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Transcript
Am J Physiol Heart Circ Physiol 298: H930–H937, 2010.
First published January 8, 2010; doi:10.1152/ajpheart.00987.2009.
Increased left ventricular twist, untwisting rates, and suction maintain global
diastolic function during passive heat stress in humans
Michael D. Nelson,1 Mark J. Haykowsky,2 Stewart R. Petersen,1 Darren S. DeLorey,1 June Cheng-Baron,3
and Richard B. Thompson3
1
Faculty of Physical Education and Recreation, 2Faculty of Rehabilitation Medicine, Department of Physical Therapy,
and 3Faculty of Medicine and Dentistry, Department of Biomedical Engineering, University of Alberta, Edmonton,
Alberta, Canada
Submitted 20 October 2009; accepted in final form 4 January 2010
hyperthermia; cardiac magnetic resonance imaging; biventricular
function
DURING PASSIVE HEAT STRESS (HS), cutaneous vascular conductance increases to augment skin blood flow to facilitate heat
loss (3, 34). To maintain blood pressure and tissue oxygen
delivery, cardiac output rises (17, 18, 33, 34, 41, 42), and
efferent sympathetic nerve activity increases to noncutaneous
vascular beds (32), redistributing blood flow away from skeletal muscle (21) and splanchnic vascular beds (7, 18, 34, 35)
toward the skin. Secondary to this redistribution of blood flow,
thoracic blood volume and central venous pressure is also
reduced significantly (17, 28, 34, 41, 42).
The effects of reduced cardiac filling pressure on ventricular
function remain unclear. A recent study reported that early
diastolic filling and mitral tissue velocities are maintained
during HS (3), suggesting that early diastolic function is
maintained despite reduced cardiac filling pressures. However,
the effect on left ventricular (LV) end-diastolic volume re-
Address for reprint requests and other correspondence: R. B. Thompson, Dept.
of Biomedical Engineering, 1082 Research Transition Facility, Univ. of Alberta,
Edmonton, AB, Canada T6G 2V2 (e-mail: [email protected]).
H930
mains equivocal, since previous studies have shown it decreases (41) or remains unchanged (7) during passive HS.
The development of minimum LV pressure is a function of
active relaxation and elastic recoil of the LV (13, 22). During
systole, basal-to-apical rotation of the LV (twisting) serves to
augment stroke volume, whereas, in addition, systolic torsional
deformation produces potential energy that is stored in myocardium (1, 2) and released as kinetic energy that facilitates LV
diastolic untwisting. LV untwisting is therefore closely associated with the generation of LV diastolic suction (4, 24, 38).
Increased twist and untwisting may provide the mechanistic
explanation for previous demonstration of maintained diastolic
function under reduced filling pressures; however, this has not
been studied to date.
The purpose of this investigation was to examine the mechanisms that maintain early diastolic function despite a reduction in filling pressures with HS. We hypothesized that LV
untwisting would increase with HS as a result of increased
systolic twist facilitating the maintenance of early diastolic
filling through increased ventricular suction.
METHODS
Eight healthy, sedentary males participated in this investigation.
All subjects provided written informed consent before study participation, which was approved by the University of Alberta Health
Research Ethics Board. Before each part of the experiment, each
subject was asked to abstain from caffeine, alcohol, and strenuous
physical activity for at least 24 h.
Experimental Protocol
Day 1. Incremental exercise test. Each subject completed an incremental exercise test on a cycle ergometer to measure maximal oxygen
consumption (V̇O2 max).
Day 2. Passive HS. Participants dressed in a tube-lined suit that
covered the entire body, with the exception of the face, hands, and feet
(Allen-Vanguard Technologies, Ottawa, ON). The subject lay in the
supine position, covered with a heavy blanket to reduce heat loss to
the environment while thermoneutral water (34°C) was circulated
throughout the suit for 30 min to establish a physiological baseline
(BL). Immediately after BL, 50°C water was circulated throughout the
suit for 60 min (whole body HS). This trial took place a minimum of
7 days before the magnetic resonance imaging (MRI) trial to avoid the
potential for acclimation. Core and skin temperatures could not be
monitored during MRI because of the presence of the ferrous metal in
the telemetry pill. Therefore, this test was used to establish the
physiological response to passive heating on day 3.
