Download Active myocyte shortening during the `isovolumetric relaxation

European Journal of Cardio-thoracic Surgery 29S (2006) S98—S106
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Active myocyte shortening during the ‘isovolumetric relaxation’
phase of diastole is responsible for ventricular suction;
‘systolic ventricular filling’
Gerald D. Buckberg a,b,c,*, Manuel Castellá b,c, Morteza Gharib a, Saleh Saleh d
b
a
Option on Bioengineering, California Institute of Technology, Pasadena, CA, USA
Department of Surgery, Division of Cardiothoracic Surgery, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue,
62-258 CHS, Los Angeles, CA 90095-1741, USA
c
Department of Cardiothoracic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
d
Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
Received 17 February 2006; accepted 27 February 2006
Abstract
Objective: To study the ‘isovolumetric relaxation’ phase of rapid ventricular filling by analysis of the shortening of cardiac muscle in the
endocardial and epicardial segments of the left ventricle in the dual helical model of the ventricular band, described by Torrent-Guasp. Methods:
In 10 pigs (27—82 kg), temporal shortening by sonomicrometer crystals was recorded while recording ECG, and measuring intraventricular
pressure and dP/dt with Millar pressure transducers. Results: The following sequence was observed; shortening began in descending or
endocardial segment, and 82 23 ms later it was initiated in the epicardial or ascending segment of the band. The descending segment stops
shortening during the rapid filling phase of fast descent of ventricular pressure, but the ascending segment shortening continues for 92 33 ms,
so that active shortening continues during the period of isovolumetric relaxation. During the rapid filling phase, dopamine decreased the interval
between completion of endocardial and termination of epicardial contraction from 92 20 to 33 8 ms. Conversely propranolol delayed the
start of epicardial shortening from 82 23 to 121 20 ms, and prolonged the duration of endocardial contraction, causing a closer (21 5 ms vs
92 20 ms) interval between termination of contraction of endocardial and epicardial fibers. The resultant slope of the rapid descent of the left
ventricular pressure curve became prolonged. Conclusions: These time sequences show that ongoing unopposed ascending segment shortening
occurs during the phase of rapid fall of ventricular pressure. These active shortening phases respond to positive and negative inotropic
stimulation, and indicate the classic concept of ‘isovolumetric relaxation’, IVR, must be reconsidered, and the new term ‘isovolumetric
contraction’, IVC, or systolic ventricular filing may be used.
# 2006 Elsevier B.V. All rights reserved.
Keywords: Isovolumetric relaxation; Isovolumetric contraction; Helical heart; Ventricular myocardial band; Systolic ventricular filling
1. Introduction
In the classical interpretation of the cardiac cycle, ejection
of blood follows myocardial contraction and subsequent
ventricular constriction. The resulting decrease in ventricular
luminal volume raises intraventricular pressure (isovolumic
contraction) which eventually opens the aortic valve. The time
interval over which the ventricular pressure increases, from
opening of the aortic valve until maximum pressure (about
120 mmHg) is reached, is about 140 ms [1]. Similarly, diastole
is comprised of an isovolumetric period characterized by a fast
* Corresponding author. Address: Department of Surgery, Division of Cardiothoracic Surgery, David Geffen School of Medicine at UCLA, 10833 Le Conte
Avenue, 62-258 CHS, Los Angeles, CA 90095-1741, USA. Tel.: +1 310 206 1027;
fax: +1 310 825 5895.
E-mail address: [email protected] (G.D. Buckberg).
1010-7940/$ — see front matter # 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.ejcts.2006.02.043
fall in ventricular pressure (from 120 mmHg to near zero after
mitral valve opening) followed by a rapid filling phase when
atrial blood is sucked into the lower pressure, relaxing
ventricle. The time interval over which this pressure drop
occurs is approximately 120 ms in the normal human heart.
