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TEACHING WITH TECHNOLOGY
1 Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana 46202
2 Department of Computer Science, University of Hawaii at Hilo, Hilo, Hawaii 96720
Abstract
The maintenance of an adequate cardiac output and systemic arterial blood pressure is a complex process with intricacies that are often difficult to understand. Cardiovascular Interactions is an active learning tool that demonstrates the interactions between the functions of the heart and peripheral circulation. This learning package consists of a Lab Book, a Model, and an Information file. The Lab Book is an interactive tutorial for exploring the relative influences of parameter changes on the cardiovascular system under normal, stressful, or pathophysiological conditions. The learners are guided to predict the direction and relative magnitude of changes of key variables in the cardiovascular system, evaluate the accuracy of their predictions, and describe the cause-and-effect mechanisms involved. Consequences of heart failure, hemorrhage, exercise, and changes in intrathoracic pressure can be explored. The results obtained in the Lab Book are based on a five-compartment mathematical Model, which reflects our current understanding of the basic control of the cardiovascular system. The Model was designed to be complex enough to be realistic, yet not so complex as to be overwhelming. An Information File contains definitions and descriptions of classical physiology about key concepts, including figures, and a detailed description of the Model. Hypertext tags embedded in the Lab Book are used to access the Information File. The Cardiovascular Interactions learning package was designed to run from its CD and so does not need to be installed.
Key words: simulation; heart; circulation; preload; afterload; contractility; Emax; capacitance; resistance
True education is much more than retrieval and memorization of mere information. Our goal with the Cardiovascular Interactions project (CVI) has been to develop a tool for "meaningful learning," as described by Michael (7). With this approach, we expect the learner to understand cardiovascular interactions well enough to predict and explain responses to disturbances by reasoning through the series of cause-and-effect relationships of the system. A reasonably complex conceptual model of the human cardiovascular system that adequately fits reality requires a set of equations and parameters that can be manipulated and solved with computer simulation. If the results of parameter changes do not meet expectations, then the learner needs to explore their conceptual model for inadequacies or find and define the error in the equations of the mathematical model.
Learning goal.
The tutorial was developed to demonstrate and clarify the interactions between the functions of the heart and peripheral circulation in the development and control of an adequate cardiac output and systemic arterial blood pressure. With the help of this project, we expect the learner to grasp how the individual components and underlying relationships are integrated, under the control of mechanical feedback mechanisms, into a self-correcting system that maintains functional integrity in the face of challenges such as moderate stress or pathological conditions. As Grodins et al. (6) stated in 1954: "The essence of physiology is regulation. It is this concern with ‘purposeful’ system responses which distinguishes physiology from biophysics and biochemistry." This Cardiovascular Interactions project is about "integrative physiology" at the total body level. The five-compartment mathematical Model thus demonstrates the concept that mechanical feedback mechanisms (such as redistribution of blood volume within the system and the vigor of cardiac contraction) control the cardiovascular system to reduce the susceptibility to disturbances that could cause deviations from optimal function. The two facets of the vigor of cardiac contraction revealed and emphasized with the Model, are 1) the magnitude of preload (the end-diastolic volume that is the basis of the Frank-Starling Law of the Heart) and 2) the magnitude of afterload [the end-systolic pressure that, with the slope of end-systolic pressure-volume relationship (Emax), determines the end-systolic volume]. [These definitions are not universally accepted (8).]
The learning package is designed for those who have a minimal working knowledge of both the structure of the cardiovascular system and the underlying basic physical principles, such as the concepts of 1) flow related to pressure gradient and resistance, 2) stressed volume related to distending pressure and compliance, and 3) change in stressed volume computed as the integral of inflow minus outflow from a compartment. These concepts, and many others, accessed by clicking on keywords in the Lab Book, are reviewed, if needed, in the Information File. Davis and Gore (3) have provided a simulation application to describe the determinants of cardiac function. Our study integrates the function of both ventricles with the peripheral circulation. Carroll (1) discusses pressure-flow relationships in detail. Our study uses that concept and the conservation of mass principle to integrate heart function with that of the peripheral vasculature.
Important topics covered to help the learner and professor:
Learners targeted.
The CVI project was designed for freshman medical and biomedical graduate students and senior bioengineering students. However, others, including professors, physicians, and other health care professionals as well as "continuing education" students should find it helpful. From the biomedical education textbooks and literature, teachers and professors of physiology will likely benefit from it also. Unfortunately, the interactive concepts about the cardiovascular system are so complex and intertwined that even professors or physicians cannot quickly and easily grasp a clear and functional understanding of the physiology of the system. Because diseases influence various parts of the system to varying degrees, the therapies to be used depend on the choice of which parameters need to be restored or enhanced to attain adequate cardiac function for pumping blood to the tissues.