Day 3. Cardiac MRI and passive HS. After arriving at the Peter S.
Allen MRI center at the University of Alberta, subjects dressed in the
tube-lined suit, and the experimental protocol described for day 2 was
repeated while cardiac MRI were acquired.
0363-6135/10 $8.00 Copyright © 2010 American Physiological Society
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Nelson MD, Haykowsky MJ, Petersen SR, DeLorey DS, ChengBaron J, Thompson RB. Increased left ventricular twist, untwisting rates,
and suction maintain global diastolic function during passive heat stress in
humans. Am J Physiol Heart Circ Physiol 298: H930–H937, 2010. First
published January 8, 2010; doi:10.1152/ajpheart.00987.2009.—Left ventricular (LV) systolic function increases with passive heat stress (HS);
however, less is known about diastolic function. Eight healthy subjects (24.0 ⫾ 2.0 yr of age) underwent whole body passive heating
⬃1°C above baseline (BL). Cardiac magnetic resonance imaging was
used to measure biventricular volumes, function, filling velocities,
volumetric flow rates, and LV twist and strain at BL and after 45 min
of HS. Passive heating reduced left atrial volume (⫺17.6 ⫾ 11.7 ml,
P ⬍ 0.05), right and LV end-diastolic volumes (⫺22.7 ⫾ 11.0 and
⫺25.7 ⫾ 24.9 ml, respectively; P ⬍ 0.05), and LV stroke volume
(⫺6.7 ⫾ 6.8 ml, P ⬍ 0.05) from BL. LV ejection fraction (EF),
end-systolic elastance, septal and lateral mitral annular systolic velocities, circumferential strain, and peak LV twist increased with HS
(P ⬍ 0.05). Right ventricular stroke volume, EF, and systolic tissue
velocities were unchanged with HS (P ⬎ 0.05). Early LV diastolic
tissue and blood velocities and strain rates were maintained with HS,
whereas untwisting rate increased significantly from 166.4 ⫾ 46.9 to
268.7 ⫾ 76.8°/s (P ⬍ 0.05). The major novel finding of this study was
that, secondary to an increase in peak LV twist and untwisting rate,
early diastolic blood and tissue velocities and strain rates are maintained despite a reduction in filling pressure.
BIVENTRICULAR FUNCTION DURING PASSIVE HEAT STRESS
Measurements
all short axis slices). Tags were applied ⬃150 ms after the R wave to
ensure tag persistence and clarity throughout diastole. All MRI data
were cardiac gated based on an electrocardiogram and acquired during
end-expiratory breath holds. The order of image acquisition was kept
consistent, with total image acquisition time between 15 and 20 min
during both BL and following 45 min of passive HS.
Data Analysis
RV and LV volumes were assessed by manual endocardial tracing of
short-axis cine images at end-diastole and end-systole by a single nonblinded observer (M. D. Nelson). The papillary muscles were included in
all tracings. End systole was defined visually as the phase with the
smallest LV and RV volumes. Left atrial volumes were also calculated
using short axis slices, at a phase just before mitral valve opening (as
determined from a 3-chamber cine image), to capture the largest volume
over the cardiac cycle. Using our custom software, long-axis cine images
were also used to delineate basal and apical cardiac borders, for both
ventricular and atrial volumes. Left ventricular end-systolic cavity area
(ESCA) and end-systolic myocardial area (ESMA, epicardial border) at
the level of the papillary muscles was used to calculate end-systolic wall
stress (1.33 ⫻ SBP ⫻ ESCA/ESMA, where SBP is systolic blood
pressure) as previously described (14). Total peripheral resistance was
calculated as mean arterial blood pressure divided by cardiac output.
End-systolic elastance was calculated as systolic arterial blood pressure
divided by end-systolic volume. Our in-laboratory intrarater and interrater reliability for measuring LV volumes, reported as a coefficient of
variation, were determined to be 2.6 and 2.1%, respectively.
