Epinephrine Infusion in Man - Circulationcirc.ahajournals.org/content/circulationaha/43/1/137.full.pdf · Epinephrine Infusion in Man Standardization, NormalResponse, andAbnormalResponse

Epinephrine Infusion in Man

Standardization, Normal Response, and Abnormal Response

in Idiopathic Hypertrophic Subaortic Stenosis

By STEPHEN H. SALZMAN, MAJOR, USAF, MC, STEVEN WOLFSON, MAJOR,

USAF, MC, BRUCE JACKSON, CAPT., USAF, MC,

AND ELIOT SCHECHTER, LT. COLONEL, USAF, MC

SUMMARYA standard test was designed for measurement of the effect of epinephrine infusion

on systolic time intervals in 14 normal subjects as a dose-response phenomenon. Inorder that we might examine the sensitivity of the test, it was applied in nine patientswith idiopathic hypertrophic subaortic stenosis.

Normal subjects had a characteristic response-a progressive shortening of the dura-tion of electromechanical systole, left ventricular ejection time, and pre-ejection period.Their left ventricular ejection time, corrected for heart rate, did not change. Patientswith idiopathic hypertrophic subaortic stenosis responded to epinephrine infusion withparadoxical lengthening of their left ventricular ejection time, corrected for heart rate.After beta blockade (with propranolol), reinfusion of epinephrine shortened the leftventricular ejection time, corrected for heart rate, to normal levels.

Additional Indexing Words:Dose response Systolic time i]

S TUDIES dealing with the interaction ofthe sympathetic nervous system and the

heart are hampered by: (a) the technicaldifficulty of the measurement of plasmacatecholamines and (b) the unknown phys-iologic significance of these measurements.Estimation of end-organ (myocardial) sensi-tivity might prove to be a useful tool for thestudy of these interactions. The systolic timeintervals standardized by Weissler are atrau-matic and easily reproducible. They offered aparameter for measurement of this response.

From the Cardiology Service, Department ofMedicine, Wilford Hall USAF Medical Center,Lackland Air Force Base, Texas.

Address for reprints: Dr. Salzman, Department ofCardiology, Cedars of Lebanon Hospital, 4833Fountain Avenue, Los Angeles, California 90029.

Dr. Wolfson's current address: Cardiology Section,Yale University School of Medicine, New Haven,Connecticut 06510.

Received May 7, 1970; revision accepted forpublication September 25, 1970.

Circulation, Volume XLIII, January 1971

Beta blockade

We have measured the systolic time inter-vals of normal individuals during gradedepinephrine infusions, thereby establishing theeffects of sympathetic stimulation upon car-diovascular dynamics as a dose-responsecurve. In order to examine the sensitivity ofthe test, we studied nine patients withidiopathic hypertrophic subaortic stenosis(IHSS). The results show that the epineph-rine infusion test is capable of identifying anabnormal response in this clinical entity, and,in addition, it can detect the normalization ofresponse that occurs with reinfusion of epi-nephrine after beta blockade.

Materials and MethodsThe study population consisted of 14 normal

males (mean age 25; range 17-41 years) andnine patients with IHSS (six males, threefemales; mean age 38; range 18-54 years).The normal subjects were evaluated by de-

tailed cardiovascular history, physical examina-tion, chest X-ray, and resting electrocardiogram.In all nine patients, the diagnosis of IHSS was

137

by guest on July 5, 2018http://circ.ahajournals.org/

Dow

nloaded from

http://circ.ahajournals.org/

SALZMAN ET AL.

