Download Effect of Acutely Increased Right Ventricular Afterload on Work

135
Effect of Acutely Increased Right Ventricular
Afterload on Work Output From the Left
Ventricle in Conscious Dogs
Systolic Ventricular Interaction
Michael P. Feneley, Craig O. Olsen,
Donald D. Glower, and J. Scott Rankin
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In seven conscious, chronically instrumented dogs, left ventricular volume was calculated
with an ellipsoidal model from the anteroposterior, septal-free wall, and base-to-apex left
ventricular dimensions, measured by implanted ultrasonic transducers. Matched micromanometers measured left and right ventricular transmural and transseptal pressures. Ventricular pressures and volumes were varied by inflation of implanted vena caval and
pulmonary arterial occluders. When compared with vena caval occlusion at matched left
ventricular end-diastollc volumes, graded pulmonary arterial occlusions were associated with
higher right ventricular systolic pressures, reduced left-to-right transseptal systolic pressure
gradients, and leftward systolic septal displacement, with increased septal-free wall segment
shortening (all p<0.05). Graded pulmonary arterial occlusions, like vena caval occlusions,
reduced left ventricular end-diastolic volume, but left ventricular stroke work at a given
end-diastolic volume was greater during pulmonary arterial occlusions (2,674±380 10 erg)
than during vena caval occlusion (l,886±450 10 erg, /><0.05). These data indicate that,
while transient pulmonary arterial occlusion reduces left ventricular preload, the concomitant increase in right ventricular systolic pressure, which is the pressure external to the
interventricular septal segment of the left ventricle, augments septal shortening and assists
left ventricular pump function at a given preload through direct systolic ventricular
interaction. {Circulation Research 1989;65:135-145)
I
nteractions between the left and right ventricles have long been recognized to occur
during diastole.1 Diastolic ventricular interaction may be viewed as a volume distribution
phenomenon between two chambers that are separated by a mobile wall, the interventricular septum. Increased filling of either ventricle alters the
transseptal pressure gradient and displaces the
interventricular septum toward the opposite ventricle, thereby decreasing the latter's diastolic
From the Departments of Surgery and Physiology, Duke
University Medical Center, Durham, North Carolina.
Supported in part by National Institutes of Health, National
Heart, Lung, and Blood Institute grants HL-09315 and HL29436 and SCOR Grant HL-17670. M.P.F. is the recipient of a
Fulbright Postdoctoral Scholarship, a Neil Hamilton Fairley
Fellowship from the National Health and Medical Research
Council of Australia, and a Telectronics Overseas Fellowship
from the Royal Australasian College of Physicians.
Address for correspondence: J. Scott Rankin, MD, Associate
Professor, Department of Surgery, Box 3851, Duke University
Medical Center, Durham, NC 27710.
Received June 11, 1987; accepted December 10, 1988.
compliance.2-12 This effect is enhanced by the
intact pericardium.6.8,13,14 Because increased filling
of either ventricle impedes filling of the other,
diastolic ventricular interaction has been aptly
described as "ventricular interference." 6
There is far less consensus concerning the nature
and significance of systolic ventricular interactions.15 Considerable evidence supports the view
that left ventricular contraction contributes to
right ventricular systolic function,16-25 although
some dissent from this view.26 Under normal
loading conditions, right ventricular contraction
has been thought to exert little direct effect on left
ventricular systolic function.24'26 Several studies
have addressed the issue of whether abnormal
right ventricular loading conditions influence left
ventricular systolic function, but the conclusions
have been somewhat conflicting.2'7'13'27-31 In part,
the different conclusions reached in these studies
reflected differences in the methods used to assess
left ventricular systolic function. For example, left
ventricular pump function curves were observed
136
Circulation Research Vol 65, No 1, July 1989
to be depressed by right ventricular volume overload when left ventricular end-diastolic pressure
was employed as the index of preload.2 Subsequent studies suggested, however, that the apparent depression of left ventricular systolic function
under abnormal right ventricular loading conditions
reflected the concomitant decrease in the diastolic
compliance and end-diastolic volume of the left ventricle due to diastolic ventricular interaction: indexes
of left ventricular systolic function were not
depressed when the reduced end-diastolic volume
(preload) was accounted f o r . -
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Left ventricular stroke work, the energy output
from the left ventricular chamber during contraction, has recently been shown to be a linear function
of the end-diastolic volume in conscious dogs.32 If
the effects of altered right ventricular loading conditions on left ventricular systolic function could be
accounted for entirely by the concomitant reduction
in left ventricular end-diastolic volume, then the
linear stroke work-end-diastolic volume relation of
the left ventricle would not be perturbed by altered
right ventricular loading conditions. Left ventricular systolic pressure has been observed to increase,
however, after sudden constriction of the pulmonary
artery.28 Moreover, right ventricular systolic hypertension has been observed to cause systolic displacement of the interventricular septum into the left
ventricular cavity,31-33-35 which might be expected to
increase the stroke volume displaced from the left
ventricular chamber at a given end-diastolic volume.
