The effect of steady-state increases in systemic
arterial pressure on the duration of left
ventricular ejection time
James A. Shaver, … , James J. Leonard, H. W. Paley
J Clin Invest. 1968;47(1):217-230. https://doi.org/10.1172/JCI105711.
The effect of steady-state increases in systemic arterial pressure on the duration of left ventricular ejection time was studied in 11 normal male subjects. Methoxamine, a pressor amine of predominantly vasoconstrictor activity but lacking significant inotropic effect, was administered intravenously resulting in an average increase in mean arterial pressure of 27 mm Hg. Heart rate was held constant by high right atrial pacing, and there was no
significant change in cardiac output. During methoxamine infusion, when stroke volume, heart rate, and inotropic state were held constant, left ventricular ejection time increased as mean arterial pressure increased. There was a highly significant correlation between the increase in mean systolic blood pressure and the prolongation of left ventricular ejection time (r = 0.870). In one subject, an increase in mean systolic pressure of 75 mm Hg prolonged left ventricular ejection time 55 msec, producing paradoxical splitting of the second heart sound. The prolongation of left ventricular ejection time during infusion was not blocked by the prior intravenous administration of atropine sulfate or propranolol
hydrochloride, thus ruling out both vagal inhibition of the left ventricle and reflex withdrawal of sympathetic tone as its cause. In three subjects, left ventricular end diastolic pressure was measured and found to be significantly increased. This finding suggests that the normal left ventricle maintains a constant stroke volume […]
Research Article
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The
Effect of Steady-State
Increases
in Systemic
Arterial
Pressure
on
the Duration of Left Ventricular Ejection
Time
JAMES A. SHAvER, FRANK W. KROETZ, JAmES J. LEONARD, and H. W.Pmiry
From the University of Pittsburgh School of Medicine, Department of Medicine, Pittsburgh, Pennsylvania
ABTR ACT The effect of steady-state increases in systemic arterial pressure on the duration of left ventricular ejection time was studied in 11 normal male subjects. Methoxamine, a pressor amine of predominantly vasoconstrictor activity
but lacking significant inotropic effect, was ad-ministered intravenously resulting in an average increase in mean arterial pressure of 27 mm Hg. Heart rate was held constant by high right atrial
pacing, and there was no significant change in
cardiac output. During methoxamine infusion,
when stroke volume, heart rate, and inotropicstate
were held constant, left ventricular ejection time increased as mean arterial pressure increased. Therewas ahighlysignificant correlation between the increase in mean systolic blood pressure and
the prolongation of left ventricular ejection time
(r =0.870). In one subject, an increase in mean
systolicpressure of75 mm Hgprolonged left
ven-tricularejectiontime55msec,producing
paradoxi-cal splitting of the second heart sound. The
pro-longation of left ventricular ejection time during
infusion was not blocked by the prior intravenous
administration of atropine sulfate or propranolol
hydrochloride, thus ruling out both vagal
inhibi-tion of the left ventricle and reflex withdrawal of
sympathetic tone as its cause. In three subjects,
left ventricular end diastolic pressure was
mea-A partial report of this work appeared in abstract
form. 1966.J. Clin. Res.14: 261.
Dr. Paley's present adress is the Mt. Zion Hospital, San Francisco, Calif.
Received for publication 23 September 1966 and in re-vised form1 September 1967.
sured and found tobe significantly increased. This finding suggests that the normal left ventricle maintains a constant stroke volume in the
pres-ence of an increased pressure load by the Frank
Starling mechanism. Thisstudy concludes that
ar-terial pressuremust beincluded as a prime deter-minant of left ventricular ejection timealong with stroke volume, heart rate, and inotropic state in intactman.
INTRODUCTION
The effect of stroke volume, heart rate, and ino-tropic stateonthe duration of left ventricular ejec-tion time has been extensively studied in both man and animals and the results by various in-vestigators are consistent
(1-6).