Volume flow rates were calculated as the sum of velocities over the
filling orifice multiplied by the pixel cross-sectional area (16, 37).
Peak early diastolic and systolic annular tissue velocities were assessed from a four-chamber cine image, using a manual tracking
program for calculation of annular position and velocity over the
entire cardiac cycle. In addition to conventional assessment of E and
A waveforms, a correction of the A wave at higher heart rates was
Fig. 1. Representative early (E) and late (A)
mitral filling rates (A and C, ml/s) and filling
velocities (B and D, m/s). Solid line, baseline
measures; broken line, heat stress. Baseline E
waves were overlaid (C and D) upon heat
stress waveforms to estimate the peak A wave
without the contribution from preceding E
wave momentum. The estimated amplitude is
indicated by the arrow (C and D).
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Maximal oxygen consumption. V̇O2 max was assessed with an incremental protocol on a cycle ergometer (Monark 894E, Varberg,
Sweden), with the workload set at 50 W increasing by 25 W every 2
min until ventilatory threshold, after which the workload was increased by 25 W every minute until volitional exhaustion. Ventilatory
threshold was defined as a systematic rise in the ventilatory equivalent
for O2, without an increase in the ventilatory equivalent for CO2 (8).
Expired gases were collected and analyzed with a metabolic measurement cart (TrueOne 2400; ParvoMedics), calibrated with known gas concentrations before each test. Flow was calibrated using a 3.0-liter syringe.
Thermal response. At least 4 h before the beginning of the familiarization trial (day 2), subjects ingested a thermistor pill and were
fitted with four dermal patches for the telemetric measurement of core
and skin temperature (VitalSense; Mini Mitter, Bend, OR). Mean skin
temperature was calculated as previously described (31).
Hemodynamic response. Arterial blood pressure was obtained from
an automatic blood pressure cuff, and mean arterial blood pressure
was calculated as one-third pulse pressure plus diastolic pressure.
Heart rate was continuously monitored by electrocardiogram.
Cardiac MRI. Short axis cine images covering the length of the
right ventricle (RV) and LV were acquired to assess end-diastolic and
end-systolic volume, stroke volume, and ejection fraction. Image
acquisition parameters were as follows: repetition time ⫽ 3.0 ms;
echo time ⫽ 1.5 ms; flip angle ⫽ 78°; slice thickness ⫽ 8 mm with
a 2-mm gap between slices; matrix ⫽ 256 ⫻ 192; field of view ⫽
300 –380 mm; 25 ms temporal resolution with 64 reconstructed
phases. Short axis through-plane phase contrast (velocity) images,
prescribed at the level of the mitral leaflet tips, were acquired to
measure early (E) and atrial (A) filling velocities and volumetric flow
rates. Peak early diastolic and systolic annular tissue velocities were
assessed from a four-chamber cine image. Myocardial tissue tagging
was applied in four to six short axis slices covering the entire LV to
assess peak twist and peak untwisting rate (using only apical and basal
slices), as well as global peak circumferential and radial strain (using
H931
H932
BIVENTRICULAR FUNCTION DURING PASSIVE HEAT STRESS
strain and strain rates were also defined as the peak value on the
corresponding strain and strain rate curves (27).
Statistical Analysis
Data are presented as a mean ⫾ SD. Paired sample t-tests were
used for statistical comparison between thermal conditions. Simple
linear regression was used to identify the relationships between
selected variables. The results of statistical analyses were considered
to be significant when P ⬍ 0.05.
RESULTS
Participant characteristics were as follows (mean ⫾ SD): age:
24.0 ⫾ 3.0 yr; height: 181.9 ⫾ 4.8 cm; body mass: 81.8 ⫾ 12.6
kg; V̇O2 max: 42.3 ⫾ 2.6 ml·kg⫺1·min⫺1 (range: 39.7 ⫺48.2
ml·kg⫺1·min⫺1). The aerobic fitness level of our subjects was
consistent with untrained members of this age category (43).
