Download Left ventricular mechanical limitations to stroke volume in healthy

Am J Physiol Heart Circ Physiol 301: H478–H487, 2011.
First published May 13, 2011; doi:10.1152/ajpheart.00314.2011.
TRANSLATIONAL PHYSIOLOGY
Left ventricular mechanical limitations to stroke volume in healthy humans
during incremental exercise
Eric J. Stöhr,1 José González-Alonso,1 and Rob Shave1,2
1
Centre for Sports Medicine and Human Performance, Brunel University, Uxbridge; and 2Cardiff School of Sport, University
of Wales Institute Cardiff, Cardiff, United Kingdom
Submitted 29 March 2011; accepted in final form 9 May 2011
twist; torsion; untwisting; diastole
IN HEALTHY INDIVIDUALS,
the increase in cardiac output at the
transition from rest to exercise is achieved by a combination of
both enhanced heart rate (HR) and stroke volume (SV) (18, 21,
25). Although some investigators have contested a plateau in
SV during incremental exercise (14, 38), a considerable number of studies have shown that SV levels off at ⬃40 –50% of
the maximal exercise capacity (18, 21, 22, 25, 26). This
leveling off of SV is the result of a plateau in both end-diastolic
volume (EDV) and end-systolic volume (ESV) (25). Maintained EDV and ESV suggest that LV filling and ejection do
not increase further above moderate exercise intensities. However, this is surprising considering that central venous pressure
Address for reprint requests and other correspondence: R. Shave, Univ.
of Wales Institute Cardiff, Cyncoed Campus, Cyncoed Road, Cardiff CF23
6XD, UK.
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and inotropic state appear to increase continuously to the point
of task failure (12, 22). Thus the plateau in SV may be related
to cardiac mechanical constraints in accommodating a greater
EDV or further decreasing ESV.
Previous studies have shown that left ventricular (LV) twist and
untwisting (“LV twist mechanics”) play an important role in
normal systolic and diastolic function at rest, contributing to LV
ejection and filling (6, 13, 27, 28, 31). Two recent studies have
further demonstrated that systolic and diastolic LV twist mechanics are significantly enhanced in healthy individuals performing
low- to moderate-intensity exercise (9, 23), whereas twist and
untwisting are unaltered in patients with hypertrophic cardiomyopathy during mild effort (23). Although these findings underline
the importance of dynamic twist mechanics for LV function in
individuals without any known cardiac disease, the normal response of LV mechanics to exercise at intensities exceeding 40%
peak power has never been assessed. It is possible that the
previously observed plateau in EDV and ESV despite progressive
increases in central venous pressure and contractility may be
reflective of an underlying limit in cardiac twist mechanics.
The aim of the present study was to examine the relationships between LV twist mechanics and SV, HR, cardiac output,
ESV, and EDV to gain insight into the factors underlying the
plateau in SV. To determine whether the relationships would
be directly caused by the exercise performed, healthy individuals were assessed during both continuous and discontinuous
incremental exercise. We hypothesized that a limit in twist
mechanics at submaximal exercise intensities is an important
factor underlying the leveling off in SV during incremental
exercise in healthy individuals.
METHODS
Study Population
Following ethical approval from the Brunel University Research
Ethics Committee, nine healthy recreationally active males (age 26 ⫾
4 yr, height 175.1 ⫾ 4.9 cm, peak power 249 ⫾ 31 W, peak HR
173 ⫾ 14 beats/min) provided verbal and written informed consent to
take part in the study. To ensure optimal echocardiographic images,
participants were examined for quality of images before enrolment.
This study conforms to the code of ethics of the World Medical
Association (Declaration of Helsinki).
Familiarization and Exercise Testing
Participants attended the laboratory a total of four times with
visits separated by 48 –72 h. On days 1 and 2, participants were
familiarized with supine cycling (Lode, Angio 2003, Groningen,
Netherlands) in the left lateral position tilted at a 45° angle [see
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Stöhr EJ, González-Alonso J, Shave R. Left ventricular mechanical limitations to stroke volume in healthy humans during incremental exercise. Am J Physiol Heart Circ Physiol 301: H478 –H487, 2011.
