects of all age groups as well asin patients with generalized arteriosclerosis,coronary arteriosclerosis, and diabetes melli-tus. The dicrotic wave has been ascribed to areflected wave from the recoil of the bloodcolumn against the closed aortic valve. Morerecent studies2-7 indicate that peripheral fac-tors also play a role in the formation of thedicrotic wave. The technic described hereinseemed to offer another means of studying themechanism of the dicrotic wave. From the Research Service, First (Columbia Uni-versity) Division, Goldwater Memorial Hospital, De- FIG. 1. Normal arterial pulse waves recorded frompartment of Hospitals, New York, N.Y., and the the third digit of a healthy 25 year old man. TheDepartment of Medicine, College of Physicians and vertical lines are time signals 0.1 second apart and theSurgeons, Columbia University. horizontal lines represent pressure increments of 10 Supported in part by grants from the Albert and inmn. Hg in the cuff applied about the finger. TheMary Lasker Foundation and the New York Heart cuff pressure (P) is recorded simultaneously but inde-Association and by a grant from George and Monique pendently of the components of the pulse wave. NoteUzielli. initial wave (I) and well defined dicrotic wave (D). 125 Circulation, Volume XVIII? December 195 Downloaded from by on October 13, 2010
  3. 3. -1 2( FEINBERG, LAXoutput. It, al))eared that investigation of the cause tile (liaplirlaglii to (lefect according to theireffeet of these 2 drugs, with their differeni intensity and direction.central and peripheral actions, Light help to Deflections of the diaphragm are transmitted by mechanical linkage either to a Statham absoluteexplain the inode of origin of the dicrotic pressure strain gage or to a piezo-electric crystalwave. Accordingly, the present study has cartridge that generates electric energy accordingbeen carried out on the effect of intravenous to the mechanical motion imposed upon it. Theinfusions of epinephrine and norepinephrine, crystal unit (Astatic inicrophone cartridge D-104)iii quantities sufficient to produce signifieaint has an output of -45 db. referred to 1 volt per micro bar. Output from the crystal is amplifiedhypertension, on the dicrotie wave of pre- with a class A balanced push-pull amplifier withsumai11.bly healthy, n ormotensive individuals. continuous variable gain from 0 to 16 db. max. The amplifier feeds a dual-coil string-type mirror METHOD AND TECHNIC g(alvanometer. Permanent recordings are made on 12 ciii. wide Ai sensitive rubber cuff with an inelastic backing electrocardiographic paper, with a Cambridge 3-is applied to the external surface of the limb or speed camera. Camera speeds are 121/2, 25, or ligit. The cuff consists of a thin rectangular 50 inma. per second. Timning. marks appear asineiabrane 11/2 by 3 inches cemented at the edges equally spaced vertical lines. Recordings can alsoto a backing piece of rubberized cloth. A 1/8 be mna(le intra-arterially amiAd takeni on (lireet-writ-inch I.D. nipple attached at the (enter of the cloth ing electrocardiograph connected to a 3 foot length of 1/8 inch rubber The frequency response of the entire systemitubing. This tubing serves the dual purpose of frcomn cuff to galvanometer shows the response toinflating the cuff and connecting it to the recording le substantially flat to 40 cps., which is well abovechamber of a differential pressure transducer. The the 5 to 6 cycle range encountered in studyingc uff is attached by an inelastic strap to the cx- arterial pulse waves.treinity to be examined. Continuously variable gain control enables the The differential pressure tramnsducer consists of operator to standardize the amplitude of record-a circular beryllium copper diaphraemn 0.006 inch inlgs without affecting the conmfiguratiomi of thethick and 11/2 inches ill diaimieter separating 2 arterial pulse wave. This feature is of value inair chambers. Air pressure required to inflate the comparative studies over a period of time on thecuff is introduced to both chambers, causing no same subject. Recording at the same basic ampli-deflection of the diaphragm. Pressure disturbances tude permits standardized conditions insofar as theoriginating at the cuff, however, are conducted to instrument itself is concerned. The only variablesthe recording chamber only. These disturbances then lie with the patient. FIG. 2. Left. Abnormal arterial pulse wave. Note diminished size of dicrotic wave (D). The cuff pressure (P) is also recorded. Right. M1ore severely albnormal arterial pulse wave sliowiiig aI complete albesenee of the dicrotic wave. Downloaded from by on October 13, 2010