Since stroke work is the product of stroke volume
and developed pressure, the hypothesis tested in this
study was that an acute increase in right ventricular
afterload would increase the stroke work output
from the left ventricular chamber at a given (albeit
reduced) left ventricular end-diastolic volume by
direct systolic ventricular interaction.
Materials and Methods
Experimental Preparation
Seven healthy adult dogs (19-30 kg) were anesthetized (thiamylal sodium, 25 mg/kg i.v.), intubated,
and ventilated with a volume respirator (Bennett
MA-1, Puritan-Bennett, Los Angeles, California).
Under sterile conditions, a left thoracotomy was
performed through the fifth intercostal space. Pulsetransit ultrasonic dimension transducers were positioned across the anteroposterior and septal-free
wall minor axis diameters, and the base-to-apex
major axis diameter of the left ventricle, as described
previously.31 In three dogs, an additional transducer
was positioned on the right ventricular free wall to
permit measttrement of the right ventricular septalfree wall diameter. The septal transducer (1.5 mm
o.d. cylinder) was placed through the tract of a
19-gauge needle that was introduced into the septum just to the right of the left anterior descending
coronary artery, and the transducer was positioned
near the right ventricular endocardia! surface mid-
way between the anterior and posterior transducers. The remaining transducers (5 mm o.d. hemispheres) were sutured to the epicardium under
direct vision.
Silicone rubber pneumatic occluders were positioned about both venae cavae and about the main
pulmonary artery. Heparin-filled silicone catheters
(2.6 mm i.d.) were implanted in the base of the left
atrium and the apex of the right ventricle. A similar
catheter with multiple side holes was placed in the
pleural space adjacent to the left ventricular epicardial surface. The pericardium was left widely open,
and the transducer leads, catheters, and occluder
tubing were exteriorized dorsal to the thoracotomy,
which was repaired in multiple layers. Procaine
penicillin G (600,000 IU i.m.) and dihydrostreptomycin (250 mg i.m.) were administered daily.
Data Acquisition and Experimental Protocol
After a recovery period of 7-14 days, each dog
was sedated lightly (morphine sulfate, 5 mg i.m.) 1
hour before data acquisition and was studied in the
conscious state as it lay quietly on its right side.
Detailed descriptions of the operating characteristics of the equipment used for data acquisition have
been given in several previous reports.31'32'3* The
dimension transducers were coupled to a sonomicrometer designed and built in our laboratory. Three
micromanometers (PC-350 or MPC-500, Millar
Instruments, Houston, Texas), which had been
prewarmed (38° C), balanced, and calibrated simultaneously against a water column, were passed via
the implanted silicone catheters to obtain the left
ventricular, right ventricular, and pleural pressures.
Resultant manometer drift was less than 0.5 mm Hg
in all studies. Analog data were digitized at 200 Hz,
either in real time (model 1012 A/D converter,
ADAC) or from FM tape.
Data were recorded under control conditions,
during transient maximal vena caval occlusion, and
during graded pulmonary arterial occlusions. Sufficient time was permitted for return to stable control
conditions between interventions. In three dogs,
the protocol was repeated after attenuation of the
autonomic nervous system with propranolol (1-2
mg/kg i.v.) and atropine (0.4 mg/kg i.v.).
At the conclusion of each study, the dog was
killed by intravenous injection of potassium chloride under deep barbiturate anesthesia. The heart
was excised, and proper position of the transducers
was verified. The volume of the left ventricle was
measured by water displacement after excising the
atria, right ventricular free wall, aortic and mitral
valves, and chordae tendineae.
Data Analysis
Analysis of digitized data was performed on a
microprocessor (model PDP 11/23, DEC) with interactive programs developed in our laboratory. Left
and right ventricular free wall transmural pressures
were calculated as the differences between the
Feneley et al Systolic Ventricular Interaction
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respective chamber pressures and pleural pressure.
The left-to-right pressure gradient across the interventricular septum, the transseptal pressure, was determined by subtracting right ventricular pressure from
left ventricular pressure. As described in detail
previously,32 the phases of each cardiac cycle were
defined with reference to the first time derivative of
left ventricular transmural pressure (dP/dt), which
was computed from the digital pressure waveform
as a running five-point polyorthogonal transformation.
