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I N N O V A T I O N S A N D I D E A S

DETERMINANTS OF CARDIAC FUNCTION:


SIMULATION OF A DYNAMIC CARDIAC
PUMP FOR PHYSIOLOGY INSTRUCTION

Michael J. Davis1 and Robert W. Gore2


1
Department of Medical Physiology, Texas A&M University System Health Science Center,
College Station, Texas 77843; and 2Department of Physiology, University of Arizona
Health Science Center, Tucson, Arizona 85724

computer model is described that simulates the cardiac cycle of a mamma-

A lian heart. The model emphasizes the pressure-volume plot as a teaching tool
to explain the behavior of the heart as a pump. It exhibits realistic responses
to changes in preload, afterload, contractility, and heart rate while displaying time-
dependent changes in pressure and volume in addition to the pressure versus volume
plot. It differs from previous models by graphing these parameters on a beat-to-beat
basis, allowing visualization of the dynamic adaptation of the pumping heart to
various stimuli. A system diagram is also included to further promote student
understanding of the physiology of cardiac function. The model is useful for teaching
this topic to medical, graduate, or undergraduate students. It may also be used as a
self-directed computer laboratory exercise.
ADV PHYSIOL EDUC 25: 1335, 2001.

Key words: pressure-volume plot; preload; afterload; contractility; heterometric regula-


tion; homeometric regulation; Frank-Starling relationship; Starlings law of the heart

The heart is a dynamic pump that can vary its output a system diagram, to explain the behavior of the
to adjust and maintain a mean systemic arterial pres- heart as a pump. The model exhibits realistic re-
sure appropriate for different physiological demands. sponses to changes in preload, afterload, Cont, and
This goal is achieved by intrinsic regulatory mecha- HR while displaying time-dependent changes in
nisms that reflect inherent properties of cardiac mus- pressure and volume in addition to a pressure-vol-
cle and also by extrinsic neural and hormonal regula- ume plot. It differs from previous models (1, 3, 5)
tory mechanisms. Collectively, these intrinsic and by graphing these parameters on a beat-to-beat ba-
extrinsic factors account for the four main determi- sis that is particularly useful when describing the
nants of cardiac function: 1) preload, 2) afterload, 3) dynamic adaptation of the pumping heart to various
contractility (Cont), and 4) heart rate (HR). stimuli. The model emphasizes intrinsic regulation
of myocardial function and therefore does not in-
In this article, we describe a computer model that clude specific simulated effects of peripheral barore-
simulates the cardiac cycle of a mammalian heart ceptors, venoatrial receptors, and other extrinsic car-
with accuracy appropriate for instruction of medi- diovascular reflexes. However, the consequences of
cal, graduate, and undergraduate students. Our goal extrinsic reflex responses can be simulated by manu-
in developing the model was to use the pressure- ally changing preload, total peripheral resistance
volume plot as a teaching tool, in conjunction with (TPR; afterload), Cont, and HR.
1043 - 4046 / 01 $5.00 COPYRIGHT 2001 THE AMERICAN PHYSIOLOGICAL SOCIETY

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The model is designed to operate in one of two supporting 832 624 or 800 600 resolution. The
different modes: the isolated heart mode and the source code occupies 750 kb of disk space, whereas
intact heart mode. The isolated heart mode is used to the compiled code with embedded libraries occupies
isolate an individual variable, such as preload, to dem- 2.5 Mb of disk space and requires 6 Mb of system
onstrate the most basic effect of that variable without memory to execute. Macintosh and Windows versions,
subsequent changes in other parameters. In this along with the worksheet found in the APPENDIX can
mode, secondary changes in mean arterial pressure be downloaded from the following internet address:
do not feed back to subsequently alter function. In ( http//mphywww.tamu.edu/davis/models/
engineering terms, this is the open-loop mode. The pvmodel.html).
intact heart mode is used to show how the pumping
function of the heart will behave when one or more Timing. The basic timing for the model is derived
of the variables is changed and the system is allowed from a sine-wave generator, adapted from Kiel and
to come to a new equilibrium. In this mode, second- Shepherd (3). Display speed is limited primarily by
ary changes in mean arterial pressure are allowed to the number of points displayed per cardiac cycle,
feed back and subsequently alter function. In engi- with a minimum of 50 points required for adequate
neering terms, this is the closed-loop mode. resolution of a pressure-volume loop. The model gen-
erates 100 points per cycle at a HR of 60 beats/min.
The model is written in the LabView programming The number of points, and hence trace resolution,
language and compiled for stand-alone use on Macin- changes with HR.
tosh Power-PC and Pentium-based microcomputers.
It is appropriate as a classroom teaching tool or as a Pressure and volume waveforms. The systolic por-
self-directed student laboratory. It can serve simply as tion of the left ventricular pressure wave was simu-
a tool to explain the timing of pressure and volume lated by clipping the sine wave (segment A in Fig. 1).
traces using the Wiggers diagram or to introduce This function was combined with a linearly increasing
students to the concept of the pressure-volume plot.
However, the most useful feature of the model is the
way shifts in the pressure-volume loop can be visual-
ized in response to changes in preload, afterload,
Cont, and HR. Compiled versions are available for free
distribution over the internet to students and faculty
along with a detailed worksheet that can be used for
step-by-step classroom instruction or for self-directed
laboratory exercises.

METHODS
Software. All components of the model were written
in LabView (version 4.0, National Instruments, Austin,
TX). The source code was complied as run-time
(stand-alone) code with embedded LabView libraries.
The program consists of a single LabView virtual
instrument calling 19 subroutines. Testing and devel-
opment were done on a 300-MHz Macintosh G3 com- FIG. 1.
puter and a 233-MHz Pentium II computer. The model Diagram of the various components of the pressure
will run on slower hardware supporting either plat- and volume waveforms. Trace A is ventricular pres-
sure in systole, trace B is ventricular pressure in di-
form, but this is not recommended because a signifi-
astole, trace C is ventricular volume during ejection,
cant sacrifice in display performance and computa- and trace D is ventricular volume during diastolic
tion speed may occur. The layout of controls and filling. Times 1 and 2 correspond to the opening and
graphs is optimized for display on a color monitor closing, respectively, of the aortic valve.

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FIG. 2.
The displays shown by the model. Top left: strip chart display. At a heart rate (HR) of 72 beats/min, the strip chart
shows 5 consecutive cardiac cycles scrolling from right to left as new cycles are generated. Aortic pressure is
drawn in red, whereas the ventricular pressure and volume are drawn in black. Top right: the pressure-volume
(PV) plot for the left ventricle. Bottom right: system diagram that shows the relationships among the different
parameters that contribute to the pumping function of the heart. Bottom left: sliders used to control the 4 main
determinants of cardiac function. See text for detailed description. TPR, total peripheral resistance; CONT, con-
tractility; SV, stroke volume; Pdia, diastolic pressure in the aorta; EDV, end-diastolic volume; ESV, end-systolic
volume; CO, cardiac output; P a, mean arterial pressure; bpm, beats/min.

ramp (segment B in Fig. 1) to simulate the diastolic ume trace. The initiation of the exponential increase or
filling phase of the cardiac cycle. The aortic pressure decrease in ventricular volume was triggered by the
wave (not shown) between the opening of the aortic closing or opening, respectively, of the aortic valve.
valve and the closing of the aortic valve was made
equal to the ventricular pressure wave. The aortic
pressure wave in diastole was simulated using a lin-
early decreasing ramp function. Displays. When the model is loaded, there are four
general areas displayed on the screen (Fig. 2): a strip
The ventricular volume change was simulated by chart record, a graph of ventricular pressure versus
combining a decaying exponential function in systole ventricular volume, a system diagram, and a set of
(segment C in Fig. 1) with a slower, but rising, expo- four sliders to manipulate the four determinants of
nential function in diastole (segment D in Fig. 1). The cardiac function. For the sake of clarity or emphasis,
time constants of the two exponentials were adjusted each of the four areas can be turned off or on with
empirically to give a realistic appearance to the vol- buttons located at the bottom of the screen.

