Acta Anaesthesiol Scand 2003; 47: 46–52
Printed in Denmark. All rights reserved
Effects of acute normovolemic hemodilution on
ventriculoarterial coupling in dogs
J. NOZAKI, H. KITAHATA, K. TANAKA, S. KAWAHITO and S. OSHITA
Department of Anesthesiology, Tokushima University School of Medicine, Tokushima, Japan
Background: Acute normovolemic hemodilution (ANH) causes
a decrease in systemic vascular resistance. Similar to vasodilat-
ing drugs, ANH might modify ventriculoarterial coupling. Left
ventricular elastance (Ees), effective arterial elastance (Ea),
stroke work (SW), and pressure volume area (PVA) were used
as indicators to examine the effects of ANH on this coupling.
Methods: After institutional approval eight dogs were anesthet-
ized with isoflurane and subjected to measurements including
aortic pressure, left ventricular (LV) pressure, and LV volume.
Left ventricular volume was measured with a conductance cath-
eter. Ees was determined as the slope of the end-systolic press-
ure-volume relationship. Ea was determined as the ratio of LV
end-systolic pressure to stroke volume. Ventriculoarterial coup-
ling was evaluated as the ratio of Ees to Ea. Mechanical ef-
ficiency, another criterion for ventriculoarterial coupling, was
calculated as the ratio of SW to PVA. Data are expressed as
mean∫SD, and P⬍0.05 was considered significant.
Results: Normovolemic exchange of 50 ml kgª1 of blood for 6%
hydroxyethyl starch (ANH50) reduced hemoglobin concen-
T HE RATIO of left ventricular elastance (Ees) to effec-
tive arterial elastance (Ea) is an indicator of the
coupling between ventricular properties and arterial
load properties. Another criterion for the coupling be-
tween an energy source and its load is the principle
of economical fuel consumption, or mechanical ef-
ficiency, which is defined as the ratio of stroke work
(SW) to myocardial oxygen consumption per beat
(MVO2). Using a simple analytical model for the inter-
action between the heart and vasculature, Burkhoff
et al. (1) revealed that the SW of ventricular contrac-
tion is maximized when the ratio of Ees to Ea is 1 and
that mechanical efficiency is maximized when Ees/
Ea Ω 2. Asanoi et al. (2) applied these observations to
humans and showed Ees/Ea to be approximately 2 in
patients with normal heart function, and in patients
with moderate myocardial depression, the ratio was
almost 1. We studied the effects of the vasodilator ni-
cardipine on ventriculoarterial coupling in humans
and found that ventricular and arterial properties
were during hypertension so matched as to maximize
46
Copyright C Acta Anaesthesiol Scand 2003
ACTA ANAESTHESIOLOGICA SCANDINAVICA
0001-5172
tration from 12.8∫3.0 g dlª1 to 6.4∫1.3 g dlª1. Acute normovo-
lemic hemodilution 50 did not change Ees significantly although
it significantly decreased Ea. Left ventricular elastance/Ea did
not change after ANH (1.0∫0.4 at baseline and 1.2∫0.5 at
ANH50). Acute normovolemic hemodilution 50 significantly in-
creased SW and PVA, preventing SW/PVA from changing sig-
nificantly after ANH (0.57∫0.10 at baseline and 0.62∫0.14 at
ANH50).
Conclusion: Before ANH, ventriculoarterial coupling was so
matched as to maximize SW at the expense of the work ef-
ficiency. This relation was preserved at ANH50.
Accepted for publication 20 August 2002
Key words: anemia; cardiac performance; conductance catheter.
c Acta Anaesthesiologica Scandinavica 47 (2003)
SW at the expense of work efficiency, whereas the
mechanical efficiency of ventricular contraction was
maximized after treatment of hypertension with ni-
cardipine (3).
Acute normovolemic hemodilution (ANH) causes
increased cardiac output and decreased systemic vas-
cular resistance (SVR) (4–6). Similar to nicardipine,
ANH might modify ventriculoarterial coupling to be
matched to and to maximize the mechanical efficiency
of ventricular contraction (Ees/Ea Ω 2). In the current
study, we used Ees/Ea and SW/PVA as indicators to
investigate whether ANH might change coupling be-
tween the left ventricle and arterial system in anes-
thetized dogs.
Methods
This study was approved by the Animal Care Com-
mittee of Tokushima University. Eight unpremedi-
cated mongrel dogs of both sexes, weighing 9–16 kg,
were anesthetized with thiamylal 20–25 mg kgª1 i.v.