Left ventricular volume (V) was calculated by
fitting the epicardial major (a), anteroposterior minor
(b), and septal-free wall minor (c) axis dimensions
of the left ventricle to a modified ellipsoidal shell
model31-37 and subtracting ventricular wall volume
(Vwau). The formula for the volume of the modified
ellipsoid is mathematically equivalent to that for a
general ellipsoid.31 Thus:
V=7T/6
abc-Vw.ii
(1)
The equatorial plane of the left ventricular minor
axis was represented by a two-compartment model
described previously.31 The left ventricular free
wall was assumed to deform uniformly according to
the left ventricular transmural pressure, while the
interventricular septum was assumed to deform
according to the transseptal pressure. Consequently, the radius of curvature of the free wall in
this plane (Rpw) was assumed to be uniform and
equal to one half of the anteroposterior minor axis
dimension (b):
Rpw=b/2
(2)
In this two-compartment model, therefore, the contribution of alterations in septal position to the total
septal-free wall dimension (c) was calculated by
subtracting the instantaneous R ^ :
d=c-b/2
(3)
where d is the distance from the septum to the
center of curvature of the left ventricular free wall.
Both the theoretical basis for the derivation of
Equations 1-3 and empirical validation of the geometric model on which these derivations were based
have been reported in detail previously.31*37
Left ventricular stroke work (SW) was calculated
as the integral of left ventricular transmural pressure (P) with respect to cavitary volume over each
cardiac cycle:
SW=/P • dV
(4)
The relation between left ventricular stroke work
and end-diastolic volume (EDV) during vena caval
occlusion was determined by linear regression analysis, as described previously,32 so that data were
fitted to the formula:
SW=MW (EDV-V W )
(5)
137
where M w and V w are the slope and x-intercept,
respectively, of the stroke work-end-diastolic volume relation. Stroke work was also plotted against
end-diastolic volume during graded pulmonary arterial occlusions. Once the right ventricular pressure
had stabilized at a new level during pulmonary
arterial occlusion, however, the variation in leftventricular end-diastolic volume was usually small.
Each stroke work data point obtained during a
stable pulmonary arterial occlusion was compared,
therefore, with the stroke work predicted at the
same end-diastolic volume by the linear stroke
work-end-diastolic volume relation obtained during
vena caval occlusion. The validity of this comparison depends on the reproducibility of repeated
determinations of the stroke work-end-diastolic volume relation under constant loading conditions (see
"Appendix"). Comparisons of cardiac dimension,
volume, and pressure data were made between the
two occlusion states from cardiac cycles with similar end-diastolic volumes. Statistical comparisons
were made by Bonferroni-adjusted paired t tests.
Results are expressed as mean±SEM.
Results
Representative, dynamic cardiac dimension and
pressure waveforms from cardiac cycles with similar left ventricular end-diastolic volumes during
vena caval and pulmonary arterial occlusions are
shown in Figure 1. Left ventricular pressurevolume loops obtained in the same study during the
two occlusion states are shown in Figures 2A and
2B. In panel C, one of the loops obtained during the
steady-state phase of pulmonary arterial occlusion
from panel B has been superimposed on the same
loops shown in panel A during vena caval occlusion. In panel D, left ventricular stroke work (the
area of the pressure-volume loops in panels A and
B) is plotted against end-diastolic volume for the
two occlusion states. As documented previously,32
the stroke work-end-diastolic volume relation during vena caval occlusion was highly linear; the
mean linear correlation coefficient for this series of
experiments was 0.98±0.01. The control beats preceding the onset of pulmonary arterial occlusion in
panel D of Figure 2 lie on the regression line
obtained during vena caval occlusion. With the
onset of pulmonary arterial occlusion, however, the
stroke work-end-diastolic volume relation shifts
rapidly leftward over several beats, so that at any
given end-diastolic volume, left ventricular stroke
work is greater during pulmonary arterial occlusion
than during vena caval occlusion. Similarly, as
illustrated in panel C, at a given end-systolic left
ventricular volume, the end-systolic transmural pressure is greater during pulmonary arterial occlusion
than during vena caval occlusion. Figure 3 demonstrates that the increased left ventricular stroke
work generated from a given end-diastolic volume
during the pulmonary arterial occlusion shown in
Figure 2 resulted from an increase in both the mean
138
Circulation Research
Vol 65, No 1, July 1989
VCO
PAO
15
LV
BASE-APEX
DIMENSION(cm)
w
LV
ANTE RO- POSTERIOR
DIMENSION (cm)
LV
SEPTAL-FREE WALL
DIMENSION (cm)
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LV
SEPTAL
DISPLACEMENT (cm)
U
36
RV
SEPTAL-FREE WALL
DIMENSION (cm)
2J
ISO
TRANSMURAL
PRESSURE (mmHj)
LV
RV
LV TRANSSEPTAL
PRESSURE (rimHg)
FIGURE 1. Representative left ventricular (LV) and right
ventricular (RV) dynamic dimension and pressure waveforms recorded during vena caval occlusion (VCO) and
pulmonary arterial occlusion (PAO) for cardiac cycles
with similar left ventricular end-diastolic volumes.
developed left ventricular ejection pressure and the
stroke volume when compared with vena caval
occlusion.