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The simulated strip chart recorder is displayed in ternal parameters have pink backgrounds. These col-
the top left quadrant of the screen, showing time- ors change appropriately as the model is switched
based records of three basic parameters of a Wig- between isolated- and intact-heart modes (see expla-
gers Diagram for the left ventricle. Starting from nation below).
the top of the chart, these include displays of aortic
pressure (mmHg) in red, left ventricular pressure Three additional buttons labeled pause, act ten-
(mmHg) in black, and left ventricular volume (ml) sion, and clear graph are also included in the lower
in black. right quadrant. They provide the following display
enhancements: 1) the pause button causes the strip
The instantaneous values for left ventricular pressure chart recorder to pause and inserts a new display with
are plotted as a function of the corresponding values a sliding vertical line (blue line, Fig. 3) that can be
for left ventricular volume, and the data are displayed used to identify the elements on the strip chart record
in the top right quadrant of the computer screen. The (Wiggers Diagram) that correspond to those same
plot is designed to retain the most recent pressure- elements in the pressure-volume loop. It is useful for
volume loops, after which all traces are automatically locating the boundaries between the different phases
cleared. The advantages of representing the data as of the cardiac cycle. Students find this especially help-
pressure-volume loops are that 1) all four determi- ful when trying to visualize the connection between
nants of myocardial function can be represented or the Wiggers Diagram and the pressure-volume
demonstrated on this graph; 2) other parameters im- loop. 2) The act tension button will display a red line
portant for understanding the pumping function of on the pressure-volume graph approximating the ac-
the heart, such as end-diastolic volume (EDV) and tive tension curve for the myocardium. It defines the
pressure (EDP), end-systolic volume (ESV) and pres- limit of isotonic shortening during the ejection phase
sure (ESP), and stroke volume (SV) are represented on and provides a visual demonstration of the effect of
the graph and can be observed directly as they changes in Cont on ESV and, hence, on SV, CO, and
change; and 3) all phases of the cardiac cycle are Pa. 3) The clear graph button clears the pressure-
more easily viewed on a pressure-volume loop than volume graph when it becomes cluttered with ac-
on a chart record. cumulated tracings. Although the graph clears auto-
matically every 15 cycles, this button can be used to
A system diagram showing the relationships among clear it at any time.
the different parameters that contribute to the pump-
ing function of the heart is located in the bottom right Controls open-loop versus closed-loop modes.
quadrant of the computer screen. A continuous dis- Slider controls for manipulating the four determi-
play of the numeric values is shown in a small win- nants of cardiac function are located in the bottom
dow for each parameter. The parameters associated left quadrant of the computer screen (see Fig. 2).
with the heart are shown in black letters and include These are used to manipulate preload, TPR (which
1) EDV and ESV of the ventricle; 2) SV, which is the affects changes in afterload), Cont, and HR. In the
difference between EDV and ESV; 3) cardiac output initial (start-up) condition, three of the variables are
(CO), which is the product of HR and SV; and 4) Cont, grayed out and only the preload slider is operative.
which determines the rate and magnitude of force The four controls can be altered by dragging the
generated by the cardiac muscle and, therefore, the central, horizontal arrow on each slider up or down
magnitude of ESV. by clicking on the vertical arrows near each control
(for fine changes) or by clicking at specific locations
Parameters associated with the peripheral vascula- in the vertical slider column (for large step changes).
ture, external to the heart, are shown in red letters. The small radio button at the top of each slider tog-
They include TPR and mean arterial pressure (Pa). Pa gles the model between open- and closed-loop modes
is proportional to the product of TPR and CO. The for that parameter. Each time one of these buttons is
digital displays are color coded so that dependent clicked on, the message isolated heart (single vari-
parameters have black backgrounds, independent able active) is displayed, the other controls are dis-
(fixed) parameters have white backgrounds, and ex- abled, and some of the displays are turned from black

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FIG. 3.
The PAUSE mode. The 2 top displays are shown when action is paused. As the slide control at the bottom is moved
from left to right, the vertical blue line (left graph) and blue dot/cross (right graph) retrace the history of pressure
and volume changes. The red arrows in both displays indicate this progression. Points A-D on the time displays
correspond to the same labels on the PV display. Point A is ESV (end of isovolumetric relaxation, start of the
ventricular filling); B is EDV (end of ventricular filling, start of isovolumetric contraction); C is the end of
isovolumetric contraction and start of ejection phase; D is the end of ejection and start of isovolumetric relaxation
phase. Arrows and text labels were added for illustrative purposes and are not displayed in the actual model.

to gray to indicate that the effects on only one vari- HR. Until that time, all of the pressure-volume loops
able are being illustrated. The isolated heart mode is are superimposed (Fig. 2).
used to isolate an individual variable, such as preload,
to demonstrate the most basic effect of the variable When the pause button is depressed, all action is
without subsequent changes in other parameters. frozen, a horizontal slider appears under the chart
This simulates the behavior of an isolated heart in record, and cursors are displayed on both graphs (Fig.
which aortic pressure is not allowed to feed back as 3). This mode is designed to help students better
an afterload during the ejection phase. If all of the visualize the relationship between the timing of the
radio buttons are clicked off (as in Fig. 2), the model ventricular pressure and volume changes in the chart
switches to the intact heart mode. Now, interac- record and the timing of the different phases of the
tions among variables are allowed to occur, and all of cardiac cycle on the corresponding pressure-volume
the controls are enabled, allowing multiple parame- plot. A slider control (note the hand symbol near
ters to be changed by the user. This mode simulates bottom of Fig. 3) synchronizes the movement of a
the behavior of an intact heart where aortic pressure vertical time cursor on the pressure-versus-time and
feeds back throughout the ejection phase but without volume-versus-time plots, with the movement of a
extrinsic, autonomic reflexes engaged. point cursor on the pressure-versus-volume plot. This
allows each phase of the cardiac cycle to be examined
RESULTS sequentially.
When the simulation is started, pressure and volume
waveforms are generated and displayed continuously Each cardiac cycle is associated with a single loop
on the computer monitor as two graphs. New cardiac on the pressure-volume diagram and is plotted in a
cycles are generated from right to left on the chart counterclockwise direction. In pause mode, this
recorder (Fig. 2), and the displays are stable until the can be demonstrated by slowly moving the cursor
user initiates a change in preload, afterload, Cont, or slide control from left to right. Starting from the

