Download Analysis of the Characteristics of the Flow Velocity Waveforms in Left

1172
Analysis of the Characteristics of the Flow
Velocity Waveforms in Left Atrial Small
Arteries and Veins in the Dog
Fumihiko Kajiya, Katsuhiko Tsujioka, Yasuo Ogasawara, Osamu Hiramatsu,
Yoshifumi Wada, Masami Goto, and Masao Yanaka
Downloaded from http://circres.ahajournals.org/ by guest on June 17, 2017
To clarify the characteristics of the phasic blood velocity pattern in small arteries and veins on
the left atrial surface, we used our newly developed fiber-optic laser Doppler velocimeter. We
intended particularly to examine the Influence of atrial contraction and relaxation on velocity
waveforms to obtain some insight into the nature of the mechanical force acting on the atrial
intramyocardial vascular beds. In 14 anesthetized open-chest dogs, the left atrial appendage was
gently displaced to expose small branches of the artery and vein. Vessels with an outer diameter
of about 150-500 fim were chosen for the measurements because their walls are transparent to
laser light. The fiber tip (velocity sensor) was fixed on the vessel surface with a drop of
cyanoacrylate when good-quality Doppler signals were consistently observed. Additional
experiments with three dogs were performed to observe the blood velocities in the atrial artery
and vein during arrhythmia. The blood velocity waveform in the artery was similar to the
pattern of aortic pressure during ventricular ejection (peak velocity, 18.8±7.8 cm/sec) but was
characterized by a pronounced dip during atrial contraction. The temporal coincidence between
the dip formation and atrial contraction was confirmed during atrial flutter with an atrioventricular block. After isoproterenol administration (2 fig i.v.), the acceleration rate of the
forward flow velocity increased by 176% (p<0.05), and reverse flow appeared during atrial
contraction in five cases out of eight (p=0.013). The blood flow velocity in atrial small veins, on
the other hand, was predominant during atrial contraction (peak velocity, 15.6±5.8 cm/sec).
Isoproterenol increased the acceleration rate of this forward flow velocity by 121% (/><0.01).
Nitroglycerin did not change the blood velocity waveform significantly in atrial arteries or in
veins. The phase opposition between arterial inflow into and venous outflow from the atrial
myocardium indicates that a large portion of the coronary inflow to the atrial myocardium may
be stored due to the presence of atrial myocardial vascular capacitance. We conclude that atrial
myocardial contraction impedes atrial inflow and promotes venous outflow from atrial
capacitance vessels. (Circulation Research 1989;65:1172-1181)
T
he blood flow in the coronary circulation has
a unique phasic nature. The distal coronary
artery flow of the left ventricle is almost
exclusively diastolic,1-2 whereas venous outflow
occurs predominantly during systole. 3 - 6 This phase
opposition between the coronary artery and the
vein flow of the left ventricle can only be explained
by the diastolic storage of arterial inflow in intramyoFrom the Department of Medical Engineering and Systems
Cardiology, Kawasaki Medical School, Kurashiki, Japan.
Supported in part by grants-in-aid 62480220 and 63113006 for
Scientific Research from the Ministry of Education, Science and
Culture of Japan.
Address for reprints: Prof. F. Kajiya, Department of Medical
Engineering and Systems Cardiology, Kawasaki Medical School,
577 Matsushima, Kurashiki, 701-01, Japan.
Received August 10, 1988; accepted May 10, 1989.
cardial capacitance vessels and subsequent displacement into the coronary veins during ventricular
contraction. Intramyocardial capacitance has been
estimated to be 0.08-0.25 ml/mm Hg/100 g left ventricular myocardium by simultaneous measurement
of coronary artery and vein flows in the dog. 7 - 9
However, the mechanical characteristics of the compressive force acting on the intramyocardial capacitance vessels during ventricular contraction have not
yet been well clarified. To better understand the
nature of this compressive force, comparison of
atrial artery and vein velocity waveforms during
atrial contraction and relaxation with those of the left
ventricle seems necessary. However, studies on the
phasic atrial flow velocities have been few because of
the technical difficulties of measurement. Therefore,
reports have been limited to evaluation of the flow in
Kajiya et al Flow Velocity Waveforms in Atrial Artery and Vein
the right sinus node artery10-11 and the microcirculation of the left atrium.12-13
The present study was undertaken to determine
the characteristics of the flow velocity waveforms
in small arteries and veins on the left atrial surface
using our laser Doppler velocimeter (LDV) with an
optical fiber. 14-17Trfis LDV has the following advantages over conventional methods: 1) fine accessibility of the optical fiber probe to small vessels on the
surface of the beating heart, 2) high accuracy of
instantaneous velocity measurements for both forward and backward flows, and 3) excellent baseline
stability for zero velocity. We intended particularly
to examine the influence of atrial contraction on
atrial artery and vein velocity waveforms to obtain
some insight into the nature of the mechanical force
acting on the intramyocardial vascular beds.