  4. 4. 4_t,I - _§fl.-,et{ _, -_, -STUDIES OF ARTERIAL PULSE WAVE A.E. B.P. 120/80 (1) I t t -4- BEFORE INFUSION A.E. B.P. 1601115 (3) 1: _, I F1 li_ T-. t- -- Ltt- t---t S. t-.-t-t- :l _:1 t i t: .1 _1:: _k_:}. ---1--1--1-:L --I-----F lE f I---I l--fl----[---l - l - -.1-E[.._t --11---1:t-1----_I-L 3 ZUII.OF N0Bnnand needle (18 gage, 2 3/64 inch. no. 488LNR) was introduced into a brachial artery.Pulse pressure waves were transmitted to aStatham P-23A absolute pressure strain gageand a continuous intra-arterial pulse wavetracing was begun. After a control periodlasting from 2 to 5 minutes, a previously in-troduced infusion of glucose and water waschanged to an infusion containing either nor-epinephrine (Levophed) or epinephrine (Sii- _1 i, . rtx - ----1- -:- 1=s--l----l----8:--1-:-> :t:- ff :--T-T4:T- ---T---7IX tI s --1 ---] z - t--- 1: -:: 1:-- t---l ---: I n t - t --:: t - I:fl: 1---1 -:I--::I::-:I- :-t:-:X--:::1.::-:1---t 6l 1: tWl-:-:l: t - 1....I .I Y iM X 1.. | t:- f T+--- |- -T -|-- t t t. | X, md t ---- I _- 1: t |_.__|___E1 A.E. B.P. A.B. MIX*. ATR FIG. 3. Effect of intravenous infusion of norephiinephlrine on the arterial pulse wvave of a 32 year old normotensive male subject. Note the diminution of the dicrotic wave (D) in .d and its virtual disappearance in 3. It starts to return in 4 after the blood I)ressure has returned to control levels. All arterial pulse wave tracings during thisstudy were recorded intra-arterially. A Cour- 170/110 (2} 1 MINOF NORFX-NP B.Ph. 12O10 (1L) D~i N.UP.N3_ STOPPED N_ a RE SULTS IVith iNorepi e phrinie i Nine normotensive, presuniably healthy 1127 subjects were given norepinephrine by intra- venous infusion. In all individuals, as the blood pressure rose, the well defined dierotic wave of the control intra-arterial pulse wave became smaller and finally disappeared comn- pletely. Upon discontinuing the norepineph- rine, the dicrotic wave reappeared within mini- utes of the return of the blood pressure toprarenin, Winthrop). The blood pressure was control levels.taken by cuff at 1 minute intervals and in Figure 3 is. illustrative of these ehlatges.some cases was also recorded on the tracing. The subject was a, 32 year old male hospitalAfter 3 minutes of sustained elevation of sys- porter with no (clinical evidences of vasculartolic and diastolic pressures, the intravenous disease. His resting blood pressure wasinfusion was discontinued but the continuous 120/80, and a well defined dicrotic wave isintra-arterial pulse wave recording was main- seen on his initial pulse tracing. The blood tained until the configuration of the pulse pressure rose to 170/110 after 1 minute of wave had about returned to its control ap- intravenous norepinephrine in doses of 0.4 1Lg. pearance. This usually took 10 to 15 minutes. per Kg. per minute and the dicrotic wave be- The blood pressure invariably fell to its base- came markedly smaller. The double peaking line levels before the control pulse w*ve con- of the anaerotie wave has been seen ins other figuration was restored. subjects with hypertension, whether natural Downloaded from by on October 13, 2010
  5. 5. 1128 F1INBERG, LAX XPI NEPBRIN TLS S.S. B.P.122/80 3.S. B.P.145/80 13.5 . B.P.160/88 I.BeUOS 1 MIN. OF 2 M OF ImJsion EMIN PHIRINE 2PINEFPRINE m~~~~~~~~~~~~~~~~~~~ . . . 5 MIN.O SMIN. OF 6 MIN. AFTER FG4.NfeeRINE ePINErINeOI EPINEPHINE STOPPED FIG. 4. Effect of intravenous infusion of epinephrine oil arterial pulse wave. Although the amplitude of the entire ws-ave increases with rise iII blocod pressure, dicrotic wave (D) is elearly seen at all times.or induced. Its cause remains unexplained. ,ug. Kg. per minute for a total of 8 mimn- perAfter 3 mitiutes of sustained hypertension, the utes. During this time the blood pressuredierotic wave completely disappeared. Five rose from 122/80 to a sustained peak of 220/minutes after stopping the norepinephrine in- 110. Although the form of the arterial pulsefusion, the blood pressure had returne to its wave reflected this chanige ini