Vol. 274, Issue 2, H552-H563, February 1998
Mitral valve opening in the ovine heart
Matts O.
Karlsson1,2,
Julie R.
Glasson3,
Ann F.
Bolger4,6,
George T.
Daughters1,3,
Masashi
Komeda3,
Linda E.
Foppiano5,
D. Craig
Miller3,6
Neil B.
Ingels Jr.1,3
(With the Technical
Assistance of Carol W. Mead, Mary K. Zasio, Erin M. Schultz, and
Terrence Tye)
1 Department of Cardiovascular
Physiology and Biophysics, Research Institute, Palo Alto Medical
Foundation, Palo Alto, California 94301;
2 Department of Mechanical
Engineering, Linköping University, S-581 83 Linköping,
Sweden; Departments of
3 Cardiothoracic Surgery,
4 Cardiovascular Medicine, and
5 Anesthesia, Stanford University
School of Medicine, Stanford 94305; and
6 Cardiac Surgery and Cardiology
Sections, Department of Veterans Affairs Medical Center, Palo Alto,
California 94304
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ABSTRACT |
To study the three-dimensional size, shape, and
motion of the mitral leaflets and annulus, we surgically attached
radiopaque markers to sites on the mitral annulus and leaflets in seven
sheep. After 8 days of recovery, the animals were sedated, and
three-dimensional marker positions were measured by computer analysis
of biplane videofluorograms (60/s). We found that the oval mitral
annulus became most elliptical in middiastole. Both leaflets began to descend into the left ventricle (LV) during the rapid fall of LV
pressure (LVP), before leaflet edge separation. The anterior leaflet
exhibited a compound curvature in systole and maintained this shape
during opening. The central cusp of the posterior leaflet was curved
slightly concave to the LV during opening. Markers at the border of the
"rough zone" were separated by 10 mm during systole. We conclude
that coaptation occurs very near the leaflet edges, that the annulus
and leaflets move toward their open positions during the rapid fall of
LVP, and that leaflet edge separation, the last event in the opening
sequence, occurs near the time of minimum LVP.
leaflets; annulus; radiopaque markers; coaptation; sheep
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INTRODUCTION |
THE MITRAL VALVE takes <100 ms during each cardiac
cycle to transform from a tightly closed configuration capable of
withstanding high left ventricular (LV) systolic pressure to a widely
open configuration permitting almost explosive early LV diastolic
filling. Long a subject of interest, the function of the mitral valve
and its relationship to the chordae tendinae were recognized by
Erasistratus a century after its anatomic description by Hippocrates
(ca. 400 BC). Eighteen centuries later, Vesalius (32) provided its
modern name, likening it to an episcopal miter.
Interest in the mitral valve intensified in the 20th century with the
development of new technology and new techniques for medical and
surgical treatment of valvular disease (34). Beginning 40 years ago,
single-plane and biplane radiographic techniques were used to study the
dynamics of radiopaque markers affixed to the valve annulus and
leaflets (19, 22, 27-30) and contrast material adherent to the
posterior leaflet (25). Subsequent echocardiographic studies made major
contributions to our understanding of mitral valvular function (6,
12-14, 18, 19). Recent developments in magnetic resonance imaging
promise to increase this fund of knowledge markedly (34).
Despite such extensive attention, however, no data are available
concerning the instantaneous three-dimensional dynamics of specific,
fixed sites in the mitral valvular annulus and leaflets throughout the
cardiac cycle. Here, we provide such data describing the dynamics of
mitral valve opening derived from biplane radiographic techniques
developed in our laboratories (9). The ovine heart was chosen for study
because of its anatomic similarity to the human heart (33) and its
highly consistent, reproducible anatomy, function, and patterns of
dysfunction (15).
We describe our findings that, before leaflet separation, the central
portion of the anterior leaflet of the closed mitral valve assumed a
compound shape, the posterior leaflet was slightly concave to the LV,
and the mitral annulus was oval and nearly planar. Mitral valve opening
began with an annular shape change at the time when LV pressure (LVP)
had just begun to fall from systolic levels. The opening process
continued with leaflet and annulus shape changes during the rapid fall
of LVP, the leaflet edges still apposed, and the valve still sealed.
Finally, both leaflet edges moved rapidly into the LV cavity, creating
a widely open mitral orifice.
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METHODS |
Surgical preparation.
Seven healthy adult male sheep (63 ± 9 kg) were
premedicated with ketamine (27 mg/kg im) and atropine sulfate (0.05 mg/kg iv) and anesthetized with thiopental sodium (6.8 mg/kg iv),
intubated, and placed on artificial ventilation (Servo Anesthesia
Ventilator, Siemens-Elema, Solna, Sweden). An orogastric tube was
placed on intermittent suction. General anesthesia was maintained with
inhalational isoflurane (1-2.2%) and supplemental oxygen. Single
doses of cefazolin sodium (1 g iv) and gentamicin sulfate (80 mg iv)
were given preoperatively, and antibiotic therapy was continued
throughout the postoperative period (1 g of cefazolin sodium
iv every 4 h and 80 mg of gentamicin sulfate iv every 8 h). By use of
sterile technique, an incision was made in the left neck, exposing the
jugular vein and carotid artery for catheterization. A
micromanometer-tipped pressure transducer (model MPC-500, Millar
Instruments, Houston, TX) was zeroed in a water bath and inserted into
the left carotid artery to monitor systemic arterial pressure. A left
thoracotomy was performed through the fifth intercostal space, the
heart was suspended in a pericardial cradle, and miniature tantalum
radiopaque helices (0.8 mm ID, 1.3 mm OD, 1.5-3.0 mm long, some
having different small extensions or "tails" to facilitate
subsequent radiographic identification) were inserted into the LV wall
and septum. Each marker was placed on the obturator of a modified
spinal needle (20 gauge), inserted through a stab wound in the
epicardial surface, and deposited into the myocardium by withdrawal of
the obturator from the sheath. Eight markers (Fig.
1, 2, 3, 5, 6, 9, 10, 12, and 13) were
placed into the LV subepicardium along four equally spaced longitudinal meridians around the LV, in the anterior (from the origin of the left
anterior descending coronary artery to the apex), lateral (obtuse
margin), posterior (inferior wall along the posterior descending
coronary artery), and septal walls. Epicardial echocardiographic guidance was used to place septal markers at the desired sites. Each
meridian contained LV markers at two levels, in equatorial and apical
planes. Four additional markers were sutured to the left atrial (LA)
epicardium (Fig. 1, 4, 8, 11, and
14). A marker was placed at the LV
apex (Fig. 1, 1).