Downloaded from http://circres.ahajournals.org/ by guest on June 17, 2017
Materials and Methods
Laser Doppler Blood Flow Velocimeter
With an Optical Fiber
Measurements of blood flow velocity were made
with an LDV with an optical fiber, previously
described in detail by Kajiya and colleagues14-16 and
Nishihara et al.17 In short, a helium-neon laser beam
(632.8 nm, 5 mW) is divided into incident and
reference beams by a beam splitter. The incident
beam is directed onto the vascular surface through
an optical fiber (external diameter, 62.5 /xm; core
diameter, 50 /i.m) and then introduced into the
vascular lumen through the vessel wall. Part of the
light that is backscattered through the vascular wall
by flowing erythrocytes is collected by the same
fiber and transmitted back. The other light that is
divided by the beam splitter is used as the reference
beam. A frequency shifter (40 MHz) is interposed in
the path of the reference beam to differentiate
forward from reverse flow. Photocurrent from an
avalanche photodiode is fed into a spectrum analyzer to detect Doppler shift frequencies. The Doppler shift frequency Af is given by
Af=2/iVcos0/A
(1)
where V is the blood flow velocity, n is the refractive index of blood (approximately 1.33), 8 is the
angle between the fiber and the blood stream axis,
and A is the laser wavelength (632.8 nm). The
maximum Doppler shift frequency in the sample
volume, that is, the maximum velocity, was detected
automatically.16
Evaluation of the Validity of Our Method for
Measurement of Blood Flow Velocity in
Epicardial Small Arteries and Veins
We have already reported on the high level of
accuracy of our method, which was evaluated by
immersing the fiber tip in blood and measuring the
known blood velocity in the circular groove of a
turntable rotated at various speeds (correlation coefficient between known and measured velocities,
1173
0.998).15-16 In this study, we examined the accuracy
of blood velocity measurements in a small vessel by
using four dogs. The animals were killed at the end
of the experiments by intravenous pentobarbital
followed by potassium chloride. The heart was
removed; then thejeft anterior descending coronary
artery or the left circumflex coronary artery was
cannulated, and the cannula end was connected to a
reservoir filled with autologous blood. The fiber tip
(velocity sensor) was placed on a small branch
(about 500 /im o.d.) of the left anterior descending
coronary artery or the left circumflex coronary
artery, and the blood velocities were measured by
the LDV at a range of different perfusion pressures.
The vascular portion distal to the velocitymeasuring section was cut, and the blood effluent
was collected with a graduated cylinder and a
stopwatch. In two dogs, the vascular diameter was
measured by a radiograph of the vessel after intracoronary injection of barium sulfate-gelatin mixtures. The blood volume flow was calculated from
the vascular diameter, and the blood velocity was
measured by the LDV (blood volume flow =
VfeXirXdiameter2xmaximum velocity). It was
assumed that the flow obeys the Poiseuille law; that
is, it follows a parabolic velocity profile across the
vessel. The calculated blood flow was compared
with the blood flow determined by timed blood
collection. In the other two dogs, the timedcollected blood flow was compared with the LDVmeasured blood velocity.
Animal Preparation
Fourteen adult mongrel dogs of both sexes (15-25
kg) were anesthetized with sodium pentobarbital
(25 mg/kg i.v.). After intubation, the animals were
ventilated by a respirator pump (Harvard Apparatus, South Natick, Massachusetts) with room air,
which was supplemented with 100% oxygen at a
rate sufficient to maintain arterial oxygen tension at
a physiological level. A left thoracotomy was performed at the fourth and fifth intercostal space. The
heart was exposed and suspended in a pericardial
cradle.
Electrocardiograms were recorded from standard
leads. Stiff polyvinyl catheters were inserted into
the ascending aorta through the carotid artery and
into the right atrium through the right atrial appendage. Pressure measurements were taken with a
fluid-filled catheter and a pressure transducer (model DHC, Nippon-Koden, Tokyo, Japan). Left ventricular pressure was measured by a catheter tip
micromanometer (model PC-470, Millar, Houston,
Texas). Left atrial pressure was measured in some
cases with a catheter tip micromanometer (model
SPR-230, Millar). All measurements were recorded
on a data recorder (model R-81, TEAC, Tokyo,
Japan), and direct writing was made by a multichannel recorder (model RIJ 5608, Nippon-Koden).
1174
Circulation Research
Vol 65, No 4, October 1989
Downloaded from http://circres.ahajournals.org/ by guest on June 17, 2017
Measurements of Blood Flow Velocities in Atrial
Small Arteries and Veins
The left atrial appendage was gently displaced to
expose small branches of the artery and/or vein.
The artery is a branch of the left circumflex coronary artery, and the vein drains into the great
cardiac vein. Vessels with an outer diameter of
about 150-500 nm were chosen for the measurements because their vascular walls are transparent
to laser light. Since the maximum detectable length
for backscattered light in the blood was found to be
around 300 /tin by our previous study,16 the sample
volume may include the central axial region in the
vessel. The fiber tip was placed on the vessel
surface and was traversed manually perpendicular
to the vascular axis. When large and good-quality
Doppler signals were consistently observed, the
fiber tip was fixed at that position with a drop of
cyanoacrylate. Then, the fiber was gently supported
so that it did not compress the vessel. This method
is especially useful for the measurement of small
atrial artery and vein flow velocity since these
vessels move with cardiac motion and the vein in
particular is easily deformed. The angle 0 between
the fiber and the vascular axis was measured to
allow blood flow velocity to be calculated from
Equation 1. The blood flow velocity was measured
under control conditions, after intravenous administration of nitroglycerin (0.5 mg i.v.), and after
isoproterenol administration (2 /xg i.v.). After blood
velocity measurement of an artery (or vein), the
fiber tip was moved onto a vein (or an artery if the
first measurement was of a vein) when a vessel of
suitable size and at a suitable position was found.
Then, the above-mentioned procedure was repeated.
Additional experiments with three mongrel dogs
(15-16.5 kg) were performed to observe the blood
velocity waveforms in the left atrial small arteries
and veins during atrial fibrillation or flutter and
ventricular premature beats induced by electrical
stimulation,10 mechanical stimulation, or by applying aconitine on the left atrium.18
Statistical Analysis
Results were expressed as mean±SD. The differences between two means were compared by the
paired t test. The relation between two parameters
was evaluated by a simple correlation analysis. The
differences between two ratios were compared by
Fisher's exact test. The criterion for statistical
significance wasp<0.05.