Remarkably, a convincing mechanism responsible for the
precipitous fall in ventricular volume, and its subsequent
rapid filling phase, is still missing. The rapidity with which
pressure drops to its final value (15—20% of the entire
diastolic phase) has perplexed many investigators. The
prevailing clinical definition of diastole associates it with
the relaxation of the entire myocardium. However, the time
scale of the ventricular isovolumetric pressure drop phase is
comparable to the time scale of myocardial contraction and
left ventricle contraction phase during systole. This time
scale gets even shorter as we look at animals with higher
heart beat rates. If an active ‘suction-producing’ mechanism
G.D. Buckberg et al. / European Journal of Cardio-thoracic Surgery 29S (2006) S98—S106
does not exist it is difficult to attribute the rapid fall of
ventricular pressure to pure isovolumetric relaxation.
To address the issue of time scale in the heart beat cycle,
some researchers suggest that active diastole is accomplished through the elastic recoil of surrounding connective
tissues [2—4]. This hypothesis has served as the impetus for
numerous studies investigating the elastic properties of
connective tissues, specifically as it pertains to release of
energy stored by the preceding systolic phase. One such
investigation attributes the rapid recoil to a network of
collagen containing elements of elastin [4,5]. To the best of
our knowledge, there is no conclusive data that can testify to
the existence of these elusive elastic properties of collagen
or other connective tissues.
Titin, a recently described protein myofilament, is
thought to deform and provide some of the restoring force
to the sarcomere [6,7]. Experiments indicate that the elastic
response time (the time it takes to produce the relaxed
length of sarcomere) of titin is too long to match the 120 ms
duration of the isovolumetric period during which the
ventricular pressure drops to 85% of its diastolic value.
Recent work [8] in rat cardiac myocytes suggests that titin
plays a role in determining passive tension. It appears that
titin may be an important viscoelastic stiffness element
rather than a spring element in the sarcomere.
We will discuss the significance of contraction by a helical
fiber band during the isovolumetric phase that follows
ventricular ejection, as viable alternative element with
spring-like activity on the micro-scale, that can generate the
heretofore unexplained ventricular pressure drop. A contractile element in the rapid filling phase during early
diastole is suggested since ‘ventricular relaxation’ is an
active, energy consuming cellular event with calcium uptake
[5,4,9]. However, the existence of such a contracting
element is counterintuitive in the sense that its contracting
action (like any contracting element) should only result in the
shortening of some linear dimension and subsequently in an
increase of pressure or decrease of volume bounded by such
contracting elements. Because of this misconception, the
field of cardiac mechanics has directed their research
activities away from searching for such active contractile
element.
A central question is whether the contraction of the
muscle could decrease the ventricular pressure. The answer
to this question can be found in many biological systems
such as Nematode worms and Squid mantle where contraction of muscle fiber bands can facilitate locomotion by
increasing or decreasing the volume that they bound [10]. It
is intriguing to know that if a beating rat heart is placed in a
saline bath, the heart continues to beat and it jets rapidly
similar to that of squid through the fluid. Fluid is forcefully
expelled through the great vessels during systole and is
sucked into the ventricle during the diastole [11]. This
observation indicates that a negative and positive wall
pressure has been exerted on the ventricular volume during
systole and diastole, respectively, thus indicating that an
active muscle like dynamics is at work both in systole and
diastole of mammalian heart. Cowey [10] showed that the
trick is in the helical arrangement of muscle fiber bands
where by a proper arrangement of fiber bands either volume
decrease or increase can be achieved through the contrac-
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tion of a helically shaped single muscle band that bounds the
said volume in a figure-of-eight configuration. It is interesting
to note that in an isovolumetric situation the tendency to
increase volume will result in an active reduction of pressure
in the volume. Brecher showed a suction component in
isolated heart experiments [12,13].
Our studies will apply the dual helical model of the
ventricular band, described by Torrent-Guasp [14,15], and
use sonomicrometer studies to identify and investigate the
interface of contraction between the descending (endocardial) and ascending (epicardial) segments of the apical
ventricular loop, to extend this structural concept to the
physiologic explanation of active diastole in the working
helical myocardial band [16—18]. Pharmacologic alterations
in contractility between these dual segments of the helix will
be tested with the positive and negative inotropic influence
of dopamine and propranolol. If valid, this contraction
related production of suction will change the concept of
‘isovolumetric relaxation’ into one of ‘isovolumetric contraction’, or systolic ventricular filling [19] and thereby
introduce a novel mechanism for the generation of the rapid
filling phase after ventricular ejection in normal hearts.