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Fig. 1.
Array of radiopaque markers in left ventricle (LV) and left atrium (LA)
and on mitral valve annulus and leaflets. See
METHODS for anatomic description of
marker locations.
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After LV marker placement, the animal was heparinized (300 IU/kg iv),
and cardiopulmonary bypass was instituted using a roller pump (Pemco,
Cleveland, OH) with a membrane oxygenator (Bentley-10, Baxter
Healthcare, Irvine, CA); a 16-Fr arterial cannula was inserted into the
previously exposed left carotid artery, and a two-stage venous cannula
was inserted into the right atrium and inferior vena cava. The
ascending aorta was cross clamped, and the heart was arrested with cold
crystalloid cardioplegia solution delivered antegrade.
The LA appendage was opened, exposing the mitral apparatus. Gold
markers (~2.5 mm diameter, 15-30 mg) with various shapes were
then sutured equidistant from each other along the central meridian of
each mitral leaflet: four on the anterior leaflet (Fig. 1,
31-34) and two on the posterior
leaflet (Fig. 1, 35 and 36). To avoid interference with
coaptation surfaces, markers
33-36 were sutured to the ventricular side of each
leaflet. Markers 31 and
32 were sutured to the atrial side of
the anterior leaflet. Eight additional miniature tantalum radiopaque
markers were sutured to the atrial side of the mitral annulus at equal
distances around its circumference: one near each commissure (Fig. 1,
16 and
20) and three along the perimeters
of the anterior (15, 21, and
22) and posterior
(17-19) leaflets. An
implantable micromanometer (model P4.5-X6, Konigsberg Instruments,
Pasadena, CA) was placed via the LV apex for subsequent LV chamber
pressure monitoring. The heart was rewarmed, the aortic cross clamp was
released, the left atriotomy was closed, and the animal was weaned from
cardiopulmonary bypass. Heparin was reversed with protamine sulfate,
and the pericardium was loosely reapproximated. To minimize immediate
postoperative pain, an intercostal block (30 ml of 0.25% bupivacaine)
was performed at the fourth, fifth, and sixth intercostal spaces.
Catheters were placed in the left jugular vein and carotid artery and
brought out through the skin, providing indwelling central venous and arterial lines. Chest tubes were placed, transducer leads and occluder
tubes were exteriorized, and the chest and neck incisions were closed.
Hydromorphone hydrochloride (0.03 mg/kg iv; Dilaudid, Knoll
Pharmaceuticals, Whippany, NJ) was given as needed to minimize incisional discomfort, and the animals recovered in the intensive care
unit.
Experimental protocol.
After 8 days of recovery (range 6-10), each animal was
taken to the animal cardiac catheterization laboratory for hemodynamic and videofluorographic data acquisition. The animals were premedicated with ketamine (27 mg/kg iv), intubated, and mechanically ventilated (Veterinary Anesthesia Ventilator 2000, Hallowell EMC, Pittsfield, MA)
with 100% oxygen. Sedation was maintained with ketamine (1-4 mg · kg
1 · h1
iv infusion) and supplemental diazepam (5 mg iv), administered as
needed. UL-FS 49 (Boehringer-Ingelheim, Ridgefield, CT) was administered (8 mg iv, single dose) to lower heart rate. Such heart rate reduction [group mean heart rate was 118 ± 8 (SD)
beats/min] facilitated subsequent cinefluoroscopic
visualization and tracking of marker motion. Hemodynamic and biplane
videofluoroscopic data were obtained with hearts in normal sinus rhythm
and with ventilation briefly arrested at end expiration.
All animals received humane care in compliance with the Principles of
Laboratory Animal Care formulated by the National Society for Medical
Research and the Guide for Care and Use of Laboratory Animals prepared by the National Academy of Sciences
and published by the National Institutes of Health [DHEW
Publication no. (NIH) 85-23, revised 1985]. This study was
approved by the Stanford Medical Center Laboratory Research Animal
Review Committee and conducted according to Stanford University policy.
Data acquisition.
All imaging studies were conducted with the animal in the right lateral
decubitus position with utilization of an Optimus 2000 biplane Lateral
ARC 2/Poly DIAGNOST C2 system (Philips Medical Systems, North America
Company, Pleasanton, CA) with the image intensifiers in the
9-in. cinefluoroscopic mode. The 45° right anterior
oblique and 45° left anterior oblique biplane fluoroscopic images
were recorded simultaneously on two Sony U-Matic 5800 3/4-in. videocassette recorders. The analog LVP signal was recorded in digital
format on each individual video image using a vertical time-base
encoder (Grey Engineering, Los Angeles, CA). At the completion of the
study, images of 1-cm grids and biplane images of a three-dimensional
helical phantom of known dimensions were recorded. The two-dimensional
coordinates of each marker in each projection were digitized
frame-by-frame, employing semiautomated image-processing and
digitization software developed in our laboratory (17) and run on a
microcomputer system (RS/20, Hewlett-Packard, Palo Alto, CA, equipped
with MVP/AT/NP image-processing boards, Matrox, Dorval, PQ, Canada).
Data from the two views were merged using software previously described
(4) to yield the three-dimensional coordinates of the centroid of each
marker every 16.7 ms.
During video data acquisition, two channels of analog data (LVP and
surface lead electrocardiogram) were also acquired and digitized
simultaneously at 240 Hz using a microcomputer (486-33, JDR
Microdevices, San Jose, CA) with a high-speed data acquisition card (DT
3831-G, Data Translation, Marlboro, MA) controlled by data acquisition
software (Labtech Control 3.2.0, Laboratory Technology, Wilmington,
MA). These analog signals were also simultaneously recorded on a
multichannel color display recorder (model 580CDR/16, Vidco, Beaverton,
OR) at a paper speed of 25 mm/s. To circumvent technical limitations in
the videotape LVP channel, the 240-Hz pressure signal from the computer
was time aligned with the pressure signal from the videotape by a
program that minimized the difference between these two signals. The
240-Hz pressure was then used as the pressure value for each frame.
Data analysis.
At each sample time, marker centroid coordinates were rotated and
translated from their original laboratory reference frame to a moving
internal Cartesian reference system (Fig.