the blood pres-control level of 120/80 and the dicrotic wave sure, the dicrotic wave remainled clearly de-had started to become evident agaiin. The fined in all was discontinued in this patient before In one of the normotensive iubjects (a 30the dicrotic wave had recovered its full height. ear old male technician) epinephrine and WVith EpincephrineC norepinephrine were given consecutively, with a 15 minute interval betweeni the administra- Four normotensive, presumably healthy tion of the 2 drugs to permit return of thesubjects were givens epinephrille intravenous- control pattern. The typical difference be-lv. Despite elevations of the systolic and tween the effects of epinephrine and norepi-diastolic blood pressure comparable to those nephrine are demonstrated in this case (fig.seemi ini the experiments with norepinephrine, 5). Both drugs produced approximately theno basic chamrge was noted in the conifigurationi same elevation of blood pressure. Norepineph-of the dicrotic wave. Specifically, the di- rime caused a complete disappearance of thecrotic wave was neither diminished nor had dicrotic wave, whereas the dicrotic wave wasdisappeared in amiy of the subjects studied, undisturbed after the administration of epi-even though the over-all amplitude of the nephrine.pulse wave increased as the blood pressure DISCUSSIONrose. Figure 4 illustrates these changes in a 21 The mode of origin and propagation of theyear old female hospital technician. Epineph- dicrotic wave has been investigated for yarsrine was infused intravenously in doses of 0.4 but remains incompletely understood. The Downloaded from by on October 13, 2010
  6. 6. STUDIES OF ARTERIAL PULSE WAVE1 1129 ao8mmao 0 MuMea= AMD NMBRMHRI5l Umy A.M. B.P. 134/86 A.M. BLP. 176/98 Am. B.P. 186/122 A.M. B.P. 146/82 BWEB INFUION z uND. 0 2 uRmT 5 KIN. 01 $11J1u 10 KIN. HiT STOPPU A.M. B.P. 138/86 A.M. B.P. 190/114 A.M. B.P. 138/88 , * PP11t1111 ! I;: ;il1 W iitl; I iisE M!! NO=l RI3 4 KIN. IW____MNE 0o Ha * ,- 10 ", A OR Wffl --:! Ii . _sO"v 2 otenw -rr FIG. 5. Effect of epinephrine and norepinephrine given consecutively to the same patient after a 15 minute interval. Note persistence of the dicrotic wave (D) in the epinephrine tracings and its disappearance after norepinephrine. Both drugs gave comparable elevations of blood pressure.classic theory explains the dicrotic peak as tients who received norepinephrine, the di-a reflected wave initiated by the recoil of the crotic wave was abolished or markedly re-arterial blood column against the closed aor- duced in size, despite a similar rise in bloodtic valve. The studies of Hamilton, Reming- pressure. These findings are well explainedton, and Dow,2-5 Wiggers,6 and Alexander7` by what is known of the pharmacologic differ-have shown that the arterial pulse wave is. ences between the 2 drugs. Goldenberg andprogressively transformed in its passage down others8 have shown that the actions of epi-the aorta and its arterial branches, suggesting nephrine and norepinephrine in man are sim-that the physiologic state of the peripheral ilar only in that they both produce significantvessels may play an important part in influ-- elevations of blood pressure. The hyperten-encing the appearance of the dicrotic wave.. sive effect of norepinephrine is due to an in-Our initial studies also suggested that crease of total peripheral resistance, with nochanges in the peripheral arteries determine significant change in cardiac output. Epi-the presence or absence of the dicrotic wave nephrine, on the other hand, raises the bloodof the arterial pulse. It was found, for exam- pressure predominantly by a central actionple, that the dicrotic wave was markedly ab- on the heart, iiicreasing the rate and force ofnormal in hypertensive subjects of all age cardiac contractions and the cardiac output. The peripheral resistance actually decreases,groups, in patients with peripheral arterio- because of an over-all vasodilating action.sclerosis, and in diabetic patients as young as The marked difference between the effects of14 years of age. epinephrine and norepinephrine on the di- The results of the present study would seem erotic wave thus support the hypothesis thatto support this view. In the 4 subjects given changes in the tonus of the arterial wall haveepinephrine, the dicrotic wave was not basi- significant effects on the configuration of thecally altered although the blood pressure rose distinctive waves seen in arterial pulse trac-significantly. On the other hand, in all 9 pa- ings. Downloaded from by on October 13, 2010