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end of systole, ESV (point A on both graphs in Fig. did previously and because aortic pressure is held
3), the ventricle fills to point B (EDV), along a constant in the open-loop mode. However, as a con-
passive pressure-volume curve that corresponds to sequence of the increase in thick and thin filament
the passive length-tension curve for ventricular overlap, the muscle contracts more forcefully yet at-
muscle. When the ventricle is electrically excited, tains the same ESV as the previous beat that was
the heart enters the isovolumetric contraction initiated from point B. Consequently, SV (B-A), is
phase, illustrated by the vertical line from B to C on increased (as is CO), and over the next few cycles, a
the diagram. At point C, pressure in the ventricle progressive shift in the loop to points B and C is
exceeds the pressure in the aorta, the aortic valve observed until EDV reaches a new steady-state value.
opens, and the ejection phase begins (point C to Digital displays that change under these conditions
D). At point D, ventricular contraction ceases and are EDV, SV, CO, and Pa.
ventricular pressure falls below aortic pressure. At
that time, the aortic valve closes, and the isovolu- In the intact (closed loop) heart mode, important
metric relaxation phase begins (point D to A). Ide- differences are introduced into the behavior of the
ally, the line from D to A should be perfectly ver- system as preload is increased (Fig. 4B). In this mode,
tical but is not because the clipped sine wave used systemic arterial pressure is allowed to change. A new
in the model does not simulate perfectly the shape digital display showing diastolic pressure in the aorta
of the actual ventricular pressure waveform. For (Pdia) and a red arrow pointing to the ESV display
the pause mode to work properly, at least five (now black) is introduced into the system diagram to
cardiac cycles must be stored in the models inter- indicate that aortic pressure feeds back to alter ESV.
nal buffer before depressing the pause button. Pa is calculated from the simple product of TPR and
CO, whereas Pdia is displayed as an estimate of the
Changes in preload. When the model is not paused,
initial afterload seen by the heart (see Ref. 2, Fig. 15.8,
upward movement of the preload control slider ini-
p. 358). The immediate effect of an increase in pre-
tiates an increase in filling pressure (preload), which
load is to shift EDV (point B) to the right (point B),
shifts EDV to a larger value. The model uses an inte-
resulting in an increase in SV (because B-A B-A). In
grator to gradually introduce the effects of preload (or
this first cycle, the aortic valve opens at the same
other) variables into the waveform generator so that
point (i.e., C C) and ejection finishes at about the
progressive shifts in the pressure-volume loop can be
seen clearly and compared from cycle to cycle. The same point (D D) as in the control loop. However,
initial (control) loop and the next several loops gen- in subsequent loops, SV and CO increase as does Pa,
erated after a 25% increase in preload are shown in so that the heart is now working against an elevated
Fig. 4. afterload. Ejection, therefore, begins at a higher dia-
stolic pressure (C) and ends at a new point (D),
As mentioned above, the model simulates two types resulting in a secondary increase in ESV and second-
of experimental systems: an isolated heart, where ary drop in SV (because B-A B-A). Nevertheless,
only one of the four control parameters is allowed to SV is still higher than it was initially, thereby sustain-
change, and an intact heart, where secondary changes ing the increase in CO and Pa. Subsequent cycles
in other variables are allowed to occur. To simulate show that the loop continues to shift upward and to
changes in preload alone, the preload radio button is the right in this manner until the increase in preload
depressed, isolating the effects of changing preload is complete.
and disabling controls for afterload, HR, and Cont. In
this mode, an increase in preload at the end of dias- If preload is lowered from its initial (control) value,
tole initiates an increase in diastolic filling during the the reverse behavior is seen. The resulting sequence
next few cycles. The change in preload is then dis- of pressure-volume loops shifts instead down and to
played as a shift in the lower right corner of the loop, the left. These progressive changes with successive
EDV, from point B to B (Fig. 4A). The points labeled cardiac cycles can be illustrated effectively to stu-
A and D are essentially unchanged from their initial dents in the classroom, first by pausing the model a
values because isovolumetric contraction occurs as it few cycles after the preload is changed and then by

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FIG. 4.
A: effect of an increase in preload when the model is in isolated heart (single-variable active) mode. Digital displays
for ESV and HR are white to indicate they are treated as independent variables in this demonstration and therefore
do not change. B: effect of an increase in preload when the model is in intact heart (all variables active) mode. Note
the appearance of digital displays for P a and Pdia and a red arrow to indicate that increases in Pdia now cause
secondary changes in ESV (now black).

manipulating the cursor to incrementally step Changes in afterload. Changes in afterload are ini-
through the time sequence on the two displays. tiated by moving the TPR/afterload control slider.
Physiologically, afterload is the instantaneous value of
An additional point to be made while illustrating the aortic pressure (force per unit area) that the heart
effects of changing preload is that shifts in the pres- sees throughout the ejection phase. It is determined
sure-volume relationship are independent of any primarily by the TPR into which the heart must eject
change in Cont under these conditions. This can be the blood volume. The aortic compliance also is an
illustrated by clicking on the act tension control but- important factor. However, to simplify the model, we
ton, which displays a red line (shown in Fig. 4B) have accepted Katzs convention that Pdia is a good
approximating the length versus active-tension rela- index of afterload (Ref. 2, Fig. 15.8, p. 358). Indeed,
tionship for cardiac muscle. When preload is the afterload would be equal to diastolic pressure if
changed, each of the successive pressure-volume the heart contracted in a purely isotonic manner from
loops intersects this line at points D, D, D, and so the moment the aortic value opened and continued to
forth. contract isotonically throughout the ejection phase.

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FIG. 5.
A: effect of an increase in TPR/afterload when the model is in intact heart mode and preload is held constant
(manual preload ON) and can be changed only by manually moving the preload slider. Afterload was increased
from 20 to 40. An intermediate loop has been omitted from the illustration for clarity. B: effect of an increase in
TPR/afterload (from 20 to 40) when the model is in intact heart mode and preload changes are allowed to occur
automatically (auto preload ON). Some intermediate PV loops have been removed for clarity.

The effects of increasing afterload are illustrated in phase before the aortic valve can open (C to C in
Fig. 5. The afterload control is slightly different from Fig. 5A). The result is an increase in peak systolic
the controls for preload and HR in that there are pressure (D to D) and an increase in ESV (A to A)
three, not two, possible conditions to consider. When as afterload increases. This effect progresses
the model is working in the isolated heart mode, an through 3 4 cardiac cycles (not shown). If preload
increase in TPR/afterload simply results in an increase is held constant (by setting the manual preload on
in Pa, as evident on the digital Pa display. There is no button), then secondary changes in venous return
change in the pressure-volume display in this state, are not allowed to occur (therefore B B). But, if
and all of the traces are grayed out to indicate the only secondary changes in preload are permitted (by
changes that occur are those external to the heart toggling the button to auto preload on), the be-
(traces not shown). havior of the model is slightly different. In this
state, the volume returned to the intact heart is
In the intact heart mode, increasing the afterload allowed to secondarily increase preload apart from
dictates that pressure in the ventricle must rise to a any manual manipulaton of the preload slider. The
higher level during the isovolumetric contraction returned volume then combines with the volume

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FIG. 6.
A: effect of an increase in CONT from 1.0 to 1.3 in isolated heart mode. Afterload is not allowed to change, so peak
systolic pressure remains unchanged (D). Original active tension line is shown as a dotted line for reference purposes,
but a dotted line does not actually appear on the display of the model. B: increase in CONT from 1.0 to 1.3 in intact heart
mode. Afterload is allowed to increase resulting in a shift from D to D and a secondary increase in ESV (A to A). Final
value of ESV (50 ml) is larger than that in A (38 ml). Preload is held constant in this example (manual preload ON).

remaining in the heart with the net result that EDV of the pressure-volume loops intersect the same
gradually increases for several cycles. Thus there is length versus active-tension line to demonstrate that
a gradual shift in EDV from B to B (Fig. 5B). After no change in Cont occurs (Fig. 5B).
several beats, the increased afterload and, subse-
quently, the increased preload come to a new Changes in Cont. An increase in Cont is simulated
steady state in which the entire pressure-volume by moving the Cont slider upward, as illustrated in
loop is shifted to the right. Over a moderate range Fig. 6. In the isolated heart (open loop) mode, sec-
of afterload increases, EDV can increase to such an ondary changes in afterload are not allowed to occur.
extent that stroke volume is restored nearly to its Hence, as Cont increases (from 1.0 to 1.3 in this
original value, thereby maintaining an elevated CO example), the simulated heart contracts more force-
and Pa. However, this compensation occurs at the fully and empties more completely. Thus there is a
expense of the so-called heterometric reserve. reduction in ESV (A to A) and subsequent enhance-
ment in SV and CO (Fig. 6A). The pressure-volume
In the case of an afterload change, the act tension loop shows a characteristic shift to the left. If the
button can again be switched on to illustrate that all active tension line is displayed, each incremental in-

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crease in Cont is associated with a corresponding shift as HR increases (in this model) up to 140 beats/min
in the line to the left (as the slope increases). Thus an (point D), reflecting the fact that the fall in SV is
increase in Cont can serve to recapture or conserve smaller than the corresponding increase in HR over
heterometric reserve. Because changes in afterload the range 30 140 beats/min. However, as HR in-
are not allowed to occur in this mode, the aortic valve creases to 140 beats/min, it is balanced progressively
opens at the same point (C C) as before and there more by the fall in SV so that CO and Pa tend to
is no change in peak systolic pressure. plateau.