First published May 13, 2011; doi:10.1152/ajpheart.00314.2011.—
During incremental exercise, stroke volume (SV) plateaus at 40 –50%
of maximal exercise capacity. In healthy individuals, left ventricular
(LV) twist and untwisting (“LV twist mechanics”) contribute to the
generation of SV at rest, but whether the plateau in SV during
incremental exercise is related to a blunting in LV twist mechanics
remains unknown. To test this hypothesis, nine healthy young males
performed continuous and discontinuous incremental supine cycling
exercise up to 90% peak power in a randomized order. During both
exercise protocols, end-diastolic volume (EDV), end-systolic volume
(ESV), and SV reached a plateau at submaximal exercise intensities
while heart rate increased continuously. Similar to LV volumes,
two-dimensional speckle tracking-derived LV twist and untwisting
velocity increased gradually from rest (all P ⬍ 0.001) and then leveled
off at submaximal intensities. During continuous exercise, LV twist
mechanics were linearly related to ESV, SV, heart rate, and cardiac
output (all P ⬍ 0.01) while the relationship with EDV was exponential. In diastole, the increase in apical untwisting was significantly
larger than that of basal untwisting (P ⬍ 0.01), emphasizing the
importance of dynamic apical function. In conclusion, during incremental exercise, the plateau in LV twist mechanics and their close
relationship with SV and cardiac output indicate a mechanical
limitation in maximizing LV output during high exercise intensities. However, LV twist mechanics do not appear to be the sole
factor limiting LV output, since EDV reaches its maximum before
the plateau in LV twist mechanics, suggesting additional limitations in diastolic filling to the heart.
LV MECHANICS AND STROKE VOLUME DURING EXERCISE
ing the two trials, the order of exercise stages within the discontinuous
trial was also randomized. Following completion of each stage during the
discontinuous trial, participants were given up to 10 min recovery in the
supine position to allow HR to return to baseline. To avoid changes in
hydration status between the continuous and discontinuous exercise test,
participants were provided with a 4.5% glucose solution to drink ad
libitum after their first trial.
Throughout both exercise trials, mean arterial blood pressure
(MAP) was assessed using a beat-by-beat arterial blood pressure
monitoring system (FinometerPRO, FMS; Finapres Measurement
Systems, Arnhem, Netherlands) and recorded continuously for
off-line analysis (PowerLab; ADInstruments, Chalgrove, UK).
MAP was calculated as the average blood pressure obtained from
the beat-by-beat pressure waveforms during the last 2 min of each
exercise stage (Chart Version 5.5.6; ADInstruments). HR was
recorded continuously via the ECG inherent to the ultrasound
(Vivid 7; GE Medical).
Fig. 1. Systemic cardiovascular and global
left ventricular (LV) function during continuous and discontinuous incremental exercise. Mean arterial pressure, heart rate (HR),
and cardiac output increased continuously
while end-diastolic volume (EDV), end-systolic volume (ESV), and stroke volume (SV)
reached a plateau at submaximal exercise
intensities. Filled and open squares represent
continuous and discontinuous exercise, respectively. W, workload. Data are means ⫾
SE. #P ⬍ 0.01 between continuous and discontinuous trials (n ⫽ 9).
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Supplemental Video 1 (Supplemental data for this article may be
found on the American Journal of Physiology: Heart and Circulatory Physiology website.)]. On day 3, each participant performed
a continuous incremental exercise test to volitional fatigue from
which individual peak power (Lode, Angio 2003) and peak HR
(Vivid 7; GE Medical, Horton, Norway) were determined. On the
experimental day, following 10 min of rest on the supine cycle
ergometer, each participant performed incremental exercise to
volitional fatigue. To have confidence that our results were reproducible and that the observation would be directly related to the
exercise performed, each participant completed both a continuous
and discontinuous exercise protocol in a randomized order separated by 1 h of rest. Exercise during the continuous and discontinuous trials was performed for 4 min at 25 ⫾ 3, 75 ⫾ 9, 125 ⫾
15, 174 ⫾ 22, and 224 ⫾ 28 W, which equated to 10, 30, 50, 70,
and 90% of the individual peak power attained during the initial
continuous incremental exercise to fatigue. In addition to counterbalanc-
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LV MECHANICS AND STROKE VOLUME DURING EXERCISE
Echocardiography
Statistical Analysis
Data are presented as means ⫾ SD unless otherwise stated. The
change in blood pressure and LV function indexes during the continuous and discontinuous protocol was analyzed using repeated-measures ANOVA. Paired-samples t-test was used post hoc to detect
differences between conditions; Bonferroni correction was applied to
account for multiple comparisons. Comparison between the responses
during the continuous and discontinuous trial was performed using
two-way repeated-measures ANOVA. Relationships between variables were assessed using Pearson’s product moment correlation.
Alpha was set a priori to 0.05. All statistical analyses were performed
using STATISTICA (version 6; StatSoft, Tulsa, OK).