Table 1

Catheterization Data in Patients with IHSS

Peak systolic gradient(mm Hg)

Patient Age Sex Rest Stress (maximum)

W.C. 53 M 10 125*J.G. 22 F 38 100*E.R. 54 M 90 -L.M. 23 F 100 -N.S. 48 M 0 65tE.A. 52 F 0 100*T.H. 18 M 17 -R.H. 40 M 20 50*R.H. 33 M 0 76*

*Valsalva.tEpinephrine infusion.

confirmed at cardiac catheterization (table 1). Ineach patient a gradient across the left ventricularoutflow tract was demonstrated either at rest withpremature beats by Valsalva's maneuver, or withepinephrine infusion. The infundibular chamberwas also demonstrated in most cases (seven ofnine) by characteristic left ventricular angio-graphic features in the LAO projection. Thepresence of a subvalvular gradient, together withapposition of ventricular septum and anteriorleaflet of the mitral valve and prolonged leftventricular ejection time, was believed sufficientfor exclusion of the possibilities that catheterentrapment or valvular aortic stenosis might haveproduced the gradient. Two patients (E.R. andL.M.) have had resection of their infundibularchambers, resulting in complete relief of their leftventricular outflow obstruction.

Epinephrine Infusion Test

One ampule of standard clinical epinephrine(1000 ,Lg) was diluted into 250 ml of 5% dextroseand water. Epinephrine was administered instepwise increments at each of six infusion ratesselected for delivery of 0.01, 0.02, 0.03, 0.06,0.10, and 0.18 ug/kg body weight/min (,ug/kg/min). A calibrated constant infusion pump wasused for delivery of the drug for 6 min at eachrate. The electrocardiogram, phonocardiogram,external carotid pulse, and blood pressure wererecorded during the last (sixth) minute of eachintfusion.The procedure was modified for the study of

the patients with IHSS. Because of the onset ofchest pain at the epinephrine infusion rate of 0.06,gg/kg/min in eight patients and at 0.03,ug/kg/min in the ninth, the initial dose-responsecu-rve was terrninated at that level. Propranololwas given intravenously (0.1 mg/kg) at a rate ofl ing/mirn. Twenty mirnlutes after propranolol

administration was completed, the epinephrineinfusion was repeated. Two normal subjects hadreinfusion of epinephrine after beta blockade (bypropranolol, 0.1 mg/kg, i.v.).

In order to define experimentally the effect of achange in heart rate, alone, on the systolic timeintervals, we measured the systolic time intervalsin the cardiac catheterization laboratory duringright atrial pacing at various heart rates in fournormal subjects.

Measurements

The Q2 interval was measured from the onsetof the QRS complex of the electrocardiogram tothe first high frequency component of the secondheart sound. Left ventricular ejection time(LVET) was measured from the carotid pulse asthe interval from the onset of the upstroke to thetrough of the incisura. The pre-ejection period(PEP) was calculated by subtraction of theLVET from the Q2 interval. The PEP/LVETratio was calculated and expressed as a per cent.To minimize beat-to-beat variation, we mea-

sured systolic time intervals at end-expiration.The ejection time intervals of one cardiac cyclewas determined to be an accurate sample (coeffi-cient of variability less than 1%) of all the cardiaccycles, hence only one cycle was measured.

Results were expressed both in absolute terms(msee) and corrected for heart rate as theper cent of the expected value for the observedheart rate. The latter was calculated by:Systolic time interval (per cent of expected) =

Predited X Systolic Time interval (msee) x 100.

The predicted systolic time interval wascalculated by the regression equations of Weis-sler: 1

Calculations:

Q2PEPLVET

Q2PEPLVET

Males(M) = -2.1(M) = -0.4(M) = -1.7

Females(F) = -2.0(F) = -0.4(F) = -1.6

hr + 546hr + 131hr + 413

hr + 549hr + 133hr + 418

Mean, standard deviation, and standard errorof the mean were calculated by standardstatistical methods.2

Differences in the same subject before and aftera change in state were tested for significance bythe t-test for paired samples. Differences betweennormal subjects and patients with IHSS weretested for significance by the t-test for unpairedsamples.