An equivalent increase in Cont in the intact heart Figure 7B illustrates the behavior of the pressure-
mode is associated with a secondary increase in after- volume loop when HR exceeds 140 beats/min. At
load (Fig. 6B). This is evident in the display by the very high HRs, ventricular filling is compromised by
higher pressure at which the aortic valve must open the very short filling time, so EDV begins to fall sig-
(C to C) and the higher peak systolic pressure (D to nificantly. SV therefore falls by a disproportionate
D). The increase in afterload now produces a second- amount so that CO and Pa fall dramatically, as indi-
ary increase in ESV that partially, but not completely, cated by a downward shift in the loop from D to D
offsets the reduction in ESV produced by the more in Fig. 7B (at HR 156 beats/min).
forceful contraction of the cardiac muscle. As a result,
increases in SV and CO are smaller than in the isolated Changes in the various ventricular volumes as a func-
heart mode. When the heart arrives at a new steady tion of HR recorded from the model (and as displayed
state, the pressure-volume loop is expanded upward in the systems diagram windows) are shown in Fig.
and leftward compared with the control curve. 8A. The corresponding data for the relationship be-
tween CO and HR for the control state are shown in
If the Cont control is put into auto preload on mode, Fig. 8B. The point at which ventricular filling be-
by depressing the button below the Cont slider, the comes the primary limiting factor is most evident in
behavior of the model is slightly altered from that Fig. 8B. Although in trained athletes, CO continues to
described above. The model now performs an auto- rise with HR until HR exceeds 180 beats/min, we
matic adjustment in EDV subsequent to a change in decided this model would be most useful and relevant
Cont. Manual changes in the preload slider are not if it approximated the relationship between volume
required. This is useful for demonstrating to students and HR for middle-aged men whose physical condi-
in the classroom how an increase in Cont will cause tioning is comparable with the average physiology
the pressure-volume curve to shift to the left with department head. Therefore, EDV is held constant at
subsequent restoration of the heterometric reserve HRs from 30 to 140 beats/min, and ESV rises in a
capacity. linear fashion. Consequently, SV falls linearly over this
range. When HR exceeds 140 beats/min, diastolic
Changes in HR. An increase in HR is easily noted on filling is compromised so that EDV falls linearly. ESV
the chart recorder display, but not on the pressure- remains fairly constant over the range 140 180 beats/
volume graph. Because each pressure-volume loop min, so that SV falls even more dramatically as HR
corresponds to a single heart beat, individual loops exceeds 140 beats/min. The overall impact on CO is
are drawn faster at higher HRs yet all of the loops are shown in Fig. 8B.
superimposed (not shown).
Anrep, Bowditch, and Woodworth effects. The
In the intact heart mode, moderate increases in HR Anrep effect is an intrinsic, afterload-dependent
cause a decrease in diastolic filling time, resulting in a change in Cont (Ref. 4, Fig. 7.7, p. 83). It helps the
secondary rise in ESV and subsequent fall in SV (see heart, independent of extrinsic reflexes, compensate
Fig. 7A). The rise in ESV is apparent on the pressure- for the increase in ESV (and consequent decrease in
volume display as a progressive shift in point A to A. SV) that occurs after a step increase in afterload. The
The fall in SV is evident as a narrowing of the loop effect is small but can be important in extending the
along the ventricular volume axis. Because CO is the mechanical operating range of the transplanted heart.
product of HR and SV, it follows that CO and Pa rise The Bowditch effect is an intrinsic, rate-dependent

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FIG. 7.
A: effect of an increase in HR with model in intact heart (all variables active) mode. Red arrow (left graph)
indicates point at which HR was changed. Points D and D indicate the progressive rise in P a as HR reaches 138
beats/min. B: effect of increasing HR from 138 to 156 beats/min (at red arrow). Point D shows the fall in peak
systolic pressure (from a maximum value at D as in A) resulting from compromised ventricular filling. The control
loop (at HR 72 beats/min) is same as in A but is omitted for clarity.

increase in Cont that occurs as HR is elevated (Ref. 4, and explained by manual adjustment of the appropri-
pages 96 97; Ref. 2, p. 323). It helps the heart com- ate controls.
pensate for the decreases in EDV and SV that occur
when HR is increased and therefore extends the op- An increase in afterload in the intact heart mode shifts
erating range over which the heart is able to increase the pressure-volume loop to the right (Fig. 9A), as
its output. The Woodworth effect (Ref. 2, p. 337) is described previously. When Anrep compensation oc-
the opposite of the Bowditch effect and occurs at curs, the heart intrinsically undergoes a slight com-
higher HRs (stimulus frequencies). These effects are pensatory increase in Cont and is thereby able to
not built into this model, but their contributions to recapture or maintain its initial, heterometric re-
the pumping function of the heart can be appreciated serve capacity. This effect can be demonstrated by

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decrease in SV (Fig. 9B). When Bowditch compensa-


tion occurs, a small intrinsic increase in Cont restores
SV toward its initial level by shortening the length of
systole, with a concomitant increase in diastolic filling
time. The Bowditch effect is therefore associated with
a leftward shift of the pressure-volume loop (from A
to A) if Cont is increased subsequent to an increase in
HR. Thus, as the heart approaches its final steady
state, it exhibits an SV and heterometric reserve com-
parable with that seen initially but is working harder
(stroke work, the area inside the loop, is greater).

Interactions of multiple parameters. Interactions


between changes in preload, afterload, Cont, and HR
can be further simulated with this model to illustrate
more complex physiological reactions. For example,
moderate activation of the sympathetic system would
typically produce simultaneous increases in preload,
Cont, and HR. If the slide controls for each of these
parameters are moved slightly upward, the combined
effects of all three mechanisms in concert or in tem-
poral sequence can be simulated. Likewise, it is pos-
sible to illustrate how compensatory changes in one
parameter can counteract alterations in another pa-
rameter. For example, the hemodynamic impact of a
mild hemorrhage can be simulated by first decreasing
preload and then increasing HR and Cont to simulate
sympathetic compensation. A number of other sce-
narios could be devised by the motivated and imagi-
native student or instructor to illustrate the integrated
behavior of the cardiovascular system. However, the
model is a linear system designed to demonstrate the
FIG. 8. basic pumping functions of the heart, which are non-
A: changes in ventricular volumes as a function of HR, linear by nature. The model therefore comes with the
when the CONT control is set to 1.0. B: changes in CO caveat that, like any simulation, it will crash if pushed
as a function of HR when CONT is set to 1.0. Increasing beyond its design limits, and confusion rather than
or decreasing CONT will shift this curve up or down,
respectively.
enlightenment will result.

DISCUSSION
comparing the effects of an afterload increase with or
without a slight increase in Cont. It is apparent on the The computer model described herein simulates a
graph as a leftward shift in ESV from A to A if Cont dynamic cardiac pump and demonstrates cardiac
is increased secondary to an increase in afterload. A function using a ventricular pressure-volume diagram
corresponding increase in peak systolic pressure oc- and a systems diagram. We envision a variety of pos-
curs, evidence that the heart has recaptured some of sible uses for the model. It may be used as an alter-
its heterometric reserve. native to an animal laboratory to demonstrate how
changes in preload, afterload, Cont, and HR impact
A sudden increase in HR in the intact heart mode cardiac function on a beat-to-beat basis. It may be
causes an initial increase in ESV, with consequent used by an instructor as a method to teach this topic

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FIG. 9.
A: response of model in intact heart mode to an increase in afterload with (A) or without (A) an increase in CONT
(the Anrep effect). Afterload was increased from 20 to 40; CONT was increased from 1.0 to 1.2. Preload was fixed
at a constant level (manual preload ON). Control loop is shown as a dotted line. The CONT increase is also apparent
as a leftward shift in the act tension line. B: response of model in intact heart mode to an increase in HR with (A)
or without (A) secondary Bowditch compensation. HR was increased from 72 to 132; CONT was increased from 1.0
to 1.2. Preload was fixed at a constant level (manual preload ON). Control loop is shown as a dotted line. The CONT
increase is also apparent as a leftward shift in the act tension line.

to medical, undergraduate, or graduate students. It signed (in whole or in part) to students as a computer
may be used as a self-directed computer laboratory laboratory exercise.
exercise for any of these student groups.