The pulmonary arterial occlusion illustrated in
Figure 2 was of relatively mild grade, as evidenced
by the small resultant decrement in the transseptai
pressure when compared with the vena caval occlusion state (Figure 1). With more severe grades of
pulmonary arterial occlusion, however, the stroke
work-end-diastolic volume relation continued to
shift leftward during the period when left ventricular end-diastolic volume was decreasing, thus
precluding valid linear regression analysis of the
data obtained during most pulmonary arterial occlusions. In Figure 4, representative examples of the
stroke work-end-diastolic volume data obtained
during the steady-state phase of several grades of
pulmonary arterial occlusion are compared with
the corresponding regression lines obtained during
vena caval occlusions. In a given animal, increasing grades of pulmonary arterial occlusion produced progressively greater leftward shifts of the
left ventricular stroke work-end-diastolic volume
relation.
As illustrated in Figure 1, even mild grades of
pulmonary arterial occlusion resulted in characteristic alterations in the right and left ventricular
pressures and in left ventricular geometry when
compared with vena caval occlusion. During pulmonary arterial occlusion, the diastolic and systolic
transmural pressures of the right ventricle and, to a
lesser extent, of the left ventricle increased, with a
consequent reduction in the corresponding transseptai pressures. Consistent with these alterations
in distending pressures, the right ventricular septalfree wall dimension increased and the left ventricular septal-free wall dimension decreased during
pulmonary arterial occlusion due to leftward septal
displacement, while the anteroposterior minor and
base-to-apex dimensions of the left ventricle
increased.
The relations between the septal-free wall and
the anteroposterior minor axis dimensions of the
left ventricle at end diastole and at end ejection
during the two occlusion states in one study are
shown in Figure 5. As observed previously,31 these
relations were shifted to the right during pulmonary
arterial occlusion, indicating that for any given
anteroposterior dimension, the septal-free wall
dimension was shorter during pulmonary arterial
occlusion than during vena caval occlusion, whether
measured at end diastole or at end ejection. Moreover, because of the free wall component of the
septal-free wall dimension (b/2 in Equation 3) at any
given volume tended to increase during pulmonary
arterial occlusion, the shortening of the septal-free
wall dimension was attributable entirely to shortening of its septal component (d in Equation 3).
The mean hemodynamic and dimensional data
from all paired vena caval occlusion and steadystate pulmonary arterial occlusion studies are presented in Table 1. Although the possibility of reflex
changes in autonomic tone during pulmonary arterial occlusion cannot be eliminated, there was no
significant difference between the heart rates
observed during the two occlusion states. Moreover, pharmacological attenuation of the autonomic
nervous system did not alter the relative impact of
pulmonary arterial and vena caval occlusions on left
ventricular hemodynamics and dimensions, as
observed previously.31 When compared with vena
caval occlusion at the same left ventricular enddiastolic volume, pulmonary arterial occlusion augmented left ventricular stroke work by an average
Feneley et al Systolic Ventricular Interaction
139
PAO
vco
2. Panel A: Left ventricular
(LV) pressure-volume loops recorded
during a vena caval occlusion (VCO).
Panel B: Left ventricular pressurevolume loops recorded during a partial
pulmonary arterial occlusion (PAO) to
a new steady-state right ventricular
pressure. Panel C: One of the pressurevolume loops from the steady-state
phase of pulmonary arterial occlusion
in panel B has been superimposed on
the loops obtained during vena caval
occlusion in panel A. Panel D: The
relations between left ventricular stroke
work and end-diastolic volume for the
two occlusion states. The relation shifts
to the left with the onset of pulmonary
arterial occlusion.
FIGURE
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LV VOLUME (ml)
LV END-WAST0L1C VOLUME (ml)
42%, peak left ventricular transmural pressure by
an average 16%, and stroke volume by an average
30%. Ejection phase shortening of the left ventricular septal-free wall dimension increased during
pulmonary arterial occlusion, due entirely to
increased shortening of its septal component (d in
Equation 3). On the other hand, shortening of the
anteroposterior minor and base-to-apex left ventricular dimensions was not altered significantly, again
suggesting that the improved left ventricular performance was not dependent on increased autonomic
tone. The enhanced septal shortening with pulmonary
arterial occlusion was consistent with the significant
reductions in both the peak systolic transseptal pressure and the peak systolic transseptal/transmural pressure ratio of the left ventricle (Figure 6).