before tracheal intubation and were ventilated mech-
anically by a Harvard respiratory pump to maintain
PaO2 at 13.3–26.7 kPa and PaCO2 at 4.7–6.0 kPa. Anes-
thesia was maintained with isoflurane 1.5% and nitro-
gen 50% in oxygen. End-tidal isoflurane and carbon
dioxide concentrations were monitored continuously
(Fukuda Denshi, HC-510, Tokyo, Japan).
Instrumentation
Each dog was placed on its right side, and an i.v. can-
nula was placed in the right femoral vein for continu-
ous infusion of 0.9% saline (5–7 ml kgª1 hª1). Muscle
relaxation was obtained with vecuronium 0.1 mg kg1
i.v. and administered at a continuous infusion rate of
0.1 mg kgª1 hª1. Rectal temperature was monitored
(Terumo, CTM-303, Tokyo, Japan) and controlled at
37–38 æC with a water-circulating heating pad.
Polyethylene cannulas were placed in the right fem-
oral artery for blood sampling and in the superior
vena cava, through the right jugular vein for ANH
with 6% hydroxyethyl starch (HespanderA, Kyorin,
Japan; average molecular weight is 70,000) and for
measurement of central venous pressure. After the
heart was exposed through a left thoracotomy in the
fifth or sixth intercostal space and suspended in a
pericardial cradle, a 7F pressure-transducer-tipped
catheter (Millar Instruments, SPC-370, Houston, TX)
was inserted into the aortic root through the right ca-
rotid artery to record the aortic blood pressure (Nihon
Kohden, RMC-1100 polygraph, Tokyo, Japan). Hep-
arin 300 IU was administered i.v. to prevent blood co-
agulation in the exchange circuit.
The volume conductance catheter and the pressure-
transducer-tipped catheter were used to measure the
LV volume and pressure. An 8-electrode 5F conduc-
tance catheter (Unique Medical, CCS-100–6, Tokyo, Ja-
pan) and a 7F pressure-transducer-tipped catheter
(Millar Instruments, SPC-370) were inserted in the left
ventricle through a small incision at the apex. Con-
ductance catheter positioning was verified by
synchronous segmental volume signals and palpation
of the aortic root; the distal tip was positioned just
above the aortic valve. The catheters were secured
with a purse-string suture. An 8F Fogarty occlusion
catheter (Baxter, 62080814F, Irvine, CA) was inserted
through the left femoral vein to the inferior vena cava
at the level of the diaphragm to create an abrupt alter-
ation of the LV preload by inflation of the catheter’s
balloon during measurement of pressure-volume (P-
V) loop parameters. A fluid-filled catheter was placed
in the pulmonary artery to inject hypertonic saline
(10%; 2 ml) to determine the parallel conductance vol-
ume (Vp). After completion of the study, the dogs
ANH preserves ventriculoarterial coupling
were killed with a bolus infusion of KCl, and we con-
firmed that all catheters were positioned properly.
Analysis of left ventricular pressure volume
relations and ventriculoarterial coupling
A full description of the principles and techniques of
the volume conductance catheter measurement
method has appeared elsewhere, and its reliability has
been confirmed (7,8). In brief, the LV volume signal
from the conductance catheter and the LV pressure
signal from the pressure-transducer-tipped catheter
were connected to a conductance module (Unique
Medical, VPR1002, Tokyo, Japan), which maintained
a constant current (200 mA at 20 kHz) between the two
outermost electrodes and measured the voltage differ-
ence between each adjacent electrode (five pairs of the
intervening electrodes, and interelectrode distance Ω
0.75 cm).
Left ventricular volume [V (t)] was determined by
the equation:
V(t) Ω (1/a)(L2/s) G(t) ª Vp
In this equation, G(t) Ω the sum of the time-varying
five segment conductances, s Ω the blood conduc-
tivity, L Ω interelectrode distance, a Ω the slope correc-
tion factor for conductance volume and real LV vol-
ume, and we assumed that ‘a’ was equal to one. These
signals and the intraventricular electrocardiogram sig-
nal were digitized simultaneously (at 500 Hz) with a
microcomputer (NEC, PC9821NW133D, Tokyo, Ja-
pan) interfaced with an on-line analog-to-digital con-
verter for real-time display. Recording and storing
data analysis of the LV pressure-volume relationships
was performed with custom software (Unique Medi-
cal, VPS-100). Approximately 5 min before each inter-
vention, calibration of blood conductivity was per-
formed in a sampling cuvette incorporated in the con-
ductance module, with precalibration carried out with
solutions of known conductivity (0.9% saline). Using
a hypertonic saline technique, we calculated Vp
caused by the signal offset as a result of conductivity
of the ventricular wall and surrounding structures (7).
Hypertonic saline was administered in the pulmonary
artery during suspended ventilation. During each
measurement, Vp was subtracted from the measured
volume to obtain the absolute LV volume.
Left ventricular elastance and Ea were determined
by calculating the slope of the LV end-systolic press-
ure volume relationship (ESPVR) and the ratio of LV
end-systolic pressure to stroke volume (1,9). During
suspended ventilation, P-V loop parameters were ob-
tained. Abrupt inflation of the caval balloon was used
for a transient reduction of LV preload, resulting in an
47
J. Nozaki et al.
approximate 30-mmHg decline in LV pressure during
10–15 cardiac cycles, which generated ESPVR (8). The
LV end-systolic pressure and end-systolic volume of
each P-V loop were fit to the regression equation:
Pes Ω Ees (Ves ª V0)
In this equation, Pes Ω LV end-systolic pressure, Ves Ω
LV end-systolic volume, and V0 Ω the extrapolated
volume intercept of the relationship. Immediately be-
fore caval balloon inflation, Ea was calculated as the
ratio of LV end-systolic pressure to stroke volume
under steady-state hemodynamic conditions (9). Left
ventriculoarterial coupling was defined as the ratio of
Ees to Ea (9). Figure 1 shows a series of LV P-V dia-
grams obtained in a typical experiment. Mechanical
efficiency is defined as the ratio of SW to MVO2. Suga
et al. (10) demonstrated that the PVA in the P-V plane
represents the total mechanical energy generated by
ventricular contraction, and that MVO2 is linearly re-
lated to the PVA. The PVA was calculated as the area
circumscribed by the ESPVR, the end-diastolic P-V
curve, and the systolic segment of the P-V loop traject-
ory (10). Stroke work was calculated as the integral of
the P-V loop under steady-state conditions. The PVA
was the sum of SW and potential energy (PE), and PE
was determined by the equation:
PE Ω 0.5 Pes (Ves ª V0)
The ratio of SW to PVA was used to evaluate the LV
work efficiency of energy transfer of the PVA to exter-
nally performed SW (2,11,12). Systemic vascular re-
Fig. 1. A series of left ventricular pressure-volume diagrams during preload reduction by vena caval balloon occlusion before (A) and after (B) 50
ml kgª1 colloid-for-blood exchange. Ees Ω left ventricular elastance; Ea Ω effective arterial elastance.
48
sistance was calculated according to the standard for-
mula.
Measurements
To stabilize the hemodynamic parameters and to ad-
just the blood gases, baseline measurements, includ-
ing Vp, were performed at least 1 h after the surgical
procedure. Thereafter, ANH was performed by re-
placing blood from the right femoral artery with a
continuous equivalent volume of 6% hydroxyethyl
starch prewarmed at 37–38 æC via the catheter in the
superior vena cava. It took approximately 10 min for
the exchange of blood with hydroxyethyl starch. The
volume of this first blood exchange was 25 ml kgª1.
After a 10-min stabilization period, measurements
were repeated (ANH25). The volume of the second
blood exchange was 25 ml kgª1 (cumulative exchange
volume was 50 ml kgª1, ANH50). Each measurement,
including calibration of blood conductivity, Vp, and
arterial blood samples, was performed after a 10-min
stabilization period, and the interval between each
measurement was approximately 30 min. Arterial
blood samples were analyzed electrometrically for
acid base-status, PaO2, PaCO2, serum concentrations
of Naπ, Kπ, Ca2π (Radiometer, ABL 505, Copenhagen,
Denmark), and hemoglobin concentration (Corning,
Co-oximeter 2500, Boston, MA).
Statistical analysis
Data are presented as mean∫SD. Data were analyzed
with repeated measures analysis of variance followed
 ANH preserves ventriculoarterial coupling