To facilitate the latter purpose, the model has been APPENDIX


compiled for use with Macintosh or Windows operating
systems and is available for free download by faculty
COMPUTER LABORATORY WORKSHEET:
and students at the following internet address: (http://
THE DETERMINANTS OF CARDIAC FUNCTION
mphywww.tamu.edu/davis/models/pvmodel.)
(A Guide for Instructors and Students)
html. A comprehensive worksheet is provided in the
APPENDIX to this manuscript, and the worksheet is I. GOALS AND OBJECTIVES:
available for download as a Microsoft Word file at the
same URL address. The worksheet may also be used 1) Use a computer stimulation model to demonstrate how pre-
by an instructor to lead students through a step-by- load, afterload, contractility, and heart rate (HR) influence
step discussion of cardiac function, or it can be as- and determine cardiac function.

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2) To help students better visualize the dynamic interactions puter screen by pressing each button off and then on in turn.
among the four determinants of myocardial function. The functions of each of these four parts of the model are
described next.
3) To help students better understand and visualize the dynamic
changes in stroke volume (SV), cardiac output (CO), and
aortic pressure that occur as a consequence of changes in the A. Strip Chart Record (top left quadrant in
four determinants of myocardial function. computer screen):
A simulated strip chart recorder is displayed in the top left quadrant
II. STUDENT PREPARATION FOR THIS of the computer screen and shows time-based records of three
LABORATORY EXERCISE: basic parameters of a Wiggers Diagram for the left ventricle.
Looking from the top chart down, these include displays of aortic
It is assumed that students have attended lectures on the appropri- pressure (mmHg) in red, left ventricular pressure (mmHg) in black,
ate subjects or done preliminary readings before doing this exer- and left ventricular volume (ml) in black.
cise. Students should at least know the definitions of the terms
preload, afterload, contractility, and HR before doing the labo- Watch the strip chart and answer the following questions:
ratory exercise. They should also have a basic understanding of the
mechanisms of muscle contraction and force generation.
1. What is a normal value for Systolic Pressure in the Aorta of a
human?
III. GENERAL INFORMATION:
2. What is a normal value for Diastolic Pressure in the Aorta of a
The simulation program name is pvmodel.rt or pvmodel.exe human?
and is located on both the PowerMac and Pentium-based comput-
ers in the College of Medicine, Learning Resource Center (LRC). 3. How would you calculate a Mean Arterial Pressure (Pa) from the
The program may also be downloaded from the World Wide Web Chart Record? Whats your answer?
for use at home. Use of the model in the LRC or acquisition of the
model from the course website requires a password. For best 4. Do you think the Pa that you just calculated would be about the
results, the program should be run on a computer with a processor same for a Giraffe? Why?
speed of 300 MHz or greater.

B. Pressure-Volume Graph (top right quadrant


IV. START/STOP/RESET DIRECTIONS:
in computer screen):
Double-click on the program icon to load the program. Wait
The instantaneous values for left ventricular pressure are plotted as
until the program is fully loaded before proceeding. Start the
a function of the corresponding values for left ventricular volume,
program by either clicking on the run button (3) in the upper
and the data are displayed in the top right quadrant of the computer
left-hand corner of the program window or by selecting Run
screen. This graph is what physiologists and cardiologists call The
from the Operate menu at the top of the program page. The
Pressure-Volume Loop.
program can be stopped at any time by clicking on the stop
button (stop-sign symbol) in the upper left-hand corner of the
At the bottom right corner of the computer screen is a button
program window. If necessary, the model parameters can be
labeled Clear Graph. This button is used to clear the graph
reset to their initial conditions at any time by selecting Reini-
when it becomes cluttered with accumulated tracings. Its
tialize All to Default from the Operate menu at the top of
value will become more evident as the students proceed with
the program page.
the study exercises. Test its function by pressing and quickly
releasing it.
V. ORIENTATION AND BRIEF DESCRIPTION
OF THE MODEL (with warm-up questions): Next, let the chart recorder run for awhile and press the button
again, but this time hold it down for several cycles. Note that as the
Load and start the program as described above. While the pro- program runs for awhile, the speed of the chart recording and the
gram is running but before beginning the laboratory exercises, cycle rate of the Pressure-Volume Loop both tend to slow down.
look at the computer screen and note that there are four general This is because the model accumulates data for the graph in a
areas displayed on the screen that comprise the model. These buffer, which slows the computer down. By holding the button
four areas include: a strip chart record, a graph of ventricular down, however, the buffer is cleared continuously so the computer
volume versus ventricular pressure, a system diagram, and a set will continue to run at full speed. Students who choose to do the
of four sliders to manipulate the four determinants of cardiac exercise on a slower machine at home can use this function to run
function. Each of the four areas can be turned off or on with the the model more efficiently.
four buttons located at the bottom of the screen labeled Chart
On, Pressure-Volume Loop On, Diagram On, Sliders The Pressure-Volume Loop is comparable to (but not the same
On. Test these buttons to identify the four areas on the com- as) the length-tension diagram for muscle and the Frank-Starling

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Curve for the heart. The advantages of representing the data 1) Pressing the Act Tension button will display a red line on
from the strip chart records as Pressure-Volume Loops are that: the Pressure-Volume Graph. The red line approximates the
1) all four determinants of myocardial function can be repre- active tension curve for the myocardium. It defines the limit
sented or demonstrated on this graph. 2) Other parameters of isotonic shortening during the ejection phase and provides
important for understanding the pumping function of the heart, a visual demonstration of the effect of changes in contractil-
such as End-Diastolic Volume (EDV) and Pressure (EDP), End- ity on ESV; and hence, on SV, CO and Pa . Press the button to
Systolic Volume (ESV) and Pressure (ESP), SV, and Stroke Work see what happens. You may wish to leave this button pressed
are represented on the graph and can be observed directly as for the remainder of the exercise. If, however, your com-
they change. 3) All Phases of the Cardiac Cycle are more puter is inherently slow, be aware that leaving the button on
easily represented and viewed on a Pressure-Volume Loop then may reduce the speed of the dynamic graphic displays.
on a chart record.
2) Pressing the Pause button causes the strip chart recorder
Watch the Pressure-Volume Loop and answer the following to pause and inserts a new display with a sliding vertical line
questions: (blue line) that can be used to identify the elements on the
strip chart record (Wiggers Diagram) that correspond to
1. Find the different phases of the cardiac cycle on the Pressure- those same elements in the Pressure-Volume Loop. It is
Volume Loop. What are they called? useful for locating the boundaries between the different
phases of the cardiac cycle. Press the button to see what
2. Locate the positions on the Pressure-Volume Loop where the happens.
aortic valve and mitral valve open and close. What heart sounds
are associated with these locations? To make this feature work properly, first, press the Clear
Graph button to clear the graph and the internal buffer. Wait
3. Can you compute Stroke Work from this graph? How would you a minimum of five cycles while the internal buffer accumulates
do it? sufficient data. Next, press the Pause button. Finally, manip-
ulate the blue line back and forth or click on the right and left
4. Estimate the normal (control) SV from the Pressure-Volume arrowheads to see what happens. This tool is particularly useful
Loop. for students who have trouble visualizing the relationship be-
tween left ventricular pressure and volume when displayed as a
Wiggers Diagram and as a Pressure-Volume Loop.
C. System Diagram of Cardiac Function
(bottom right quadrant of computer screen):
A system diagram that shows the relationships among the differ-
D. Controls for Manipulating the Determinants
ent parameters that contribute to the pumping function of the of Cardiac Function (bottom left quadrant of
heart is located in the bottom right quadrant of the computer computer screen):
screen. A continuous display of the numeric values is shown in
the small window for each parameter. The parameters associ- Slider controls for manipulating the four determinants of cardiac
ated with the heart are shown in black letters and include: function are located in the bottom left quadrant of the computer
screen. These are used to manipulate Preload; TPR, which affects
changes in Afterload; Contractility, and HR. In the starting, initial
1) EDV and ESV of the ventricle. condition, note that three of the variables are grayed out, and only
the Preload Slider is operative. The reason for this will become
2) SV, which is the difference between EDV and ESV. obvious in a moment.