Discussion
Evidence from two previous studies suggested
that when the effects of altered right ventricular
loading conditions on left ventricular preload are
accounted for, right ventricular pressure overload,
or combined pressure and volume overload, does
not impair left ventricular systolic function.27-31
Although transient pulmonary arterial occlusion
decreases left ventricular preload, and thus stroke
work, the highly linear and reproducible relation
between stroke work and end-diastolic volume32
(see "Appendix") permitted a comparison to be
made in the present study between left ventricular
stroke work with high right ventricular systolic pressures and stroke work with low right ventricular
systolic pressures at the same end-diastolic volume.
The new finding from this study is that an acute
increase in right ventricular pressure significantly
increases the work output from the left ventricular
chamber at a given end-diastolic volume.
The left ventricular model employed to determine
left ventricular volume in this study has been
described and validated in previous reports from
this laboratory,31-37 and very similar models have
been validated by others.30-38 Because of the relatively small changes in left ventricular end-diastolic
volume during the steady-state phase of pulmonaiy
arterial occlusion in most cases, it was not possible
to apply linear regression analysis to the steadystate data to determine quantitatively whether the
increment in left ventricular stroke work with pulmonary arterial occlusion resulted solely from a
parallel leftward shift of the stroke workend-diastolic volume relation or whether the slope
of the relation also increased. Qualitative observation suggested, however, that the slope of the
relation did increase with higher grades of pulmonary arterial occlusion (Figures 2 and 3).
For the same reasons, it was not possible to
quantify the end-systolic pressure-volume relation
during steady-state pulmonary arterial occlusion by
linear regression analysis. Nevertheless, it is clear
that the increase in left ventricular transmural systolic pressure and stroke volume from a given
end-diastolic volume during pulmonary arterial occlusion indicates an increase in the end-systolic
pressure-volume ratio of the left ventricle (Figure
140
Circulation Research
Vol 65, No 1, July 1989
4000
PAO Grade 1
PAO Grade 2
O
o
en
I
' 0.997
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LV END-DIASTOLIC VOLUME (ml)
70
50
LV END-DIASTOLIC VOLUME (ml)
4500
• PAO Grade 1
° PAO Grade 2
o
o
r- 0.950
70
LV END-DIASTOLIC VOLUME (ml)
FIGURE 3. Mean developed left ventricular (LV) ejection
pressure (A) and left ventricular stroke volume (B) plotted
against end-diastolic volume for the same vena caval
occlusion (VCO) and pulmonary arterial occlusion (PAO)
shown in Figure 4. Both the ejection pressure and stroke
volume increase with pulmonary arterial occlusion.
2). This observation is consistent with the leftward
shift of the left ventricular end-systolic pressurevolume relation observed in isolated hearts when
right ventricular volume was increased, i3-24-39 Left
ventricular systolic pressure has been observed
previously to increase after sudden constriction of
the pulmonary artery during the preceding diastole.28
Although repeated determinations of the endsystolic pressure-volume relation have been shown
recently to be subject to significant variability,40 this
variability cannot account for the consistent, unidirectional shift (i.e., increase) in the end-systolic
0
B
50
LV E N D - D I A S T O L I C VOLUME ( m l )
FIGURE 4. Left ventricular (LV) stroke work-enddiastolic volume relations for mild and moderate grades
of steady-state pulmonary arterial occlusion (PAO) in
one dog (A) and for two severe grades of steady-state
pulmonary arterial occlusion in another dog (B). The
linear regression lines obtained during vena caval occlusion (VCO) are stiown for comparison.
elastance of the left ventricle with increased right
ventricular load.
The augmentations in both stroke work aad the
end-systolic pressure-volume ratio of the left ventricle with pulmonary arterial occlusion indicate
improved left ventricular systolic performance.
While increased autonomic tone might have contributed to this increased systolic performance, there
was no significant change in heart rate during pulmonary arterial occlusion, and a similar increase in
Feneley et al
Systolic Ventricular Interaction
141
END-EJECTION
END-DIASTOLE
60
FIGURE 5. The relation between
the septal-free wall and the
anteroposterioT left ventriccular
minor axis dimensions at end
diastole (A) and at end ejection
(B) during vena caval occlusion
(VCO) and pulmonary arterial
occlusion (PAO) in one study.
Both relations are shifted to the
right during pulmonary arterial
occlusion.