Circulation, Volumre XLIII, January 1971

138


Dow

nloaded from


139EPINEPHRINE INFUSION IN MAN

TIME( MILLISECONDS )Ann Tr 4ORMALS- EPINI

CONTROL

i-. .02 Q-.. X

E .03

.06

+10

CONTROL

" *1 ' .02 .18'+- .03

TIME( MILLISECONDS)

100-j

80

70'

60-

LVET

50

40-.10

.18

30-

9 l

60 70 80 90 100

HEART RATE

CONTROL

.02

NORMALS - EPI

PEP

.03

.06

.10

.18

9 1 1

60 70 80 90 100

HEART RATE

Figure 1

The effect of graded epinephrine infusion on the systolic tinm intervals of normal subjects.represents the mean + SEM for heart rate and systolic time interval. The epinephrine in-

fusion rate is noted to -he right of each marker.

ResultsNormal SubjectsEpinephrine Infusion Test

See figure 1 and table 2. Epinephrineadministration in the normal subjects pro-

duced a progressive rise in mean heart ratefrom 64.1 + 2.5 to 90.1 + 4.1 beats/min,(P < 0.001) and a progressive increase inmean systolic blood pressure from 123.8 4.6to 160.8 11.5 mm Hg, (P < 0.01). Diastolicblood pressure fell from 75.1 2.3 to61.7 +4.8 mm Hg, (P< 0.01).Concomitant with these changes in heart

rate and blood pressure, there was progressiveshortening of the: PEP from 91.9 3.8 to42.5 3.9 msec (P < 0.001); LVET from298.2 + 5.9 to 251.4 + 5.1 msec (P<0.001);Q2 from 390.1 + 6.8 to 294.0 7.4 msec

(P < 0.001); and PEP/LVET ratio from31.0 + 1.4 to 17.0 + 1.4% (P < 0.001). Whencorrected for heart rate by the regression data


of Weissler, the PEP shortened, but the LVETdid not (fig. 2). The PEP decreased from87.4 3.6 to 44.8 + 3.8% of the expected value(P < 0.001), whereas the LVET did notchange significantly.

Coexistent with these changes in hemody-namics (fig. 3), the first heart sound in eachnormal subject became progressively louder. Athird or fourth heart sound appeared, or if itwere present in the control tracings, becamelouder. A systolic murmur developed in allsubjects. Premature beats occurred infrequent-ly. Various emotional states including anxiety,fear, and elation were experienced by normalsubjects. Most were aware that their heartbeat faster, but none complained of chestpain. None experienced uncontrollable emo-

tional lability as has been reported byFrohlich.3

Epinephrine reinfusion after beta blockadein two normal subjects resulted in a slowing of

380-

360-

340-

320-

300-

280-

260-

240-

44UU kjd

- 2


Dow

nloaded from


SALZMAN ET AL.

*--X d_(= nt O^-' X Cd d -14; C~rC zb 1,Cl C0

(O_z C~L-~'t X C> 'I -PN C

Co s CT CT C: m

cs = mo- X -* -s

- C~TClCr~C

0- C+ C CS < Z: Z^C

CT or C L I

a c Cri 0- COO O l00

000 O0 <u,>

C~C l- COCli ~ C

cd cl clP -1 CS lcO;

00T CA Cl bCT 00 Cl

0 LC Cl C0 CS 401-Cl O iA OC0 CT ~ CO Cl

- CCACl R

00 0A O N N C> 00 CO Cl

CTCO cAT0- 0-O-NN C5) 0

0- Cl O C £) OC CT 0- Cl

NCl CT 90 C Cl CA Cl CN

CO CT CT CT Z CO0-sCO NO CA tBCAT _ICT\ 3 )00

LO CNA 00 TO0 0 CT CT> CO N

_I ClCCO CT

NO Cl 0 CT CT CT N CT 0 A

,-N CATClbb +-E- NE..