2. Material and methods
All animals received humane care in compliance with the
‘Principles of Laboratory Animal Care’ formulated by the
Institute of Laboratory Animal Resources and the ‘Guide for
the Care and Use of Laboratory’ prepared by the National
Institutes of Health (NIH Publication no. 86-23, revised
1985).
Ten Yorkshire-Duroc pigs (27—82 kg) were premedicated
(ketamine 15 mg/kg, diazepam 0.5 mg/kg intramuscularly)
and anesthetized with inhaled isoflurane 1.5% (MAC 1%)
throughout the operation. Support with a volume-controlled
ventilator (Servo 900C, Siemens-Elema, Sweden) was started
after tracheostomy and endotracheal intubation. The
femoral artery and vein were cannulated and arterial blood
gases measured to keep oxygen tension, carbon dioxide
tension, and pH values within the normal range. A balloontipped catheter (Model 132F5, Baxter Healthcare Corp.,
Irvine, CA) was advanced into the pulmonary artery through a
jugular vein to measure cardiac output (thermodilution
technique) and pulmonary artery pressure.
The pericardium was incised after median sternotomy and
a solid-state pressure transducer-tipped catheter (Model
MPC-500, Millar Instruments, Inc., Houston, TX) was inserted
through the apex to monitor left ventricular pressure (LVP).
Regional contractility within the right and left ventricle was
measured with pairs of 2 mm ultrasonic microtransducer
crystals (Sonometrics, London, Ont., Canada). Each pair of
crystals was oriented in order to measure contractility at
certain myocardial depth and orientation. The placement
position of each crystal was made by using a 1 mm cut of the
epicardium and introduction of the crystal to reach the depth
selected. In the left ventricle two depths were chosen,
endocardial, where the crystals were positioned transmurally
to reach the inner surface via the ventricular cavity, or
subepicardial, by insertion 1 mm deep into the ventricular
muscle. In the left and right ventricle, crystals were
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positioned in the posterior free wall above the coronary
sunus, and laterally by the atrioventricular groove.
Aortic pressure, LVP, dP/dt, and sonomicrometer crystals
data were digitally processed by specific hardware and
software (Sonometrics, London, Ont., Canada). Velocity of
sound through cardiac tissue was fixed to 1590 m/s.
Sonomicrometer measurements were recorded with a
sampling rate of 95.8 samples/s, a transmitter spacing of
652 ms, transmit inhibit delay of 1.81 ms, and transmit pulse
length of 375 ms. Synchronicity between myocardial contractility was compared to left ventricular performance with
1 ms precision, by real time plotting and processing of
segment shortening, EKG, LVP and dP/dt. Sequence of
contraction of different segments of the heart was then
established and compared with ventricular hemodynamics.
All cases were performed and analyzed by the same surgeon.
3. Experimental protocol
The insertion of pairs of sonomicrometer crystals in
different positions/depth, allowed the extent of segment
shortening to be measured in the anterior wall of the left
ventricle, recording the dimension angle of contraction and
myocardial depth.
Segmental shortening was calculated as follows:
100 ðEDL ESLÞ
EDL
where EDL and ESL are end diastolic and end systolic length,
respectively.
The pattern of orientation is described in the next section.
This dimension (angle of highest contractility relative to the
long axis of the heart) was registered for both endocardial
and subepicardial contraction, and compared with synchronized EKG, LVP and dP/dt. These measurements were
compared in real time with different pharmacologic changes
of regional contractility, and position sites in the left and
right ventricle.
Fig. 1. (a) Progressive unscrolling of left ventricle in comparison with underlying rope-like model. These figures unfold the horizontal basal loop. Note (A)
the intact heart, (B) detachment of the right ventricle free wall or transverse
orientation of basal segment. A genu adjacent to the septum separates right
and left ventricles, (C) the detached apical loop with segment showing (left
side) on right ventricle, and (right side) left ventricle to complete basal loop.