Whole body passive HS significantly elevated skin temperature
from 33.8 ⫾ 1.0°C at BL to 38.8 ⫾ 0.5°C, and core body
temperature increased from 37.1 ⫾ 0.3°C at BL to 38.0 ⫾ 0.5°C.
Passive HS reduced (P ⬍ 0.05) RV and LV end-diastolic
and end-systolic volumes and left atrial volume (Figs. 3 and 4).
LV systolic annular velocities at the septum (BL 7.1 ⫾ 1.0 cm/s
vs. HS 8.8 ⫾ 1.5 cm/s; P ⬍ 0.05) and lateral wall (BL 8.5 ⫾ 2.0
cm/s vs. HS 12.1 ⫾ 2.8 cm/s; P ⬍ 0.05) and LV end-systolic
elastance (BL 1.7 ⫾ 0.4 mmHg/ml vs. HS 2.3 ⫾ 0.6 mmHg/
ml) significantly increased with HS (P ⬍ 0.05), whereas LV
end-systolic wall stress (BL 79.5 ⫾ 7.3 mmHg·cm2 vs. 66.8 ⫾ 9.2
mmHg·cm2; P ⬍ 0.05) was reduced, resulting in a significant
Fig. 2. Representative illustration of peak twist (A),
peak untwisting rate (B), peak circumferential strain
(C), and peak circumferential strain rate (D) at
baseline (solid line) and during whole body heat
stress (broken line). Arrows indicate the peak value
for each measure.
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performed to estimate the contribution from the overlapping E wave,
as shown in Fig. 1.
The time of aortic valve closure and mitral valve opening was
determined using short axis blood velocity images that were oriented to
contain the leaflet planes. Cardiac events were referenced to aortic valve
closure (%systolic duration) and mitral valve opening (ms). Systolic
duration started from the time of ventricular depolarization (R wave,
electrocardiogram) and ended with the time of aortic valve closure. All
subsequent events were referenced to a percentage of this duration.
Tag analysis was fully automated, using image morphing software
developed in house, to determine the spatial deformation field for the
myocardium as a function of cardiac phase, relative to a reference
cardiac phase. The tag processing software was developed and is used
in the MATLAB environment using an open source algorithm for the
image morphing calculations (http://elastix.isi.uu.nl/index.php). User
input was limited to tracing the endo- and epicardium at a single
reference cardiac phase for each slice. The angle of rotation for each
short axis slice, ⌽, was calculated as the average rotation of each point
relative to the reference phase. The reference phase, relative to which
all deformations are referenced, was selected in diastasis, before atrial
contraction. All values were averaged over all positions, spanning
endo- to epicardium and all circumferential positions, and over all
slices for strain measurements. The global LV twist, ␪, was calculated
as the difference between the counterclockwise rotation at the apex
and clockwise rotation at the base (viewed from apex to base), ␪ ⫽
⌽apex ⫺ ⌽base. The rate of untwisting was calculated as the discrete
time derivative of the twist vs. time curve. Twist was defined as the
peak value on the curve, and peak untwisting rate was calculated as
the minimum value of the time derivative of the twist curve directly
following the time of peak twist (23). The peak rates of rotation were
also calculated separately for the apex and base. As shown in Fig. 2,
BIVENTRICULAR FUNCTION DURING PASSIVE HEAT STRESS
H933
increase (6.5%) in LV ejection fraction (Fig. 3). Peak twist and
peak systolic circumferential strain was greater during HS
compared with BL, whereas radial strain was unchanged (Table
2). Despite the significant improvement in systolic function, LV
stroke volume was reduced with HS (Fig. 3). As a result, cardiac
output was augmented entirely by an increase in heart rate (BL
69.8 ⫾ 3.9 beats/min vs. HS 108.1 ⫾ 9.8 beats/min; P ⬍ 0.05).
RV stroke volume tended to decline in response to HS, but
the changes were not statistically significant (Fig. 4, P ⫽ 0.08).