However, the effect of increasing systemic arterial pressure has been variably reported to increase, decrease, or have no significant effect on left ventricular ejec-tion time. In the metabolically supported, isolated heart preparation of Braunwald, Sarnoff, andStainsby (4), substantial changes in mean arterial
pressures had little influence on the duration of left ventricular ejection time in six of seven hearts. However, Wallace, Mitchell, Skinner, and Sarnoff (5), in a right heart by-pass preparation,
showed thatas mean blood pressure was increased
left ventricular ejection time decreased, isometric contraction time increased, and the total duration of systole remained unchanged. Weissler, Peeler, and Roehl have reported that when compared to normal controls, no significant difference was found in left ventricular ejection time in a group
of 11 patients with severe hypertension (6). Nevertheless, hypertensive cardiovascular disease has been cited as a cause of paradoxical splitting of the secondlheart sound (7-9) whichpresumably
is due to
prolongation
of left ventricular ejectiontime.
The purpose of this investigation was to study the effect of steady-state increases in systemic arterial pressure on the duration of left ventricular ejection time in the intact human left ventricle. The technique of high rightatrial pacing was used to maintain a constant heart rate. By preventing the reflex bradycardia associated with an acute in-crease in arterial pressure, cardiac output was maintained; and, therefore, stroke volumewasheld constant. It was possible, then, to study the effect of arterial pressure alone on the duration of left ventricular ejection time when heart rate, stroke volume, and inotropic state were held constant.
METHODS
12 studies were performed on 8 healthy male volunteers and 3 male subjects withfunctional murmurs, whose ages ranged from 15 to 29 yr. No premedication was adminis-tered and all studies were performed in the supine posi-tion. A No. 8, bipolar, Zucker1 catheter was placed at the superior vena cava-right atrial junction. Right atrial pressure was monitored through this catheter while heart rate was held constant by pacing. Arterial pressure was recordedthrough a 15 cmpolyethylene catheter (PE No. 160, 0.045 inch I.D.) that was introduced percutaneously into the left brachial artery. In three subjects, left ven-tricular pressure was recorded through a radiopaque, polyethylene catheter (PE No. 160) placed retrograde through the right femoral or brachial artery. Cardiac output was determined bythe indicator dilution technique. Indocyanine green dye (1.5 mg) was injected through a 90 cm polyethylene catheter (PE No. 50, 0.023 inch I.D.) that had beenintroduced percutaneously through an ante-cubital vein into the superior vena cava. Blood was
sampled fromthebrachialartery catheter and delivered to a cuvette densitometer2 by means of a constant rate, motor driven syringe. Cardiac outputs were performed in duplicate and recorded as the average of the two deter-minations in all but two observations. Individual deter-minations checked within 5 ±3.7% of their paired
aver-age. Calculations were performed after the inscribed dilution curves had been replotted on semilogarithmic paper utilizing the formula of Hamilton, Moore, Kins-man, and Speerling (10).
In each subject, simultaneous recordings of pressures (right atrial, brachial artery, aild left ventricular), elec-trocardiogram, phonocardiogram, and the indirect
caro-1 U. S.Catheter andInstrument, Inc. GlensFalls,N.Y. 2Gilford Instruments Laboratory, Oberlin, Ohio.
tid pulse were made on a multichannel, photographic re-cording unit3 at a paper speed of 100 mm/sec, with time markers indicating 0.02 sec (Fig. 1). All pressure mea-stirements were made with P23G Statham pressure trans-ducers.4 The zero level for pressure was taken as 5 cm below the angle of the sternum with the subject in the supine position. Mean systolic pressure was obtained by )lanimetry of the systolic portion of five consecutive brachial artery pressure curves. The standard lead II of the electrocardiogram was selected. Heart sounds at the base were recorded with a contactmicrophone,5 and care was taken to maintain a constant position on the chest wall at a point where clear inscription of both heart sounds could be made. The indirect carotid pulse was obtained with a standard, funnel-shaped pick-up con-nected to a P23D transducer. The pick-up was placed over the point of maximal pulsation of the carotid artery, and leftventricular ejection time was measured as the in-terval from the beginning of the upstroke to the trough of theincisural notch. The QA2interval was measured from the onset of the Q wave on the electrocardiogram to the first majorvibration of the second heartsound.Each deter-mination of left ventricular ejection time, QA2 interval, and RR interval was determined from the average of 10 well-inscribed complexes taken in close succession. Heart rate was calculated dividing 60 by the average RR in-terval. The difference between measured andderived data was evaluated by the method ofpaired means (11).