CON -

C 0S 0) s

8 2 H

P4S o

NORMALS- EPI

LVET

r 0- 2

PEP

CONTROL .01 .02 .03 .06 .10 .18

EPINEPHRINE INFUSION MICROGRAMS Kg. BODY WEiGHT MINUTE)

Figure 2

The effect of graded epinephrine infusion on thesystolic time intervals corrected for heart rate innormal subjects. Note the marked shortening of PEPwith little change of LVET.

the heart rate with no change in the LVETcorrected for heart rate.

Pacing StudyRight atrial pacing in four normal subjects

resulted in a shortening of the Q2 and LVET,but not in the PEP. The regression equationsfor Q2 and LVET are:Q2 -=-1.0 hr + 458 (r -0.94, P <0.01)LVET =-0.96 hr + 342 (r = 0.86, P <0.01).The PEP did not change with even largechanges in heart rate (fig. 4).

Patients with Idiopathic HypertrophicSubaortic StenosisEpinephrine Infusion Test

Epinephrine administration resulted in aprogressive rise in heart rate from 76.1 + 3.5 to95.1 + 4.7 beats/min, (P < 0.01) (table 3).There was no significant change in either thesystolic or the diastolic blood pressure.There was shortening of the PEP from

93.0 + 6.2 to 62.8 + 7.3 msec, (P < 0.01). TheLVET and Q2 initially lengthened at lowepinephrine infusion rates and then shortened.When corrected for changes in heart rate,

the PEP shortened from 92.7 ± 6.9 to68.1 ± 8.6% of the expected value (P <0.01).The LVET lengthened maximally from113.0 + 3.8 to 123.9 + 4.5% of the expectedvalue (P < 0.02), at an epinephrine infusionrate of 0.02 ,ug/kg/min.


140

~000

00SO

CO

000200

~0

0

6

c0oo

co

cq0

0

0

0

C.

e1

Hdcn

0

CO~

0)

1

cO

0t.

0o0)

C)00

0

1

-J Cl>

ui

ir ULLJ W

1 XLLI

:E LL.p 0U

z

0 Ut; W

ui[L


Dow

nloaded from


EPINEPHRINE INFUSION IN MAN

NORMAL

C1S2

CONTROL

Figure 3

The effect of epinephrine infusion (0.10 ,ug/kg/min)on the phonocardiogram. The rate is more rapid; Siincreases in intensity; S. and S4 appear, and an earlysystolic murmur develops.

The phonocardiographic correlates were thesame in the patients with IHSS as in thenormal subjects except that most of thepatients with IHSS had a systolic mur-

mur during the control record, whichincreased in intensity with increasing epineph-rine infusion rates (fig. 5).

Eight of the nine patients experienced chestpain at an epinephrine infusion rate of 0.06,ug/kg/min. One patient (E.R.) experiencedchest pain and dyspnea at an epinephrineinfusion rate of 0.03 ,ig/kg/min. In allpatients the chest pain and/or dyspnea were

relieved within minutes after epinephrineinfusion was discontinued and propranolol(0.1 mg/kg) was administered.

Epinephrine Infusion Test afterAdministration of Propranolol

After beta blockade (with propranolol) thebaseline systolic time intervals corrected forheart rate were not significantly different fromthe control measurements before blockade(table 3 and fig. 6). Reinfusion of epinephrineresulted in a decrease in heart rate and LVETcorrected for heart rate, and both the systolicand diastolic blood pressures increased.

Differences in the results of epinephrineinfusion in patients with IHSS before andafter beta blockade were most marked at an

epinephrine infusion rate of 0.06 ,ug/kg/min.Circulation, Volume XLIII, January 1971

After administration of propranolol, the heartrate was slower, 62.4 3.5 compared to95.1 +4.7 beats/min, (P <0.01); the systolicblood pressure was higher, 148.1 + 11.0 com-

pared to 128.8 9.2 mm Hg (P < 0.01); thediastolic blood pressure was higher, 86.9 + 4.7compared to 69.4 + 3.9 mm Hg (P < 0.01).The PEP was longer, 98.8 + 5.6 compared to62.8 + 7.3 msec (P < 0.01). When correctedfor heart rate, the LVET was shorter,104.1 2.5 compared to 121.4± 4.1% of theexpected value (P < 0.01), and the PEP was

longer, 93.4 + 6.1 compared to 68.1 + 8.6% ofthe expected value (P < 0.01).