Table 1. Cardiovascular responses to incremental exercise
Workload, %peak power output
Heart rate, beats/min
Cont
Discont
EDV, ml
Cont
Discont
ESV, ml
Cont
Discont
SV, ml
Cont
Discont
Q, l/min
Cont
Discont
MAP, mmHg
Cont
Discont
IVRT, ms
Cont
Discont
Control
10%
30%
50%
70%
90%
62 ⫾ 9
63 ⫾ 7
95 ⫾ 10&
105 ⫾ 14*
112 ⫾ 17&
117 ⫾ 21*
134 ⫾ 19&
138 ⫾ 21&
159 ⫾ 18&
147 ⫾ 16*†‡
171 ⫾ 14&
158 ⫾ 12&
P ⬍ 0.001
135 ⫾ 6
128 ⫾ 10
145 ⫾ 13
138 ⫾ 10
153 ⫾ 10*
139 ⫾ 11
153 ⫾ 14*
145 ⫾ 13
153 ⫾ 11*
145 ⫾ 10*
148 ⫾ 18
150 ⫾ 11*
NS
46 ⫾ 4
44 ⫾ 6
41 ⫾ 6*
37 ⫾ 8
35 ⫾ 8*
31 ⫾ 8*
28 ⫾ 8*†‡
26 ⫾ 7*†
26 ⫾ 8*†‡
28 ⫾ 8*
89 ⫾ 8
84 ⫾ 5
104 ⫾ 11*
101 ⫾ 12*
118 ⫾ 13*†
109 ⫾ 11*
125 ⫾ 15*†
119 ⫾ 13*
127 ⫾ 11*†
117 ⫾ 8*
124 ⫾ 14*†
122 ⫾ 9*†‡
5.5 ⫾ 0.8
5.2 ⫾ 0.6
9.8 ⫾ 0.7*
10.7 ⫾ 2.5*
13.2 ⫾ 1.9&
12.7 ⫾ 2.5&
16.6 ⫾ 2.0&
16.3 ⫾ 2.7&
20.1 ⫾ 1.8&
17.1 ⫾ 2.0*†‡
21.1 ⫾ 1.6*†‡$
19.2 ⫾ 1.5*†‡$
P ⬍ 0.001
79 ⫾ 8
84 ⫾ 9
99 ⫾ 5*
98 ⫾ 8*
104 ⫾ 4*
97 ⫾ 10*
109 ⫾ 6&
110 ⫾ 12*‡
113 ⫾ 9*†‡
120 ⫾ 13*†‡
121 ⫾ 10&
126 ⫾ 12*†‡$
P ⬍ 0.01
75 ⫾ 10
75 ⫾ 16
69 ⫾ 11*
67 ⫾ 12
58 ⫾ 6*†
55 ⫾ 10*
51 ⫾ 10*†
50 ⫾ 12*†
44 ⫾ 9*†‡
45 ⫾ 12*†
44 ⫾ 11*†‡
41 ⫾ 14*†
NS
24 ⫾ 10*†‡
28 ⫾ 8*
Cont vs. discont
NS
NS
Values are means ⫾ SD. Cont, continuous incremental exercise; Discont, discontinuous incremental exercise; IVRT, isovolumic relaxation time; Q, cardiac
output; EDV, end-diastolic volume; ESV, end-systolic volume; SV, stroke volume; MAP, mean arterial pressure. *P ⬍ 0.01 compared with rest. †P ⬍ 0.01
compared with 10%. ‡P ⬍ 0.01 compared with 30%. $P ⬍ 0.01 compared with 50% exercise. &P ⬍ 0.01 compared with 70%. NS, not significant.
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Standard measurements. Echocardiographic images were recorded
with a 1.5- to 4-MHz phased array transducer on a commercially
available ultrasound system (Vivid 7; GE Medical) at baseline (rest)
and during the last 2 min of each exercise stage. All images were
taken by a highly experienced trained sonographer. Participants were
familiarized with brief periods of end-expiratory breath-hold during
exercise. Parasternal short-axis and apical four-chamber views were
recorded at end-expiration, and three consecutive cardiac cycles were
saved for offline analysis. Because of increasing HRs with incremental exercise, the time that participants had to perform end-expiratory
breath-hold to acquire three cardiac cycles was progressively reduced.
LV parasternal short-axis images on the level of the papillary muscles
were analyzed for end-diastolic and end-systolic diameters. Because
of the high HRs during later stages of incremental exercise, we used
M-mode with its high temporal resolution (up to 2,000 frames/s;
see Ref. 11) to calculate EDV, ESV, and SV according to the
method by Teichholz et al. (36). Cardiac output was calculated as
the product of HR and SV averaged over three cardiac cycles.
Isovolumic relaxation time (IVRT) was assessed using pulsedwave tissue Doppler of the septal mitral annulus as previously
described (3).
