Download Is left ventricular volume during diastasis the real equilibrium volume

J Appl Physiol 105: 1012–1014, 2008;
doi:10.1152/japplphysiol.00799.2007.
Perspectives
VIEWPOINT
Is left ventricular volume during diastasis the real equilibrium volume,
and what is its relationship to diastolic suction?
Wei Zhang, Charles S. Chung, Leonid Shmuylovich, and Sándor J. Kovács
Cardiovascular Biophysics Laboratory, Cardiovascular Division, Washington University School of Medicine,
St. Louis, Missouri
Whatever role cardiac suction of venous blood may play in
determining circulatory dynamics, no one can deny that mention of this term (diastolic suction) has proven a most effective
method of raising blood pressure in several generations of
cardiovascular physiologists.
GA Brecher, 1958
Recent articles (31, 32) illustrate the challenge in providing
a self consistent definition of ventricular suction. Conceptually
different definitions are treated equivalently despite the fact
that they lead to disparate conclusions. We discuss various
definitions of suction, their physiological implications, and
propose a unifying concept based on an in vivo definition that
requires a new perspective on the meaning of diastolic equilibrium volume.
THE HISTORY OF DIASTOLIC SUCTION
The experimental observation of diastolic suction or “vis a
fronte” (a force acting from in front) dates back nearly 2
millennia to Galen, who concluded that the heart can fill itself
(26). However, controversy regarding diastolic suction (7) has
persisted. Brecher noted (5) experimental evidence of diastolic
suction by showing that excised beating animal hearts submerged in fluid draw fluid back into the ventricle after systole.
Numerous investigators have described similar events (2, 3, 8,
28 –30, 32), but quantification of diastolic suction had to wait
until the pioneering work of Louis Katz (17) in 1930.
Katz observed that in early diastole, turtle ventricular pressure (PLV) decreases simultaneously with increasing ventricular volume (VLV). This observation provided a conceptually
simple and elegant quantitative definition of ventricular diastolic suction, namely that diastolic suction is present when:
dP LV/dVLV ⬍ 0
(1)
This definition is a “relative” index, as it depends only on
intraventricular pressure and volume changes, and therefore is
independent of “absolute” ventricular pressures or volumes.
That dPLV/dVLV ⬍ 0 after mitral valve opening is well established (8, 29) and depends on the endocardium mechanically
recoiling faster than blood can fill the chamber, which has been
observed even in the developing zebrafish heart (9). Filling
involves more than the lumped “ventricular perspective” of
Address for reprint requests and other correspondence: S. J. Kovács,
Cardiovascular Biophysics Laboratory, Washington Univ. Medical Center,
660 South Euclid Ave Box 8086, St. Louis, MO 63110 (e-mail: sjk
@wuphys.wustl.edu).
1012
DIASTOLIC SUCTION, SUBATMOSPHERIC PRESSURE,
AND THE OPEN-CHEST EQUILIBRIUM VOLUME
While early diastolic intraventricular and atrioventricular
gradients causally guarantee LV generated diastolic suction,
alternative definitions regarding suction exist in both physiology and clinical echocardiography (31, 32). One alternative
definition stems from pioneering experimental work by Nikolic
et al. (21). They occluded the mitral valve at various filling
volumes and determined the minimum pressure reached by
fully relaxed canine ventricles in an open-chest, open-pericardial setting. They defined the development of subatmospheric
pressures as evidence of suction. Therefore suction exists only
when:
P LV ⬍ Patmospheric
(2)
The postocclusion asymptotic pressures were the fully relaxed chamber pressures for the particular volume at which
occlusion occurred. The lower the volume when the mitral
valve is occluded, the stronger the suction force is, as shown by
the more negative fully relaxed pressure. The asymptotic P-V
points generated a nonlinear relationship that was fit logarithmically (see Fig. 1). The occlusion volume, where the corresponding relaxed pressure was atmospheric, defined the openchest equilibrium volume (14, 15, 21, 27). Accordingly, ventricles achieving end-systolic volumes below this equilibrium
volume were defined as suction pumps.
While the experimental definition proposed by Nikolic is
widely accepted (10, 25, 28), others have also measured
equilibrium volume (20, 21, 27). In particular, the Patmospheric
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DEFINING SUCTION: A PERSISTENT PROBLEM
equation 1. However, when going beyond the “ventricular
perspective,” the source of filling must be considered with care,
because the atrium rather than the atmosphere represents the
source for filling, and flow requires generation of a pressure
gradient. During early-rapid ventricular filling the atrium is a
passive conduit and atrial pressure always decreases immediately after MVO. Therefore as LV pressure decreases below
atrial pressure inscribing the atrioventricular pressure gradient,
it accelerates flow into the chamber. Indeed, a consistent
definition of diastolic suction, incorporating the atrium, recognizes the role of atrioventricular gradients (1, 12, 18, 32). Since
all ventricles generate atrioventricular gradients in early diastole it follows that all ventricles must operate as suction pumps
in early diastole.
Perspectives
1013
DIASTASIS DEFINES VENTRICULAR EQUILIBRIUM
recoil (11, 24). Deactivation (cross-bridge uncoupling) unmasks stored elastic strain energy and leads to decreased elastic
wall stress, wall torsion, and ventricular chamber pressure (by
LaPlace’s law). Abnormal crossbridge deactivation, has been
associated with (clinically defined) delayed relaxation (16) and
has been shown to prevent the recoil (release of stored strain)
of myofibrils (24).