In each patient epinephrine reinfusion afterbeta blockade resulted in a progressivedecrease in the intensity of the ejectionmurmur.

Comparison of Normal Subjects withPatients with IHSS

Patients with IHSS had resting heart ratesthat were more rapid than those of normalsubjects, 76.1 3.5 compared to 64.1 + 2.5beats/min. (P < 0.02). VVhen corrected forheart rate, all the resting mean systolic timeintervals were longer in patients with IHSS:LVET, 113.0 3.8 compared to 98.6 + 0.9%of the expected value (P < 0.01); PEP,92.7+6.9 compared to 87.4 + 3.6% of theexpected value; and Q2, 106.5 + 3.5 compared

130 ' t i NORMALS - PACING

PEP

120- A

110-

190-

Xi 80-NO-

70

60

S0 60 70 8O 90 100 110 10 130 140 150

HEART RATE

Figure 4The effect of right atrial pacing in four normal sub-jects. There is no change in PEP over a wide rangeof atrial pacing rates.

S1 SM s2 53 S4 S

~'EPI ( 0 10,tg Kg MIN

141


Dow

nloaded from


SALZMAN ET AL.

Table 3Cardiovascular Responses to Epinephrine Infusion in 9 Patients with, IHSS before and after Beta Blockade

Epinephrine infusion rate (ag/kg body weight/min)Before propranolol

Control 0.01 0.02 0.03 0.06

Heart rate (beats/min) 76.1 - 3.5 82.5 - 5.3 85.3 - 3.6 87.0 3.8 95.1 - 4.7Systolic BP (mm Hg) 130.6 7.7 131.7 12.7 123.6 10.8 126.1 7.4 128.8 9.2Diastolic BP (mm Hg) 76.1 - 4.1 71.6 i 5.9 71.4 - 5.9 72.2 4.9 69.4 *3.9Q2 (msec) 410.2 10.9 425.0 13.2 397.1 - 9.2 390.0 11.9 364.0 9.4LVET (msec) 317.2 9.6 334.2 14.3 328.6 8.3 317.4 6.5 301.3 8.3PEP (msec) 93.0 6.2 90.8 6.0 68.6 3.9 72.6 9.9 62.8 7.3Q2 (% expected) 106.5 3.5 114.7 5.3 108.4 3.7 107.6 4.0 105.8 4.0LVET (% expected) 113.0 3.8 121.8 6.0 123.9 4.5 120.8 3.2 121.4 4.1PEP (% expected) 92.7 6.9 99.0 - 9.2 70.7 4.5 75.8 10.9 68.1 8.6

BEFORE PROPRANOLOL AFTER PROPRANOLOL

EFFECTS OF EPINEPHRINE INFUSION

BEFORE AND AFTER PROPRANOLOL ADMINISTRATION

Figure 5

An unusual example of a patient with idiopathic hypertrophic subaortic stenosis who had no

murmur and a normal carotid pulse during the control record. With epinephrine infusion(0.06 ,ug/kg/min), a harsh systolic murmur and characteristic carotid pulse tracing appeared.The control tracing after administration of propranolol resembled the record before propranololwas given. After administration of propranolol, reinfusion of epinephrine resulted in a slowerheart rate, softer S1, and normal phonocardiogram and carotid pulse tracing.

to 94.9 0.9% of the expected value(P< 0.01).