LV speckle tracking twist mechanics. LV systolic and diastolic
rotation were assessed from parasternal short-axis images recorded
at the LV base on the level of the mitral valve and at the apex as
close to the point of end-systolic luminal obliteration as possible
(37), which was achieved by moving the transducer one to two
intercostal spaces lower than the basal image. To ensure reproducibility of images at all stages of exercise, the position of the
ultrasound transducer during baseline assessment was marked on
the participant’s chest. This enabled rapid identification of a
similar apical imaging window, allowing the sonographer to then
visually adjust and acquire comparable cross-sectional views.
Furthermore, frame rate was kept constant between all subjects and
all conditions at 97 frames/s; imaging depth for both LV basal and
apical short-axis views was also standardized within participants
(33). A single focal point was positioned in the center of the
ventricular cavity for all short-axis images. Images were analyzed
off-line for two-dimensional (2-D) speckle tracking-derived basal
and apical rotation and rotational velocities (EchoPAC, Version
7.0.0; GE Medical). 2-D speckle tracking was successful at low
and high exercise intensities up to near maximal effort (see
Supplemental Video 2). To adjust for inter- and intraindividual
variability of HR, raw data were exported to a spreadsheet (Microsoft, Seattle, WA) and normalized to the percentage of systolic and
diastolic duration, respectively (7). Normalization was achieved by cubic
spline interpolation of systolic and diastolic data to 300 points, respectively (GraphPad Prism 5.00 for Windows, San Diego, CA). LV twist,
untwisting, and the respective velocities were obtained by subtraction of basal rotation/rotation velocity data from apical rotation/
rotation velocity data. Peak untwisting velocity was determined as the
greatest negative deflection following peak twisting velocity. In addition to peak values, the absolute time it took for LV twist indexes to
reach their peak was determined from the frame-by-frame speckle
tracking analysis and expressed in milliseconds. Comparison between temporal occurrence of mitral valve opening and peak
diastolic untwisting velocity was performed to assess whether peak
diastolic twist indexes occurred before, simultaneously with, or
following mitral valve opening.
LV MECHANICS AND STROKE VOLUME DURING EXERCISE
RESULTS
LV Volumes and Arterial Blood Pressure
the increase in LV twist, twist velocity, and untwisting velocity
reached a plateau at ⬃50% peak power and remained at this level
for all subsequent exercise stages (Table 2). Compared with the
discontinuous trial, twist and twisting velocity were significantly
higher at 70% peak power during continuous incremental exercise
(P ⱕ 0.01); however, all other twist indexes did not differ between
the two protocols (P ⬎ 0.05). In both trials, the increase in
diastolic apical rotation velocity from rest to 90% maximal exercise capacity was significantly higher than the increase in basal
rotation velocity (P ⬍ 0.01, Fig. 3). In addition to the significant
change in peak values, temporal analysis showed that peak diastolic apical rotation and peak untwisting velocity reached their
peak at the same time as mitral valve opening at all exercise stages
(P ⬍ 0.01) while peak LV diastolic basal rotation velocity
occurred significantly after mitral valve opening at 70 and 90%
maximal exercise capacity (all P ⬍ 0.01, Fig. 4).
As shown in Figs. 5 and 6, during continuous exercise LV,
twist mechanics correlated linearly with SV, HR, cardiac output,
and ESV (P ⬍ 0.01), whereas the relationships between LV
mechanics and EDV appeared to have an exponential pattern.
Furthermore, during both trials, LV twist and untwisting velocity
were strongly related (P ⱕ 0.01, Fig. 7).
LV Twist Mechanics
Peak LV systolic and diastolic basal rotation, apical rotation,
twist, and the respective velocities increased significantly from
rest to exercise (all P ⬍ 0.01, Fig. 2). Similar to the SV response,
DISCUSSION
This is the first study to examine whether the plateau in
SV at submaximal exercise intensities is underpinned by
Fig. 2. Graphical representation of the mean LV twist
mechanics over the course of an entire cardiac cycle
during continuous (A) and discontinuous (B) incremental exercise (n ⫽ 9). LV systolic and diastolic
twist mechanics increased continuously up to moderate exercise intensities and leveled off thereafter. Red,
blue, and black lines represent LV apex, base, and
twist, respectively. Vertical lines show aortic valve
closure (AVC, solid line) and mitral valve opening
(MVO, broken line). Data are means ⫾ SE. Rot,
rotation. For the purpose of clarity, error bars have
been omitted, but values are provided in Table 2.