Both RV ejection fraction (Fig. 4) and systolic annular tissue
velocity (BL 12.3 ⫾ 1.6 cm/s vs. HS 14.3 ⫾ 2.9 cm/s; P ⫽
0.164) increased with HS (P ⬎ 0.05).
LV untwisting rate increased significantly with HS (see
Table 2), with no change in early diastolic filling velocity
AJP-Heart Circ Physiol • VOL
(Table 1). Peak early diastolic filling rates were reduced with
HS while the late filling rates and filling velocities were
unchanged (Table 1). All other diastolic functional parameters
were unchanged with HS, including the early diastolic annular
tissue velocities at the septal and lateral wall (Table 1) and the
’
RV free wall (12.4 ⫾ 1.7 vs. 13.5 ⫾ 5.8 cm/s), E/Esept
(6.7 ⫾
’
1.1 vs. 7.1 ⫾ 2.3), E/Elat (6.4 ⫾ 1.5 vs. 6.2 ⫾ 4.8), and the
circumferential and radial diastolic strain rates (Table 2).
Event Timings
Tables 1 and 2 report selected cardiac events in both absolute time (ms) and as a percentage of systolic duration. At both
BL and with HS, the sequence of events was as follows: peak
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Fig. 3. Effects of heat stress on left ventricular
(LV) and left atrial (LA) volumes as well as LV
ejection fraction (EF) and cardiac output (CO) at
baseline (BL) and heat stress (HS). *Significant
difference between conditions, P ⬍ 0.05. EDV,
end-diastolic volume; ESV, end-systolic volume; SV, stroke volume.
H934
BIVENTRICULAR FUNCTION DURING PASSIVE HEAT STRESS
twist, followed by the peak untwisting rate and finally the peak
blood and tissue velocities associated with early ventricular
filling.
Timing Changes With HS
Peak twist was delayed with respect to aortic valve closure
with HS. The early diastolic annular tissue velocities, E’lat and
’
Esep
, that normally precede the peak filling E wave velocity are
significantly delayed (P ⬍ 0.05) and follow the E wave peak
velocity with HS. The isovolumic relaxation time decreased by
13.6 ms with HS (P ⬍ 0.05).
DISCUSSION
The primary findings of this investigation were that whole
body passive HS significantly reduced biventricular preload
and left atrial volume while early diastolic functional parameters were maintained. It is proposed that increased LV recoil
and suction, associated with augmented LV twist and subsequent untwisting rates, offset the reduction in diastolic function
that normally accompanies reductions in central blood volume
and filling pressures.
Biventricular Function During Passive HS
Whole body HS is associated with a large increase in
cutaneous vascular conductance and concomitant decreases in
central venous pressure (6, 7, 17, 28, 36, 42) and LV filling
pressure (41, 42). The effect of HS on LV end-diastolic volume
AJP-Heart Circ Physiol • VOL
has not been definitively established, since the available literature is conflicting. Crandall et al. (7), using multiple-gated
acquisition imaging, demonstrated that LV end-diastolic volume was unaltered by passive heating (despite reduced central
venous pressure). In contrast, Wilson et al. (41), using twodimensional echocardiography, found that passive heating reduced LV end-diastolic volume and pulmonary capillary
wedge pressure by ⬃11% and ⬃29%, respectively. Our results
confirm that HS reduces LV end-diastolic volume (11.3%) and
expand on prior work by showing a 13.5% reduction in RV
end-diastolic volume. The difference between these studies
remains difficult to explain; however, measurement sensitivity
is a likely explanation for the differing results.
During periods of reduced preload, the maintenance of
stroke volume is largely dependent on enhanced LV contractility and/or reduced afterload. Consistent with previous reports
(3, 7), passive HS significantly increased LV systolic function,
as evidenced by an increase in LV ejection fraction, endsystolic elastance, and peak septal and lateral mitral annular
velocities, which were coupled with reduced LV end-systolic
wall stress. Basal-to-apical systolic rotation (twist) was also
found to increase with HS, contributing to the reduction in
end-systolic volume. To our knowledge, this is the first study
to report that passive HS increases LV twist and circumferential strain. Notwithstanding enhanced contractility, we observed a small but significant decrease in stroke volume (4%).