2) having its origin at the midpoint of the
line joining markers 22 and 18, its negative
y-axis passing through apical
marker 1, and markers 22 and 18 in the
z = 0 plane, with the positive
z-axis direction being toward the
anterior commissure. The angle 
was calculated as
arctan(
y/z)
(Fig. 2), and the angle 
was between the
x-axis and the line connecting
markers 18 and
22.
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Fig. 2.
Schematic of mitral annulus illustrating moving internal Cartesian
coordinate system. See METHODS for
definitions.
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The distance Dij
between any two points i and
j with coordinates
(xi,yi,zi)
and
(xj,yj,zj)
was computed as
At
each sample time a least-squares best-fit plane in intercept form
was
fit to the mitral annular markers
(15-22), its direction cosines
were found, and the distance from each annular marker to the plane was
computed.
At each sample time the scalar product was used to compute the angle
between an annular reference vector defined from
marker 22 to
18 and vectors from annular
marker 22 to anterior leaflet markers 31-34 (e.g.,
34 is illustrated in Fig.
3). A similar approach was used to obtain
the angles between an annular reference vector defined from
marker 18 to
22 and vectors from annular
marker 18 to posterior leaflet
markers 35 and
36 (e.g.,
35 is illustrated in Fig. 3).
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Fig. 3.
Schematic showing angles between septal-lateral annulus dimension
(between markers 18 and
22, D18-22) and markers on
mitral leaflets. Angle between
D18-22 and
vector from marker 22 to
34 (at edge of anterior leaflet),
34, is defined as positive
clockwise. Similar constructions apply for angles
31,
32, and
33. Angle between
D18-22 and
vector from marker 18 to
35 (at edge of posterior leaflet),
35, is defined as positive
counterclockwise. A similar construction applies for angle
36. Note that angles are not
generally coplanar, nor are they necessarily in plane defined by apex
and markers 18 and
22.
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For each beat, maximum and minimum LVP
(LVPmax and
LVPmin) were obtained (Fig.
4), and the quantities
LVPhigh = LVPmax 
0.1(LVPmax LVPmin) and
LVPlow = LVPmin + 0.1(LVPmax LVPmin) were computed. The time
sample immediately preceding
LVPlow was assigned the value
t = 0 (Fig. 4), and the time sample
immediately following LVPhigh was
taken as the onset of LV rapid pressure decay. The period of rapid
pressure decay was defined between the times of LVPhigh and
LVPlow (Fig. 4).
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Fig. 4.
LV pressure (LVP) and ECG for a typical cardiac cycle. Period of rapid
pressure decay (RPD) and 333-ms interval are indicated.
LVPmax and
LVPmin, maximum and minimum LVP.
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In all, 20 beats were analyzed from 7 hearts: 3 consecutive beats in 6 hearts and (because of technical limitations) 2 consecutive beats in 1 heart. Inasmuch as similar dynamics were observed in all beats, data
from all beats were time aligned at t = 0, and the mean and standard error of the mean for each variable were computed at t = 0 and at 10 time
samples before and 10 after t = 0. The
sampling rate was 60/s; thus the total interval studied was 333 ms
(indicated in Fig. 4), centered roughly at the time of expected mitral
valve opening. Mean LV weight was 164 ± 20 g.
Statistics.
Values are means ± SE. Minimum and maximum values were determined
from unsmoothed data. The significance of differences between values of
a given variable at different times or between times of events during
the interval of interest was assessed using Student's t-test for dependent (paired)
observations, comparing the mean difference with zero. A two-tailed
P < 0.05 was taken as significant.
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RESULTS |
Figure 5 displays mean LVP for each sample
over the interval studied. The maximum value of mean LVP was 135.1 ± 2.1 mmHg at t = 117 ms,
and the minimum value of mean LVP was 2.5 ± 2.0 mmHg at
t = +50 ms. Mean LVP fell from maximum
to 123.3 ± 1.5 mmHg (P < 0.001) or by 9% of its total excursion at
t = 67 ms and to 22.0 ± 1.9 mmHg (P < 0.001) or by 86% of its
total excursion at t = 0 ms in
accordance with the definition of t = 0 described in METHODS.
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Fig. 5.
LVP, septal-lateral dimension of mitral annulus
(D18-22),
and intercommissural dimension
(D16-20)
during late systole and early diastole. Values are means ± SE.
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Mitral annular geometry.
Figure 5 also shows the mean values of the mitral annular
septal-lateral dimension, i.e., the distance between
markers 18 and
22 (D18-22,
Fig. 1). The late systolic minimum of 2.53 ± 0.03 cm occurred at
t = 67 ms, when LVP had fallen
~10%. At t = 0 this dimension had
increased to 2.59 ± 0.04 cm (P < 0.001) or 33% of its total increase during the period analyzed.
D18-22 reached a maximum value of 2.71 ± 0.03 cm at
t = +83 ms, just after the time of
minimum LVP. It then fell rapidly, reaching a local minimum of 2.53 ± 0.02 cm, identical to the late systolic minimum
(P = NS).
Figure 5 also shows the mean values of the commissure-commissure
dimension
(D16-20)
of the annulus, i.e., the distance between markers
16 and 20 (Fig. 1).
D16-20
decreased to a minimum of 3.42 ± 0.04 cm at
t = 33 ms, 33 ms later
(P = 0.02) than the
D18-22
minimum. It increased to 3.43 ± 0.07 cm (P = 0.03) at
t = 0, then to a maximum of 3.68 ± 0.05 cm
(P < 0.001) at
t = 83 ms, 17 ms after the maximum of
the septal-lateral dimension. It then decreased slowly over the
remainder of the interval studied.
Figure 6 displays the instantaneous ratio
of D18-22 to
D16-20 over
the interval studied. This ratio is an estimate of the shape of the
oval annulus (a ratio closer to 1.0 suggesting a more circular annulus,
a ratio closer to 0.0 a more oval annulus, although
D18-22 and
D16-20 are
not necessarily in the same plane). Annular shape was relatively
unchanged during the latter half of ejection, with a minimum ratio of
0.73 ± 0.01 (i.e., the septal-lateral dimension was about
three-fourths of the intercommissure dimension) at
t = 100 ms. The ratio rose steadily (more circular annulus) during rapid pressure decay, reaching
a broad maximum of 0.75 ± 0.01 near
t = 0 (P < 0.001 compared with minimum).