by application of Student’s t-test with Bonferroni’s cor-
rection for comparison between experimental periods.
A P-value of ⬍0.05 was accepted as significant.
Results
The arterial blood analysis and cardiac hemodynamic
variables obtained during ANH are summarized in
Tables 1 and 2. Acute normovolemic hemodilution re-
duced hemoglobin concentrations from 12.5∫3.0 g dlª1
at baseline to 6.4∫1.3 g dlª1 at ANH50. Blood gases and
serum Naπ, Kπ, and Ca2π concentrations remained
within normal ranges. Heart rate, LV end-diastolic
pressure, stroke volume, and cardiac output increased
significantly, and SVR decreased significantly at
ANH25 and ANH50. Mean aortic blood pressure,
mean central venous pressure, and LV end-systolic vol-
ume remained stable throughout the study period.
Figure 2 shows the effects of ANH on Ees, Ea, and
Ees/Ea. Left ventricular elastance did not change dur-
ing stepwise ANH (13.0∫4.4 mmHg mlª1 at baseline,
13.6∫7.2 mmHg mlª1 at ANH25, and 12.1∫5.5 mmHg
mlª1 at ANH50; Fig. 2A, open bars). In contrast, Ea
significantly decreased from 14.1∫5.7 mmHg mlª1 at
baseline to 9.7∫2.1 mmHg mlª1 at ANH50 (Fig. 2A,
solid bars). The Ees/Ea ratio slightly increased (from
1. 0∫0.4 at baseline to 1.2∫0.5 at ANH50; Fig. 2B), but
this change was not significant.
Figure 3 shows the effects of ANH on SW, PVA, and
SW/PVA. Stroke work significantly increased from
658∫196 mmHg ml at baseline to 1152∫317 mmHg ml
at ANH50 (Fig. 3A, open bars). The PVA significantly
increased from 1162∫301 mmHg ml at baseline to
1948∫682 mmHg ml at ANH50 (Fig. 3A, solid bars).
Acute normovolemic hemodilution slightly increased
the SW/PVA ratio but not significantly (from
0.57∫0.10 at baseline to 0.62∫0.14 at ANH50; Fig. 3B).
Discussion
The fact that either Ees/Ea or SW/PVA slightly in-
creased after ANH suggests that ANH preserved the