(b) Continued unscrolling. These images unfold the oblique apical loop. Note
(D) unfolding of the trigone to pull the pulmonary artery laterally and
demonstrate the descending segment of apical loop and overlying ascending
segment containing the aorta. (E) Unwrapping of the helix formed by the
transverse muscle band to show unfolding of the descending segment, with
trigone removed and (F) the complete transverse myocardial band, with the
central muscle fold to separate the basal and apical loops. The left segment is
the transverse basal loop, the right segment is the apical loop. Note that,
before this folding, both segments have transverse muscle orientation. The
oblique orientation of the descending and ascending segments derive from the
architectural folding initiated by the spiral within transverse band, between
the basal and apical loops.
define the external principal direction trajectories of
oblique muscle mass thought to comprise the architectural
scaffold.
4. Crystal orientation
Torrent-Guasp’s model of the helical heart is presented in
Fig. 1a and b, that includes the cardiac structures that produce
two simple loops that start at the pulmonary artery and end
in the aorta. These two components include a horizontal
basal loop, comprised of right and left segments that surround the right and left ventricles that changes direction to
form an oblique dual apical loop. This change develops through
a spiral fold in the ventricular band to cause a dual ventricular
helix produced by now obliquely oriented fibers, forming
an endocardial or descending and epicardial or ascending
segment of the apical loop with an apical vortex.
The sonomicrometer crystals were placed into the intact
heart, to test any relationship between sequential temporal
and mechanical extent of fiber shortening between couples
of crystals to model shape and timing. Their orientation
was nested within the principal pathways comprising the
suggested rope like arrangement of the helical heart, in
concert with the patterns described previously [18,20] that
5. Results
5.1. Anterior wall of the left ventricle
The extent of contraction of the anterior wall of the left
ventricle results in larger displacement of the crystals, and
thus in a steeper slope in the endocardial side of the
myocardium than in the epicardial one (Fig. 2). The onset of
contraction at this anterior wall myocardial depth precedes
the systolic rise of LVP and dP/dt, and occurred between the
Q and R waves of the EKG (Fig. 3). Subendocardial muscle
shows two distinct rates as it shortens. First, a short and
steep descent followed by a longer and less steep contraction
phase. A notch was present on this curve, and divided these
phases. In normal hearts, the end of endocardial contraction
consistently coincided with the beginning the descent phase
of the left ventricular pressure, which is also coincided with
the appearance of the negative slope of dP/dt (Fig. 2).
G.D. Buckberg et al. / European Journal of Cardio-thoracic Surgery 29S (2006) S98—S106
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Fig. 2. Different segment shortening tracings of the endocardial and epicardial sites of the anterolateral left ventricle. These sites conform to: (A) The model (upper
tracing) and intact ventricle (lower tracing) with position of sonomicrometer crystals. The descending segment is deep, with hatched lines, whereas the ascending
segment is superficial (solid line). (B) The simultaneous recording of descending segment and ascending segment contractions, left ventricular pressure and dP/dt
from the pressure tracing. Note the delayed start of ascending segment contraction (first dotted line), and its termination after descending segment stopped (second
dotted line). The longitudinal lines show the start contraction of descending segment, the start contraction of ascending segment, the stop contraction of descending
segment, and the stop contraction of ascending segment.
Subepicardial contraction averaged 12 2% segment
shortening, when the angle of cystal placement was oriented
at 150 10%, and placed approximately 608 opposite
endocardial placement. Subepicardial segment shortening
followed contraction of the subendocardial muscle by
82 23 ms, starting at the maximum of height of dP/dt,
and finishing 90 20 ms after subendocardial contraction’s
end, towards the end of the negative wave of dP/dt (Fig. 2).
The force or extent of contraction was more intense
towards the apex in both the endocardial and epicardial
sides of the left ventricle (Fig. 4). This reflected an
anisotropic contractile effort as we compared basal and
apical segment shortening. For example, basal contraction
averaged 35 5% less than apical contraction, and this
conical difference was consistent for both the endocardial
and the epicardial muscle.
5.2. Sequence of contraction
Fig. 3. Comparison of simultaneous recording of tracings from the descending
and ascending segments of the apical loop, left ventricular pressure (LVP), the
electrocardiogram (EKG) and dP/dt analysis of LVP from recordings from Millar
catheters.