3) CO, which is the product of HR and SV. The model is designed to operate in one of two different modes:
1) The Isolated Heart (single variable active) mode and 2) The
4) Contractility (Cont), which determines the rate and magnitude Intact Heart (all variables active) mode. The Isolated Heart
of force generated by the cardiac muscle and, therefore, the
mode is used to isolate an individual variable, such as Preload, to
magnitude of ESV.
demonstrate the most basic effect of the variable without sub-
sequent changes in other parameters. The Intact Heart mode is
The parameters associated with the peripheral vasculature, exter- used to show how the pumping function of the heart will
nal to the heart, are shown in red letters. They include Total behave when one or more of the variables is changed and the
Peripheral Resistance (TPR) and Pa
. Recall that Pa is proportional other parameters in the system are allowed to come to a new
to the product of TPR and CO. equilibrium. Keep in mind that this model does NOT include
simulated effects of baroreceptors and other extrinsic cardiovas-
Two additional buttons labeled Act Tension and Pause are cular reflexes. Familiarize yourself with the two operating
also included in the lower right quadrant. They provide the follow- modes (Isolated Heart and Intact Heart) by performing the fol-
ing display enhancements: lowing procedures.

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1) Pull down the Operate menu at the top of the program page 8) When you have completed these simple manipulations, you
and select Reinitialize All to Default to reset the program to should be ready to begin the laboratory exercise.
the initial conditions.

2) Click the Act Tension buttons to display the active tension VI. LABORATORY EXERCISE:
line.
Start the laboratory exercise by first reinitializing everything to the
3) Now, watch the screen for several cycles. Then, click on the default condition. Press the Act Tension button so the active
radio button above the Preload Slider to turn it off and tension line (red line) is displayed on the Pressure-Volume Loop.
observe what happens. Do NOT move the sliders at this time. Then, click the Clear Graph button.
You should see three things change.

a) All the grayed out sliders and traces are now displayed clearly. A. Preload:
b) The label above the sliders changes so it now reads: Intact The purpose of this part of the exercise is to observe how changes
Heart (all variables active). in preload during the filling phase of the cardiac cycle influence
the pumping function of the heart. While performing this part of
c) A feedback arrow and a window showing the diastolic the exercise, consider the following general questions:
pressure in the aorta appear in the system diagram (lower
right quadrant). What is the effect of an increase in preload on the pumping
functions of the heart and the mean arterial pressure?
4) Repeat the above procedure several times by switching the
Preload radio button on and off. Watch what changes occur in Define Starlings Law of the Heart.
the system diagram and what traces are grayed out.
Define Heterometric Autoregulation of the Heart.
Questions:
What is the physiological significance of Heterometric Autoregula-
a) What does the arrow labeled afterload represent? tion of the Heart?

b) Why does it point to the ESV window? What are the underlying molecular mechanisms that account for
the length-tension relationship for cardiac muscle?
c) What does feedback mean? Learn the concept if it is foreign
to you. 1. Isolated Heart Mode (no feedback):

5) Turn off the Preload radio button to return to the Intact Heart With the Preload radio button pressed and set to the Isolated
mode. Heart mode and the Preload Slider in the initial control position
(5.0 mmHg, red dot), watch the Pressure-Volume Loop for
6) Now, switch from the Intact Heart mode to the Isolated several cycles. Next, look at the system diagram and write down
Heart mode and back again by clicking the radio button above the Control Values for the different parameters in the Data
the TPR Slider. Watch carefully to see how the systems diagram Table 1A below. Next, quickly increase the preload to 7.0
changes and what traces are grayed out in this case. mmHg so that the EDV increases to 134 ml. This can be done
by either double-clicking on the Up Arrow above the slider or by
7) Repeat this procedure for Contractility and then HR by click- simply clicking in the vertical slider scale (white column) in the 7.0
ing the radio buttons above each of these two variables. position. For best results, increase the preload at the very end

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of the filling phase just before the beginning of the isovolu- Adjust the Preload Slider back to the control condition (5.0 mmHg)
metric contraction phase in the cardiac cycle. so that the EDV returns to 120 ml. Make certain that the Preload
radio button is set so the system is in the Intact Heart Mode. Clear
Watch the Pressure-Volume Loop for several cycles after increas- the Pressure-Volume Loop graph.
ing the preload to see what happens. If necessary, clear the
graph and repeat the procedure until you get a clean picture. Let the model run for several cycles, then look at the system
Next, look at the system diagram and record in Data Table 1A diagram and write down the Control Values for the different
the new values for the parameters at equilibrium after increasing parameters in Data Table 1B below. Next, quickly increase the
the preload. preload to 7.0 mmHg so that the EDV increases to 134 ml.
Remember that for best results, preload should be increased at
What parameters have changed and why? the very end of the filling phase or at the beginning of the
isovolumetric contraction phase in the cardiac cycle. Watch the
What was the sequence of changes that occurred during the car- changes develop in the Pressure-Volume Loop and also observe
diac cycle after increasing the preload? the changes in the system diagram. When a new equilibrium is
achieved, record the new values for the different parameters in
After studying the above data and thinking about the sequence of
Data Table 1B below. If you have trouble seeing the changes or
events during the cardiac cycle, it should become obvious that in
if you are confused, then simply clear the graph and repeat the
the INTACT HEART, something else must change in both the strip
procedures until you get a better picture of the sequence of
chart record and on the Pressure-Volume Loop. What other
events.
changes would you anticipate? Why?
Compare the experimental results following the increase in preload
If you are stumped by these questions about the INTACT HEART,
continue with the next part of the procedure and the answers for the different parameters in Table 1B vs. A.
should become self-evident.
What happened to the ESV? Why?
2. Intact Heart Mode (feedback):
What did the introduction of feedback do to the equilibrium
To see a visual representation of the answer to the above value for Pa? Why?
question, do the following. Leave the preload radio button
depressed and in the Isolated Heart mode with the preload set at Use the data in Table 1B to calculate values for Systolic Pressure in
7.0 so that EDV is at 134 ml. Clear the graph and let the the Aorta for the control case and following the increase
Pressure-Volume Loop run for several cycles. When the cardiac in preload .
cycle enters the filling phase, quickly press the radio button over
the Preload Slider to switch the system to the Intact Heart mode. How does this change in Pa relate to Heterometric Autoregulation
This procedure introduces the passive feedback effect of the of the Heart?
systemic arterial pressure on the performance of the heart dur-
ing the Ejection Phase of the Cardiac Cycle. Indeed, what is Why is it important for normal function? What is its physiological
now introduced into the model is the effect of afterload on the significance?
final equilibrium condition.
3. Explore:
To better understand the sequence of events associated with an
increase in preload in the intact heart with feedback allowed to Before moving on to the next part of the exercise, try changing the
occur, perform the following procedures: preload up and down over a wider range to see what happens to

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the performance of the simulated heart. Try it in both the Isolated rectly proportional, and the proportionality constant is a measure
Heart and Intact Heart modes. of the resistance (i.e., TPR) to flow.