Table 1
Arterial blood analysis during acute normovolemic hemodilution.

Baseline ANH25 ANH50

pH 7.365∫0.49 7.337∫0.58 7.300∫0.64

PaCO2 (kPa) 4.8∫0.4 5.2∫0.4 5.4∫0.5
PaO2 (kPa) 19.2∫2.9 21.2∫2.0 21.2∫5.5
Naπ (mEq lª1) 148∫2 145∫2 144∫2
Kπ (mEq lª1) 3.5∫0.2 3.3∫0.3 3.3∫0.2
Ca2π (mEq lª1) 1.2∫0.1 1.2∫0.1 1.2∫0.1

Data are presented as mean∫SD.

ANH, acute normovolemic hemodilution.
Cumulative exchange volumes are 25 ml kgª1 (ANH25) and 50 ml kgª1 (ANH50).

Table 2

Hemodynamic data and parallel conductance volume during acute normovolemic hemodilution.

Baseline ANH25 ANH50

ª1
HR (beats min ) 137∫24 143∫23* 148∫23*
MAP (mmHg) 99∫8 99∫5 96∫8
CVP (mmHg) 4∫2 4∫2 5∫2
LVEDP (mmHg) 5∫2 8∫4* 9∫4*
LVEDV (ml) 23∫8 24∫5 26∫4
LVESV (ml) 15∫6 14∫4 15∫2
SV (ml) 8.6∫3.2 10.0∫3.2* 12.0∫3.6*†
CO (l minª1) 1.18∫0.50 1.43∫0.52* 1.78∫0.59*†
SVR (dynes s cmª5) 7806∫3257 5997∫1783* 4596∫1053*
Vp (ml) 24∫9 18∫8* 17∫7*

Data are presented as mean∫SD.

*P⬍0.05 compared with baseline; †P⬍0.05 compared with ANH25.
Cumulative exchange volumes are 25 ml kgª1 (ANH25) and 50 ml kgª1 (ANH50).
ANH, acute normovolemic hemodilution; HR, heart rate; MAP, mean aortic blood pressure; CVP, mean central venous pressure; LVEDP, left
ventricular end-diastolic pressure; LVEDV, left ventricular end-diastolic volume; LVESV, left ventricular end-systolic volume; SV, stroke volume;
CO, cardiac output; SVR, systemic vascular resistance; Vp, parallel conductance volume.