Results
Accuracy of Blood Flow Velocity Measurements
in Small Vessels by the Laser Doppler Method
Figure 1 shows the relation between the blood
volume flow rate calculated from the measured
velocity by our LDV method and vascular diameter
and blood flow rate determined by timed collection
in one dog. An excellent correlation was found
between the two values in two animals (r=0.99,
/?<0.01; r=0.97, /><0.01). However, the absolute
volume flow rate was underestimated by about
10%. The correlation coefficients between the blood
velocity measured by the LDV method and the
timed-collected blood flow rate in the other two
dogs were also significantly high (r=0.99, p<0.01;
r=0.96, /><0.01). These results indicate that our
method accurately measures blood flow velocity in
small vessels with thin walls.
Blood Velocity Waveforms in Small Arteries on
the Left Atrium
Figure 2 shows a representative tracing of the
blood flow velocity in a left atrial small artery under
control conditions. The velocity increased with the
aortic pressure and decreased gradually after reaching a peak in midsystole. The blood flow velocity
waveform showed a dicrotic notch, as seen in the
aortic pressure waveform. Thus, the outline of
blood velocity waveform resembled the pattern of
aortic pressure during ventricular ejection. However, a sharp transient decrease in flow velocity,
that is, a dip formation, corresponding to the atrial
contraction phase was always observed in late
ventricular diastole. The dip was initiated with the
rise in the left atrial pressure and ceased at the end
of left ventricular isovolumic contraction (also see
Figure 7).
Figure 3 shows a typical example of the effect of
isoproterenol administration on the bloodflowvelocity in a small atrial artery. Compared with the
control tracing, isoproterenol caused an increased
rate of acceleration of the systolic velocity wave
(p<0.05) without a significant change in the peak
flow velocity (Figure 4 and Table 1). Another characteristic of the blood flow velocity waveform after
isoproterenol administration was the first appear-
1.0 -\
E
|
0*1
0.6
0.4
o
o
o
0.2
0.0
0.0
t m oaox +0.01
RoOS9
0.2
0.4
0.6
0.8
1.0
timed-collected blood flow (ml/mln)
1. Graph showing relation between tfie blood
flow rate in a small branch of the left circumflex coronary
artery calculated from the measured velocity by our laser
Doppler velocimeter (LDV) method and vascular diameter (vertical axis) and flow rate determined by timed blood
collection (horizontal axis).
FIGURE
Kajiya et al
Flow Velocity Waveforms in Atrial Artery and Vein
ECG
1175
ECG
AoP
AoP
(mjnHg)
(mmHg)
LVP
(mmHg)
LA small
artery
velocity
LA small
artery
velocity
(cm/s*c)
(cm/sac)
LA
pressure
(nuiHg)
Isec
H
Downloaded from http://circres.ahajournals.org/ by guest on June 17, 2017
2. A representative tracing of the blood flow
velocity in a left atrial (LA) small artery under control
conditions. The outline of the blood velocity waveform
resembled the pattern of aortic pressure (AoP) during
ventricular ejection, but a sharp transient decrease in
flow velocity corresponding to the atrial contraction
phase was observed in end diastole. LVP, left ventricular
pressure, AV, velocity change; At, time in 0.1-second
increments. The maximum acceleration rate (AVIAt) of
the forward flow in Table 1 and Figure 5 was read as
shown in this figure.
FIGURE
ance of reverse flow during atrial contraction (five
cases out of eight,/>=0.013). The peak flow velocity
after aortic valve closure decreased by 21%, but
this was not significant statistically. The heart rate
increased (/?<0.05) after isoproterenol administration, but changes in the systolic and diastolic aortic
pressures and the right atrial pressure were not
significant.
Intravenous administration of nitroglycerin increased the peak flow velocity in the atrial artery
during ventricular ejection by 20% and the peak
Isec
FIGURE 3. A typical blood velocity waveform in the left
atrial (LA) small artery after isoproterenol administration. Reverse flow was noted during atrial contraction
(arrows). AoP, aortic pressure; LVP, left ventricular
pressure.
flow velocity after aortic valve closure by 12%
compared with velocities under control conditions,
but these changes were not significant statistically
(Figure 4 and Table 1). Reverse flow was observed
in only one case (p=0.5). Although nitroglycerin
reduced both systolic and diastolic pressures significantly, the heart rate and right atrial pressure did
not change significantly.
Figure 5 shows the atrial artery blood flow velocity waveform during atrial flutter with an atrioventricular block. Dips on the velocity waveform were
clearly observed after the P waves of the electrocardiogram. The outline of velocity waveform, however, was similar to that under control conditions
shown in Figure 2. During atrial fibrillation, dips
appeared temporally at random, varying in size and
Comparison of Hemodynamic Values and tbe Dimensions of Velocity Waveforms in Atrial Small Arteries and Veins Under
Control Conditions and After Administration of Isoproterenol and Nitroglycerin
TABLE 1.
Aortic
(beats/min)
pressure
(mm Hg)
Left atrial artery (n=8)
Control
Isoproterenol
NitrogJycerin
105±25
138±25*
101±21
109±21/86±25
95±26/63±22
97±13/72±14
Left atria] vein (n=9)
Control
Isoproterenol
Nitroglycerin
112±22
130±13
116±22
Heart rate
Right atrial
Peak
pressure
velocity
Maximum velocity Maximum velocity
after aortic
before atrial
valve closure
contraction
(mm Hg)
(cm/sec)
(cm/sec)
3.6±1.1
4.8±2.2
3.4±1.0
18.8±7.8
20.7±9.6
22.5 ±7.1
15.5±7.9
12.3 + 7.8
17.3±6.5
122±18 /104±16
2.8±1.2
103+15'/ 80±14t 3.8±1.6
93+1617 71 ±14* 3.0+1.5
15.6±5.8
19.2±5.3
16.7±8.7
(cm/sec)
Maximum
acceleration
rate
(cm/sec/0.1 sec)
25.7±12.9
7L0±43.4*
39.6±22.0
2.8±4.2
1.4±1.4
3.3±2.5
34.5±22.5
76.3±25.9t
46.6±29.5
Values are mean±SD. Maximum acceleration rate is velocity change per time (0.1-second increments). Aortic pressure, systole/diastole.