Contraction starts initially in the endocardial side of the
antero-septal wall of the left ventricle. The initiation of this
early contraction corresponded with the Q wave of the EKG
and LVP rose, but did not have rapid acceleration, as pressure
generation remained below 15 mmHg. The contraction of the
anterior wall endocardial segments began before contraction
of the rest of the myocardium produced a rapid acceleration
or ascent in ventricular pressure recording, rising to exceed
aortic diastolic pressure. The early steep slope of segmental
shortening of the endocardial regions (Fig. 2) occurred while
there was no contraction detected in the subepicardial sites
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Fig. 4. Sequential shortening of the LV endocardial muscle, showing the anisotropic recording, with more forceful contraction, as the sites of the crystal pairs are
moved toward the apex.
of the segments, located in the subepicardial anterior wall of
the left ventricle. Contraction at epicardial segments began
84 10 ms after the initial muscle contraction (the endocardial wall of the left ventricle), and corresponded to the
peak of the positive dP/dt wave, the S wave on the QRS
complex of the EKG signal (Fig. 2), and most importantly, the
steep rise (equivalent to the peak dP/dt) in left ventricular
pressure for ejection of blood. For the rest of systole during
ejection, contraction was present in all segments of the heart
resulting in ‘co-contraction’ of both endocardial and
epicardial fibers. The initiation of contraction in the
subepicardial fibers, was maximal in a 908 opposite direction
from endocardial ones, and coincided with a reduction of the
slope of contraction of the subendocardial fibers (Fig. 2).
The termination of active contraction in the LV anterior
wall was different in subendocardial and subepicardial
segments, thereby producing a disassociation between the
absence of contraction in endocardial fibers, during ongoing
active contraction in epicardial fibers, as shown in Fig. 2. The
first regions to stop shortening were the segments that
started first, located in the endocardial side of the anteroseptal left ventricle wall. The end of endocardial contraction
coincided with the end of the flat peak component values in
the left ventricular pressure tracing, corresponding with the
start of the negative wave of dP/dt. Simultaneously,
contraction persisted in the epicardial component of left
anterior wall These segments finished their contraction phase
92 20 ms after that of the RV free wall, posterior LV, and
endocardial LV segments.
A linking of velocity of left ventricular pressure descent
followed this dissociation between ongoing contraction of
subepicardial segment, and stoppage of contraction in the
subendocardial segment: this time interval corresponded to
the LV tracing recording the previously termed isovolumetric
relaxation. During absent contraction of endocardial regions
LV pressure deceleration rate was maximal as active shortening of the epicardial fibers persisted as shown in Fig. 2.
Analysis of the pressure recordings, coupled with
simultaneous analysis of regional recordings of contraction
in endocardial and epicardial, left ventricular segments,
shows a linkage between the acceleration and deceleration
phases of developed pressure (i.e. the slope velocity of the
pressure recording) and regions of contraction. During the
initial rapid acceleration, or isovolumetric contraction of left
ventricular pressure, all segments shortened simultaneously,
whereas, during the later deceleration of LV pressure, only
the subepicardial segment was actively shortening. The slope
of the rapid fall in ventricular pressure corresponded closely
with the dissociation between termination of contraction in
the endocardial muscle, and ongoing contraction of the
epicardial muscle (Fig. 2). Consequently, a systolic shortening phase persisted throughout the entire LV pressure
recording, including during the phases of rapid acceleration
and deceleration of ventricular pressure, so that there was no
interval of isovolumetric relaxation.
These persistent contractions in the anterior wall
epicardial fibers during the cessation of endocardial shortening was associated with a reversal, or upward slope of the
endocardial crystal tracing as shown in Fig. 2. This separation
or widening between crystals reached the point of maximum
fiber stretch (i.e., separation between crystals), only
surpassed by the added stretch due to ventricular filling by
atrial contraction.