75 60
LV ANTERO-POSTERlOR DIMENSION (cm)
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left ventricular systolic performance was observed
after autonomic blockade. The augmented left ventricular performance appears attributable predominantly, therefore, to the altered loading conditions
during pulmonary arterial occlusion. The present
experimental preparation, however, does not permit definite conclusions to be drawn concerning the
mechanism of this ventricular interaction.
Leftward systolic interventricular septal displacement due to right ventricular systolic hypertension
increases the radius of septal curvature,31'33-35 which
would tend to increase septal tension, but a previous study from this laboratory demonstrated in an
identical experimental preparation that systolic septa] tension decreased during pulmonary arterial
occlusion because the reduction in the left-to-right
transseptal pressure gradient outweighed the
increase in the radius of curvature.31 Moreover,
because the mass of the interventricular septum is
constant, leftward systolic septal displacement and
enhanced septal shortening must be accompanied
by increased septal thickening. The combination of
decreased systolic septal tension and increased septal thickness during pulmonary arterial occlusion
implies a reduction in systolic septal stress (i.e.,
TABLE 1.
75
septal afterload). On this basis, the increment in the
work output from the left ventricular chamber during pulmonary arterial occlusion could be viewed as
resulting, in some part, from the transduction of
right ventricular energy expenditure to the services
of the left ventricular chamber via the inter ventricular septum. The common muscle fiber pathways
that invest both ventricles,41 however, could provide the primary mechanistic basis for this energy
transfer.
It is well recognized that the forces acting on the
external surface of the left ventricle must be
accounted for when assessing left ventricular myocardial performance, but this is usually done by
subtracting the pericardial pressure (or the intrapleural pressure) from the left ventricular chamber
pressure, yielding free wall transmural pressure.
This approach fails to account for the much greater
external pressure acting on the remaining one third
of the left ventricular surface area during systole. In
effect, it is falsely assumed that the right ventricular
systolic pressure is equivalent to the pericardial
pressure; that is, it is assumed that the transseptal
pressure is equivalent to the free wall transmural
pressure.
Hemodynamic, Volume, and Dimension Data
Peak
Peak
Peak
RVTMP/ TSP/
Peak
Peak
SW
(beats/ EDV
TSP
LVTMP LVTMP SV at* Aa b*. Ab Cb, A c db. Ad
RVTMP LVTMP
min) (ml) (10-3 erg) (mm Hg) (mm Hg) (mm Hg) (mm Hg) (mm Hg) (ml) (cm) (%) (cm) (*) (cm) (%) (cm) (*)
HR
VCO
Mean 128.7
SEM
8.0
PAO
Mean
SEM
1,886
450
32.2
6.7
106.2
83.2
6.0
7.8
7.0
125.7
38.4
2,674
76.8
123.5
52.8
9.6
6.5
380
9.5
5.5
8.9
39.1
0.30
0.05
0.78
0.03
13.8 7.67 1.7 5.99 3.2 5.21 6.1 2.25 10.3
2.5 0.22 0.6 0.25 0.5 0.17 0.8 0.06 1.7
0.63
0.08
0.43
0.07
18.0 7.82 2.0 6.16 3.4 4.94 9.4 1.86 20.0
2.5 0.25 0.5 0.24 0.6 0.18 1.2 0.09 3.6
HR, heart rate; EDV, end-diastolic volume; SW, left ventriccular stroke work; RV, right ventriccular; LV, left ventriccular; TMP, free
wall transmural pressure; TSP, transseptal pressure; SV, left ventriccular stroke volume; a, base-apex dimension; b, anteroposterior
dimension; c, septal-free wall dimension; d, septal component of septal-free wall dimension; be, beginning ejection; A, fractional
systolic shortening; VCO, vena caval occlusion; PAO, pulmonary arterial occlusion. All statistical comparisons between the two
occlusion states were significant (p<0.05), with the exception of HR, EDV, Aa, and Ab.
142
Circulation Research
Vol 65, No 1, July 1989
weighted average of the right ventricular pressure
{?„) and the pericardial pressure (Pp^) using the
proportion of the external surface area of the left
ventricle on which these pressures act as the weighting term,42 so that
150
E
PRESSUR
.
a
m
O
TRANSMURAL
D
a
D
P«t=(Sivs/Slv) •
(6)
VC0°
•z.