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During the initial stages of both continuous and discontinuous
incremental exercise, EDV and SV significantly increased while
ESV significantly decreased compared with rest (all P ⬍ 0.01;
Fig. 1). Following this initial response, EDV reached a plateau at
⬃30% peak power while ESV and SV leveled off at ⬃50% peak
power (Table 1). As a result of the progressive rise in HR, cardiac
output increased continuously up to 70% peak power and then
also plateaued (all P ⬍ 0.01). Because of a significantly higher
HR during the later stages of the continuous trial, the increase in
cardiac output was also larger during the continuous protocol
(both P ⬍ 0.01). In contrast, the increase in MAP was significantly lower during the later stages of the continuous trial (P ⬍
0.01). During both continuous and discontinuous exercises, IVRT
declined continuously and was not significantly different between
trials (P ⬍ 0.01). Body mass was unaltered before and following
both protocols (precontinuous: 70.5 ⫾ 8.3 kg; postcontinuous:
70.4 ⫾ 8.4 kg; prediscontinuous: 70.5 ⫾ 8.3 kg; postdiscontinuous: 70.2 ⫾ 8.4 kg; all P ⬎ 0.05).
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LV MECHANICS AND STROKE VOLUME DURING EXERCISE
Table 2. Peak systolic and diastolic LV twist indexes at rest and during incremental exercise
Workload, %peak power output
Control
10%
30%
50%
70%
90%
Cont vs. discont
Peak (systole)
13.9 ⫾ 3.9
11.0 ⫾ 4.2
15.4 ⫾ 2.4
17.2 ⫾ 3.9
19.8 ⫾ 5.1*
20.1 ⫾ 6.3*
23.8 ⫾ 6.0*†
25.3 ⫾ 7.0*
26.8 ⫾ 4.2*†‡
21.2 ⫾ 3.6*
24.7 ⫾ 6.9*†
22.4 ⫾ 3.1*
P ⫽ 0.01
10.0 ⫾ 2.7
8.0 ⫾ 3.4
11.7 ⫾ 2.2
14.3 ⫾ 3.4*
15.4 ⫾ 4.7
16.5 ⫾ 4.3*
18.3 ⫾ 5.6*†
19.1 ⫾ 5.4*
19.5 ⫾ 3.1*†‡
16.8 ⫾ 3.3*
18.5 ⫾ 5.2*†
15.8 ⫾ 2.8*
NS
⫺4.4 ⫾ 2.3
⫺3.6 ⫾ 2.3
⫺4.2 ⫾ 2.0
⫺4.2 ⫾ 2.1
⫺6.2 ⫾ 2.3*†
⫺4.3 ⫾ 2.8*†
103 ⫾ 21
91 ⫾ 22
105 ⫾ 18
130 ⫾ 36
150 ⫾ 31*†
147 ⫾ 42*
⫺63 ⫾ 15
⫺57 ⫾ 24
⫺73 ⫾ 19
⫺71 ⫾ 29
89 ⫾ 22
75 ⫾ 36
107 ⫾ 32*
131 ⫾ 28*
⫺95 ⫾ 30*
⫺74 ⫾ 29
149 ⫾ 37*†
150 ⫾ 30*
⫺6.5 ⫾ 2.6†
⫺7.2 ⫾ 3.7†
200 ⫾ 49*†‡
208 ⫾ 43*†‡
⫺8.0 ⫾ 2.5†
⫺5.6 ⫾ 2.2†
⫺7.8 ⫾ 3.3
⫺7.1 ⫾ 2.5
NS
232 ⫾ 35*†‡
193 ⫾ 38*
216 ⫾ 42*†‡
206 ⫾ 53*
⫺141 ⫾ 32*†‡
⫺106 ⫾ 32*
⫺142 ⫾ 36*†‡
⫺113 ⫾ 36*†
NS
199 ⫾ 45*†
178 ⫾ 53*
192 ⫾ 44*†
163 ⫾ 52*
NS
93 ⫾ 41
89 ⫾ 28
122 ⫾ 44*†
93 ⫾ 34*
103 ⫾ 35
90 ⫾ 32
NS
⫺114 ⫾ 42*
⫺113 ⫾ 43*†
183 ⫾ 43*†
177 ⫾ 48*
P ⫽ 0.01
Peak (diastole)
Basal rot vel, degree/s
Cont
Discont
Apical rot vel, degree/s
Cont
Discont
Untwisting vel, degree/s
Cont
Discont
Untwisting rate, degree/s
Cont
Discont
67 ⫾ 22
59 ⫾ 19
70 ⫾ 22
65 ⫾ 16
80 ⫾ 22
74 ⫾ 37
⫺69 ⫾ 18
⫺66 ⫾ 35
⫺111 ⫾ 35*
⫺132 ⫾ 57*
⫺165 ⫾ 74*
⫺180 ⫾ 70*
⫺235 ⫾ 76*†‡
⫺223 ⫾ 99*
⫺301 ⫾ 118*†‡
⫺235 ⫾ 100*†
⫺267 ⫾ 106*†‡
⫺254 ⫾ 97*†
NS
⫺116 ⫾ 28
⫺101 ⫾ 38
⫺147 ⫾ 39
⫺157 ⫾ 59
⫺211 ⫾ 61*†
⫺218 ⫾ 96*
⫺286 ⫾ 88*†
⫺264 ⫾ 113*
⫺336 ⫾ 110*†‡
⫺278 ⫾ 93*†
⫺300 ⫾ 101
⫺284 ⫾ 94*†
NS
⫺66 ⫾ 24
⫺65 ⫾ 37
⫺102 ⫾ 32*
⫺111 ⫾ 47
⫺132 ⫾ 57*
⫺133 ⫾ 61*
⫺202 ⫾ 89*†‡
⫺150 ⫾ 65*
⫺236 ⫾ 64*†‡
⫺193 ⫾ 85*
⫺195 ⫾ 50*†‡
⫺186 ⫾ 83*
NS
Values are means ⫾ SD. Rot, rotation; vel, velocity. *P ⬍ 0.01 compared with rest. †P ⬍ 0.01 compared with 10%. ‡P ⬍ 0.01 compared with 30%. NS,
not significant.