What’s new and valuable about this project?
We hope that professors developing course material may find the tools used in this project worthy of adopting.
The tutorial Lab Book includes:
1) coding with hypertext tags to move data from the model to the tutorial and for jumps from the tutorial to the Information File for definitions and descriptions of key concepts;
2) a column for predictions and a site for answers to provocative questions;
3) conversion of the model results to percent of control and transfer of them from the model to a column in the tutorial to ease the comparison of the learner’s predictions to the results of the simulation;
4) a table of contents for both the tutorial Lab Book and the Information File for quick jumps to the topic of interest;
5) provision for copying the Lab Book on the CD to the learner’s own copy on a floppy disk that can be retrieved for future additions of results of experiments and printed, if desired.
Details about architecture and design of the hypertext coding used are provided in Gersting and Rothe (4).
The Information File includes:
1) instructions and help for using the project;
2) strategies based on five fundamental equations for predicting the effect of a change in the value of a variable, given the change in the other variable and the value of the governing parameter; applied to each compartment, these equations make up the simulation model.
3) a mini-physiology textbook (with figures, mostly from Ref. 14) that defines and explains many basic concepts of the cardiovascular system;
4) a discussion of each of the 17 experimental modules (See Table 1) in terms of evidence available and cause-and-effect consequences; answers to the questions asked in each "experiment" are also provided;
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6) references to some of the relevant physiology literature and citations justifying the parameter values used; and
7) a button to jump to the Index for instant jumps to the topic of interest.
Audio-Video Interleaved (*.avi) files provide a succinct instructional description of the Main Menu, the Model, the Lab Book, and saving the Lab Book to a floppy disk.
With the goals of being accurate, inclusive, easy to use, and concise, the development of the Tutorial and Information File has been very intellectually challenging and time consuming.
MODEL
The layout of the mathematical Model is shown in Fig. 1. The Model includes a left heart, arterial bed, venous bed, right heart, and lung bed. This layout display can be printed during a run to show the data and the magnitude of parameter(s) changed at that time in the "experiment." The Model display (Fig. 2) provides the data for the tutorial and shows the parameter values currently in use. This example shows left ventricular failure. There are 27 variables displayed to represent a typical adult human and 15 parameters that can be changed. A plot of the time course of changes in mean systemic arterial blood pressure, cardiac output, and venous return, during the development of ventricular failure, are shown at 60-ms intervals in Fig. 3.
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Each of the three vascular compartments are simulated by the following:
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where Vt is the volume at the current time (t), Vt-1 is the volume at the previous time interval, Fin is the inflow, which is the same as the outflow from the upstream compartment, Fout is the outflow into the downstream compartment, and 
t is the step size (e.g., 0.001 min). If outflow from a compartment is not identical to inflow, then the volume in the compartment will change.
Each of the two ventricles are simulated by:
1) cardiac output (CO) = HR x SV = HR x (EDV - ESV)
2) venous return (VR; into the ventricles) = K2 x (Pv - EDP)/Rv
where HR is heart rate, SV is stroke volume, EDV and ESV are ventricular end-diastolic and end-systolic volumes, respectively, Pv is the peripheral venous pressure, EDP is the end-diastolic ventricular pressure, and Rv is the venous outflow resistance. K2 is a factor "impeding" inflow when diastolic filling time is curtailed at high heart rates. K2 is 1.000 between a heart rate of 0 to 
125 beats/min. It then declines to 0.5 at 200 beats/min, and is 0 at 250 beats/min.
EDV is the complex result of interacting factors influencing the preload of the heart and is a major determinant of cardiac output and the work done by the heart during each beat. For each ventricle, the EDV is determined by several factors, including:
1) EDP, the internal pressure at the end of the filling phase. It is computed as: EDP = EDV/compliance during diastole, and is the downstream pressure influencing the rate of inflow from the veins;
2) intrathoracic pressure (Pit), the pressure in the chest outside the heart. It is a factor determining the ventricular distending pressure: Pdistend = EDP - Pit;
3) ventricular compliance (C), the ease of ventricular distention during diastole;
4) diastolic filling time limits the amount of filling at high heart rates, because the time for filling (the duration of diastole minus that of systole) is seriously limited at high heart rates. The relationship between heart rate and cardiac output is complex. Quality data are not readily available to quantify the relationship, because an increased heart rate is usually associated with exercise or stress. These disturbances induce a reflex increase in sympathetic nervous system activity that increases heart rate and also increases cardiac contractility and causes venous and arterial constriction. Pacing the heart (i.e., stimulation of the right atrium at various time intervals) changes the heart rate but does not provide useful data if the cardiovascular reflexes are intact, because these reflexes tend to nullify any heart rate effects on cardiac output by changing other cardiovascular parameters.