o
O
1—
JJ
o
O
O
—}
UJ
MEAN
vco°
TRANSSEPTAL
•
•
*
*
_i
A
VI
45
LV END-DIASTOUC VOLUME (ml)
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END-EJECTION
LV TRANSSEPTAL PRESSURE
END-
LV
EJECTION
TRANSSEPTAL
PRESSURE
° 95
FIGURE 6. Panel A: Illustration of the differing effects of
pulmonary arterial occlusion on the mean ejection left
ventricular transseptal and free wall transmural pressures when compared with vena caval occlusion (VCO)
over the same range of end-diastolic volumes. Panel B:
End-ejection relation between the ratio of the septal and
free wall components of the left ventricular septal-free
wall dimension and the ratio of the transseptal and
transmuralpressures during VCO and pulmonary arterial
occlusion (PAO), over the same range of end-diastolic
volumes. The dimension and pressure ratios are related
linearly when the pressure ratio is low, but the dimension
ratio approaches an upper limit as the pressure ratio
approaches unity.
In broad terms, there are two ways to account for
the forces external to the entire left ventricular
surface. One approach is to use modeling procedures to normalize the nonuniform external pressures. The simplest of these procedures is to calculate an effective external pressure (P m ) as the
where S^ is the surface area of the right side of the
interventricular septum and SK, is the total external
surface area of the left ventricle. The assumption
inherent in Equation 6 is that the compliance of the
interventricular septum is identical to that of the left
ventricular free wall. Little and coworkers demonstrated that this assumption is incorrect. They
found that at end diastole, when the ventricle may
be modeled as a passive structure, the ratio of the
change in left ventricular pressure (Ph,) for a given
change in P^ (APh/AP^) averaged 0.43 during vena
caval occlusion, while the S,JS^ ratio averaged
0.33. Moreover, after interventricular septal hypertrophy was induced by pulmonary artery banding,
the average S^SK, ratio increased to 0.38, but the
average AP^/AP^ ratio declined to 0.21, indicating
diminished septal compliance.
The effects of vena caval and pulmonary arterial
occlusions on the mean ejection left ventricular
transseptal and free wall transmural pressures are
illustrated over the same range of end-diastolic
volumes in Figure 6A. If the systolic compliance
of the interventricular septum were equal or proportionate to the compliance of the free wall, then
a proportionate relation should exist between the
ratio of the septal (d) and free wall (b/2) components of the left ventricular septal-free wall dimension (Equation 3), on one hand, and the ratio of the
transseptal pressure and the transmural pressure,
on the other. That this is not the case is illustrated
in Figure 6B, where the end-systolic septal/free
wall dimension ratio is plotted against the endsystolic transseptal/transmural pressure ratio for
cardiac cycles during vena caval and pulmonary
arterial occlusions over the same range of enddiastolic volumes. A linear relation exists between
the dimension and pressure ratios when the pressure ratio is low (during pulmonary arterial occlusion), but the dimension ratio asymptotically
approaches an upper limit, which is appreciably less
than unity, when the pressure ratio is high (during
vena caval occlusion). This relation indicates that
the compliance of the interventricular septum diminishes abruptly as the transseptal pressure approaches
the free wall transmural pressure and is compatible
with evidence that when the transseptal and free
wall transmural pressures are equal, the radius of
curvature of the septum is considerably greater than
that of the free wall.43 Septal compliance increases
as the septum is shifted, thus explaining the progressive, beat-to-beat leftward shift of the stroke
work-end-diastolic volume relation observed after
abrupt pulmonary arterial occlusion, until the end-
Feneley et al Systolic Ventricular Interaction
Downloaded from http://circres.ahajournals.org/ by guest on June 18, 2017
diastolic volumes of the two ventricles approached
a new steady state. This phenomenon explains the
very recent observation that left ventricular performance increased only slightly during the first systole after diastolic pulmonary arterial occlusion,44
since the diastolic position of the septum had not
yet changed. The dynamic variation in septal compliance with variation in the transseptal/transmural
pressure ratio precludes the use of simple weighting
functions, such as Equation 6, to normalize the
nonuniform left ventricular external pressures.
An alternative approach to this problem is to
create experimental conditions in which the right
ventricular pressure is made to approximate the
pressure external to the left ventricular free wall.
This approach is possible in isolated heart preparations, in which the right ventricle can be surgically opened to the ambient pressure and drained
continuously, but is not applicable to studies of
the intact circulation. One of the advantages of the
vena caval occlusion technique as a method for
assessing left ventricular performance in the intact
subject is that this technique produces a rapid
reduction in right ventricular volume and pressure, which precedes the reduction in left ventricular volume and pressure, thereby reducing the
interactive contribution of the right ventricle to
left ventricular function.31
A third approach, which has not been explored
thus far, would be to express ventricular interaction directly in terms of biventricular energetics.