It then decreased steadily (more elliptical annulus) from the time of
minimum pressure onward to an early diastolic minimum of 0.69 ± 0.01 at t = +150 ms
(P < 0.001 compared with maximum).
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Fig. 6.
LVP and ratio of mitral annular septal-lateral and intercommissural
dimensions
(D18-22/D16-20).
Values are means ± SE.
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Figure 7 shows the time course of the tilt
of the septal-lateral
(D18-22)
and commissure-commissure
(D16-20) axes, and (Fig. 2), respectively. In late systole, was 19.6 ± 6.4°
and was 14.3 ± 2.9°. In early diastole, decreased 3.3 ± 1.6° (P = 0.03) to its
minimum at t = +100 ms and then
increased. Later, fell, decreasing 3.6 ± 1.1°
(P < 0.001) by
t = +150 ms.
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Fig. 7.
LVP and mitral annular angles and (as defined in Fig. 2) during
late systole and early diastole. Values are means ± SE.
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Figure 8 shows a typical mitral annular
marker array in three-dimensional space at
t = 0. The best-fit plane through the
eight annular markers is placed at
y = 0. Figure 8 also shows
the projections of the annular shape in x-y,
y-z, and x-z planes.
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Fig. 8.
Three-dimensional depiction (heavy line) of a typical mitral annulus at
t = 0, with projections in
x-y, y-z, and
x-z planes.
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Figure 9 shows the distance from each
annular marker to the best-fit annular plane. Each data point is the
mean distance for all beats in all hearts for the given marker at each
sample time (Fig. 4) for the interval studied. Thus each curve in Fig.
9 reflects annular geometry at a single sample time. (The direction
cosines of the best-fit annular planes for all hearts changed
<2.5° during the interval studied.)
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Fig. 9.
Distance from each annular marker to best-fit annular plane. Each data
point is mean ± SE for all beats in all hearts for given marker at
each sample time (Fig. 4) for interval studied. Each curve reflects
annular geometry at a single sample time.
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Mitral leaflet geometry.
Figure 10 plots the coordinates of
markers defining the midline of the anterior leaflet
(22 and
31-34) and posterior leaflet (18, 35, and
36, Fig. 1) during opening, from
t = 0 to
t = +83 ms. Figure
10A plots the projection of the marker
centroids in the x-y plane, and Fig.
10B plots the projection in the
x-z plane. The consistency of position
of each marker at each time suggests that
1) the variability of leaflet size
and anatomy between animals was small,
2) the placement of markers was
highly reproducible, 3) the
beat-to-beat physiological variability was small,
4) the submillimeter spatial
resolution in locating marker centroids (4) was adequate to resolve
leaflet position, and 5) the 60-Hz sampling rate was adequate to capture the essential dynamics of the
rapidly moving leaflets.
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Fig. 10.
A: x-
and y-positions of mitral leaflet
markers from t = 0 until leaflet edge
markers, 34 and
35, are maximally separated.
B: x-
and z-positions of mitral leaflet
markers from t = 0 until leaflet edge
markers, 34 and
35, are maximally separated.
Values are means ± SE.
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Figure 10A allows appreciation of the
19.6 ± 6.4° tilt of the septal-lateral axis (from
marker 22 to
18) with respect to a plane
perpendicular to the long axis, as well as the very small change in
this angle over the interval depicted. During this interval, markers 31-33 and
36 began to move in the direction of
opening before the leaflet edges began to separate.
Figure 10A also shows that the shape
of the anterior mitral leaflet was a compound curve. Near the annulus
(markers 22, 31, and 32), it was
convex to the LV during late systole and opening. Near the edge
(markers 33 and
34), however, it was concave to the
LV during late systole and opening. This can be appreciated by noting
that markers 33 and
34 were placed on the ventricular side
of the leaflet (Fig. 3). The posterior leaflet was slightly concave to
the LV during late systole and rapid pressure decay.
Figure 10B shows that motion of the
anterior leaflet edge during opening was not straight (i.e., was not
confined to the x-y plane) along the
septal-lateral diameter but was directed anteriorly (in the positive
z-direction) as well. During the
interval studied, maximum anterior leaflet edge excursion was 5.8 ± 0.6 mm apically, 13.2 ± 1.1 mm septally, and 4.0 ± 0.9 mm
anteriorly (all P < 0.001).1
Maximum posterior leaflet edge excursion was 3.3 ± 0.4 mm apically, 6.9 ± 0.6 mm laterally (both P < 0.001), and 0.4 ± 0.6 mm anteriorly (P = 0.05).
Figure 11 shows the sum of the chord
lengths for the posterior leaflet
(D18-36 + D36-35)
and for the anterior leaflet (D22-31 + D31-32 + D32-33 + D33-34)
vs. time. These lengths were virtually unchanged during late systole, rapid pressure decay, and until t = +33 ms. This implies that the leaflets are very stiff in the radial
direction during this period, inasmuch as LVP varied by >130 mmHg
during this time. Each component of the chord length sum was invariant
over this time; thus this constant sum was not the result of some
chords lengthening and others shortening by a compensating amount.
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Fig. 11.
LVP and sum of chord lengths for posterior leaflet
(D18-36 + D36-35)
and anterior leaflet
(D22-31 + D31-32 + D32-33 + D33-34)
vs. time. Values are means ± SE.
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Figure 12 shows the angles
35 (Fig. 3) and
36 between the septal-lateral axis,
D18-22, and
the vectors from marker 18 to
markers 35 and
36, respectively, vs. time. The angle
35 was essentially constant
(range 54.8 ± 1.9 to 56.0 ± 1.8°) during late systole and
rapid pressure decay, with a minimum of 54.8 ± 1.9° at
t = 100 ms. It was 55.4 ± 1.9° at t = 0 (P = NS) and increased rapidly from
55.5 ± 1.5° at t = +33 ms to a
maximum of 91.5 ± 2.7° at t = +83 ms (P < 0.001). It fell steadily
to 74.2 ± 3.4° at t = +167 ms
(P < 0.001 from maximum). Similarly, the angle 36 was essentially
constant (with the same value as 35: range 54.3 ± 4.4 to
57.1 ± 4.3°) during late systole and rapid pressure decay and
began to increase rapidly at t = 0 to a maximum of 99.2 ± 2.7° at t = +83 ms (P < 0.001 relative to late
systole) just after the time of minimum LVP. Thereafter, it fell
steadily to 84.0 ± 5.4° at t = +167 ms (P < 0.001 relative to
maximum).