The key feature in the epinephrine infusiontest which helped identify the patient with


142

CONTROL

EPI(0.06)


Dow

nloaded from


EPINEPHRINE INFUSION IN MAN

Epinephrine infusion rate (jg/kg body weight/min)After propranolol (0.1 mg/kg body weight

Control 0.01 0.02 0.03 0.06

69.2 3.2 64.3 - 4.6 61.1 - 2.1 64.0 3.5 62.4 - 3.5130.3 9.1 131.5 12.2 136.4 - 11.6 140.9 9.6 148.1 - 11.074.4 5.4 76.7 7.1 83.6 4.7 83.3 4.0 86.9 4.7

427.8 15.3 448.3 12.2 422.9 16.3 426.7 12.8 416.5 9.1328.3 12.6 343.3 i 14.1 325.7 15.4 323.3 11.4 317.8 9.599.4 6.7 101.6 6.5 97.1 5.8 103.3 6.8 98.8 5.6

106.9 - 4.1 109.5 4.0 101.1 4.1 104.0 3.4 100.7 2.3112.0 - 4.0 114.0 - 5.1 106.3 5.3 107.2 3.9 104.1 2.596.7 - 7.1 100.2 - 7.2 91.1 5.3 98.2 7.0 93.4 6.1

IHSS was the paradoxical lengthening of theLVET corrected for heart rate at lowepinephrine infusion rates (0.02 ,ug/kg/min)when compared to normal subjects whoseLVET corrected for heart rate did not change.

DiscussionAs evidenced by the dose-response curves,

measurement of the systolic time intervals is areproducible technique for measurement ofthe changes in left ventricular function thatoccur during epinephrine infusion. Normalsubjects had a characteristic response-aprogressive shortening of their Q2, LVET, andPEP intervals. Their heart rate and systolic

140

UJ 130_-UW

u. 120-

z

GC 1 10 -

-u.

100

90-

L-- t I HSS (BEFORE PROPRAHOLOL )

.I>-

L '.. IHSS( AFTER PROPRANOLOL )r I-> (0.lmg/ Kg)

_--1~~~-1-~~ ~1 NORMAL

CONTROL .01 .02 .03 .06

EPINEPHRINE INFUSION RATE keag/ Kg/ IN)

Figure 6

The effect of epinephrine infusion on LVET correctedfor heart rate in normal subjects and patients withIHSS. Note the similar resting value in patients withIHSS before and after propranolol administration.With reinfusion of epinephrine, there is progessivenormalization of the LVET corrected for heart rate.


blood pressure increased and their diastolicblood pressure decreased.These results are in agreement with the

results of a single epinephrine infusion rate of5 ug/min reported by Harris.4 Calculationsfrom his data show that this represents anaverage infusion rate of 0.07 gg/kg/min. Theheart rate, Q2, LVET and PEP were: 80 beats/min, 344 msec, 280 msec, and 63 msec,respectively, in Harris' subjects. This comparesfavorably with 82 beats/min, 334 msec, 273msec, and 62 msec, respectively, from ourdata at an infusion rate of 0.06 gg/kg/min.

Also in agreement with the data of Harriswere the results of reinfusion of epinephrineafter beta blockade in normal subjects. Thiswas characterized by progressive bradyeardiawith increasing epinephrine infusion rates.However, there was no change in the LVETcorrected for heart rate. The mechanism forthis response was probably peripheral arterialconstriction (an unopposed alpha-adrenergiceffect) producing reflex bradyeardia.

Right atrial pacing, alone, produced noshortening of the PEP over a wide range ofheart rates in any normal subject studied. Thisagrees with data reported in patients withorganic heart disease.5 These data imply thatthe shortening of PEP produced by epineph-rine is a function of increased performance ofthe myocardium unrelated to the increase inheart rate,6 i.e., it reflects the inotropic ratherthan the chronotropic influence of the drug.The patients with IHSS had an abnormally

long resting mean LVET, presumably reflect-

143


Dow

nloaded from


SALZMAN ET AL.

ing the left ventricular outflow obstruction.7The response of these patients to epinephrineinfusion differed qualitatively from that ofnormal subjects. Although the heart rateincreased, the LVET lengthened (normalsubjects had shorter LVET with tachycardia).This was most marked at low epinephrineinfusion rates (0.02 gg/kg/min). Three of thepatients with IHSS had normal systolic timeintervals at rest. Provocation by epinephrineinfusion was needed for demonstration of theabnormality.