Care was taken to familiarize all subjects with the
ex-perimental design before the procedure. When all cathe-ters were in place the patient rested for 10-15 min, and control measurements were recorded, after which high
right atrial pacing was instituted through the bipolar
catheter with a battery powered, external pacing unit.8 Pacing was accomplished at the slowest possible rate at
which complete atrial capture occurred. After a
mini-mum of 5 min of atrial pacing, repeat observations were made. Methoxamine
[jP-hydroxy-jS
(2,5 dimethoxy-phenyl)-isoprophylamine], a pressor amine ofpredomi-nantly vasoconstrictor activitybut lacking significant ino-tropic effect (12-15), was then administered intrave-nously (0.3-0.7 mg/min), which resulted in an average increase of 27 mm Hg in mean arterial pressure. When a new steady state was apparently reached, complete ob-servations were again recorded. Pacing was then discon-tinued, whereas blood pressure was maintained, elevated
with methoxamine, and final measurements were then made. In two subjects, after control observations 2 mg of atropine sulfate was given intravenously. The induced sinus tachycardia was then captured by high right atrial pacing, and the study was continued as described. In one
additional subject, 15 mg of propranolol hydrochloride7 was given intravenously after control observations. High
8 Electronics for Medicine, White Plains, N. Y.
4Statham Instruments, Inc., Hato Rey, Puerto Rico.
5Electronics for Medicine, White Plains, N. Y.
6Westinghouse, Baltimore, Md.
7Inderal, through courtesy of Dr. A. Sahagian-Ed-wards, Ayerst Laboratories, New York.
: -.L -L i-I
I-Ldmwllklm.
FIGURE 1 Simultaneous recordings of hemodynamic data. From top tobottom: plhonocardiogram
at the second left interspace; indirect carotid pulse; lead II of the electrocardiogram with high right atrial pace; brachial artery pressure trace: bottom to top line=200 mm Hg; leftventricular pressure trace: bottom to top line= 30 mm Hg. Left ventricular ejection time (LVET) is mea-sured from the beginning of the upstroke of the indirect carotidpulseto thetrough of the incisural notch. TheQA2 interval is measured from the onset of the Q wave to the first majorvibration of thesecondheart sound. Paper speed 100mm/sec; time markers=0.02 sec.
right atrial pace was established and the above study was repeated.
The following derived calculations were made:
Stroke work index (SWI)(g-m/m2)
=13-6
X Sm X SVIwhere
Sm = meansystolic arterial pressure (mm Hg) SVI = stroke volume index(ml/m2)
13.6 = mercuryconversion factor.
Total peripheral resistance (TPR)(dyne-sec-cm5) = BA X 1.332 X 60
Co
where
BA = meanbrachial arterial pressure
1.332 = factor to convert mm Hg todynes-cm-5 CO = cardiac output (liters/min)
60 =sec/min.
RESULTS
Control vs. control pace. High right atrial pacing was established in the 9 control subjects with an increase in the average heart rate from 68 to 75 beats/min. Pacing produced no significant
change in cardiac index (P > 0.20). Dependent
upon the degree of tachycardia induced necessary to capture the control sinus rhythm, variable ef-fects on stroke volume index, blood pressure, left ventricular ejection time, and other measured parameters were produced and are presented in detail in TableI.