*p<0.05 vs. control.
tp<0.01 vs. control.
1 vs. control.
1176
50 n
Circulation Research
Vol 65, No 4, October 1989
• peak velocity during ventricular ejection
0 maximum velocity after aortic valuve closure
E3 maximum acceleration rate
ECG
-10 0
80
40-
a
n
-•
3 3
6 0
30
40
cu
>
100i
LAD flow
(ml/min)
20
10-
CNT
ISP
»
B>
? o
?!
ȣ
2.
NTG
Downloaded from http://circres.ahajournals.org/ by guest on June 17, 2017
shape. Figure 6 shows an example of the blood
velocity waveform during ventricular premature
contraction. The dip appeared with the increase in
left atrial pressure during sinus rhythms and ventricular premature contractions. However, the depth
of the dip after ventricular premature contraction
was smaller than that of sinus rhythms although the
developed left atrial pressure was greater after
ventricular premature beats.
Blood Velocity Waveform in Small Veins
The blood flow velocity waveform in small veins
on the left atrial surface was always characterized
by a prominent atrial systolic velocity wave. Figure
7 shows both left atrial small artery and vein flow
velocities under control conditions simultaneously
AoP
LVP
"»•
lOO-i
/Y
J
LA small 5 0
artery
velocity
(cm/sec)
_T\_
iV
* i
1 0
(mmHg)
Isec
5. Tracings of the blood flow velocity in a left
atrial (LA) small artery during atrial flutter with an
atrioventricular block. The dips on the velocity waveform
were clearly observed after the P waves of the ECG
(arrows). LAD, left anterior descending coronary artery;
AoP, aortic pressure; LVP, left ventricular pressure;
RAP, right atrial pressure.
FIGURE
to indicate the temporal relation between the two
velocity waveforms. In this case, artery blood velocimetry was performed before the vein blood velocimetry, and the artery velocity waveform was added
to the tracings during vein blood velocity measurement since the heart rate, left ventricular pressure,
and left atrial pressure were almost identical for
artery and vein blood velocity measurements. The
vein blood velocity increased rapidly with atrial
contraction and decreased with atrial relaxation.
After a midsystolic nadir, the blood flow velocity
increased gradually before the onset of the atrial
contraction phase. The major forward velocity wave
^ \
10 0n^—_t-.TT=>I
0
(mmHg)
LVP
(mmHg)
RAP
FIGURE 4. Bar graphs showing comparison of blood
flow velocity waveforms in left atrial small arteries among
those under control conditions (CNT), after isoproterenol
administration (ISP), and after nitroglycerin administration (NTG). The maximum acceleration is the velocity
change per time (0.1-second increments). *Statistical
significance at p<0.05.
ECG
100I
AOP
(mmHg)
" ~_Z7—'_
,00-, - p^> • - -
|- IV
— 1 _ ~_
f--\ •• - C7A—.. r - \
:.-
"_riT _JI
(-y..::^
._..L.-X.-. - \ — j - l ":"_" _":"T~"V—fi~\
^ J ^ J : . A ^ . ::"'.T J,'....;:;..^ ".N^J:. : : . \ ^ " . ' : :.^'".:;\^...:_
-• - —
— —
"I
"
"
(mmHg)
o-l"
LA small 3 ° - |
artery
velocity
(cm/sec) 0 J
f
"
FIGURE6. Tracing ofthe bloodflowvelocity in a left atrial (LA) small artery during
ventricularpremature contraction (arrows).
^ o / > aortic pressure; LVP, left ventricular
pressure; LAP, left atrial pressure.
Kajiya et a! Flow Velocity Waveforms in Atrial Artery and Vein
1177
D peak velocity during atrial contraction
• maximum velocity before atrial contraction
• maximum acceleration rate
ECO
-10 0
50
ioo-i—J^!z~^-~JLl
-8 0
(mmHg)
I
0J
^ 3
n c
3 3
:~r~—.
100-1
LVP
(mmHg)
-4 0
» £
0 J2 0-,
2 0
LAP
(mmHg)
jT
oJ -V
CNT
LA small 3 0-,
v e l n
/±AV_
Downloaded from http://circres.ahajournals.org/ by guest on June 17, 2017
valoclty
I
(cm/aec) o J
LA tm«l|3 0artery
velocity
(cm/aac)
1 tec
7. A representative recording of the blood flow
velocity in a left atrial (LA) small vein under control
conditions. A recording of small artery blood flow velocity is displayed simultaneously (see the text for details).
The atrial vein velocity waveform was characterized by a
prominent atrial systolic flow wave that showed a reciprocal relation to the dip of the arterial flow velocity. AoP,
aortic pressure; LVP, left ventricular pressure; LAP, left
atrial pressure; AV, velocity change; At, time in 0.1second increments. The maximum acceleration rate (AVI
At) in Table 7 and Figure 8 was read as shown in this
figure.
ISP
NTG
8. Bar graphs showing comparison of blood
flow velocity waveforms in left atrial small veins among
those under control conditions (CNT), after isoproterenol
administration (ISP), and after nitroglycerin administration (NTG). The maximum acceleration rate is the velocity change per time (0.1-second increments). fStatistical
significant at p<0.01.
FIGURE
FIGURE
of the vein showed a reciprocal relation to the dip of
the artery velocity waveform.