Previous studies have reported stroke volume to be maintained
or even slightly elevated during HS (34, 41, 42). However, our
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Fig. 4. Effects of HS on right ventricular (RV)
EDV, ESV, SV, and EF at BL and HS. *Significant difference between conditions, P ⬍ 0.05.
H935
BIVENTRICULAR FUNCTION DURING PASSIVE HEAT STRESS
Table 1. Effects of passive heat stress on diastolic filling
HS
293 ⫾ 13
100 ⫾ 0.0
207 ⫾ 16*
100 ⫾ 0.0
341 ⫾ 17
116.5 ⫾ 2.9
242 ⫾ 20*
116.8 ⫾ 2.9
48 ⫾ 9
35 ⫾ 7*
61.9 ⫾ 6.5
444 ⫾ 16
151.8 ⫾ 7.2
102.8 ⫾ 12.3
58.3 ⫾ 5.5
333 ⫾ 30*
161.3 ⫾ 9.3*
91.9 ⫾ 17.3
616.9 ⫾ 97.9
438 ⫾ 19
149.8 ⫾ 5.6
97.0 ⫾ 10.6
553.4 ⫾ 86.7*
326 ⫾ 19*
158.1 ⫾ 5.6*
84.9 ⫾ 4.3*
33.4 ⫾ 2.2
48.9 ⫾ 12.3*
33.4 ⫾ 2.2
805 ⫾ 67
275.0 ⫾ 17.5
463.9 ⫾ 55.3
38.0 ⫾ 10.4
452 ⫾ 44*
218.6 ⫾ 16.9*
210.2 ⫾ 37.1*
260.2 ⫾ 44.7
380.6 ⫾ 37.2*
260.2 ⫾ 44.7
804 ⫾ 68
274.9 ⫾ 18.0
463.5 ⫾ 57.2
266.1 ⫾ 63.1
450 ⫾ 46*
217.5 ⫾ 19.4*
208.2 ⫾ 40.6*
9.4 ⫾ 1.1
417 ⫾ 19.4
141.9 ⫾ 7.9
73.2 ⫾ 19.3
8.9 ⫾ 2.4
353 ⫾ 20.2*
170.9 ⫾ 11.8
112.0 ⫾ 19.3*
10.0 ⫾ 1.4
397 ⫾ 15
136.2 ⫾ 8.4
56.9 ⫾ 18.6
12.0 ⫾ 4.1
336 ⫾ 21
162.9 ⫾ 12.0
95.6 ⫾ 18.4
Data reported as means ⫾ SE; n ⫽ 8 subjects. Time is the duration from
ventricular depolarization (R wave) to the onset of the cardiac event. Systole
refers to the %systolic duration from the R wave. BL, baseline; HS, heat stress.
*Significant difference between conditions (P ⬍ 0.05).
results suggest that, during passive HS, the reduction in endsystolic volume does not completely compensate for the decrease in end-diastolic volume.
LV Diastolic Function During Passive HS
It is well known that reductions in venous return and thus
filling pressures will significantly reduce both early mitral
inflow velocity and mitral annular velocities (11, 20, 26, 29).
Mild unloading (⫺30 mmHg of lower body negative pressure)
has been shown to reduce E wave velocities from 77 to 53 cm/s
and E= in the lateral wall from 15.0 to 10.1 cm/s (11). Similar
unloading, at ⫺40 mmHg of lower body negative pressure, in
healthy young volunteers reduced LV end-diastolic volume by
14.8 ml with a reduction of E wave velocities by 15 cm/s (10).