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Fig. 12.
LVP and posterior leaflet angles
35 and
36 (see Fig. 3) between
septal-lateral axis,
D18-22, and
vectors from marker 18 to
35 and
36, respectively, vs. time. Values are
means ± SE.
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Figure 13 shows the angles
31-34
(Fig. 3) between the septal-lateral axis,
D18-22, and
the vectors from marker 22 to markers 31-34, respectively. The
angle 31 decreased steadily throughout late systole and rapid pressure decay, to a minimum of 60.8 ± 2.0° at t = 17 ms. It
was 61.7 ± 2.1° at t = 0 (P = NS) and increased to a maximum of
72.1 ± 1.8° at t = +83 ms
(P < 0.001 relative to
t = 0). Thereafter it fell slowly to
69.3 ± 1.6° at t = +167 ms
(P < 0.01 relative to maximum). The
angle 32 fell during late
systole and rapid pressure decay to a minimum of 43.5 ± 1.7° at
t = 33 ms and began to increase
rapidly (more rapidly than
31) at
t = 0 to a maximum of 72.3 ± 1.9° at t = +83 ms
(P < 0.001 relative to late
systole). Thereafter, it fell (again, more rapidly than
31) to 58.0 ± 1.5° at
t = +167 ms
(P < 0.001 relative to maximum). The
angle 33 decreased during late systole and early in rapid pressure decay to a minimum of 36.6 ± 1.4° at t = 33 ms and began
to increase rapidly (more rapidly than
31 and
32) at
t = 0, reaching a maximum of 77.0 ± 2.8° at t = +100 ms
(P < 0.001 relative to late systolic
minimum). Thereafter, it fell (more rapidly than
31 and
32) to 53.1 ± 2.1° at
t = +167 ms
(P < 0.001 with respect to maximum).
Finally, the angle 34 to the
marker on the anterior leaflet edge decreased during late systole and
early rapid pressure decay to a minimum of 32.9 ± 1.7° at
t = +17 ms, essentially the same time
(P = NS) as the minimum of
35 on the posterior leaflet.
The angle 34 increased (more
rapidly than 31,
32, and
33), reaching a maximum of
77.0 ± 3.0° at t = +100 ms
(P < 0.001 relative to minimum). Thereafter, it fell (more rapidly than
31,
32, and
33) to 49.1 ± 2.0° at
t = +167 ms. Similar to the posterior
mitral leaflet, all portions of the anterior leaflet reached their
maximum angular displacements at a time just after the nadir of the
broad LVP minimum.
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Fig. 13.
LVP and anterior leaflet angles
31,
32,
33, and
34 (see Fig. 3) between
septal-lateral axis,
D18-22, and
vectors from marker 22 to
31-34, respectively, vs. time.
Values are means ± SE.
|
|
Figure 14 shows the distance between the
markers on the two leaflet edges (34 and 35) vs. time. This distance was
constant through late systole and rapid pressure decay (range 0.53 ± 0.03 to 0.56 ± 0.04 cm). The leaflet edges began to separate
at t = +17 ms
(P = 0.05) and reached a maximum
separation of 2.40 ± 0.10 cm at t = +83 ms (P < 0.001 relative to
minimum) 33 ms after the time of minimum LVP. The separation decreased
rapidly to 1.12 ± 0.10 cm, ~70% of the way toward the fully
closed state, at t = +167 ms
(P < 0.001 relative to maximum).
| |
DISCUSSION |
Mitral annulus geometry.
We found that the ovine mitral annulus is roughly elliptical, with its
longest dimension from commissure to commissure, similar to that of
other animals (29-31) and of humans (18, 20, 21, 24). The annular
shape in the hearts we studied, however, was virtually constant during
the latter half of systole rather than becoming more elliptical, as
previously reported (18, 29, 31). We do not know the basis for this
difference, but we believe that it could reflect, alone or in
combination, 1) a difference in
hemodynamic conditions between studies,
2) a difference due to the species
studied, and 3) a difference in
measurement technique between our computation of annular axis
dimensions from the three-dimensional coordinates of fixed annular
sites and previous measurements from two-dimensional coordinates.
During systole, constant annular shape was maintained by virtue of a
small but equivalent shortening of both annular axes (Fig. 5). Whereas
mitral annular size has been reported to decrease during systole (7,
18, 29, 31), Tsakiris et al. (29) observed that increases and decreases
in annular size could be recorded during systole in the same heart
depending on the hemodynamic conditions. Annular size may also depend
strongly on LA and LV size (26). It is generally agreed, however, that
mitral annular size is always less in systole (resulting in a
significant reduction in the area that the leaflets must bridge) than
in diastole (3, 18, 30), as we also found.
Studies of human (18) and animal (5, 30) hearts have reported a minimum
annular "size" in midsystole, with annular size increasing during
isovolumic relaxation. We found this to depend on the dimension
studied. Although, as shown in Fig. 5, the septal-lateral dimension
indeed increased throughout isovolumic relaxation (presumably favoring
opening by beginning the separation of the anterior and posterior
leaflets), the commissure-commissure dimension continued to decrease
until LVP had fallen by nearly one-half, when this dimension began to
increase rapidly.
Although a gradual increase in annular size after mitral
valve opening to a maximum in late diastole in human (18) and animal (5, 30) hearts has been reported, we again found that this depended on
the dimension examined. The hearts we studied exhibited at least a
local maximum in annular dimensions 50-70 ms after mitral valve
opening, with the septal-lateral dimension falling rapidly thereafter,
whereas commissure-commissure dimensions fell very little (Fig. 5;
i.e., there was a more elliptical annular shape).
Thus we found that the annulus became slightly smaller and slightly
more circular from the moment LVP began to drop at end systole. It
became most "circular" (albeit still oval) when the leaflet edges
were just beginning to separate, then rapidly resumed its more oval
shape, and its dimensions increased as the leaflets opened widely
during early filling.