Isoproterenol administration increased the rate of
the rise in the venous velocity during atrial contraction by 121% (p<0.01) compared with the rate of
rise under control conditions and increased the
peak blood flow velocity in the atrial small vein by
23% (Figure 8 and Table 1). This latter change,
however, was not significant. The systolic and
diastolic aortic pressures decreased significantly,
but the heart rate and right atrial pressure did not
change significantly. Nitroglycerin administration
increased the acceleration rate of the forward flow
velocity during atrial contraction by 35% and the
magnitude of the velocity component, with its earlier resumption during ventricular diastole, before
atrial contraction by 18% compared with those
values under control conditions. These changes,
however, were not significant statistically (Figure 8
and Table 1). The peak blood flow velocity was
similar to the control value.
Figure 9 shows an example of the atrial vein
blood velocity waveform during a ventricular pre-
mature beat. The outline of the major forward
velocity during ventricular premature contraction
did not differ from that of sinus rhythms. However,
the peak velocity was lower than that of sinus
rhythms although the peak left atrial pressure was
higher during the ventricular premature beat. During atrial fibrillation, small multiple forward velocity components appeared temporally at random,
varying in shape and size.
ECQ
AoP
(mmHg)
100
LVP
(mmHg)
LAP
(mmHg)
LA amall 1 5
vain
valoclty
(cm/sac) 0
'
Tsec
9. Tracings of the blood flow velocity in a left
atrial (LA) small vein during ventricular premature contraction (arrow). AoP, aortic pressure; LVP, left ventricular pressure; LAP, left atrial pressure.
FIGURE
1178
Circulation Research Vol 65, No 4, October 1989
Downloaded from http://circres.ahajournals.org/ by guest on June 17, 2017
Discussion
This investigation provides the first systematic
study of the blood velocity waveforms of atrial
myocardial arterial inflow and venous outflow. The
main observations were 1) that the velocity waveform in the artery flow resembled the aortic pressure pattern except during the atrial contraction
phase, 2) that atrial contraction caused a transient
sharp decrease in arterial flow velocity, and 3) that
the velocity waveform in the atrial veins was characterized by a prominent atrial systolic velocity
wave.
For this study we used the LDV with an optical
fiber developed in our own laboratory.14-18 In previous studies, we have shown that the blood flow
velocities in the proximal and distal coronary
arteries2 and in the great cardiac vein6 can be
successfully measured by inserting the optical fiber
into the vessels with the aid of a light rubber cuff.
Kilpatrick et aJ19 also have shown the high level of
accuracy of the laser Doppler anemometer with an
optical fiber catheter for measurements of coronary
sinus flow in the dog. Hellenbrand et al20 successfully measured the anterior interventricular vein
flow velocity by inserting a fiber probe into the vein.
However, the measurement of blood flow velocities
in superficial fine vessels is facilitated since the
laser beam can be introduced into the vascular
lumen from outside the walls without surgical isolation of the vessel. The blood volume flow rate
calculated from measured velocity by our LDV
method and vascular diameter showed an excellent
correlation with the timed-collected volume flow
rate with slight underestimation of the absolute
blood flow. This underestimation may be mainly
due to the assumption of a parabolic velocity configuration; the actual configuration may be blunter.
Some errors in measurements of the vascular diameter and the angle between the fiber and blood
stream axis may also result in underestimation of
the absolute blood flow. To measure blood flow
velocities, the fiber tip was fixed onto the outer wall
of the vessel with a drop of cyanoacrylate. We
succeeded in measuring the flow velocity in all
cases when vessels of suitable size (about 150-500
/im o.d.) could be found on the left atrial surface.
However, the amount of small arteries and veins on
the left atrium is much smaller than the amount on
the ventricle. In addition, flow velocities must be
measured several millimeters from each other to
avoid any effect by the above-mentioned cyanoacrylate treatment although arteries and veins of suitable size usually run close to each other. Eventually, we succeeded in making measurements of both
artery and vein flow velocities for the same animal
in only three of 14 dogs. Therefore, artery and vein
velocity measurements were performed separately
in the remaining dogs (artery, five dogs; vein, six
dogs). In three additional dogs, measurements of
both artery and vein velocities for the same animal
were successfully carried out in one dog, and separate velocity measurements in an artery or a vein
were performed in the other two dogs. The change
in vascular diameter during the cardiac cycle, especially that in the vein, may cause the variation in
velocity measurements. Hellenbrand et al20 measured the diameter of the anterior interventricular
vein angjographically and found little change in the
diameter during the cardiac cycle. A preliminary
study we performed with a 25-MHz ultrasound
echo system (spatial resolution, 0.2 mm) showed
that the configuration of the anterior interventricular vein was changed slightly from round to ellipsoid
during the cardiac cycle, but that the crosssectional area remained almost unchanged (authors'
unpublished data). Therefore, the change in the
vascular diameter of atrial veins may be of only
minor importance for interpretation of the velocity
waveform.
One of the major aims of our work was to study
the previously unreported phase relation between
the inflow and outflow of the atrial myocardium.
This relation is extremely important to our understanding of the atrial coronary circulation in the
beating heart. We found a phase opposition between
arterial inflow and venous outflow, that is, a dip
formation with reverse flow in the artery and a
predominant forward peak flow velocity in the vein
during atrial contraction (see Figure 7). The temporal coincidence between the dip formation on the
atrial artery flow velocity and atrial contraction was
confirmed during atrial flutter with an atrioventricular block. The phase opposition cannot be explained
without considering the possibility of a relatively
large intramyocardial capacitance in the left atrium.