The link between the delay of the contraction between
endocardial and epicardial segments was evaluated by
intravenous infusions of inotropic drugs or b-blocker therapy
(Fig. 5). The delay between the start of contraction in
endocardial and epicardial muscle of the anterior wall of the
left ventricle decreased to 26 7 ms with dopamine infusion
at 10 mg/kg/min. Simultaneously the extent of shortening
increased from 25.7 to 29.1% in the endocardial wall, and
heart rate rose from 88 to 112 beats per minute to confirm
the inotropic and chronotropic catecholamine effect. The
time interval between completion of endocardial and
termination of epicardial contraction was shortened from
92 20 to 33 8 ms. Conversely, propranolol therapy
prolonged the delay between initiation of contraction in
endocardial, and epicardial segments to 121 20 ms,
reduced the extent of shortening to 19%, and slowed heart
rate to 78 beats per minute to define its negative inotropic
effect.
This propanalol induced pharmacologic prolongation of
the duration of separation between the onset of contraction
between the endocardial and epicardial segments at the
origin of contraction, was also associated with a prolongation
of the duration of the endocardial contraction. Thus, the
G.D. Buckberg et al. / European Journal of Cardio-thoracic Surgery 29S (2006) S98—S106
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Fig. 5. Sequence of contraction of different segments during a study in one subject during basal conditions (left) and with dopamine (middle) or propranolol infusión
(right). Black and hatched lines mark the start and end of shortening of endocardial and epicardial muscle, respectively. There is a delay between start of the
endocardial and the epicardial myocardium of the anterior wall, that decreases with dopamine from 84 10 to 26 7 ms and increases with propranolol to
121 20 ms. The termination of endocardial shortening is reduced by dopamine, but prolonged with propranolol to (a) narrow the separation during baseline, and (b)
flatten the slope of descent of the LV pressure tracing.
interval or hiatus of separation shortened between the end of
endocardial contraction with ongoing epicardial contraction
was shortened. Compared to control, termination of
contraction of endocardial and epicardial fibers occurred
at a closer (21 5 ms vs 92 20 ms) interval. This is in
contrast to the prolongation that existed at the time of rapid
ascent of the left ventricular pressure curve, while the
resultant slope of the rapid descent of the left ventricular
pressure curve became prolonged.
6. Discussion
The concept of active diastole remains one of the
fundamental challenges of the modern understanding of
cardiac function. The early phase of diastole is known to be
an energy consuming process accompanied with calcium
uptake [9]. This aspect of early cardiac diastole does not fit to
the prevailing concept of recoil due to the release of elastic
energy by some passive elements of myocine such as titin or
connective tissues such as collagen [7,8,11]. These elements
are not known to consume energy or have a need for calcium
to function. In addition, these passive elements by their
nature are incapable of providing the short time scale that is
needed to explain the rapid fall of pressure in the early stages
of diastole. In this respect, our approach in resolving this
dilemma was to shift the emphasis in search for an element
that can provide a mechanism for recoil from these passive
elements to the cardiac muscles where a global rather than
local process could explain the early phases of diastole.
However, in order to prove that cardiac muscle may play an
active role during diastolic phase, we needed to search and
find an element of cardiac muscle that remains activated
(contracting) during the so-called ‘relaxation’ phase.
The next challenge was to have a model of cardiac
structure that can have a use for this contracting element to
correctly predict the nature of the cardiac function during
the diastolic phase. Perhaps the most challenging aspect of
our experimental approach, in order to avoid blind searches,
was to design a model driven intelligent search strategy. In
this regard, we adopted the helical fiber band model of
Torrent-Guasp as a guide to start our search strategy. This
model adheres to previous recognition of helical features of
endocardial and epicardial muscle fibers. In addition, it
treats these bands as the connected elements of an
integrated double helical structure: a feature that was not
recognized by the previous investigators in this field. The
most important contractile aspect of this model as has been
described and documented by Buckberg et al. [16—18] is in its
ability to provide a preferential pathway for the maximum
shortening of muscle bands along their principle direction.
Therefore, a search strategy could be devised in order to find
locations and orientation in muscle band that present such
maximal contractual displacement.
In our studies, we used sonomicrometer crystals with
high temporal and spatial resolution [21] to determine the
timing and principle axis of contraction. The maximum
extent of shortening between crystal probes was used as a
criteria to identify the principal fiber pathway orientation
suggested by Torrent-Guasp’s helical heart model [14,15].
We explored the relationship of how these two-dimensional
devices could identify function in the underlying threedimensional muscle.