Levine et al. (12, 14) suggested, on the basis of their
three-dimensional echocardiographic reconstructions, that the mitral
annulus in the normal human heart is saddle-shaped (a hyperbolic paraboloid) in systole. They found the high points of the saddle (i.e.,
furthest from the LV apex) at the aortic insertion and posterior LV
wall and the low points (closest to the apex) medially and laterally,
near the commissures. Our annular marker
22 (Figs. 1 and 8) was placed under direct
visualization at the point of aortic insertion of the anterior leaflet
and marker 18 at the point of LV
insertion of the middle scallop of the posterior leaflet. The medial
and lateral annular regions would be identified near our commissure
markers 20 and
16. Thus, if the annulus is saddle shaped, the 22-18 axis would be
the length of the saddle and the 16-20 axis its width. Figure 9
shows that if the annulus in these hearts is considered to be saddle
shaped, then 1) the saddle is nearly
flat except for the region nearest the aorta, identified by
marker 22, and
2) unlike the finding of Levine et
al. (12, 14), the annulus was asymmetric about the
commissure-commissure (16-20)
axis. These findings are consistent with our earlier observations of
the shape of the canine mitral annulus (7). It is of interest that
although annular dimensions changed (Fig. 5), three-dimensional annular
shape (Fig. 9) was virtually invariant over the interval studied.
It is possible that the mitral annulus of the sheep and dog are indeed
roughly planar and do not resemble the saddle shape of the human heart.
Furthermore, annular geometry may have been altered by surgery. The
very definition of the mitral annulus may also be at issue here,
however. The annulus is not a clearly defined anatomic structure (33).
In the present study we chose to define it as the locus of points of
attachment of the mitral leaflets to the surrounding atrial and
ventricular tissue, which we observed directly and to which radiopaque
markers were sutured. It is not as clear what should be used to define
the "annulus" in echocardiographic and magnetic resonance images,
which generally rely on the observed leaflet "hinge point." For
example, these imaging modalities might not be capable of observing the
subtle details of the shape of the anterior mitral leaflet connection to the aorta. Furthermore, our three-dimensional reconstructions utilize the coordinates of specific sites fixed on cardiac structures and stereoimaged at 60 samples/s. Other imaging modalities reconstruct the annulus from sites that may be changing with time, which may be
obtained from data averaged over many cardiac cycles, and have coarser
temporal resolution. Further experimental studies are needed to resolve
the origin of these differences.
Previous studies have suggested that the mitral annular plane is
oriented at nearly right angles to the LV long axis (30) and that this
orientation changes very little throughout the cardiac cycle (8, 30).
We found that the septal-lateral and commissure-commissure axes of the
annular plane were tilted roughly 75° to the LV long axis and that
their orientation changed <4° from systole to diastole (Fig. 7).
Besides being of basic physiological interest, mitral annular tilt may
be of considerable importance in the clinical assessment of transmitral
flow by echocardiographic and magnetic resonance imaging techniques.
We believe that the unloaded shape of the mitral annulus in these
hearts may be closely approximated by the minimum
septal-lateral-to-commissure-commissure ratio of ~0.70 at
t = +150 ms in Fig. 6, although
residual stresses remain. At this middiastolic portion of the cardiac
cycle there are presumably few forces distorting the annulus; LVP is at
low diastolic levels, muscle in the annular region is relaxed, the LA
is relaxed, LV myocardial and papillary muscles are relaxed, and the
leaflets are open. Thus the change to a more circular shape of the
annulus during systole most likely results from forces associated with
myocardial contraction, papillary/chordal traction, and LVP acting on
the closed mitral leaflet surfaces. When these forces are removed
during early opening, particularly after mitral leaflet edge
separation, the annulus rapidly resumes its more relaxed oval
configuration. Note that this maximally oval configuration is brought
about by means of a reduction in the septal-lateral dimension after
edge separation, with the commissure-commissure dimension remaining
elongated throughout the middiastolic period (Fig. 5). This suggests
that the septal-lateral annular dimension is already moving toward its
closed value during early valve opening and the annulus continues to
move toward its closed configuration during rapid early diastolic
filling. Thus the unloaded annular configuration in diastole may be
moving toward valve closure, even while the leaflets are opening
widely. We believe this is a new finding. Tsakiris et al. (30) found
that annular regions adjacent to the posterior leaflet moved toward and
away from relatively immobile annulus regions adjacent to the anterior
leaflet. Any such movement of the lateral marker
(18) toward the septal marker (22) moves the base of the posterior
leaflet closer to the base of the anterior leaflet, a characteristic of
potential importance to valve opening and closing (2).
Mitral leaflet geometry.
Rushmer et al. (22) noted that in intact, normal animals the valve did
not bulge into the atrium during ventricular systole, and they
attributed this to papillary muscle contraction. We also found that at
no time during late systole and early diastole were any of the anterior
or posterior leaflet markers observed on the atrial side of the
septal-lateral (i.e., 22-18)
mitral annular axis.
Anterior leaflet.
During the latter half of systole, in all hearts and all beats
analyzed, the curvature of the central portion of the anterior leaflet,
the shape of which is approximated by the sequence of line segments
joining markers 22 and
31-34, was found to be compound (Fig. 15). Although concave curvature of
this leaflet has been reported from echocardiographic studies in canine
(19) and human (12, 14) hearts, Levine et al. (13) emphasized the
importance of the appropriate long-axis echocardiographic view to
evaluate this aspect of leaflet shape and its relationship to the
mitral annulus. Echo long-axis views have shown anterior leaflet
curvature convex to the LV in human hearts, as we found in the annular
region of the anterior leaflet in these ovine hearts (Fig. 5 in Ref. 13
and Figs. 3 and 6 in Ref. 12). Leaflet curvature convex to the LV
implies an interplay between myocardial/papillary/chordal forces and
annular tension on the leaflet, because without such external forces
the anterior leaflet would be expected to assume a concave shape to the
LV in response to the forces on the leaflet associated with the high
systolic LVP. In these sheep hearts, as in the human heart (Figs.
2-7 in Ref. 1 and Fig. 6 in Ref. 10), numerous chordae attach to
the ventricular surface ("rough zone") of the anterior leaflet,
away from the leading edge, although no chordae are attached to the
midportion of the leaflet along which markers
31-34 were attached. We presume that, during
systole, these chordae (including the 2 strut chordae) pull the central portion of the anterior leaflet into a convex shape from their adjacent
leaflet attachment sites nearer the commissures. Sufficient chordal
attachments exist to account for a wide variety of complex (and
compound) anterior leaflet curvatures in systole, depending strongly on
the forces applied to the leaflets by the chordae throughout systole.
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Fig. 15.