We have previously investigated the functional characteristics of the intramyocardial capacitance vessels of the canine left ventricle during prolonged
diastole by analyzing coronary venous flow after
stepwise increases in coronary artery pressure after
coronary artery occlusion. Great cardiac vein flow
resumed after a delay of 1-2 seconds after restoration of artery flow. Venous flow subsequently
increased with a first-order time delay. We have
explained our results using a model incorporating
an "unstressed volume" in addition to vascular
capacitance and resistance. During systole, blood is
squeezed from the intramyocardial vessels, which
partially or totally collapse. The diastolic refilling of
these vessels requires a finite volume before any
appreciable pressure develops. These results suggested to us the possibility of significant intramyocardial vascular capacitance in the atrial myocardium. To be specific, the greater part of the artery
inflow into the atrial myocardium during ventricular
systole may be stored in the atrial unstressed volume since the vein outflow from the atrium during
this period was negligibly small. Therefore, we
roughly estimated the blood volume stored in the
left atrial unstressed volume from the amount of the
artery inflow during ventricular systole. We approx-
Kajiya et al
Downloaded from http://circres.ahajournals.org/ by guest on June 17, 2017
imated the value as one fourth of that of the left
ventricular myocardium stored during ventricular
diastole. This is based on the following reports: 1)
the systolic atrial artery flow was almost equal to
the diastolic flow in the atrium,11 and 2) the left
atrial blood flow was about one half of that in the
ventricular myocardium.21-23
Since the tension that developed within the left
atrial myocardium during atrial contraction is less
than that within the left ventricle during ventricular
contraction, can atrial contraction squeeze the blood
in the capacitance vessels out into the vein? Although
the intraluminal pressures in intramyocardial veins
and venules may be small, the radial stresses developed during atrial contraction are unlikely to be
sufficient to propel a large amount of blood into the
venous outflow. Therefore, it is likely that active
stresses at right angles to the radial direction generated by contracting muscle may play a major role
in the displacement of the blood from the capacitance vessels to the venous outflow. This is inferred
from the report of Baird et al24 that the coronary
artery flow in the beating empty heart showed a
similar velocity waveform (diastolic-predominant
pattern) to that observed when the heart was generating pressure. This similarity indicates the importance of tangential stress in the impedance to coronary inflow and the promotion of coronary outflow.
The myocardial fiber strain during atrial contraction
may also contribute to the compressive force exerted
on the capacitance vessels.
Little has been published on the phasic characteristics of blood flow velocities in the atrial circulation. To our knowledge, there is no available data
on the atrial vein flow velocity. Bing et al12 and
Hellberg et al13 first studied the coronary microcirculation of the cat left atrium by a transillumination
method. They reported that two major peaks in red
blood cell velocities were observed in the capillary
under control conditions; the first is a large peak
immediately preceding or at the onset of ventricular
systole, and the second is a small peak immediately
after aortic valve closure. As they stated, it is
difficult to determine detailed phasic movement of
red blood cells in the capillaries during the various
phases of the cardiac cycle. However, the outline of
the red blood cell velocity pattern in the capillaries
under control conditions is similar to the velocity
waveform that we observed in the small vein
although the forward flow continues throughout the
cardiac cycle in the capillaries. The similarity of the
velocity waveform in the small veins and the capillaries may indicate that the capillaries can act as
capacitance vessels in a similar manner to the veins.
The presence of forward flows throughout the cardiac cycle may be one of the characteristics of the
capillary blood flow. White and colleagues10-11 measured the blood flow velocity in the sinus node
artery in the dog to study the effect of atrial fibrillation on the atrial blood flow and mechanics. They
reported that the phasic blood flow in the sinus node
Flow Velocity Waveforms in Atrial Artery and Vein
1179
artery was similar in systole and diastole. Although
they did not discuss the velocity waveform itself in
detail, the peak velocities of the sinus node artery
can be seen during systole in their original tracings
(Figure 3 in Reference 10 and Figure 1 in Reference
11). This is consistent with our observations and
indicates that the outline of the blood flow velocity
waveform between the left and right atria does not
differ although the detailed configuration (phase and
amplitude) of the velocity pattern may.
Coronary-luminal communications in the left
atrium may modify the blood velocity waveforms of
the atrial artery and vein flows. Part of the artery
flow may enter directly into the left atrium through
the arterioluminal channels, and some blood flow
may exist between the atrial vein and the atrial
lumen through the thebesian veins. However, the
anatomic channels of the coronary-luminal communication are reported to be much more prominent in
the right ventricle and atrium.25 Thus, their physiological importance in the left atrium may be small.
Isoproterenol administration accentuated the transient decrease in arterial flow velocity during atrial
contraction and caused flow reversal in five cases
out of eight, but it increased acceleration of forward
flow velocity in the veins during atrial contraction
(see Figures 3 and 4 and Table 1). Since the atrial
pressure was not changed significantly by isoproterenol, the radial stresses may not differ greatly
from those under control conditions. This again
indicates the importance of active stresses at right
angles to the radial direction generated by contracting muscle on the coronary inflow into and the
outflow from the left atrial myocardium. Bellamy26
analyzed the origin of the atrial cove, that is, the
transient decrease in the left anterior descending
and the left circumflex coronary artery flows that
occurs during atrial contraction. He indicated that
the flow reduction is a direct function of the increase
in the left ventricular intramyocardial pressure.
This intramyocardial pressure rise is considered to
be a passive phenomenon caused by the ejection of
blood into the left ventricle by atrial contraction.
However, it is unlikely that a passive rise in left
atrial intramyocardial pressure in the left atrial
myocardium can produce reverse flow in the atrial
artery during atrial contraction although such an
increase in pressure may contribute partly to a
decrease in forward flow. Recently, McHale and
Greenfield27 indicated significant importance of
mechanical contraction of the atrial musculature for
the cove in the left circumflex coronary artery. The
"stop-cork effect" of Spaan28 may be helpful in
understanding the arterial flow reduction during
atrial contraction.
