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Transcript
DIAGNOSTIC METHODS
PERICARDIAL DISEASE
Direct assessment of right ventricular transmural
pressure
WILLIAM P. SANTAMORE, PH.D., MARTIN CONSTANTINESCU, M.D., AND WILLIAM C. LILE, M.D.
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ABSTRACT Although the measurement of transmural pressure is important, calculation of transmural pressure is complicated by the difficulties in measuring pericardial pressure. Recently, flat
balloons have been proposed to measure pericardial pressure. Over a wide range of volumes, right
ventricular diastolic pressure and pericardial balloon pressure were similar in diastole, suggesting that
the right ventricle is unstressed at physiologic volumes and that right atrial pressure can be used to
estimate pericardial pressure. To evaluate these concepts and to assess indirectly the accuracy of
measuring pericardial pressure using flat balloons, six canine hearts were examined postmortem. The
pericardium was removed and the hearts were submerged in cold cardioplegic solution. Balloons were
inserted into the right and left ventricles, and right and left ventricular pressure-volume curves were
obtained. Right ventricular transmural pressures of 2.6 0.5, 3.9 0.9, 5.9 ± 1.4, and 8.9 ± 2.4
mm Hg were required to distend the right ventricle to 10, 20, 30, and 40 ml, respectively. For the left
ventricle, transmural pressures of 3.4 0.7, 5.4 1.2, 8.6 2.1, and 14.1 3.8 mm Hg were
recorded at volumes of 10, 20, 30, and 40 ml, respectively. Although the right ventricular transmural
pressures were less than the left ventricular transmural pressures over the physiologic range, right
ventricular transmural pressures were always positive and increased with increments in ventricular
volume. Thus the right ventricle is not unstressed over the entire range of physiologic volumes,
suggesting that pericardial balloon pressures may overestimate pericardial pressure and that right atrial
pressure cannot be used to estimate pericardial pressure.
Circulation 75, No. 4, 74-747, 1987.
±
±
THE FILLING PRESSURE (or transmural pressure)
for the cardiac chambers is the intracavity pressure
minus the pericardial pressure. The determination of
filling pressures in the heart in situ has been complicated by the difficulty in measuring pericardial pressure.
Fluid-filled catheters have been used to measure pericardial pressure,' but Tyberg et al.2 have clearly demonstrated the inadequacies of fluid-filled catheters to
measure pericardial pressure, especially at lower or
minimal pericardial fluid volume. Catheters are designed to measure fluid pressure, whereas the pericardial cavity is a potential space under normal circumstances and thus pericardial pressure may be best
described as surface pressure.2'3 Smiseth, Tyberg, and
From the Section of Cardiology, Bowman Gray School of Medicine,
Wake Forest University, Winston-Salem, NC.
Supported in part by NIH grants HL36068 and HL37324 and a Grantin-Aid from the American Heart Association. Dr. Santamore is a recipient of an NIH Career Development Award. Dr. Little is an Established
Investigator of the American Heart Association.
Address for correspondence: William P. Santamore, Ph.D., Section
of Cardiology, Bowman Gray School of Medicine, 300 S. Hawthorne
Rd., Winston-Salem, NC 27103.
Received Sept. 9, 1986; revision accepted Dec. 26, 1986.
744
±
±
±
±
associates,2 4' 5using flat balloons to measure pericardial pressure, observed that the right atrial and pericardial balloon pressures were almost identical. If this
balloon measurement of pericardial pressure is accurate, then right atrial pressure can be used to estimate
pericardial pressure and determine transmural filling
pressures.4 Since right atrial and right ventricular diastolic pressures are almost identical, the balloon measurements of pericardial pressure suggest that right
ventricular transmural pressure is nearly zero over a
wide range of right ventricular end-diastolic volumes.
If this is correct, the right ventricle is unstressed at
physiologic volumes; that is, large changes in ventricular volume could occur with minimal or no changes in
transmural ventricular pressure, and right ventricular
filling is limited only by the pericardium.
To assess the accuracy of balloon measurement of
pericardial pressure independently, we examined the
hypothesis of an unstressed right ventricle in a postmortem canine preparation in which the transmural
pressure could be measured directly. We compared the
right ventricular pressure-volume curves to the left
CIRCULATION
DIAGNOSTIC METHODS-PERICARDIAL DISEASE
ventricular pressure-volume curves. Our results indicate that significant transmural right ventricular pressures are necessary to distend the right ventricle, suggesting that the pericardial balloon may overestimate
pericardial pressure and thereby underestimate right
ventricular transmural pressure.
35T
3025I
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2015-
Methods
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Six mongrel dogs (13 to 24 kg), free of heart worms, were
deeply anesthetized with sodium pentobarbital (60 mg/kg iv).