DIFFICULTIES WITH SUCTION RELATIVE
TO THE ATMOSPHERE
definition has been applied in the closed-chest, in vivo setting,
generating controversy regarding diastolic suction. Levine et al.
(20), defined diastolic suction by equation 2 and concluded that
intact closed-chest ventricles did not generate suction after bed
rest-associated atrophy because their end-systolic volumes
were higher than the equilibrium volume. Rankin et al. (25),
and others using the closed-chest measurements (10, 28),
concluded that in vivo hearts, in general, do not exhibit
diastolic suction. These conclusions are inconsistent with the
work of Katz. Thus, while it is proper to consider the volume
at which relaxed ventricular pressure is atmospheric in the
open-chest setting, in the in vivo closed-chest setting this
choice may be less applicable.
PHYSIOLOGIAL MECHANISMS RESPONSIBLE
FOR DIASTOLIC SUCTION
Irrespective of how diastolic suction and equilibrium volumes are defined in pressure-volume terms, there is general
agreement that the hypothesized causal mechanisms for ventricular diastolic suction are similar. All definitions assume that
ventricular recoil, and associated torsion as quantified by MRI
(6) is powered by stored elastic strain energy (18, 21, 30).
Recent experiments indicate that proteins such as titin, acting
as a bidirectional, linear spring, together with extracellular
matrix and microtubules, etc., play roles in generating elastic
J Appl Physiol • VOL
THE DISTINCTION BETWEEN A TRANSMURAL FORCE
BALANCE AND ZERO FORCE
It is appropriate to define diastolic suction as Nikolic and
others have, relative to an equilibrium volume, but this volume
must reflect a mechanical equilibrium. Despite the presence of
non-zero residual intramyocardial stress (23), all forces are
balanced and the chamber remains static (nonmoving) during
diastasis. In other words, mechanical and kinematic equilibrium is achieved when all residual forces and stresses (including pressure in the atrium, residual stress in the wall, etc.) are
balanced, rather than only when the transmural forces or
transmural pressure gradients are zero. This distinction is
physiologically realistic, it is unambiguous, and its consequences (static vs. moving) are easily discernable. Defining the
equilibrium volume of the ventricle as a state of mechanical
equilibrium, defined by a zero-motion (static) condition over a
finite time interval, rather than a zero-force condition, yields:
V eq ⬅ Vdiastasis
(3)
In analogy to the Nikolic et al. determinations of equilibrium
volume and suction, equation 3 implies the presence of diastolic suction only if the end-systolic volume (ESV) is below
the diastasis volume (equilibrium volume). In general, ESV is
always ⬍ diastatic volume and thus, because dP/dV ⬍ 0 as the
ventricle initiates filling (E-wave), our definition of equilibrium volume being the diastatic volume is consistent with
Katz’s definition of diastolic suction and is consistent with the
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Fig. 1. Experimental, open chest canine pressure-volume (P-V) data for
equilibrium volume determination using the pioneering mitral valve occluder
method of Nikolic et al. (21). In their study, the completion of suction initiated
filling, i.e., the transition from kinematics to statics defines the equilibrium
state. Solid line, normal pressure volume loop for one diastole. Points 1– 6
represent a sequence of fully relaxed left ventricular pressure (LVP) at variable
filling volumes, which were achieved via an electronically controlled mitral
valve occluder. The fully relaxed pressure and the corresponding volume (data
points 1–7) were fit logarithmically. Open-chest equilibrium volume (Veq) is
the intersection of the dashed (logarithmic) curve and the volume axis (pointed
out by arrow), and corresponds to the LV volume when the fully relaxed
LVP ⫽ 0. End systolic volume (VES) is also marked by arrow on the figure.
[Figure from (21), used with permission.] See text for details.
There are some issues with the application of the Patmospheric
definition (equation 2). To put these in context, we note that
that the absolute pressure (PLV ⬍ Patmospheric) condition uses a
presumption of zero transmural wall stress, where transmural
forces are balanced because the transmural pressure gradient
vanishes (2, 3, 5, 21, 28). However, in the closed-chest setting,
PLV ⬍ Patmospheric does not imply zero transmural pressure
gradient, since pericardial pressure is usually not atmospheric
(13). Finally, and most importantly, while the PLV ⬍ Patmospheric
definition assumes a zero wall stress state, Omens and Fung
(22) showed that fully relaxed ventricles, with zero transmural
pressure gradient, possess stored elastic strain. Therefore, the
zero transmural wall stress condition is unlikely to exist even
when the chamber is fully relaxed, and for transmural pressure
gradients to play a role in vivo, they must be great enough to
overcome the residual wall stress present.
One way to resolve the difficulties of defining suction
relative to atmospheric pressure is to adhere to Katz’s definition: a “relative” definition that remains applicable regardless
of atmospheric pressures, external pressure conditions such as
diving or high altitudes (4, 19), and experimental conditions
such as an open-chest preparation.
Perspectives
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DIASTASIS DEFINES VENTRICULAR EQUILIBRIUM
conclusion that diastolic suction is present when ESV ⱕ
equilibrium volume. In a temporal sense, abatement of the
dP/dV ⱕ 0 suction mechanism (release of stored elastic strain)
allows the chamber to settle down to its “equilibrium” or
force-balanced state. In our view, equation 3 is the functional
in vivo closed-chest equilibrium volume, because it defines an
easily discernible mechanical equilibrium, resolves (“relative”
vs. “absolute”) inconsistencies between various definitions,
and does not require a zero transmural pressure gradient.
CONCLUSIONS
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