Propranolol reversed the paradoxical re-sponse to epinephrine. After beta blockade,increasing epinephrine infusion rates resultedin progressive shortening of the LVET,probably indicating diminished obstruction ofleft ventricular outflow.

This study emphasizes the practicality ofthese relatively simple methods in evaluationof left ventricular function. We have standard-ized an epinephrine infusion test in normalsubjects and have applied it in patients withIHSS. The test is capable of demonstratingthe epinephrine-induced exacerbation of thissyndrome and the prevention of this effectafter beta blockade.

This relatively simple test, a bioassay of the

results of epinephrine administration on theleft ventricular function, may offer a tool forstudy of the interaction of the sympatheticnervous system and the heart.

References1. WEISSLER AM, HARMS WS, SCHOENFELD CD:

Systolic time intervals in heart failure in man.Circulation 37: 149, 1968

2. SNEDECOR GW: Statistical Method. Ed 5, Ames,Iowa, The Iowa State College Press, 1956

3. FROHLICH ED, TARAzi RC, DUSTAN HP: Hyper-dynamic p-adrenergic circulatory state. ArchIntem Med (Chicago) 123: 1, 1969

4. HARRIs WS, SCHOENFELD CD, BROOKs RH, ETAL: Effect of beta adrenergic blockade on thehemodynamic responses to epinephrine in man.Amer J Cardicl 17: 484, 1966

5. LEIGHTON RF, ZARON SJ, ROBINSON JL, ET AL:Effects of atrial pacing on left ventricularperformance in patients with heart disease.Circulation 40: 615, 1969

6. SARNOFF SJ, MITCHELL JH: The control of thefunction of the heart. In Handbook of Physi-ology, Section 2: Circulation, Vol 1. Washing-ton, D.C., American Physiological Society,1962, chap 15

7. WIGLE ED, AUGER P, MARQUIS Y: Muscularsubaortic stenosis. The direct relation betweenthe intraventricular pressure difference and theleft ventricular ejection time. Circulation 36:44, 1967


144


Dow

nloaded from


JACKSON, CAPT and ELIOT SCHECHTER, LT. COLONELSTEPHEN H. SALZMAN, MAJOR, STEVEN WOLFSON, MAJOR, BRUCE

Abnormal Response in Idiopathic Hypertrophic Subaortic StenosisEpinephrine Infusion in Man: Standardization, Normal Response, and

Print ISSN: 0009-7322. Online ISSN: 1524-4539 Copyright © 1971 American Heart Association, Inc. All rights reserved.

75231is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TXCirculation

doi: 10.1161/01.CIR.43.1.1371971;43:137-144Circulation.

http://circ.ahajournals.org/content/43/1/137located on the World Wide Web at:

The online version of this article, along with updated information and services, is

http://circ.ahajournals.org//subscriptions/

is online at: Circulation Information about subscribing to Subscriptions:

http://www.lww.com/reprints Information about reprints can be found online at: Reprints:

document. Permissions and Rights Question and Answer

of the Web page under Services. Further information about this process is available in thewhich permission is being requested is located, click Request Permissions in the middle columnClearance Center, not the Editorial Office. Once the online version of the published article for

can be obtained via RightsLink, a service of the CopyrightCirculationoriginally published in Requests for permissions to reproduce figures, tables, or portions of articlesPermissions:


Dow

nloaded from

http://circ.ahajournals.org/content/43/1/137

http://www.ahajournals.org/site/rights/

http://www.lww.com/reprints

http://circ.ahajournals.org//subscriptions/


Documents

Epinephrine Infusion in Man - Circulationcirc.ahajournals.org/content/circulationaha/43/1/137.full.pdf · Epinephrine Infusion in Man Standardization, NormalResponse, andAbnormalResponse