The hearts were removed and placed in cool (10° C) cardioplegic solution (sodium chloride 602 mg/100 ml, calcium chloride
23.1 mg/100 ml, potassium chloride 199.3 mg/100 ml, sodium
bicarbonate 37 mg/100 ml, mannitol 1250 mg/100 ml, and
dextrose 300 mg/100 ml). The cool temperature retarded postmortem changes in ventricular compliance.6 Via a No. 7F Sones
catheter, 20 to 30 ml of cool cardioplegic solution were injected
into the left anterior descending, circumflex, and right coronary
arteries. Throughout the experimental procedures the hearts
were kept submerged in the cool cardioplegic solution. Large
helium balloons7 were inserted retrograde into each ventricle
(figure 1). Via the pulmonary artery, a No. 11 helium balloon
was inserted into the right ventricle and a ligature tied around
the pulmonary artery to secure the balloon in place. Similarly,
via the aorta, a No. 9 helium balloon was inserted into the left
ventricle and a ligature tied around the aorta. The balloons had
an unstressed volume in excess of 45 ml and were inflated and
deflated several times to ensure their proper positioning within
the ventricles. In one experiment, to prevent the balloons from
herniating into the atrium, the tricuspid valve was loosely sutured closed through an atrial approach. The ventricular pressures were measured with fluid-filled catheters positioned within the ventricular balloons. The catheters were connected to
pressure transducers (Cobe Laboratories, Lakewood, CO) and
the pressures recorded on a physiologic recorder (Model VR-6
Electronics for Medicine/Honeywell, White Plains, NY). The
Pump
Balloons
Myocardium
FIGURE 1. Sketch of the experimental set-up. PI and Pr are pressure
transducers for the left and right ventricles.
Vol. 75, No. 4, April 1987
U)
LLJ
0~
10-
W
5-
0
10
20
30
40
50
60
70
VOLUME (m1)
FIGURE 2. Plot of pressure vs ventricular volume. E = right ventricular pressures; + = left ventricular pressures.
zero pressure level was set midway between the apex and the
base of the heart. During the experimental procedures, the pressure signals were sampled at 0.5 sec intervals, converted by
analogue-to-digital processing, and stored in an Apple II+
computer.
Ten millimeters of cool water (10° C) were injected into the
right ventricular balloon. The left ventricle was filled with cool
water until left ventricular pressure reached 15 mm Hg. With a
syringe pump, cool water was injected into the right ventricular
balloon at a rate of 38.2 ml/min while right and left ventricular
pressures were recorded. The right ventricular infusion was
halted when right ventricular pressure equaled or exceeded 30
mm Hg. With the same approach, left ventricular pressurevolume data were recorded.
Data analysis. Since the hearts were submerged in cardioplegic solution, the difference (in mm Hg) between the reference
level and the fluid height was subtracted from the measured left
and right ventricular pressures. Ventricular volume was calculated as the initial volume in the ventricle (10 ml) plus the
amount that had been injected into the ventricle. The pressures
needed to distend the right ventricle to volumes of 10, 20, 30,
40, and 50 ml were compared with zero by a paired Student's t
test. Data were summarized as the mean + SEM.
Results
Figure 2 shows typical pressure-volume plots for the
right and left ventricles from one experiment in vitro.
In this example, at every ventricular volume right ventricular pressure was less than the left ventricular pressure. However, throughout the volume range, right
ventricular pressure was different from zero.
Table 1 summarizes the results from the six experiments and presents the mean transmural ventricular
pressures for the right and left ventricles. Transmural
pressuresof2.6 + 0.5, 3.9 + 0.9, 5.9 + 1.4, and8.9
+ 2.4 mm Hg were required to distend the right ventricle to 10, 20, 30, and 40 ml, respectively. At each of
these right ventricular volumes the distending pressure
was significantly (p < 0.05) different from zero.
To further investigate the concept of an unstressed
745
SANTAMORE et al.
TABLE 1
Right and left ventricular pressure-volume data
Volume (ml)
10
Right ventricular
pressure (mm Hg)
Left ventricular
pressure (mm Hg)
20
30
40
50
2.6+0.5A
3
0.9A
5.9± 1.4A
8.9±2.4A
13.6±4.OA
3.4 ± 0.7A
5.4 ± 1.2A
8.6 ± 2.1A
14.1 ± 3.8A
22.9 ± 6.8A
All data expressed as mean ± SE.
Ap < .05, value significantly greater than zero.
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ventricle, the minimal change in pressure for any given
volume increment was calculated in each experiment.
For the right ventricle, the minimal pressure change
per volume change was 0.13 ± 0.06 mm Hg/mi with a
range of 0.06 to 0.38. For the left ventricle, the minimal pressure change per volume change was 0.24 ±
0.07 mm Hg/mI with a range of 0.19 to 0.37. These
pressure increments per volume increments were significantly different (p < 0.05) between the right and
left ventricles.
Discussion
End-diastolic volume is one of the primary determinants of cardiac output. In turn, transmural end-diastolic pressure determines the end-diastolic volume.