B. TPR (Afterload): This relationship is demonstrated in its simplest form in this part
of the exercise. Look at the system diagram while moving the
The purpose of this part of the exercise is to observe how changes TPR Slider up and down through a series of steps. Note that CO
in afterload affect the pumping function of the heart. The afterload is held constant in this demonstration. It should be obvious that
is manipulated in the model by changing the TPR. While perform- when TPR is changed during the filling phase of the cardiac
ing this part of the exercise, consider the following general ques- cycle, the Pa will change in direct proportion following the
tions: ejection of fluid from the heart into the aorta in the face of the
new resistance.
Define the term afterload for the left ventricle.
Move the TPR Slider up and down several times and watch to
Hypertension is a major cardiovascular health problem. How does values for TPR and Pa change in the system diagram windows.
hypertension, if not controlled, compromise the pumping ability of Next, return the TPR Slider to the control position (red dot) and
the heart? proceed with the next part of the exercise.

Define Stroke Work. How would you calculate it? 2. Intact Heart Mode (feedback):

Define Cardiac Efficiency. How would you measure it? Click on the radio button over the TPR Slider to set the system to
the Intact Heart mode. Make certain that all the sliders are set to the
What other data, not included in this exercise, would you need to control conditions (red dots). Watch the chart record and the
estimate Cardiac Efficiency? Pressure-Volume Loop for several cycles and record the control
data in the appropriate box in Data Table 2, below. Calculate the
1. Isolated Heart Mode (no feedback): Ejection Fraction for the control condition.

Return all the sliders to their initial conditions (red dots). Depress Now, to see the effect of an increase in TPR afterload when the
the Act Tension button so that the active tension line is visible preload is held constant (Manual Preload On), perform the fol-
on the Pressure-Volume Graph. Switch into the Isolated Heart lowing manipulations:
Mode by clicking the radio button above the TPR Slider. Notice
that all the chart functions are now grayed out. a) Increase TPR (Manual Preload On):

Recall that TPR is controlled primarily by neural and humoral Make certain the Act Tension button is on. Press the Clear
stimuli extrinsic to the heart. Indeed, those parameters that Graph button to clear the Pressure-Volume Loop and the internal
influence the pumping function of the heart, but are in the periph- buffer. Let the model cycle for two or three cycles, then suddenly
eral vasculature or are part of extrinsic regulatory mechanisms, are increase TPR to 35 by clicking in the TPR Slider Scale (white
represented in the system diagram in red. column) at the 35 position. Watch what happens. For best re-
sults, increase TPR at the beginning of the filling phase in
The equations that relate flow (i.e., CO) and pressure (i.e., Pa
) in the cardiac cycle. Try this procedure several times, if you wish, to
the peripheral vasculature dictate that flow and pressure are di- get a clear record. Record the new equilibrium data [TPR Increased

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to 35 (Manual Preload On)] in Data Table 2 and calculate the new mode to see what happens to the performance of the simulated
value for the Ejection Fraction. heart. Try it in the automatic preload mode (Auto Preload On) and
also in the manual, or fixed, preload mode (Manual Preload On).
What changed? Why? Try changing TPR in the Manual Preload ON mode and then
adjust the preload slider to see what happens.
In the intact heart at equilibrium, Cardiac Output must always
equal Venous Return; otherwise blood will accumulate in the lungs.
Consequently, whenever CO changes, there will be a correspond- C. Contractility:
ing adjustment in Venous Return and hence the filling characteris-
tics of the heart. The purpose of this part of the exercise is to observe how changes
in contractility affect the pumping function of the heart. While
To simulate this effect and to complete the sequence of events performing this part of the exercise, consider the following general
resulting from an increase in afterload, do the following. Simply questions:
click on the large, rectangular button below the TPR radio button
to switch from the fixed preload condition (Manual Preload On) Define Homeometric Autoregulation of the Heart.
to the automatic preload condition (Auto Preload On). Make this
change during the filling phase of the cardiac cycle, then watch What is the physiological significance of Homeometric Autoregula-
what happens. After four or five cycles, record the new equilibrium tion of the Heart?
data [TPR Increased to 35 (Auto Preload ON)] in Data Table 2 and
calculate the new value for the Ejection Fraction. What is the Bowditch Effect?

What changed? Why? How do the data compare with the case What is the Anrep Effect?
when the preload was held constant?
What is the Woodworth Effect?
b) Increase TPR (Auto Preload On):
What is the difference between intrinsic regulation and extrinsic
To see the full sequence of events in response to a change in regulation of myocardial contractility?
TPR-afterload, repeat the procedure with the automatic preload
condition set as follows. Return the TPR Slider to the control What are the basic molecular and cellular mechanisms that account
position (Red Dot). Press the Clear Graph button to clear the for changes in myocardial contractility as a result of sympathetic
Pressure-Volume Loop. After two or three cycles, suddenly increase stimulation of the heart? Are these mechanisms the same for the
TPR to 35 by clicking the slider scale at the appropriate level during Bowditch Effect? Explain.
the filling phase in the cardiac cycle. Watch what happens as the
cardiac cycle changes and shifts to the right on the passive, filling 1. Isolated Heart Mode (no feedback):
curve.
Return all the sliders to their initial conditions (red dots). Return
Knowing that CO must always be equal to venous return when the the system back to the (Manual Preload On) condition by clicking
system is in steady state, what do you think is the most important on the rectangular button below the TPR and Contractility Sliders.
function of Heterometric Autoregulation of the Heart? Now, press the radio button above the Contractility Slider to put
the system into the Isolated Heart Mode. Notice that the arbitrary
3. Explore: value (1.0) for contractility is displayed in the appropriate window
in the system diagram. Make certain that the Act Tension button
Before moving on to the next part of the exercise, try changing TPR is depressed so that the active tension line is visible on the Pressure-
(afterload) up and down over a wider range in the Intact Heart Volume Graph.

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Let the Pressure-Volume Loop run for several cycles, then look at ing in the slider column (white column) next to the red dot.
the system diagram and write down the Control Values for the Watch what happens.
different parameters in Data Table 3A below.
2. Intact Heart Mode (feedback):
Now, clear the graph and let the system cycle for two or three
loops. Next, quickly increase the contractility one step to a value of Click on the radio button over the Contractility Slider to set the
1.1 by clicking once on the Up Arrow above the slider. Let the system in the Intact Heart mode. Make certain that all the sliders are
system cycle for two more loops and on the third loop, increase the set to the control conditions (red dots). Look at the system dia-
contractility one step more to a value of 1.2. Continue this process gram and write down the Control Values for the different param-
until you reach a contractility value of 1.3 and then press the eters in Data Table 3B below. They should be the same as the
Pause button. control values in Data Table 3A.

For best results, click the Up Arrow to increase the con- Now, clear the graph and let the Pressure-Volume Loop run for
tractility just as the isovolumetric relaxation phase ends and several cycles. Next, quickly increase the contractility to 1.3 and
the filling phase begins. This may take a little practice, so try it watch what happens. This is easily done by triple-clicking on the
several times until you get a nice family of curves. Also, remember up arrow above the contractility slider. Remember that for best
that you can use the Clear Graph button under the Pressure- results, increase the contractility at the end of the isovolumetric
Volume Loop to clear the computer screen if it gets too cluttered relaxation phase and the beginning of the filling phase in the
with multiple traces. cardiac cycle. Watch the changes develop in the Pressure-Volume
Loop and also observe the changes in the system diagram. When a
After you have accumulated a family of three or four curves and set new equilibrium is achieved, record the new values for the differ-
the Pause button, look at the resulting Pressure-Volume Graph ent parameters in Data Table 3B below. If you have trouble seeing
and see how the increases in contractility caused the ESV to the changes or if you are confused, then simply clear the graph and
change. repeat the procedures until you get a better picture of the sequence
of events.
What happened to SV?
Compare the results in the Intact Heart mode when contractility is
What happened to CO and Pa? Why? 1.3 (Table 3B) with the comparable data in the Isolated Heart mode
(Table 3A).
After examining the results and thinking about the above questions,
release the Pause button and let the system continue to cycle How have ESV, SV, CO, and Pa changed?
with the contractility set at 1.3.
Why are they different?
Look at the system diagram and record in Data Table 3A the new
values for the parameters with the contractility at 1.3. Compare the What caused them to change?
control data with the experimental data; note what parameters
have changed and think again about your answers the above ques- Use the data in Table 3B and calculate the Ejection Fraction when
tions. Contractility was set at the control level and when it was
elevated to 1.3 . Now, think again about the definition of
Finally, in preparation for the next part of the contractility demon- Homeometric Autoregulation of the Heart and its physiological
stration, return the contractility back to the control level by click- significance.