Control
pacevs.methoxamine pace. Heart rate washeld constant byhigh right atrial pacing. There was no significant change in cardiac index (P > 0.20), and stroke volume index remained un-changed (P > 0.20) (Fig.2). Withheart rateand stroke volume index held constant, the infusion ofm 11No -Tt
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methoxamine produced an average increase in mean arterial pressure of 27 mm Hg, and an aver-age increase in mean systolic pressure of 31 mm Hg. Fig. 3 shows the effect of this increased pres-sure load on the duration of the various phases of systole. The total duration of systole, as meas-ured by the QA2 interval, increased significantly (P < 0.001). This increase was a result of a sig-nificant increase in both left ventricular ejection
time (P <0.005) and QA2-ET interval (P < 0.010), the latter being a reflection of isometric contraction time plus ventricular electrical de-polarization.
Fig. 4shows the change in left ventricular ejec-tion time plotted against the change in mean sys-tolic pressure during steady-state methoxamine in-fusion. Mean systolic pressure was correlated with left ventricular ejection time rather than with mean arterial pressure, as only this phase of the arterial pressure is encountered by the contracting left ventricle. A highly significant correlation coef-ficient was found between this plot (r= 0.870,
P < 0.005). In one subject, A.P. (Table I), the effect of increased mean systolic pressure on left ventricular ejection time was studied at mean
systolic pressure elevations of 39 and 75 mm Hg.
0s 5.00
4.00
3.00 80
E
A1
70
60 60
E
50
CONTROL PACE
METHOXAMINE PACE
I I
P>.20
I HEART RATE
ID>.20
I STROKE VOLUME INDEX I
FIGURE 2 Comparison of mean hemodynamic
measure-ments duringcontrolpaceandmethoxamine pace. Cardiac
index is unchanged, and with heart rate held constant,
thereisnosignificant changein strokevolume index (P>
0.20). 13 studies in 9subjects are included in themean.
395
390
,, 385 E 380
375
370
315
310
o 305 E 300
295
290
88
86 , 84 E 82 80
78
CONTROL PACE
METHOXAMINE
PACE
FIGURE 3 Comparisonof the mean durationofthephases of systole during control pace and methoxamine pace. During methoxamine infusion, the total duration of sys-tole, as measured by the QA2interval, is increased by a
significant increase in both left ventricular ejection time (LVET) and the electromechanical preejection period
(QA2-ET).
Figs. 5, 6, and 7 show the effect of this elevation
on left ventricular ejection time and the splitting of the second heart sound. Fig. 7 shows that with heart rate and stroke volume held constant, an
elevation of75mm Hgmean systolicpressure pro-longed left ventricular ejection time 55 msec, creating paradoxical splitting of the second heart sound.
Venous pressure showed a slight but significant
increase (P < 0.025) with methoxamine infusion. In two subjects, left ventricular end diastolic pres-sure was monitored. R.H. increased his left ven-tricular end diastolic pressure from 4 to 9 mm Hg and M.B. increased his left ventricular end diastolic pressure from 5 to 8 mm Hg, with eleva-tions of mean systolic pressure of 18 and 17 mm
Hg, respectively (Table I). Both total peripheral
Arterial Pressure and Left Ventricular Ejection Time
P < .001
0A2 I
I I
P<.010
1 OA2-ET I
P >.20
CARDIAC INDEX
P<.005
1 LVET I
i
40
FIGURE 4 Change in mean systolic pres-sure (Sin) plotted against the change in
left ventricular ejection time (LVET). A highly significant correlation is obh served between the two (r=0.870, P<
0.005). In subjects A.P., M.G., R.DP., and R.DR., only the maximum response
is plotted.
0 10 20 30 40 50 60
A LVET miec
resistance and stroke work index increased
pro-portionately withthe bloodpressure elevation
dur-ing methoxamine infusion.
Control vs. methoxamine. Both cardiac index
and heart rate were significantly decreased from
control values during methoxamine infusion
with-out rate being maintained by pacing. There were
significant increases in stroke volume index, blood
pressure, left ventricular ejection time, total
dur-ation of systole, venous pressure, left ventricular
end diastolic pressure, total
peripheral
vascularresistance, and stroke volume index, which are
presented indetail in TableI.