Thus the measurement of transmural pressure is important in evaluating ventricular function and assessing
efficacy of therapeutic interventions. However, calculation of transmural pressure in intact animals and
clinical situations is complicated by the difficulties in
measuring pericardial pressure. Frequently, pericardial pressure is assumed to be zero, but this assumption
may be inaccurate and can produce serious errors. Esophageal pressure has been used as an estimate of pericardial pressure. However, Fewell et al.8 showed that
pericardial pressure was significantly different from
esophageal pressure. Fluid-filled catheters have been
used to directly measure pericardial pressure,' but they
cannot accurately determine pericardial pressure in the
absence of pericardial fluid.2 Recently, a flat balloon
inserted into the pericardium has been proposed as an
appropriate method to measure pericardial pressure in
the absence of pericardial fluid.2 Data obtained in dogs
suggest that pericardial pressure measured in this manner closely approximates right heart diastolic pressures. If this is so, then right atrial pressure can be
substituted for pericardial pressure to determine transmural left ventricular pressure. This finding also
means that the right ventricular diastolic transmural
pressure is close to zero, thus the filling of the right
746
ventricle is restrained by the pericardium, not by the
right ventricle itself.
To examine the concept of an unstressed right ventricle, we directly measured right ventricular pressurevolume curves in vitro. To circumvent any potential
problems in measuring transmural pressure, the pericardium was removed so that the intracavity and transmural pressures were identical. A transmural pressure
significantly different from zero (p < .05) was always
required to distend the right ventricle to physiologic
volumes. For small dogs (10 to 15 kg) the normal right
ventricular end-diastolic volumes are in the range of 30
to 40 ml.`2 We found that a substantial transmural
pressure of 4 to 9 mm Hg was required to distend the
right ventricle to a size of 20 to 40 ml. Thus, even in
the low volume range, we observed right ventricular
transmural pressures significantly different from zero.
Furthermore, the right ventricular pressure always increased as right ventricular volume increased. Thus the
right ventricle did not behave as unstressed ventricle.
These results are in agreement with those of other
experimental studies7' 'S' that directly examined ventricular interdependence and indirectly assessed right
ventricular pressure-volume relationship. The findings
showed positive transmural pressure and increasing
transmural pressure with increasing ventricular volume.
The findings of our study are in conflict with the
concept of an unstressed right ventricular and zero
transmural diastolic pressure.2'4',5 hy do the results
of our study conflict with the results reported by Smiseth, Tyberg, and associates, using the pericardial balloon to measure transmural pressure? First, their studies were performed in intact dogs, while our data were
obtained from excised hearts. We used this preparation
so that transmural right ventricular pressure could be
determined directly and right ventricular volume measured accurately. We do not believe that these experimental differences explain the conflicting results,
since fresh cardioplegic preserved hearts have preCIRCULATION
DIAGNOSTIC METHODS-PERICARDIAL DISEASE
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viously been shown to accurately reflect diastolic
properties of the intact heart.6 Furthermore, we excluded dogs with heart worms, whose right ventricles
may be abnormally stiff.
Another possible explanation for the difference in
our results and those obtained with the pericardial balloon is that the pericardial balloon overestimates pericardial pressure, thus underestimating right ventricular
transmural pressure. This might occur for several reasons. Under normal circumstances, with little pericardial fluid the pericardial cavity is a potential space
only a few microns thick. Thus the flat pericardial
balloon that is several hundred microns thick may
cause local distortion of the pericardial space. Based
on physical principles,16' 17 the flat balloons might systematically overestimate pericardial pressure, thereby
systematically underestimating transmural cavity pressure.
The calibration of the flat balloons is also a potential
problem since small variations in balloon volume may
greatly affect the recorded pressure.2 Tyberg et al.5
have minimized this problem by carefully calibrating
the balloons before and immediately after each experiment, using a special chamber. However, even with
pre- and postcalibration the recorded pressures may
still be uncertain because the fluid within the balloon
may be distributed unevenly during the experimental
procedure. This uneven distribution could cause measurement errors. Mann et al. 8 have recently measured
pericardial pressures using an air-filled balloon of a
different design. In agreement with our observations,
they found that right atrial pressure exceeded pericardial pressure by 2 to 7 mm Hg.
In summary, although the measurement of transmural pressure is important, calculation of transmural
pressure is complicated by the difficulties in measuring
pericardial pressure. The inadequacies of fluid-filled
catheters to measure pericardial pressure have been
clearly demonstrated. From flat balloon measurements, nearly identical pericardial and right ventricular diastolic pressure have been reported, suggesting
that right ventricular transmural pressure is near zero.
However, we found that a right ventricular transmural
pressure other than zero is needed to distend the right
ventricle to its normal size. This suggests that use of
the flat balloon may overestimate pericardial pressure
Vol. 75, No. 4, April 1987
and that right atrial pressure cannot be accurately substituted for pericardial pressure in determining left
ventricular transmural pressure. Since a fluid-filled
catheter is not adequate to measure pericardial pressure, further investigation into methods of determining
pericardial pressure is needed.
We thank Christy Butler and Joye Zafuto for their careful
preparation of this manuscript and Brad Trott for his technical
assistance.
References
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747
Direct assessment of right ventricular transmural pressure.
W P Santamore, M Constantinescu and W C Little
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Circulation. 1987;75:744-747
doi: 10.1161/01.CIR.75.4.744
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1987 American Heart Association, Inc. All rights reserved.
Print ISSN: 0009-7322. Online ISSN: 1524-4539
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