The crystal dimension gauges provide a local view of a
global concept, exploring all cardiac regions. These local
barometers do not measure either thickening [21—23],
twisting [24], torsion [3], cross fiber shearing forces
[21,22,25] or inception of the calcium trigger of contraction
[5,4]. We recognize these local shortening measurements are
influenced by the overlying cross fiber strain and shearing
forces of the inner and outer halves of the ventricular wall,
thus, in general, they do reflect the deformation influence
from neighboring fibers. Consequently, each change in time
related regional function is comprised of how threedimensional spatial architecture alters function within the
ventricular wall.
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Distinction between each of the varied factors that
influence the term ‘contractility’ is not the intent of this
manuscript, since no effort was made to measure deformation [26,23], as it influences strain of the cross fiber or
transmural shearing forces [22] that may result in a motion
that may not be aligned with local myofibers. Therefore, we
employed the hypothesis that orientation that renders the
maximal contraction are least influenced by the dynamics of
neighboring structures. Consequently, despite the limitations
of the crystals used for sonomicrometric measurements,
these local records take maximal advantage of their
temporal and spatial resolution.
Perhaps one of the astonishing aspects of our reported
crystal studies is the discovery of a period of the contraction
during a time period that previously was termed isovolumetric relaxation. The segment of the heart that showed this
unexpected continuous contraction was aligned with what
Torrent-Guasp identifies as the epicardial ascending segment. This finding also confirms that the systolic contraction
exists both during the phase of ejection, and during the time
related period previously termed isovolumetric relaxation.
This interval coincides with the rapid drop of ventricular
pressure thought previously to reflect elastic recoil related
to potential energy stored during the systolic contraction
[2,27]. This muscle continues to shorten beyond the end
contraction phase of the endocardial muscle forming the
descending segment. This finding clearly indicates that the
notion of ‘an entire relaxed heart’ during the early diastolic
phase is flawed. In addition, one cannot overlook the distinct
possibility that the ongoing contraction of the epicardial
muscle which forms the ascending segment is the key process
in providing an active diastole through reciprocal untwisting
of the heart.
It is important to mention that this contraction is most
evident when crystal pair orientation were optimized to show
the maximum negative displacement. Therefore, it was easy
to miss this period if care was not given to optimize the
orientation of crystals while searching for the principle
orientation of the fiber bands [20]. This fact may explain why
so many other investigators missed the opportunity to detect
this phenomena.
This active contractile role was also suggested by Shapiro
and Rademakers [27] by MRI studies, defining that 50% of
filling develops during this time frame, and accentuation of
speed and rate untwisting (or reciprocal twisting in a reverse
direction) for rapid filling can be made by inotropic drug
infusion. Elastic recoil, rather than contraction was thought
to be the responsible factor. Brutsaert [5,4,9] further
amended the infrastructure for rapid filling by a observing
a prolonged contractile phase of systole. Our findings tested
this concept with sonomicrometer crystals, and characterized the role of calcium dynamics in this process by infusion
with dopamine or propranolol. We did not measure calcium,
but rather defined how modulation of calcium flux with either
positive or negative inotropic influences by infusión of these
agents influenced the linkage of the initiation and completion
of contraction of these endocardial and epicardial (or
descending and ascending segments) of the dual helical band.
The mechanism of reciprocal twisting for suction relates
to the ongoing contraction of the ascending segment, that
persists as the only functional component of the apical loop
following the cessation of descending segment shortening.
This sequence is shown in Fig. 2, which documents (a) coshortening of the descending and ascending segments during
ejection, and (b) prolongation of ascending segment shortening after completion of descending segment shortening.
The twisting pattern shown by MRI [27] involves a
predominantly counterclockwise twist during ejection and
subsequently a clockwise twist during suction [28].
The proposed helical heart contributions to these events
include first, a co-shortening of both descending and
ascending segments during ejection, with each segment
twisting in a different direction. The descending segment is
the dominant force to account for the counterclockwise twist
and global shortening as seen by echo or MRI during ejection
[29]. Second, the ongoing predominantly clockwise twist of
the ascending segment (already in action during ejection)
now becomes unopposed due to the cessation of descending
segment shortening. The resultant cardiac motion from this
torsion and reciprocal twisting is the rapid global lengthening
observed during the active suction phase by MRI or
echocardiogram [29].