49
J. Nozaki et al.
Fig. 2. Effects of acute normovolemic hemodilution (ANH) on (A) left
ventricular elastance (Ees; open bars) or effective arterial elastance (Ea;
solid bars), and (B) left ventriculoarterial coupling (Ees/Ea). Cumula-
tive exchange blood volumes with 6% hydroxyethyl starch are 25 ml
kgª1 (ANH25) and 50 ml kgª1 (ANH50). Data are presented as
mean∫SD. *Significant (P⬍0.05) difference from baseline.
left ventriculoarterial coupling. Acute normovolemic
hemodilution 25 and ANH50 produced significant in-
creases in heart rate, LV end-diastolic pressure, stroke
volume, and cardiac output and significant decreases
in SVR. The LV end-diastolic volume increased, but
this change was not significant, and the LV end-sys-
tolic volume remained unchanged. Significant in-
crease in cardiac output was the result of increases
in heart rate and stroke volume, which resulted from
increased preload (LV end-diastolic pressure and end-
diastolic volume) and significant decreases in
afterload (SVR). Slight but significant increases in pre-
load resulted from ANH-induced decreases in blood
viscosity and resulting increases in venous return (13).
Significant decreases in SVR are thought to be primar-
ily the result of lowered blood viscosity (4–6).
The cardiac hemodynamic effects of ANH were
quite similar to those of nicardipine except that nicar-
dipine caused significant decreases in arterial blood
pressure (3). In our previous study with humans (3),
nicardipine produced slight but significant increases
50
Fig. 3. Effects of acute normovolemic hemodilution (ANH) on (A)
stroke work (SW; open bars) or pressure volume area (PVA; solid bars)
and (B) work efficiency (SW/PVA). Cumulative exchange blood vol-
umes with 6% hydroxyethyl starch are 25 ml kgª1 (ANH25) and 50
ml kgª1 (ANH50). Data are presented as mean∫SD. *Significant
(P⬍0.05) difference from baseline. †Significant (P⬍0.05) difference
from ANH25.
in stroke volume index, cardiac index, and ejection
fraction, and significant decreases in arterial blood
pressure and the systemic vascular resistance index.
Using these cardiac hemodynamic data, we evaluated
the effects of nicardipine on ventriculoarterial coup-
ling, and found that during hypertension, ventricular
and arterial properties were so matched as to maxim-
ize SW at the expense of work efficiency, whereas the
mechanical efficiency of ventricular contraction was
maximized after nicardipine (3). Acute normovolemic
hemodilution, like nicardipine, may affect the relation
between LV properties and arterial load properties.
Thus we investigated the effects of ANH on the ven-
triculoarterial coupling using Ees/Ea and SW/PVA as
indicators. Suga et al. (14) showed that in the canine
left ventricle, Ees is sensitive to changes in contrac-
tility independent of loading conditions. Sunagawa
et al. (9) extended the ventricular pressure-volume
analysis to include its interaction with the arterial bed,
revealing that with a constant heart rate, arterial prop-
erties can be represented as an effective arterial elas-