  7. 7. 1130 3FEINBERG, LAX SUMMARY dicrotic in association con le augmento del Previous studies have shown a diminution pression de sanguine. Le unda dicrotic re-to disappearance of the dicrotic wave in the appareva quando le pression de sanguine re-presence of clinical evidences of arteriosclero- tornava a nivellos normal. Del altere latere,sis, diabetes mellitus, and hypertensive vas- 4 subjectos recipiente epinephrina exhibivacular disease. nulle alteration del unda dicrotic in despecto Transitory hypertension was induced in 13 de comparabile augmentos del pression de san-normotensive subjects by intravenous infu guine.sions of either norepinephrine or epinephrine. Le differentia inter le effectos exercite superA continuous intra-arterial pulse-wave tracing le undas dicrotic es possibilemente relationatewas recorded from the brachial artery before, al differentias pharmacologic inter le duo dro-during, and after the infusions in most in- gas. Hypertension a epinephrina es producitestances. per un augmento del rendimento cardiac in The pulse waves of all 9 subjects given nor- despecto de un reducite total resistentiaepinephrine demonstrated disappearance of peripheric. Hypertension a norepinephrinathe dicrotie wave as the blood pressure rose. es causate per un augmento del resistentiaThe dicrotic wave reappeared as the blood peripheric con pauc o nulle alteration delpressure returned to normal. Contrariwise, rendimento cardiac.4 subjects given epinephrine had no change Le datos presentate supporta le theoria quein the dicrotic wave despite comparable ele- factores peripheric ha un rolo importante invation of the blood pressure. le production del culmine dicrotic que charae- The different effects on the dicrotic wave terisa le unda del pulso arterial.may be related to the pharmacologic differ- REFERENCESences between the 2 drugs. Epinephrine hy- 1. LAX, H., FEINBERG, A. W., AND COHEN, B. M.:pertension is produced by an increased car- Studies of the arterial pulse wave. I. Thediac output in spite of a reduced total normal pulse wave and its modification inperipheral resistance; norepinephrine hyper- the presence of human arteriosclerosis. J.tension is caused by an increased peripheral Chron. Dis. 3: 618, 1956. 2. HAMILTON, W. F., AND Dow, P.: An experi-resistance with little or no change in cardiac mental study of the standing waves in theoutput. pulse propagated through the aorta. Am. The evidence presented lends support to J. Physiol. 125: 48, 1939.the theory that peripheral factors play an 3. -: The patterns of the arterial pressureimportant role in the production of the di- pulse. Am. J. Physiol. 141: 235, 1944. 4. -, REMINGTON, J. W., AND Dow, P.: Theerotic peak of the arterial pulse wave. determination of the propagation velocity of the arterial pulse wave. Am. J. Physiol. SUMMARIO IN INTERLINGUA 144: 521, 1945. Previe studios ha monstrate un diminution 5. REMINGTON, J. W., AND HAMILTON, W. F.:o dispariton del unda dicrotic in le presentia The construction of a theoretical cardiac ejection curve from the contour of thede manifestationes clinic de arteriosclerosis, aortic pressure pulse. Am. J. Physiol. 144:diabete mellite, e hypertensive morbo vascu- 546, 1945.lar. 6. WIGGERS, C. J.: Physiology in Health and Hypertension transitori esseva inducite in Disease, Ed. 5. Philadelphia, Lea & Febiger,13 subjectos normotensive per infusiones intra- 1954, chaps. 37 and 38. 7. ALEXANDER, R. S.: Factors determining thevenose de norepinephrina o de epinephrina. contour of pressure pulses recorded fromUn registration continue del unda del pulso the aorta. Fed. Proc. 2: 738, 1952.intra-arterial esseva effectuate pro le arteria 8. GOLDENBERG, M., PINES, K. L., BALDWIN, E.brachial ante, durante, e post le infusiones D. F., GREENE, D. G., AND ROH, C. E.: The(in le majoritate del casos). hemodynamic response of man to nor-epi- Le undas de pulso del 9 subjectos recipiente nephrine and epinephrine and its relation to the problem of hypertension. Am. J. Med.norepinephrina exhibiva disparition del unda 5: 792, 1948. Downloaded from by on October 13, 2010