The positive inotropic effect of dopamine shortened the
interval between initiation and termination of shortening in
these segments, raised the extent of shortening, and these
sonometric recordings are consistent with the more rapid
filling reported by Rademakers on MRI scanning, with an
increase from 50 to 60% by MRI recordings [2]. Dobutamine
similarly enhances restoring forces, and Bell [30] ascribed
this suction to contraction to a smaller volume. Their recent
study focuses upon untwisting responsible for elastic recoil,
with possible deformation of ‘springs’ that are related to titin
as the cause. This concept considers deformation of
extracellular matrix with collagen as the suggested mechanism. Our findings of active contraction contradict the prior
prevailing opinión of rapid elastic recoil as the responsible
element. We have recently also focused upon ‘springs’ [16],
but think they relate to deformation of the internal muscle
springs conforming to the helical spiral within the descending
and ascending segments of the apical loop [16,18] a ‘coil
within coil’ formation may exist in the dual helical heart
model. Fig. 6 shows the muscular band within the spatial
configuration described by Torrent-Guasp.
The negative inotropic effect of propranolol, aside from
reducing pressure and heart rate, widened the onset of
contraction of the epicardium versus the contraction of the
endocardium to thereby slow ejection (Fig. 5). Simultaneously,
it produced narrowing of the interval for rapid filling, by
decreasing the time frame for otherwise unbridled epicardial
contraction while the descending segment muscle was not
contracting. The result was a delay or prolongation of the
downslope of LV pressure and less negative dP/dt. Clearly,
further prolongation of the stoppage of the endocardial
contraction relative to the ongoing epicardial shortening will
increasingly compromise the contractile forces responsible for
rapid filling and derail the mechanisms for suction, so that
pressure, rather that muscle motion now becomes the
principal filling determinant. The consequence is that these
tracings introduce a contractile mechanism that both
contributes to suction filling in the normal heart, and more
importantly implies that when this action becomes disrupted,
a contractile cause for diastolic dysfunction may prevail.
G.D. Buckberg et al. / European Journal of Cardio-thoracic Surgery 29S (2006) S98—S106
Fig. 6. This double external spiral arrangement reflects the descending and
ascending segments of the apical loop interact for ejection and suction. The
‘springs’ are placed internally, to show the proper fiber orientation of the
descending and ascending segments of the helical apical loop. The upper image
shows the basal loop with horizontal right and left segments surrounding the
apical loop with oblique fibers. This double spiral arrangement is amplified in
the lower tracings of the apical loop, colored white, that reflects how the
descending and ascending segments of the apical loop interact for ejection and
suction. These segments are in repose in diastole in (a). Note that, in (b),
during the initiation of ejection, the descending loop becomes dominant and
shortens from base to apex, while this motion may stretch the ascending
segment. The later contraction of the ascending segment causes ‘co-contraction’ during systole. The descending segment stops shortening before the
ascending segment, whose ongoing contraction will lengthen the chamber in
(c). However, the non-contracting descending segment stops and retains
tension to act as a fulcrum for lengthening.
Evidence for this prolongation of late systole in hearts
with diastolic dysfunction is evident in studies of stunning
after ischemia [31], hypertrophy during aortic stenosis [32],
post transplant dilatation [33], and tachycardia induced
cardiomyopathy [34,7]. Our findings show that this is an
active phenomenon, related to loss of the critical gap
between completion of shortening in the endocardial region,
and ongoing contraction of the epicardial or ascending
segment. Such recognition may give rise to using pharmacologic agents that favorably alter calcium flux, either in Na/
H exchange inhibitor distribution [35], calcium sensitization
without inotropic drugs [36] or other manipulation of systolic
factors, since a contractile process now compromises the
rapid filling period.
These results imply that the concept of ‘isovolumetric
relaxation’ must be discarded, and replaced by the concept
of ‘isovolumetric contraction’ or systolic ventricular filling
[19] as the basis of rapid filling in the normal heart, and more
importantly may introduce a innovative pharmacologic
means to deal with diastolic dysfunction that is generated
by disruption of this normal contractile element.
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