Afteratropine. The intravenous administration
of 2 mg of atropine sulfate caused a significant
increase in both cardiac index and heart rate in
two subjects, C.H. and A.P. (Table I). In both subjects, when heart rate was held constant by
pacing, elevation of the mean systolic pressure
with methoxamine caused an increase in left
ven-tricular ejection time, whereas stroke volume
in-dex remained unchanged. After cessation of
pac-ing, there was only aslight decrease ill heart rate,
and cardiac index was unchanged while
methox-amine infusion maintained blood pressure.
After propranolol. The intravenous adminis-tration of 15 mg of propranolol hydrochloride
caused a decrease in both the cardiac index and
heart rate (R.H., Table I). When heart rate was
heldconstantbypacing,anelevation of36mm Hg
in mean systolic pressure by metlhoxamine caused an increase in left ventricular ejection time of 26 msec and stroke volume index remained
un-changed. Left ventricular end diastolic pressure
increased from 10 to 15 mm Hg with this increase
in meansystolic pressure.
DISCUSSION
By the use of high right atrial pacing, it has
been possible to prevent the reflex bradycardia
associated with an acute increase in arterial blood
pressure (16). With heart rate held constant, the
so
70
60
50
5
E
n
30
20
10
HR
SVI
Fu(;uRE 5 Phonocardiogram during control pace (subject A.P.). From top to bottom: phonocardio-gram at the second left interspace; lead II of the electrocardiogram with high right atrial pacing; indirect carotid pulse. Note the presence of an early ejection sound and normal splitting of S2. No diastolic sounds are present. Paper speed 100 mm/sec; time markers=0.02 sec. Values for left ven-tricular ejection time and QA2 interval are the average of 10 well-inscribed complexes.
systemic arterial pressure was increased by the
intravenous administration of methoxamine. The assumption was made that during the procedure,
neither a positive nor a negative inotropic
inter-\vention was imposed upon the subject. It has been
wvell established by previous studies that
methox-aminie has no significant inotropic effects on the
ventricular dynamics in animals (13, 15). Gold-berg, Bloodwell, Braunwald, and Morrow (14) have demonstrated that in man the administration
of methoxamine does not increase the myocardial
contractile force as measured by the strain-gauge
arch. Although Brewster, Osgood, Isaacs, and
Goldberg (17) have shown evidence of myocardial failure with repeated injections of methoxamine in dogs, this failure was always associated with a highly significant decrease in cardiac indexes, stroke volumeindexes, left ventricularstroke work
indexes, and systemic arterial pressure. The
main-tenance of control cardiac output and the increase
in both left ventricular stroke work indexes and systemic arterial pressure observed in our subjects after methoxamine infusion are evidence against any significant negative inotropic effect. Also, the
maintenance of control cardiac output with pacing and methoxamine, and the subsequent drop in
car-diac output with methoxamine alone strongly sup-port the statement by Brewster and coworkers that the cardiac output with methoxamine infusion decreases in proportion to the decrease in heart rate.
During methoxamine infusion when heart rate was heldconstant bypacing, cardiac index didnot
change. As a result,stroke volume index remained
unchanged, and with the assumption of a constant
inotropic state it was possible to evaluatethe effect
EARLYMETHOXAMINE
L.:-iii
PACE A2SVI 48mom2 Sm 158mm Hg
QOA
320msec
391 msec
FI(;uIUE 6 Phonocardiogramri (luring early miethoxamine pace. With heart rate and stroke volume held constant, nmethoxamine has increased mean systolic arterial pressure 39 mm Hg. A prominent third heart sound has appeared, and the intensity -of A2 is increased. Left ventricular ejection time has in-creased 23 msec and splitting has narrowed.
of increased systemic arterial pressure on the dy-namics of the intact Ilmman left ventricle. As ar-terial pressure was increased, there
wvas
asigniif-icant increase in all
phases
of left ventricularsys-tole. When the prolongation of left ventricular ejection time
wvas compare(l
with the change inthemean arterial systolic pressure, a highly significant correlation was found (r = 0.870). Even when there was amarked increase in mean systolic
pres-sure of 75 nmm Hg, no significant change was
present in stroke voJume index. Therefore, the
prolongation
of left ventricularejection
time of 55 msec, which produced paradoxical splitting of the second heart soun(l, coul(l not l)e attributed to leftventricular failure.