tance, Ea. Because the left ventricle and the arterial
system can be treated as elastic chambers that have
volume elastance, Ees and Ea, energy transfer from
the left ventricle to the arterial system can be deter-
mined by calculating the ratio of their volume elas-
tance values (9). Thus, the ratio of Ees to Ea is an indi-
cator of the coupling between ventricular properties
and arterial load properties. Another criterion for the
coupling between an energy source and its load is the
principle of economical fuel consumption, also called
mechanical efficiency, which is defined as the ratio of
SW to MVO2. Myocardial oxygen consumption per
beat was assessed by estimating the ventricular PVA,
which represents the total mechanical energy gener-
ated by ventricular contraction. Suga et al. (15,16)
showed that the LV PVA is linearly related to MVO2
per beat at a given heart rate with a stable inotropic
background.
Using Ees/Ea and SW/PVA as indicators, Burkhoff
et al. (1), Little et al. (11), and Sunagawa et al. (17)
showed that the SW of a ventricular contraction is
maximized when Ees/Ea Ω 1, while mechanical ef-
ficiency is maximized when Ees/Ea Ω 2. Burkhoff
et al. (1) suggested that, under physiological con-
ditions, ventricular and arterial properties might ad-
just more toward efficiency than toward SW. In the
current study, Ees was equal to Ea before ANH (Fig.
2B). This suggests that before ANH in dogs anesthet-
ized with isoflurane 1.5%, ventriculoarterial coupling
was so matched as to maximize SW at the expense of
work efficiency. Little et al. (11) reported that the left
ventricle and arterial system might operate close to
the point at which maximal SW is produced in anes-
thetized animals. Left ventricular elastance did not
change throughout stepwise ANH and Ea decreased,
reaching statistical significance at ANH50 (Fig. 2A).
The Ees/Ea ratio therefore slightly increased, but not
significantly (Fig. 2B). The SW/PVA ratio also slightly
increased because of higher increases in SW than PVA
(Fig. 3B). These results suggest that ANH slightly im-
proves the coupling between the left ventricle and ar-
terial system.
Considering the limitations of our study, the ma-
nipulation of preload to generate multiple PV loops
may cause reflex inotropic changes, evidenced by al-
tered heart rate because of sympathetic activation or
withdrawal (18). Kass et al. (8) observed that the
ESPVR can be reliably determined in situ with a con-
ductance catheter with rapid load alterations of less
than 8 s to minimize measurement disturbance from
reflex. In the current study, we used less than 8-s
periods of inferior venocaval balloon occlusion to de-
termine ESPVR. We assumed that the slope correction
ANH preserves ventriculoarterial coupling
factor (a) was equal to one in the volume catheter
technique. There is some error in estimating the abso-
lute volume because the value of a may vary because
of LV geometry (7,8,19). However, geometric change
within the same heart probably would not alter the
accuracy of the estimated volume using a conduc-
tance catheter (20), so that the potential error in a in
this study probably will be minimum. Another limi-
tation relates to the lack of LV contractility change
after ANH (Fig. 2A) in contrast to the significant in-
creases in heart rate and preload (LV end-diastolic
pressure) at ANH25 and ANH50 (Table 2). Effective
arterial elastance reflects the afterload during constant
heart rate, ventricular preload, and LV contractility
(9). Left ventricular PVA is linearly related to MVO2
per beat at a given heart rate with a stable inotropic
background (15,16). Although the changes in heart
rate and end-diastolic pressure were statistically sig-
nificant in our present study, the magnitude of these
changes was quite small (Table 2). Maughan et al. (21)
studied heart rate-dependent changes in Ees in heart
rates between 60 and 200 beats minª1 and found little
change in Ees at between 120 and 180 beats minª1. It
is unlikely that the small changes in these factors af-
fect the reliability of Ea and PVA as indicators of
afterload and MVO2 per beat. We think the Ees/Ea
and SW/PVA ratios calculated in the current study
are reliable indicators of left ventriculoarterial coup-
ling. The subjects of the current study were anesthet-
ized with 1.5% (approximately 1.2 MAC in dogs) iso-
flurane. One major reason that we chose isoflurane as
the anesthetic is that maintaining the level of anes-
thesia during hemodilution is difficult with intra-
venous anesthetic agents, including opioids. Cardiac