Estimates of anterior and posterior mitral valve leaflet shapes during
opening (from t = 0 to
t = +83 ms) in
x-y plane based on positions of marker
centroids from Fig. 10A, with 2.5-mm
marker diameter taken into account as in Fig. 3.
|
|
Human and ovine mitral valves exhibit some differences. Walmsley (33)
reported that, unlike humans, sheep have no intervalvular membranous
septum, so the mitral anterior leaflet and the associated leaflets of
the aortic valve are attached to a common aorticomitral ring. He also
suggested, on the basis of palpation and the appearance of the collagen
lamina, that the central zone of the anterior leaflet is more rigid in
sheep hearts than in human hearts. Although such rigidity might be
invoked to account in part for the minimal curvature change we observed
during rapid pressure decay, it must be a minor contributor, inasmuch
as ovine anterior leaflets are nonetheless very flexible.
In late systole and the first two-thirds of rapid LVP decay, the
anterior leaflet markers moved nearer the mitral annulus (reduction in
angles in Fig. 13), whereas markers 22 and 34 maintained relatively fixed
positions over this interval. This indicated a slight flattening of the
anterior leaflet. We speculate that such flattening resulted from a
progressive reduction in chordal tension during ejection and rapid
pressure decay, which has been reported (23). A balance of forces
exists between hydrostatic forces due to LVP acting to push the closed
mitral valve leaflets toward the atrium and opposing chordal tension.
We postulate that if chordal tension is reduced in late systole and the
first two-thirds of rapid LVP drop, then LVP moves the midsection of
the leaflet slightly toward the annulus, resulting in slight flattening
of the leaflet.
During the final one-third of LVP decay, but before leaflet edge
separation, the leaflet midsection markers
(31-33) began to move away from
the mitral annulus (increase in angles in Fig. 13), resulting in a
slight increase in the convex curvature of the anterior leaflet. We
speculate that this is the result of chordal tension (23) pulling the
leaflet midsection toward the LV chamber more forcefully than the
opposing forces of the rapidly falling LVP.
As shown in Fig. 10A (interpreted in Fig.15),after
t = 0 the central portion of the anterior leaflet
nearest the annulus continued (in the
x-y plane) to curve convex to the LV
during late systole and opening. Pohost et al. (19) found that the
anterior leaflet in dogs changed curvature during late systole and
early diastole, being initially concave to the LV in midsystole,
flattening ~10 ms before edge separation, then becoming concave to
the LA ~10 ms after edge separation. Although we do see a concave
portion near the edge of the anterior leaflet, we do not see such a
curvature reversal in the ovine anterior leaflet, but we do find that
the leaflet midsection bows slightly into the LV before separation of
the leaflet edges (Fig. 10A). Pohost
et al. also found that after leaflet separation the canine anterior
leaflet free edge leads the remainder of the leaflet with a
"whipping motion" progressing from free edge to base. We found
the opposite in these ovine hearts; the anterior leaflet free edge
followed the remainder of the leaflet. Although this may possibly
reflect the somewhat stiffer ovine anterior leaflet, or perhaps a
difference in chordal attachments to the leaflet, it is also possible
that echocardiographic studies track different leaflet cross sections
at each sampling instant, whereas we track the three-dimensional
trajectories of sites fixed on the leaflet. Pohost et al. suggested
that the edges in the midportion of the valve (the region we are
observing) might separate on the order of tens of milliseconds before
the edges closer to the commissures, which could add to the
uncertainties associated with echocardiographic determinations of
leaflet shape. Further three-dimensional studies with denser marker
arrays on the mitral leaflet (yielding improved spatial resolution) are
planned to investigate this point.
In late rapid pressure decay, when LVP had dropped to one-third of its
maximum value, but before edge separation, the anterior leaflet
markers 31-33 stopped moving
toward their closed positions and began to move in the opening
direction into the LV (Fig. 13). Thirty-three milliseconds later, when
LVP had fallen to less than one-tenth its maximum value, the anterior
leaflet edge (34) pulled away from
its systolic position.
In the x-z plane the markers along the
anterior leaflet midportion (which were placed as nearly linearly in
the x-z plane as possible at the time
of surgery) maintained their linear relationship during late systole
and rapid pressure decay, then curved convex to the anterior wall after
leaflet edge separation, finally whipping to an opposite curvature,
with a significant increase in the
z-coordinate, at maximum excursion
(Fig. 10B). The net excursion of the
central portion of the anterior leaflet margin into the LV during early diastole was thus toward the interventricular septum and the LV anterior wall, and the 22-18 axis
was not an axis of symmetry for anterior leaflet opening. This finding
was quite unexpected and may be important to the basic understanding of
mitral valve function, as well as its echocardiographic evaluation.
This motion of the anterior leaflet both into the LV chamber and toward
the anterior septum likely indicates the influence of early filling hydrodynamic forces on the anterior leaflet as well as asymmetric mitral anatomy and anisotropic elasticity.
Rushmer et al. (22) suggested that mitral leaflet motion was
predominantly along the LV long axis, with limited lateral motion. In
the hearts we studied, however, the anterior leaflet swung widely into
the outflow tract, achieving a nearly perpendicular relationship to the
annulus at maximum excursion (Fig.
10A). During early opening the
anterior leaflet edge marker described an arc of constant radius about
its septal "hinge" (22)
marker, then as the leaflet straightened as it opened, this arc
increased in radius. The chordae may also limit the extent of this
opening excursion (16, 22, 35). These concepts need
further study.
The anterior leaflet edge marker
(34) reached its fully open position
in ~83 ms (Fig. 13), ~33 ms slower than that of the posterior leaflet edge marker (35; Fig. 12).
Tsakiris et al. (27) also found that posterior cusp opening was delayed
8-40 ms from anterior cusp opening.
Posterior leaflet.
Unlike the anterior leaflet, the mean shape of the central scallop of
the posterior leaflet, as defined by markers 18, 35, and 36, exhibited
slight curvature concave to the LV during late systole or rapid
pressure decay in the x-y plane (Fig.
15), although some variations, either convex or concave to the LV, were
noted in individual hearts. Previous studies also reported both convex (12) and concave (25) posterior leaflet curvature with respect to the
LV in closed valves. If LVP alone were acting on the surface of the
posterior leaflet that was tethered at its edges, one would expect the
leaflet to appear concave to the LV in the
x-y plane during systole and rapid
pressure decay. Thus, to the extent that any convex curvature to the LV
is observed, both myocardial/papillary/chordal forces and annular
tension would also have to be acting on the posterior leaflet to
maintain such a profile. Although the posterior leaflet is considerably
smaller than the anterior leaflet, there are ample chordal attachments
to its margins and its LV surface to provide such forces (10). Chordal
attachment angles differ between anterior and posterior leaflets,
however, and the posterior leaflet also has many direct chordal
attachments to the nearby LV endocardium, as well as to the papillary
muscles; thus the nature of the force balance between chordal tension
and LVP of the posterior leaflet is likely to be quite different from
that of the anterior leaflet.