The reduction in these velocities is associated with reduced
atrial pressure, particularly at the time of mitral valve opening
(5, 15). In the present study, we found that passive HS yielded
a significant reduction in LV end-diastolic volume, similarly to
AJP-Heart Circ Physiol • VOL
Table 2. Effects of passive heat stress on left ventricular
torsion, elastic recoil, and strain
Peak torsion
°
Time, ms
Systole, %
Time from mitral valve opening, ms
Peak untwisting rate
°/s
Time, ms
Systole, %
Time from mitral valve opening, ms
Basal diastolic rotation rate
°/s
Time, ms
Systole, %
Time from mitral valve opening, ms
Apical diastolic rotation rate
°/s
Time, ms
Systole, %
Time from mitral valve opening, ms
Peak circumferential strain
%
Time, ms
Systole, %
Time from mitral valve opening, ms
Peak radial strain
%
Time, ms
Systole, %
Time from mitral valve opening, ms
Peak circumferential strain rate
(diastole)
1/s
Time, ms
Systole, %
Time from mitral valve opening, ms
Peak radial strain rate (diastole)
1/s
Time, ms
Systole, %
Time from mitral valve opening, ms
BL
HS
12.8 ⫾ 4.1
291 ⫾ 20
99.6 ⫾ 4.7
⫺49.3 ⫾ 18.9
21.1 ⫾ 4.2*
228 ⫾ 24*
110.2 ⫾ 6.6*
⫺13.6 ⫾ 18.6*
166.4 ⫾ 46.9
350 ⫾ 28
119.9 ⫾ 9.5
9.6 ⫾ 30.0
268.7 ⫾ 76.8*
268 ⫾ 17*
129.9 ⫾ 6.9*
30.9 ⫾ 11.8*
44.8 ⫾ 18.5
377 ⫾ 18
129.0 ⫾ 7.1
36.1 ⫾ 20.3
35.3 ⫾ 9.1
291 ⫾ 34*
141.5 ⫾ 21
49.4 ⫾ 42
146.0 ⫾ 37.9
337 ⫾ 26
115.3 ⫾ 9.9
28.5 ⫾ 13.4
251.2 ⫾ 75.9*
267 ⫾ 16*
129.5 ⫾ 7.3*
30.1 ⫾ 17.3
⫺19.0 ⫾ 1.6
288 ⫾ 36
98.2 ⫾ 9.5
⫺53.1 ⫾ 28.9
⫺21.7 ⫾ 2.7*
222 ⫾ 21*
107.8 ⫾ 12.2
⫺19.5 ⫾ 25.1*
31.6 ⫾ 4.9
287 ⫾ 50
98.1 ⫾ 16.1
⫺53.5 ⫾ 45.0
31.1 ⫾ 8.6
209 ⫾ 51*
101.2 ⫾ 24.7
⫺32.6 ⫾ 48.8
1.84 ⫾ 0.28
420 ⫾ 30
143.4 ⫾ 6.7
78.9 ⫾ 24.6
1.80 ⫾ 0.34
337 ⫾ 13*
163.5 ⫾ 9.9*
95.4 ⫾ 15.9
⫺2.15 ⫾ 2.2
407 ⫾ 33
139 ⫾ 8.6
66.0 ⫾ 27.9
⫺2.47 ⫾ 2.3
336 ⫾ 26*
163 ⫾ 14.8*
94.4 ⫾ 26.8
Data reported as means ⫾ SE; n ⫽ 8 subjects. *Significant difference
between conditions (P ⬍ 0.05).
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Aortic valve closure (end systole)
Time, ms
Systole, %
Mitral valve opening
Time, ms
Systole, %
Isovolumic relaxation time
Time, ms
Early diastolic peak filling velocity (E)
cm/s
Time, ms
Systole, %
Time from mitral valve opening, ms
Early diastolic peak filling rate
ml/s
Time, ms
Systole, %
Time from mitral valve opening, ms
Late diastolic peak filling velocity (A)
cm/s
cm/s (with subtraction of E wave
component)
Time, ms
Systole, %
Time from mitral valve opening, ms
Late diastolic peak filling rate
ml/s
ml/s (with subtraction of E wave
component)
Time, ms
Systole, %
Time from mitral valve opening, ms
Septal early diastolic annular tissue velocity
cm/s
Time, ms
Systole, %
Time from mitral valve opening, ms
Lateral early diastolic annular tissue velocity
cm/s
Time, ms
Systole, %
Time from mitral valve opening, ms
BL
these unloading studies, by 20.3 ⫾ 11.7 ml (P ⬍ 0.05), with a
reduction in left atrial volumes, by ⫺17.6 ⫾ 11.7 ml (P ⬍
0.05). However, in contrast to unloading studies, early mitral
inflow and mitral annular velocities were unchanged. The
maintenance of early diastolic blood and tissue velocities, as
well as circumferential and diastolic strain rates, given the
significant volume unloading suggests that the ventricular
contribution to early diastolic function is augmented with
passive heating. Our results therefore suggest that the increased
LV untwisting rate, which is strongly associated with increased
recoil and LV suction (9, 12, 19, 24, 25, 30), is responsible for
maintaining early diastolic function, counteracting the effects of
the reduction in left atrial volume and, likely, filling pressures.