In three subjects,
inl
wvhom left ventricular end diastolic pressure was monitored, there was amarked increase in end diastolic pressure after methoxamine infusion. Braunwald, Frye, and Ross
found no alterationof left ventricular end diastolic pressure-end-diastolic-circumference relationship
in dogs, when both aorticpressureand cardiac
out-putwerevaried over wide ranges(18). Itis, there-fore, probable that the increased end diastolic
pres-sure observed during methoxamine infusion was
associated with an increase in end diastolic size. This would be consistent with thefindings of
Har-rison, Glick, Goldblatt, and Braunwald who ob-served an increase in left ventricular dimensions during methoxamine infusion (19). This increase in left ventricular dimensions was also present af-ter the administration of atropine sulfate and,
therefore, could not be attributed tothe associated
hradycardia. These observations suggest that the
LATEMETHOX)MINEPACE!'.
L '---;| | ^ *: Jo :, | t ;;; ^
FIGURE 7 Phonocardiogram during late methoxamine pace. An increase in mean systolic arterial pressure of 75 mm Hg has now prolonged left ventricular ejection time 55 msec, producing paradoxi-cal splitting of S2. There is marked increase in the intensity of A2, and the prominent S3 persists. Heart rate and stroke volume index remain unchanged.
Although much controversy exists as to the ef-fect of vagal stimulation on left ventricular
con-tractility, the recent study by DeGeest, Levy, Zieske, and Lipman (20) has indicated a depres-sion of ventricular contractility in both the iso-volumetric left ventricle and the pumping left heart. For this reason, two subjects were given 2 mg of intravenous atropine sulfate to completely block the reflex vagal stimulation associated with methoxamine infusion. Results after injection (Fig. 8) were similar in both direction and mag-nitudetothe controlsubjects,thusruling outvagal inhibition of the left ventricle as the cause for prolongation of the left ventricular ejection time during methoxamine infusion. It isalsointeresting to note that when pacing was stopped while
me-thoxamine was continued in the two atropinized
sul)jects, there was only a slight decrease in heart rate, and cardiac output was maintained. This is in sharp contrast to the nine control subjects who developed a significant bradycardia with a
consistent decrease in cardiac output when pacing was stopped and methoxamine infusion continued. This, again, is consistent with the observation that the decrease in cardiac output observed with
methoxamine infusion is proportionate to the de-gree of bradycardia. The observation by Wilber and Brust (21) that atropine potentiates norepi-nephrine, asmanifestedibyincrease in bothcardiac
output and blood pressure, might possil)ly be ex-plained by the vagal blocking effect of atropine alone. Tnstead of maintaining only cardiac output, as seen with methoxamnine when reflex
brady-cardia is prevented, norepinephrine, because of its
I0I
Ir
I.
160
150
_-* CONTROL
A ATROPINE
* PROPRANOLOL
270 280 290
LVET msec
FIGURE 8 Mlean systolic pressure (Sm)
1)lotted against left ventricular ejection
time (LVET).Circles representthemean
data of 13 control observations in 9 sub-jects; triangles, themeandata in thetwo
atropinized subjects; and the squares represent the data after propranolol in a
single subject. The direction of the
ar-row represents the response during the methoxamine infusion, while heart rate
and stroke volume were held constant.
The response to methoxamine after the administration of both atropine and pro-pranolol is similar in both direction and magnitude to the control response.
300 310 320 330
potent inotropic effect on the heart, is able to
greatly increasecardiac output when the canceling
effect of bradycardia is removed.
Sarnoff and coworkers have shown that eleva-tion of carotid pressure can decrease ventricular
contractility by reflex withdrawal of sympathetic tone (22). To rule out this mechanism as a
pos-sible explanation for the prolongation of left
ven-tricular ejection time during methoxamine infu-sion, complete beta sympathetic blockade was
ef-fected in one subject by the intravenous
adminis-tration of 15 mg of propranolol hydrochloride.