In addition to the direct interactive effect of reduced
left ventricular diastolic compliance, the reduced
left ventricular preload during pulmonary arterial
occlusion results from the "in series" effect of
reduced right ventricular stroke volume, despite
increased right ventricular end-diastolic volume.
Consequently, the energy cost of the leftward
displacement work performed on the interventricular septum and the increased external work output from the left ventricular chamber during pulmonary arterial occlusion could be expressed in
terms of the reduction in the external work output
from the right ventricular chamber for a given
right ventricular preload. At present, the limitation to the quantitative development of such a
model is the lack of an accurate method for
determining the absolute right ventricular volume
and, thus, the right ventricular stroke work-preload relation, during acute perturbations of loading conditions. Any such energetic model would
have to account also for the effects of altered
loading conditions on the mechanical efficiency of
both ventricles.
The observations made in this study pertain to an
acute increase in right ventricular afterload. During
chronic right ventricular pressure overload, hypertrophy of the interventricular septum might be
expected to reduce the impact of direct ventricular
interaction on left ventricular systolic function.38
Moreover, even under acute conditions, the pri-
143
mary effect of increased right ventricular afterload
on left ventricular function is to cause a reduction in
left ventricular preload, and thus stroke work and
cardiac output. The present findings indicate, however, that the net reduction in stroke work in this
situation is less than would be predicted by the
reduction in preload. Finally, the important, coexistent effects of diastolic ventricular interaction
with increased right ventricular afterload must not
be overlooked; due to diminished left ventricular
compliance, the increased end-diastolic pressure
required to generate a given amount of stroke work2
may be the most important functional variable in
some clinical situations.
In summary, this study has implications concerning both systolic ventricular interaction and the
impact of this interaction on the assessment of left
ventricular systolic function. It demonstrates that at
a given left ventricular end-diastolic volume, an
acute increase in right ventricular systolic pressure
increases the stroke work output from the left
ventricular chamber. This increment in left ventricular stroke work represents energy transmitted to
the left ventricle from the right ventricle. Current
methods of assessing systolic left ventricular myocardial performance in vivo do not account for the
nonuniform systolic transmural pressure of the ventricle. Consequently, these methods primarily reflect
the net performance of the left ventricular chamber.
This may be of little consequence in many situations. When comparing ventricular performance
under conditions in which the relative hemodynamic load on either ventricle is altered, however,
methods that account for energy transmission
between the two ventricular chambers may be
needed to accurately assess the myocardial performance of either ventricle.
Acknowledgments
The authors wish to gratefully acknowledge Ms.
Barbara Lovell and Ms. Paula Poe for their expertise
in manuscript preparation and editorial assistance.
Appendix
Tabulated below are experimental data demonstrating the reproducibility of repeated determinations of the left ventricular stroke workend-diastolic volume relation by linear regression
analysis under constant loading conditions, in the
presence and absence of autonomic blockade.
The data were obtained for nine conscious dogs
(18-30 kg). The methods of surgical instrumentation, data acquisition, and data analysis employed
have been described in detail previously.32 Pharmacological autonomic blockade was achieved by
administration of propranolol (1 mg/kg i.v.) and
atropine (0.1 mg/kg i.v.). Linear regression data
are presented for sequential pairs of vena caval
occlusions (VCO).
144
Dog
Circulation Research Vol 65, No 1, July 1989
Autonomic
blockade
Slope (erg • cm-3 • 103)
VCO2
VC01
Jt-intercept (cm3)
VCO1
VCO2
1
N
55
53
22
23
2
N
83
81
6
5
3
N
102
9
90
96
94
10
Y
6
6
N
Y
101
80
92
24
24
32
33
N
57
82
54
8
7
Y
64
64
10
10
N
112
116
9
10
Y
102
96
11
N
63
12
13
14
26
4
5
6
Y
65
65
67
8
Y
56
51
18
26
15
9
Y
7
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44
45
10
11
Mean
77
75
15
15
SEM
8
8
3
3
r
VCO1
vco:
0.920
0.991
0.993
0.997
0.993
0.996
0.976
0.991
0.991
0.996
0.974
0.992
0.988
0.990
0.985
0.008
0.958
0.993
0.992
0.998
0.968
0.997
0.969
0.994
0.987
0.997
0.991
0.986
0.983
0.985
0.986
0.005
N, no; Y, yes; VCO, vena caval occlusion; r, linear correlation coefficient.
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KEY WORDS
interaction
ventricular interdependence
•
ventricular
Effect of acutely increased right ventricular afterload on work output from the left ventricle
in conscious dogs. Systolic ventricular interaction.
M P Feneley, C O Olsen, D D Glower and J S Rankin
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Circ Res. 1989;65:135-145
doi: 10.1161/01.RES.65.1.135
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