The relationships between twist, untwisting rates, and early
filling have been documented previously. End-systolic volume
and the extent of LV systolic twist are inversely related to the
magnitude of untwisting generated during diastole (22, 39, 44).
Nearly half of untwisting occurs before mitral valve opening,
during isovolumic relaxation (19, 24, 30), and the extent of this
H936
BIVENTRICULAR FUNCTION DURING PASSIVE HEAT STRESS
tematic errors in these values because of limitations of temporal resolution.
In conclusion, our study demonstrates that whole body
passive HS: 1) reduces cardiac preload, as evidenced by
reduced LV and RV end-diastolic volumes, 2) increases LV
contractility, as demonstrated by an increase in mitral systolic
tissue velocities, increased LV end-systolic elastance and ejection fraction, and augmented LV twist, and 3) that increased
LV twisting gives rise to increased untwisting rates during HS,
and maintains indexes of global diastolic function despite
decreases in filling pressures, as reflected by reductions in left
atrial volumes. LV untwisting has previously been associated
with increased LV suction (9, 24, 38); as such, we reason that,
without an increase in LV untwisting rate in the presence of
reduced left atrial volume, LV end-diastolic volume would be
reduced to a greater extent during passive heating, leading to
larger reductions in stroke volume.
Limitations
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Several limitations must be considered when interpreting the
present results. Core temperature could not be measured on the
same day as MRI for safety reasons (i.e., telemetry pill contains ferrous metal). We are confident, however, that we can
predict core temperature from prior HS exposures within a very
small margin of error. Pilot work in heat-stressed subjects
confirmed a low between-day variation in the relative change
in core and skin temperature from BL (0.1 and 0.6°C, respectively), equivalent to 12.4 and 10.1% coefficient of variation,
respectively. Central venous pressure or pulmonary capillary
wedge pressure was not measured in the present experiment;
however, numerous investigations using similar protocols have
previously documented this response (7, 41, 42). A complete
cardiac scan took ⬃10 –15 min, which corresponded to a 0.4 ⫾
0.1°C change in core temperature during the passive HS
condition. It is therefore possible that measurements near the
beginning of the scan (e.g., volumes) may not correspond
precisely with measurements taken near the end of the scan
(e.g., tissue velocities). However, any error made would be
systematic and therefore not selectively influence one condition over the other. Finally, the reported average changes in the
timing of some events with HS, such as the reduction in
isovolumic relaxation time, are less than the temporal resolution of the imaging studies. It is possible that there are sysAJP-Heart Circ Physiol • VOL
ACKNOWLEDGMENTS
We acknowledge Zoltan Kenwell for technical assistance, Brad Welch and
Meredith Giroux for assistance with data collection, and Gordon Sleivert and
the Canadian Sport Centre, Pacific, for the use of equipment.
GRANTS
M. D. Nelson and J. Cheng-Baron were supported by doctoral scholarships
from the Natural Sciences and Engineering Research Council of Canada. M. J.
Haykowsky has a career award from the Canadian Institutes of Health
Research. S. R. Petersen was supported by the Department of National
Defense. R. B. Thompson is an Alberta Heritage Foundation for Medical
Research Scholar.
DISCLOSURES
No conflicts of interest are declared by the authors.
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