function (LV contractility) is decreased less by iso-
flurane than by other volatile anesthetics, such as
halothane, enflurane, and sevoflurane. However, in
one study, isoflurane but not the equivalent of halo-
thane or sevoflurane reduced total arterial resistance
(22). Thus, isoflurane may have influenced left ven-
triculoarterial coupling during ANH in our present
study.
In conclusion, our results demonstrate that before
ANH in anesthetized dogs, ventriculoarterial coup-
ling was so matched as to maximize SW at the ex-
pense of work efficiency. This relation was preserved
after ANH.
References
1. Burkhoff D, Sagawa K. Ventricular efficiency predicted by
an analytical model. Am J Physiol 1986: 250: R1021–R1027.
2. Asanoi H, Sasayama S, Kameyama T. Ventriculoarterial
51
J. Nozaki et al.
coupling in normal and failing heart in humans. Circ Res
1989: 65: 483–493.
3. Tanaka K, Oshita S, Kitahata H et al. Effects of nicardipine
on ventriculo-arterial coupling in humans. Br J Anaesth 1998:
81: 180–185.
4. Spahn DR, Leone BJ, Reves JG, Pasch T. Cardiovascular and
coronary physiology of acute isovolemic hemodilution. a re-
view of nonoxygen-carrying and oxygen-carrying solutions.
Anesth Analg 1994: 78: 1000–1021.
5. Fontana JL, Welborn L, Mongan PD, Sturm P, Martin G,
Bunger R. Oxygen consumption and cardiovascular func-
tion in children during profound intraoperative normovo-
lemic hemodilution. Anesth Analg 1995: 80: 219–225.
6. Hirose Y, Kimura H, Kitahata H, Kawahito S, Oshita S. Ni-
tric oxide does not play a major role in the regulation of
systemic hemodynamic responses to acute normovolemic
hemodilution. Acta Anaesthesiol Scand 2000: 44: 96–100.
7. Baan J, van der Velde ET, de Bruin HG et al. Continuous
measurement of left ventricular Volume in animals and
humans by conductance catheter. Circulation 1984: 70: 812–
823.
8. Kass DA, Yamazaki T, Burkhoff D, Maughan WL, Sagawa
K. Determination of left ventricular end-systolic pressure-
Volume relationships by the conductance (volume) catheter
technique. Circulation 1986: 73: 586–595.
9. Sunagawa K, Maughan WL, Burkhoff D, Sagawa K. Left
ventricular interaction with arterial load studied in isolated
canine ventricle. Am J Physiol 1983: 245: H773–H780.
10. Suga H. Ventricular energetics. Physiol Rev 1990: 70: 247–277.
11. Little WC, Cheng CP. Left ventricular-arterial coupling in
conscious dogs. Am J Physiol 1991: 261: H70–H76.
12. Nozawa T, Yasumura Y, Futaki S, Tanaka N, Uenishi M,
Suga H. Efficiency of energy transfer from pressure-Volume
area to external mechanical work increases with contractile
state and decreases with afterload in the left ventricle of the
anesthetized closed-chest dog. Circulation 1988: 77: 1116–
1124.
13. Guyton AC, Richardson QT. Effect of hematocrit on venous
return. Circ Res 1961: 9: 157–164.
14. Suga H, Sagawa K, Shoukas AA. Load independence of the
52
instantaneous pressure-volume ratio of the canine left ven-
tricle and effects of epinephrine and heart rate on the ratio.
Circ Res 1973: 32: 314–322.
15. Suga H. Total mechanical energy of a ventricle model and
cardiac oxygen consumption. Am J Physiol 1979: 236: H498–
H505.
16. Suga H, Hayashi T, Shirahata M, Suehiro S, Hisano R. Re-
gression of cardiac oxygen consumption on ventricular
pressure-Volume area in dog. Am J Physiol 1981: 240: H320–
H325.
17. Sunagawa K, Maughan WL, Sagawa K. Optimal arterial re-
sistance for the maximal stroke work studied in isolated can-
ine left ventricle. Circ Res 1985: 56: 586–595.
18. Robotham JL, Takata M, Berman M, Harasawa Y. Ejection
fraction revisited. Anesthesiology 1991: 74: 172–183.
19. Hettrick DA, Pagel PS, Warltier DC. Alterations in canine
left ventricular-arterial coupling and mechanical efficiency
produced by propofol. Anesthesiology 1997: 86: 1088–1093.
20. Burkhoff D, van der Velde E, Kass D, Baan J, Maughan WL,
Sagawa K. Accuracy of Volume measurement by conduc-
tance catheter in isolated, ejecting canine hearts. Circulation
1985: 72: 440–447.
21. Maughan WL, Sunagawa K, Burkhoff D, Graves WL Jr,
Hunter WC, Sagawa K. Effect of heart rate on the canine
end-systolic pressure-Volume relationship. Circulation 1985:
72: 654–659.
22. Lowe D, Hettrick DA, Pagel PS, Warltier DC. Influence of
volatile anesthetics on left ventricular afterload in vivo. Dif-
ferences between desflurane and sevoflurane. Anesthesiology
1996: 85: 112–120.
Address:
Junpei Nozaki, MD
Department of Anesthesiology
Tokushima University School of Medicine
3-18-15 Kuramoto
Tokushima 770-8503
Japan
e-mail: jnozaki/clin.med.tokushima-u.ac.jp