During ejection, the posterior leaflet markers moved slightly closer to
the mitral annulus (i.e., 35
and 36 decreased; Fig. 12).
Again, as with the anterior leaflet, we speculate that this most likely
resulted from a progressive reduction in chordal tension during
ejection (23), which changed the leaflet force balance, resulting in
the hydrodynamic force due to LVP pushing the leaflet toward the
annulus. This force balance appeared to reverse at an ever-increasing
rate during the last half of rapid pressure decay, when posterior
leaflet curvature began to change, as evidenced by the increase in
36 after
t = 33 ms in Fig. 12, with no
equivalent change in 35.
We found that, during opening, on average, the central portion of the
posterior leaflet appeared (in the x-y
plane) to continue to curve slightly concave to the LV before edge
separation and vary this curvature somewhat throughout opening (Fig.
15). The posterior leaflet marker 36 began to move away from the annulus (demonstrating a slightly
flattening leaflet) when LVP had fallen by approximately one-half (Fig.
12). The posterior leaflet edge marker
35 moved toward its open position 67 ms later. These
findings are in agreement with those of Sovak et al. (25), who
concluded that the opening movement of the posterior leaflet did not
start at the free margin, but rather at the center of the cusp.
During mitral opening, the markers on the posterior leaflet, unlike
those on the anterior leaflet, showed no increase in
z-coordinate, but instead moved
parallel to the septal-lateral (i.e.,
22-18) axis (Fig.
10B). Thus, unlike the anterior
leaflet, the net excursion of the central portion of the posterior
leaflet into the LV during opening was simply away from the
interventricular septum. As with the anterior leaflet, the posterior
leaflet swung widely into the LV, becoming nearly perpendicular to the
septal-lateral axis at maximum excursion (Fig.
10A). Also, unlike the anterior
leaflet, the posterior leaflet edge marker described an arc with
decreasing radius about its basal hinge
(18) marker during earliest opening (because of the increasing curvature of the leaflet), then maintained this arc throughout subsequent opening (Fig.
10A).
Leaflet coaptation.
There is an anatomic demarcation line on each leaflet that can be
visually observed at surgery (33, 34). On the marginal side of this
line, there is a so-called "coaptation zone," where the leaflet
is thin and smooth surfaced on the atrial side. On the annular side of
this line, the leaflet is thicker and rougher in texture. Coaptation is
thought to occur by apposition of the coaptation zones of both
leaflets. Marker 33 was placed at the demarcation line on the anterior leaflet and marker
36 at the demarcation line on the posterior leaflet. It
became clear that actual coaptation was not at these points, inasmuch
as they are separated by >10 mm during systole and rapid pressure
decay (Fig. 10A).
Marker 34 was placed on the LV side of
the anterior leaflet margin and marker
35 on the LV side of the posterior leaflet margin (Fig.
3). These markers are separated by only 5 mm during systole and rapid
pressure decay (Fig. 14). With consideration of the size of the markers
(we measured the position of their center points) and the thickness of
the leaflet tissue, this suggests that the actual coaptation region in
these hearts was essentially at the very edge of each leaflet (Fig.
15). Coaptation at this location requires rather precise positioning of
each leaflet with respect to the other, positioning that is likely the
result of the leaflets being tightly coupled anatomically at the
commissures and aligned by the chordae from each papillary muscle. That
the edge-edge distance
D34-35 (Fig.
14) is remarkably constant throughout late systole (changing LV volume)
and rapid pressure decay (changing LV pressure) suggests that the
geometry of the coaptation region over this interval, which is likely
to be the apposition of two leaflet surfaces concave to the LV, as
shown in Fig. 15, is rather insensitive to LV size and pressure.
Leaflet edge separation did not occur until LVP was nearly at its
minimum value (Fig. 14). In contrast, all other annular and leaflet
structures began moving toward their open configuration during rapid
pressure decay. Previous workers have reported rapid leaflet opening at
(19) or before (28) diastolic pressure crossover and that mitral flow
may begin before leaflet separation (11).
Thus leaflet edge separation is the last event in a cascade of changes
occurring throughout the mitral valvular and subvalvular apparatus
during the rapid fall of LVP.
| |
ACKNOWLEDGEMENTS |
The authors gratefully acknowledge B. W. Brown for help with the
statistical analysis.
| |
FOOTNOTES |
This work was supported by National Heart, Lung, and Blood Institute
Grants HL-48837 and HL-29589 and by the Department of Veterans Affairs
Medical Research Service. J. R. Glasson and M. Komeda are Carl and Leah
McConnell Cardiovascular Surgical Research Fellows. M. O. Karlsson was
supported by the Swedish Ministry of Education, the Pharmacia Research
Foundation, and the Ingeströmska Research Foundation.
1
Maximum anterior leaflet velocity during
opening, computed from three-dimensional marker coordinates, was 0.49 ± 0.03 m/s, equivalent to maximum opening velocities we and others
(25) measured with M-mode echocardiography, suggesting that inertial loading of the leaflets by the markers is minimal.
Address for reprint requests: N. B. Ingels, Jr., Dept. of
Cardiovascular Physiology and Biophysics, Research Institute, Palo Alto
Medical Foundation, 860 Bryant St., Palo Alto, CA 94301.
Received 9 January 1997; accepted in final form 20 October 1997.
| |
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Top
Abstract
Introduction
![<IT>D</IT><SUB><IT>i j</IT></SUB> = [(<IT>x<SUB>i</SUB></IT> − <IT>x</IT><SUB><IT>j</IT></SUB>)<SUP>2</SUP> = (<IT> y</IT><SUB><IT>i</IT></SUB> − <IT>y</IT><SUB><IT>j</IT></SUB>)<SUP>2</SUP> + (<IT>z</IT><SUB><IT>i</IT></SUB> − <IT>z</IT><SUB><IT>j</IT></SUB>)<SUP>2</SUP>]<SUP>1/2</SUP>.](/content/vol274/issue2/fulltext/H552/img001.gif)