constraints in LV twist and untwisting in healthy individuals. There were five novel findings. 1) Similar to the previously observed plateau in SV, LV systolic and diastolic
twist mechanics also reached an upper limit at moderate
exercise intensities and remained at this level thereafter.
2) The change in LV twist mechanics during incremental exercise
correlated with ESV, SV, HR, and cardiac output. 3) At all
exercise intensities, enhanced peak LV untwisting velocity was
Fig. 3. Peak diastolic rotation velocities at rest and
during continuous (A) and discontinuous (B) incremental exercise. Peak diastolic apical rotation velocity
was significantly higher at all exercise intensities compared with peak diastolic basal rotation velocity. Consequently, the increase in LV untwisting velocity was
almost solely meditated by enhanced apical untwisting. Data are means ⫾ SE. For clarity, all data are
expressed as positive values. *P ⬍ 0.01 compared
with apical diastolic velocity (n ⫽ 9).
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Twist, degrees
Cont
Discont
Apical rotation, degrees
Cont
Discont
Basal rotation, degrees
Cont
Discont
Twist vel, degree/s
Cont
Discont
Basal rot vel, degree/s
Cont
Discont
Apical rot vel, degree/s
Cont
Discont
LV MECHANICS AND STROKE VOLUME DURING EXERCISE
the result of faster apical than basal untwisting. 4) Peak LV
untwisting velocity occurred before or simultaneously with mitral
valve opening at all exercise intensities. 5) There were little
differences in the response of LV twist mechanics between discontinuous and continuous incremental exercise. Together,
the findings suggest that, in healthy individuals, maximal
systolic and diastolic LV twist mechanics are reached at
submaximal exercise intensities. Their close relationship
with SV and cardiac output may indicate that a limit in
rotational mechanics during moderate- to high-intensity exercise possibly contributes to the plateau in SV. However,
the plateau in EDV before the leveling off of LV twist
mechanics further suggests that the ability to maximize LV
filling may not be related to LV twist mechanics but to
peripheral or cardiac structural factors.
LV Twist Mechanics and SV
In the present study, the changes in EDV, ESV, and SV during
continuous and discontinuous incremental exercise were similar
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to those reported by previous studies, showing an initial increase
followed by a plateau at moderate exercise intensities (4, 18, 22,
25). The present data further support the concept of a limit in
cardiac function at submaximal exercise intensities by showing
that, during both continuous and discontinuous incremental exercise, LV systolic and diastolic twist velocities also reach their
peak at moderate exercise intensities.
In previous studies, central venous pressure has been shown to
increase continuously during incremental exercise up to maximal
oxygen consumption (12, 18, 22). Thus, the presently observed
plateau in EDV may, therefore, have been related to an inability of
the LV to further improve diastolic filling above moderate exercise intensities. During continuous incremental exercise, this does
not, however, appear to be related to diastolic untwisting, since
diastolic untwisting increased further when maximal EDV had
been attained. The mechanisms for the linear increase in EDV
during discontinuous exercise and the plateau in EDV during
continuous exercise in this study are not clear. Previous studies
have shown conflicting EDV responses to incremental exercise,
possibly related to differences in training status or posture (supine
vs. upright exercise) (14, 25, 38). In relation to this, it must be
noted that the present results were obtained during supine cycling
exercise and that altered hemodynamics during upright exercise
may be associated with different LV twist mechanics. Additionally, it has been shown that greater myocardial compliance plays
an important role in the generation of a large EDV at a given
filling pressure (20). Maximal LV diastolic expansion may be
limited by pericardial constraint (10), especially during high levels
of exercise (5). During incremental exercise, the plateau in EDV
may thus be caused by the pericardium constraining end-diastolic
distension and also reduced filling time due to elevated HRs rather
than a limitation in diastolic untwisting performance.