After sympathetic blockade, both left ventricular ejection time and left ventricular end diastolic
pressure increased as mean systolic pressure was
increased with methoxamine (Table I). Since the mechanism of reflex withdrawal of sympathetic tonecouldplaynopart inprolongingleft ventricu-lar ejection time after sympathetic blockade, the
prolongation of left ventricular ejection time ob-served in this subjectmustbeattributed to the in-creasedpressureloadimposeduponthecontracting
left ventricle. This response to the methoxamine infusion after propranolol was identical to the re-sponsein the control group (Fig. 8). It is,
there-fore, unlikely that reflex withdrawal ofsympathetic toneplays a significant role in the prolongation of
leftventricular ejection time in the control group,
and that the prolongation consistently observed is due to the increased arterial pressure induced by
the methoxamine infusion.
Our findings on the duration of the phases of
left ventricular systole are not consistent with the
findings of Wallace and coworkers (5). In their
right heart by-pass
prep)aratioll,
elevating aortic pressure shortened left ventricular ejection time,prolonged theisometric contraction phase, and had
either no effect or showed only a slight decrease
in the duration oftotal systole. They also observed
no significant increase in left ventricular end
dia-stolicpressure when aortic pressure was increased as seen in our study. However, in a more recent communication, Mitchell, Wallace, and Skinner
(23) have shown that the effect of increasing aortic pressure on both left ventricular ejection
time and left ventricular end diastolic pressure was dependent upon the degree of elevation of
aorticpressure. With right heart by-pass
prepara-tion in the areflexic(log, increasing aorticpressure
from 58 2 to 120 + 4 mm Hg, while stroke
volume and heart rate were constant, caused little or nochange in left ventricular end diastolic pres-sure and ejection time. However, a higher
eleva-tion of aortic pressure from 114 8 to 139+ 8 mm Hgcaused an increase in leftventricular
ejec-tion time and an increase in left ventricuilar en(l
diastolic pressure. This latter response is identical
to our findings. Also, the range of mean aortic pressure and the degree of elevation causing this
increase in left ventricular end diastolic pressure
and ejection time are similarto the range ofmean
arterial pressure and degree of elevation in our
study.
Thefindings ofWeisslerand his coworkers (6)
of a normal left ventricular ejection time in a group of 11 patients with severe hypertension is
not completely inconsistent with our observations.
In fact, ifthe following sequence of events can be
cx
E
E
(I)
140 _
130
_-120
110
K
2vu 2
250 260 170
considered, apossible explanation for thesporadic case of paradoxical splitting of the second-heart sound associated with severe hypertensive
cardio-vascular disease can be made. Since hypertensive cardiovascular disease isusually aslowly progres-sive process, there is ample time for the ventricle to compensate for the increased pressure load by hypertrophy; and thus, by increasing its mass of
contracting tissue,maintain a normal left ventricular
ejection time.Ananalogycanbe made between our
normal subjects and the compensated patient
with hypertensive cardiovascular disease, both of whomhave normal left ventricular ejection times.
When the normal subject is artificially stressed
with an acute rise in arterial pressure, paradoxical splitting of the second heart sound can occur. In
the compensated hypertensive, we need only
sub-stitute two common clinical situations in the
nat-ural historyof hypertensive cardiovascular disease
and we have createda similar situation. The first of these isa rapid acceleration of hypertension
as-sociated with the development of the malignant phase, and the second is thecommon development of left ventricular failure. The superimposition of
either of these acute stresses on the compensated
left ventricle, if properly timed and of significant
degree, may well explain the rare episodes of para-doxical splitting of the second heart sound seen in
hypertensive cardiovascular disease. Moreover,
with proper therapy the acute stress can be
re-moved, and the paradoxical splitting will
disap-pear as the ventricle again becomes compensated.
ACKNOWLEDGMENTS
We express gratitude to Mrs. Joanne Spanovich for her interest and nursing assistance, and to Mr. John Fabrizio for his invaluable technical assistance.
This study was supported in part by a grant from the Health Research and Services Foundation (F-10).
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