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3. Explore: How does heart rate affect ESV?

Before moving on to the next part of the exercise, try changing What is the Bowditch Effect? How does it affect the relationship
the contractility up and down in the Intact Heart mode over a between CO and HR?
wider range to see what happens to the performance of the
simulated heart. Also, watch the strip chart to see what happens. 1. Isolated Heart Mode (no feedback):
While doing this, you may wish to manipulate the preload up
and down to simulate compensatory changes in venous return Return all the sliders to their initial conditions (red dots). Again,
and the filling of the heart following changes in contractility. make certain the Act Tension button is depressed. Make
Finally, to better simulate what you have just done, leave the certain that the rectangular button below the TPR and Contrac-
system in the Intact Heart mode. Then, return the Preload to the tility Sliders is returned to the (Manual Preload ON) position.
original setting (red dot). Next, click the rectangular button Switch into the Isolated Heart Mode by clicking the radio button
above the TPR and Contractility Slides to set the system so that above the HR Slider. Notice that all the chart functions are now
preload will adjust automatically (Auto Preload ON) when con- grayed out.
tractility is changed. Now, manipulate the Contractility Slide and
see what happens. The physiological significance of Homeomet-
The primary determinants of CO are HR and SV. Indeed, the
ric Autoregulation of the Heart should be on your mind when
product of HR and SV equals CO.
you do this manipulation.
This relationship is demonstrated in its simplest form in this part
D. HR:
of the exercise. Look at the system diagram while moving the
The purpose of this part of the exercise is to observe how HR Slider up and down through a series of steps and watch
changes in HR affect the pumping function of the heart. While what happens. Note that SV is held constant in this demonstra-
performing this part of the exercise, consider the following tion. It should be obvious that when HR is increased at any time
general questions: during the cardiac cycle, CO increases, and therefore Pa in-
creases because the cycling rate of the heart increases. However,
How does heart rate affect EDV and the filling of the heart? in the intact heart, it is clear that the relationship between CO

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and HR is not linear and increases in HR can severely limit the slowly, then briefly hold down the Clear Graph button. Now,
output of the heart at very high HRs (tachycardia). record the values for EDV, ESV, and SV in the appropriate
columns in Data Table 4A and record the value for CO in the
To better understand the effect of HR on the pumping function of appropriate column (control contractility level 1.0) in Data
the heart, proceed with the next part of this exercise. Table 4B. Next, increase the HR in 6-beats/min steps by clicking
once for each step on the Up Arrow above the HR Slider.
2. Intact Heart Mode (feedback): Watch the Pressure-Volume Loop and the system diagram at
each new HR until steady state is achieved, then record the new
Click on the radio button over the HR Slider to set the system to values for EDV, ESV, SV, and for CO in Data Table 4A and Data
the closed loop mode. Make certain that ALL the sliders are set to Table 4B, respectively. When you have recorded the data for the
the control conditions (red dots) and that the Act Tension range of HRs, 42 to 180 beats/min, plot the results in the
button is pressed. accompanying graphs and use the results to answer the follow-
ing questions:
Slowly move the HR Slider up and down, watch the strip chart
recording and the Pressure-Volume Loop, and see what hap- SV decreases almost linearly as HR increases over a wide range
pens. Depending upon the speed of your computer, you may (See your graph of Data in Table 4A). Why? If CO increases in
find it necessary to periodically clear the Pressure-Volume Loop direct proportion to SV, why then doesnt CO decrease rather
by briefly holding down the Clear Graph button to obtain a than increase in this case? What limits CO and causes it to fall
more realistic simulation at the higher HRs. When you have sharply at the highest HRs?
familiarized yourself with the manipulations, then continue with
the next procedure to generate a more quantitative picture of 3. Interaction between HR and Contractility and their effects
the effect of HR on the pumping function of the heart. on CO:

Reduce the HR to 42 beats/min by pulling the HR Slider down to The final part of this exercise is designed to help you understand
the appropriate level. You may find it easier to click on the the physiological significant of the Bowditch Effect and to explore
Down Arrow at the bottom of the HR Slider. Wait until a how intrinsic changes in myocardial contractility can extend the
steady state is achieved. Again, if the system seems to run too operating range of the heart at higher HRs.

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Repeat the above procedures (D. Heart Rate, 2. Intact Heart libraries, to faculty and students who contact our websites. Drs. Jeff
Mode) for three additional levels of Contractility (0.8, 1.2 and Kiel and Pete Shepherd generously provided the source code to
1.4) while adjusting the Heart Rate through the range 42 beats/ their published model (3), which motivated us to start this project
minute to 180 beats/minute. Record only the values for Cardiac and transform our ideas into a working simulation. Judy Davidson
Output and fill in the remaining columns in Data Table 4B. assisted with proofreading and printing. We thank Dr. Brian Duling,
Director of the Cardiovascular Research Center at the University of
When you have recorded all the data, plot the results in the Virginia, for testing the model well beyond its limits and for making
accompanying graph so that you have a complete family of curves heart-piercing criticisms and invaluable suggestions for its improve-
showing CO versus HR for the contractility range 0.8 1.4. Then, ment. Finally, we thank all the undergraduate physiological science
use the results to answer the following questions: students in the cardiovascular physiology 485 course at the Univer-
sity of Arizona, who helped test this model in a real classroom
Define the Bowditch Effect. How can you stimulate it using this setting during the spring semester, 2000.
model? How does it help extend the operating range of the heart at
Address for reprint requests and other correspondence M. J. Davis,
higher HR?
Rm. 346 Reynolds Medical Building, Texas A&M University HSC,
College Station, TX 77843.
E. Play Time in Closed Loop Mode:
Received 8 February 2000; accepted in final form 18 December
Now that you have completed the laboratory exercise, you may 2000.
wish to test your understanding of the dynamics of the heart by
manipulating several of the variables (preload, afterload, HR, and
contractility) at once.
REFERENCES
For example, try to simulate the Anrep Effect.
1. Coleman TG Modeling Workshop. Deptartment of Physiology
and Biophysics, Univ. of Mississippi Medical Center website:
Also, try to simulate the compensatory changes in cardiac function
http://phys-main.umsmed.edu/workshop/workshop.htm.
that you expect might occur following hemorrhage.
2. Katz AM. Physiology of the Heart (2nd ed.). New York: Raven,
1992.
Remember that this is only a stimulation model and not a real
3. Kiel JW and Shepherd AP. A graphic computer language for
heart, so the model may not work perfectly in the extreme
physiology simulations. Computers in Life Science Education 5:
ranges. That fact, however, should give you a better apprecia-
49 56, 1988.
tion for the beauty of the biological system and a better under-
4. Levick JR. An Introduction of Cardiovascular Physiology (2nd
standing of why there is no substitute for your own, normal,
ed.). Oxford, UK: Butterworth/Heinemann, 1995.
healthy heart.
5. Rothe CF and Selkurt EE. A model of the cardiovascular system
for effective teaching. J Applied Physiol 17: 156 158, 1962.
The authors thank Dan Phillips at National Instruments for easing 6. West JB The Cardiac Pump. In: Best and Taylors Physiological
the licensing restrictions and thereby allowing free distribution of Basis of Medical Practice. Baltimore, MD: Williams & Wilkins,
reasonable numbers of this program, along with complied LabView 1991.

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