While the plateau in EDV did not appear to be directly
related to LV mechanics, the plateau in twist and untwisting at
high to severe exercise intensities likely contributed to the
leveling off of SV, which is supported by the strong correlation
between these indexes. In contrast to the curvilinear relationship between twist mechanics and EDV, the strong linear
correlation between twist mechanics and ESV is suggestive of
a limit in end-systolic function. Previous studies have demonstrated that sympathetic stimulation enhances LV twist mechanics (8, 16) and that, during incremental exercise, sympathetic activity increases progressively up to the point of
volitional fatigue (12). Accordingly, it may have been expected that LV twist should also have increased in a similar
fashion. Similar to diastolic distensibility, the lack of a
continuous increase in LV twist beyond moderate exercise
intensities may be indicative of a mechanical constraint
during moderate to high levels of exercise. Maximal endsystolic tissue compression may have caused the plateau in
peak systolic basal and apical rotation. An inability to twist
further during systole would in turn impact diastolic untwisting (15, 17). Although theses hypotheses require further
examination, it is plausible that, in the intact human heart during
moderate- to high-intensity exercise, the pericardium and tissue
compression properties may limit both LV systolic and diastolic
twist mechanics, which would consequently contribute to the
plateau in SV.
Another factor that may have influenced the observed plateau
in LV twist mechanics during incremental exercise is the exerciseinduced elevation in arterial blood pressure. In the present study,
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Fig. 4. Time-to-peak diastolic mechanics in relation to the time to MVO. In
parallel to the significant reduction in the time to MVO with increasing
exercise intensity, time-to-peak LV diastolic apical rotation velocity and
untwisting velocity was also shortened, and peaks were reached at the moment
of MVO. In contrast, time-to-peak diastolic basal rotation velocity did not
shorten continuously and its peak occurred significantly later than MVO at
high to severe exercise intensities. Data are means ⫾ SE. *P ⬍ 0.01 compared
with time to MVO for base and apex (n ⫽ 9).
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although absolute differences were small, MAP was significantly
higher during the discontinuous protocol compared with the continuous trial. Conversely, LV twist was significantly lower during
the discontinuous protocol. These data are in accordance with
earlier findings showing that increased afterload reduces peak LV
systolic twist (8). Thus enhanced arterial blood pressure may
offset the positive inotropic effect caused by augmented sympa-
thetic activity during exercise intensities exceeding 50% maximal
capacity and thereby limit the increase in LV twist. Because the
energy required for active diastolic untwisting is stored during
systole (15, 17), the increase in arterial blood pressure may also
indirectly attenuate the increase in LV untwisting velocity. This
would explain the strong relationship between systolic twist and
diastolic untwisting velocity observed in the present investigation.
Fig. 6. Relationships between LV twist mechanics and EDV
and ESV during continuous () and discontinuous (Œ) incremental exercise (n ⫽ 9). Although the relationships with ESV
were clearly linear, the relationships between LV twist mechanics and EDV during continuous incremental exercise
were not significant and appeared more exponential, suggesting that the early plateau in SV is the result of reduced filling that
may not be related to cardiac systolic or diastolic mechanics. The
y-axes for untwisting velocity are inversed to reflect the increase
in untwisting velocity. Data are means ⫾ SE.
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Fig. 5. Relationships between LV twist mechanics and SV, HR, and cardiac output during continuous () and discontinuous (Œ) incremental exercise (n ⫽ 9).
The increase in LV twist mechanics correlated significantly with the change in SV, HR, and cardiac output during both continuous and discontinuous incremental
exercise. The y-axes for untwisting velocity are inversed to reflect the increase in untwisting velocity. Data are means ⫾ SE.
LV MECHANICS AND STROKE VOLUME DURING EXERCISE
In addition, Takeuchi and Lang (35) have reported a reduced peak
LV untwisting velocity in arterial hypertension at rest, further
suggesting an impact of elevated arterial blood pressure on LV
twist mechanics. However, in contrast to the present data, Takeuchi and Lang (35) also reported a delay in peak LV untwisting.
Our study shows that, during exercise in healthy individuals,
despite extensive shortening of the cardiac cycle, peak LV untwisting occurs simultaneously with mitral valve opening at all
exercise intensities. Therefore, a delay in peak LV untwisting
velocity beyond mitral valve opening during exercise is likely
indicative of cardiac dysfunction.