After nitroglycerin administration, the resumption of venous flow velocity during atrial relaxation
occurred earlier than that under control conditions.
This may have been due to earlier saturation of the
unstressed volume by the increase in the arterial
inflow. Although isoproterenol and nitroglycerin
1180
Circulation Research
Vol 65, No 4, October 1989
Downloaded from http://circres.ahajournals.org/ by guest on June 17, 2017
modified the velocity waveforms in the arteries and
veins on the left atrium, their general characteristics
remained unchanged from control values. These
drugs may change the vascular diameter from that
under control conditions, and this change in diameter could result in the variation in velocity measurements. Therefore, we decided not to discuss
changes in the absolute value of the blood velocity
after drug administration in any detail.
After premature ventricular contraction, the left
atrial pressure was higher than that of sinus rhythms.
However, both the depth of the systolic artery dip
and the peak forward velocity in the vein were
smaller than those of sinus rhythms. These results
may again indicate that the magnitude of the left
atrial pressure does not correlate directly with the
depth of the dip on the artery velocity waveform
and the peak vein flow velocity. The higher instantaneous artery pressure during ventricular premature contraction may partly contribute to the smaller
atrial artery dip. We speculate that the blood volume pooled in the atrial capacitance vessel before
atrial contraction and contracting muscle force are
the major factors contributing to the phase opposition between atrial inflow and venous outflow.
The present experiments were performed in an
open-chest-open-pericardium canine model. This
preparation may affect the atrial artery and vein
blood velocities in the following ways. First, it has
been reported by Maruyama et al29 that the size of
the heart chambers increased after pericardiectomy
under constant intracardiac pressure. This enlargement of the atrium may increase its developed
active stresses and possibly result in an enhancement of the phase opposition between the artery
and vein blood velocities. Second, the presence of
pericardium may allow the atrial myocardium to be
more effectively compressed by an increase in the
left atrial pressure. In addition, the pericardium
may augment the pressure interaction between the
left atrium and other cardiac chambers.29 However,
the effect of the passive radial stresses caused by
these factors may be relatively small for the aforementioned reasons. Third, there may be a direct
effect of intrapericardial pressure and/or pericardial
surface pressure on the atrial arteries and veins,
especially on the veins. That is, one might expect
pericardiectomy to lower venous resistance by
removing the compressive force on the veins. If the
waterfall mechanism acts in the epicardial vein30 on
the left atrium with pericardium, the zero-flow
pressure may be decreased by pericardiectomy.31
However, the direct effect may be too small to
cause a significant change in the general characteristics of the atrial artery and vein blood velocity
waveforms although it might change the absolute
values of the velocities slighdy.
In summary, we measured the blood flow velocities in the small arteries and veins on the left atrium
using our LDV with an optical fiber. The velocity
waveform in the artery was similar to the pattern of
aortic pressure during ventricular ejection but was
characterized by a pronounced dip during atrial
contraction. The vein flow velocity was characterized by a prominent atrial systolic flow. The phase
difference between inflow and outflow indicates that
a large portion of the coronary inflow to the atrial
myocardium may be stored due to the presence of
atrial intramyocardial vascular capacitance (probably unstressed volume and ordinary capacitance).
We concluded that atrial myocardial contraction
impedes the arterial inflow (the systolic dip) and
promotes the venous outflow from atrial capacitance vessels.
Acknowledgments
We wish to thank Dr. Chris J.H. Jones, Physiological Flow Studies Unit, Imperial College of Science and Technology, London, for his critical comments and English revision and Mr. Swee C. Tjin,
Department of Medicine, University of Tasmania,
Australia, for valuable technical assistance. We are
also grateful to Miss Mayumi Yokomizo for her
help in preparation of the manuscript.
References
1. Chilian WM, Marcus ML: Phasic coronary blood flow in
intramural and epicardial coronary arteries. Ore Res 1982;
50:775-781
2. Kajiya F, Tornonaga G, Tsujioka K, Ogasawara Y, Nishihara H: Evaluation of local blood flow velocity in proximal
and distal coronary arteries by laser Doppler method. /
Biomech Eng 1985;107:10-15
3. Anrep GV, Cruickshank EWH, Downing AC, Subba RA:
The coronary circulation in relation to the cardiac cycle.
Heart 1927;14:111-133
4. Scholtholt J, Lochner W: Systolischcr uad diastolischer
Antcil am Coronarsinusausfluss in Abhangigkeit der Grosse
des mittleren Ausflusses. Pflugers Arch 1966;290:349-361
5. Stein PD, Badeer HS, Schuette WH, Glaser JF: Pulsatile
aspects of coronary sinus blood flow in closed-chest dogs.
Am Heart J 1969;78:331-337
6. Kajiya F, Tsujioka K, Goto M, Wada Y, Tadaoka S, Nakai
M, Hiramatsu O, Ogasawara Y, Mito K, Hoki N, Tomonaga
G: Evaluation of phasic blood flow velocity in great cardiac
vein by laser Doppler method. Heart Vessels 1985;l:16-23
7. Spaan JAE: Intramyocardial compliance studied by venous
outflow arterial occlusion (abstract). Circulation 1982;
66(suppl 2):42
8. Chilian WM, Marcus ML: Coronary venous outflow persists
after cessation of coronary arterial inflow. Am J Physiol
1984;247:H984-H990
9. Kajiya F, Tsujioka K, Goto M, Wada Y, Chen X-L, Nakai
M, Tadaoka S, Hiramatsu O, Ogasawara Y, Mito K, Tomonaga G: Functional characteristics of intramyocardial capacitance vessels during diastole in the dog. Ore Res 1986;
58:476-485
10. White CW, Kerber RE, Weiss FTR, Marcus ML: The effects
of atrial fibrillation on atrial pressure-volume and flow relationships. Ore Res 1982;51:205-215
11. White CW, Holida MD, Marcus ML: Effects of acute atrial
fibrillation on the vasodilator reserve of the canine atrium.