Implications for Pathological and Physiological Adaptations
Uncoupling of Basal and Apical Twist Mechanics During
Incremental Exercise
To establish an intraventricular pressure gradient that maximizes LV suction for diastolic filling, pressure at the LV apex
must be lower than at the base. Accordingly, during exercise,
greater apical untwisting compared with basal untwisting is
beneficial for LV filling. Indeed, Doucende et al. (9) showed
that the increase in apical untwisting during incremental exercise up to ⬃40% maximal exercise capacity was significantly
higher than the increase in basal untwisting. Our data extend
these findings by showing that this uncoupling increases more
as exercise intensity increases to near maximal levels. This
finding underlines the importance of an apical untwisting
reserve to meet an enhanced cardiovascular demand in healthy
individuals, which may be absent in cardiac disease (23).
Furthermore, the previous and present data indicate that, during
exercise, a differential response in LV rotation at the base and
the apex is normal. Similarly, Akagawa et al. (2) observed a
greater increase in apical subendocardial rotation than basal
subendocardial rotation following dobutamine infusion in
healthy individuals at rest. Some authors have proposed that
this response may be caused by region-specific adrenoreceptor
sensitivity (24). In this regard, data are available showing that
electrical activation at the apex persists longer than at the base
(29), which may result in an enhanced Ca2⫹ release and a
faster reuptake in apical myocytes. Moreover, we have previously shown that basal rotation predominates over apical rotation during heat stress, a condition that is characterized by a
reduction in EDV (34). In contrast, the greater apical rotation
during incremental exercise in the present study is likely
AJP-Heart Circ Physiol • VOL
related to the increase in EDV, as has recently been shown
using saline infusion (39). Thus enhanced venous return from
the exercising muscles and the resultant increased EDV may
have contributed to a change in myofiber alignment and increased LV twist and untwisting in a mechanically more
efficient manner (1). Collectively, the present data suggest that
the LV apex, in contrast to the base, has a greater “reserve” to
respond to exercise. By implication, it follows that the lower
potential of the LV base to respond may represent a key factor
in the limitation of overall LV twist mechanics to increase
beyond moderate exercise intensities.
Similar to the observed difference in peak basal and apical
rotation, the time taken for diastolic rotation velocities to reach
their peak also differed between the base and the apex at higher
exercise intensities. Figure 4 shows that, during continuous
incremental exercise at 70 and 90% of peak power, peak LV
diastolic basal rotation velocity occurred after mitral valve
opening, whereas peak apical untwisting still occurred before or
simultaneously with the start of early LV filling. Because both
peak apical and basal diastolic untwisting plateau at these exercise
intensities, it is possible that the higher peak basal untwisting later
in diastole is reflective of an enhanced atrial contribution to filling
action rather than a reduction in basal function. This agrees with
the previous observation of a relationship between peak diastolic
basal rotation velocity and early filling velocity during moderateintensity exercise (9). The functional significance of this association during exercise and other conditions of altered hemodynamics and inotropic state is, however, currently not clear and requires
further study.
In recent years, the number of clinical trials examining LV
twist mechanics in acute and chronic pathology has risen
steadily (13, 30, 32), yet the normal response of LV twist
mechanics to stress in healthy individuals is still poorly understood. In the clinical and athletic environment, exercise tests
are frequently used to expose cardiovascular abnormalities and
establish physiological performance. The present study provides insight into the normal response of LV twist mechanics
during incremental exercise to near maximal exercise capacity.
Failure of LV twist mechanics to progressively increase up to
moderate relative exercise intensities, peak LV untwisting
velocity occurring markedly following mitral valve opening,
and apical mechanics not increasing to a greater extent than
basal rotation during the course of a diagnostic exercise test
may all reflect underlying pathology. Equally, highly trained
individuals that have a higher SV at rest and during exercise
may display a different response in LV twist mechanics reflecting chronic myocardial adaptations to exercise training.
Despite some small differences between trials, the present
investigation also demonstrates that LV twist and untwisting
are very similar whether incremental exercise is performed
continuously or discontinuously. The option to employ a discontinuous protocol, which drastically reduces the time that
individuals are exposed to acute cardiovascular stress, may be
an important advantage in some populations and conditions.
Technical Considerations and Limitations
At present, the assessment of LV twist mechanics with 2-D
speckle tracking ultrasound entails some inherent methodological
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Fig. 7. Relationship between LV twist and untwisting velocity during continuous () and discontinuous (Œ) incremental exercise (n ⫽ 9). Systolic twist and
diastolic untwisting velocity were closely related during both continuous and
discontinuous incremental exercise, suggesting a strong interdependence between systolic and diastolic function in healthy individuals. The y-axis is
inversed to reflect the increasing untwisting velocity. Data are means ⫾ SE.
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ACKNOWLEDGMENTS
We thank all participants for their commitment throughout the study. We
also thank Emilie Timlin for excellent assistance during data collection.
DISCLOSURES
None.
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