Cardiovasc Res 1986;20:683-689
12. Bing RJ, Wayland H, Rickart A, Hellberg K: Studies on the
coronary microcirculation by direct visualization. Ciom It
Card l971;l:40l-408
13. Hellberg K, Wayland H, Rickart AL, Bing RJ: Studies on
the coronary microcirculation by direct visualization. Am J
Cardiol 1972;29:593-597
Kajiya et al Flow Velocity Waveforms in Atrial Artery and Vein
Downloaded from http://circres.ahajournals.org/ by guest on June 17, 2017
14. Kajiya F: Laser Doppler blood velocimetry with optical
fiber. Digest of 2nd Internationa] Conference on Mechanics
in Medicine and Biology, Osaka, Japan, June 5-7,1980, p 16
15. Kajiya F, Hoki N, Tomonaga G, Nishihara H: A laserDoppler-velocimeter using an optical fiber and its application
to local velocity measurement in the coronary artery. Expenenria 1981*37:1171-1173
16. Kajiya F, Hiramatsu O, Mito K, Ogasawara Y, Tsujioka K:
An optical-fiber laser Doppler velocimeter and its application to measurements of coronary blood flow velocities. Med
Prog Techno! 1987;12:77-85
17. Nishihara H, Koyama J, Hoki N, Kajiya F, Hironaga M,
Kano M: Optical-fiber laser Doppler velocimeter for highresolution measurement of pulsatile blood flow. Appl Optics
1982;21:1785-1790
18. Winbury MM, Hemmer ML: Action of quinidine, procaine
amide and other compounds on experimental atrial and
ventricular arrhythmias in the dogs. J Pharmacol Exp Ther
1955;113:402-413
19. Kilpatrick D, Linderer T, Sievers RE, Tyberg JV: Measurement of coronary sinus blood flow by fiber-optic laser
Doppler anemometry. AmJPhysiol 1982;242:H1111-H1114
20. Hellenbrand WK, Klassen GA, Armour JA, Sezerman O,
Paton B: Autonomic nervous system regulation of epicardial
coronary vein systolic and diastolic blood velocity as measured by a laser Doppler velocimeter. Can J Physiol Pharmacol 1986;64:1463-1472
21. White CW, Marcus ML, Abboud FM: Distribution of coronary artery flow to the canine right atrium and sinoatrial
node. Ore Res 1977;40:342-347
22. Neil WA, Scwell D, Gopal M, Oxendine J, Painter L:
Independent regulation of atrial coronary blood flow by
atrial contraction rate in conscious dogs. PflugersArch 1980;
388:193-195
1181
23. McHale PA, Rembert JC, Greenfield JC: Effect of atrial
fibrillation on atrial blood flow in conscious dogs. Am J
Cardiol 1983;51:1722-1727
24. Baird RJ, Goldbach MM, De La Rocha A: Intramyocardial
pressure. The persistence of its transmural gradient tn the
empty heart and its relationship to myocardial oxygen consumption. J Thorac Cardiovasc Surg 1972;64:635—646
25^ Cohen MV: Coronary Collaterals: Clinical and Experimental Observations. New York, Furura Publishing Co, Inc,
1985, pp 63-70, 324-331
26. Bellamy RF: Effect of atrial systole on canine and porcine
coronary blood flow. Ore Res 1981;49:701-710
27. McHale PA, Greenfield JC Jr: Origin of atrial coving in
canine phasic coronary artery blood flow. Am J Physiol
1986;251:H774-778
28. Spaan JAE: Coronary diastolic pressure-flow relation and
zero flow pressure explained on the basis of intrarnyocardial
compliance. Ore Res 1985;56:293-309
29. Maruyama Y, Ashikawa K, Isoyama S, Kanatsuka H,
Ino-oka E, Takishima T: Mechanical interactions between
four heart chambers with and without the pericardium in
canine hearts. Ore Res 1982;50:86-100
30. Uhlig PN, Baer RW, Vlahakes GJ, Hanlcy FL, Messina LM,
Hoffman JIE: Arterial and venous coronary pressure-flow
relations in anesthetized dogs—Evidence for a vascular
waterfall in epicardial coronary veins. Ore Res 1984;
55:238-248
31. Watanabe J, Maruyama Y, Satoh S, Keitoku M, Takishima
T: Effects of the pericardium on the diastolic left coronary
pressure-flow relationship in the isolated dog heart. Circulation 1987;75:670-675
KEY WORDS • left atrial artery and vein • blood velocity
waveform • laser Doppler velocimeter • atrial contraction
and relaxation
Analysis of the characteristics of the flow velocity waveforms in left atrial small arteries and
veins in the dog.
F Kajiya, K Tsujioka, Y Ogasawara, O Hiramatsu, Y Wada, M Goto and M Yanaka
Downloaded from http://circres.ahajournals.org/ by guest on June 17, 2017
Circ Res. 1989;65:1172-1181
doi: 10.1161/01.RES.65.5.1172
Circulation Research is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1989 American Heart Association, Inc. All rights reserved.
Print ISSN: 0009-7330. Online ISSN: 1524-4571
The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://circres.ahajournals.org/content/65/5/1172
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in
Circulation Research can be obtained via RightsLink, a service of the Copyright Clearance Center, not the
Editorial Office. Once the online version of the published article for which permission is being requested is
located, click Request Permissions in the middle column of the Web page under Services. Further information
about this process is available in the Permissions and Rights Question and Answer document.
Reprints: Information about reprints can be found online at:
http://www.lww.com/reprints
Subscriptions: Information about subscribing to Circulation Research is online at:
http://circres.ahajournals.org//subscriptions/