ESV of each ventricle is determined by:
1) the cardiac contractility, represented by Emax, and
2) the ventricular (end-systolic) pressure, which is the afterload on the heart.
The ventricle contracts to eject blood until the arterial back pressure (force) matches the contractile force generated by the heart muscle. At this time, ejection stops. The end-systolic pressure-to-volume relationship (ESPVR) determining the ESV is
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where ESV is the ventricular volume and ESP is the ventricular pressure at about the time of maximum ventricular elastance [P(t)/V(t)]. We assume, as discussed in the Information File, that the mean systemic arterial pressure (Psa) adequately represents the end-systolic-pressure (ESP). Emax is the slope of the ESPVR: Emax = ESP/(ESV - V0), and V0 is the ESV extrapolated to zero generated pressure.
As the Model is run, blood volume progressively redistributes between the compartments to 1) meet the constraints set by the equations and parameters and 2) reach a steady equilibrium state such that the flows through each compartment are equal. (Data are displayed at 0.1-min intervals after each 100 iterations.) The redistribution of blood volume between the various compartments explains, in large measure, why the system is inherently self-correcting in response to various disturbances. The control data (at time = 0) are shown in the Layout screen (Fig. 1). Subsequent changes in variable values depend on the magnitude of changes of parameters, including total or unstressed blood volume. With a Pentium CPU chip with 32-bit registers and double precision, the error is less than a nanoliter, with a total normal blood volume of 5,000 ml. The model runs at least 100 times faster than clock time. Blood volume changes caused by hemorrhage or transfusions are made at the venous compartment, which contains >75% of the total unstressed volume. The concepts of stressed and unstressed volumes and mean circulatory filling pressure (12) are discussed in the Information File.
Although the Model does not include provision for transcapillary fluid shifts, changing total blood volume simulates such fluid shifts. Similarly, changing appropriate parameters simulates autonomic reflex compensation or drug action. Although details of the pattern of arterial pressure during each cardiac cycle are not included, values for systemic arterial systolic and diastolic pressures are computed and displayed.
In a stand-alone mode, the Model (Fig. 2) and the plot of model data (Fig. 3), along with the windows for changing parameters, can be used to demonstrate various responses during a lecture.
LAB BOOK
The Lab Book provides a tutorial in which the learner explores details about the interactions between various parameters and variables. A list of the 17 experimental modules (Table 1) is available in the Lab Book by clicking the "Show Table of Contents" button and then clicking the desired experiment.
The primary objective of the tutorial is for the learner to be able to explain the influences and mechanisms involved in response to changes of the parameters listed in Table 1. Of particular importance are the changes in 1) cardiac output, 2) mean systemic arterial pressure, and 3) blood volume distribution. The Lab Book (example shown in Fig. 4) provides an interactive learning environment for the learner(s) who are asked to:
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INFORMATION FILE
An extensive Information File of 100 pages with 14 figures provides 1) an introduction about the purpose of the learning project, 2) the objectives, 3) detailed instructions, 4) suggested strategies for predicting responses, 5) a physiology section, which defines and explains the major cardiovascular concepts and includes textbook-type figures [see Rothe and Friedman (13)], 6) a discussion of the results of each module and sample answers keyed to the questions at the end of each experimental module, 7) a detailed description of the Model with the equations used plus documentation for parameter values used, the rationale for choosing parameter values, and the assumptions governing the model, 8) a parameter sensitivity analysis matrix, which is an important part of a mathematical model, and 9) a bibliography section providing citations to some of the relevant physiology and references supporting the choice of normal variable and parameter values.
Hypertext links connect the Lab Book with the relevant sections of the Information File. A dynamic table of contents (for both the Information file and the Lab Book file) helps the learner navigate quickly to relevant sections of each. In addition an index to items in the Information File is readily available, including a list of abbreviations used.
Because this learning project is complex, an effort has been made to minimize learner frustration with the user interface by including a set of four audio-visual clips (*.avi files) on the CD. These clips demonstrate the mechanics of how to use the project effectively. They may be played with a multimedia player and are a highly recommended time saver for the learner who has no readily available consultant.
Suggestions for use of the project.
The CVI project can be used by a single person, but from experience with the pencil-and-paper version (11) and Michael’s (7) definition of effective learning, the most effective approach is to ask two to at most four students to "experiment" and learn together. The Lab Book should be saved to a named file on the learner’s computer or floppy disk to save the predictions and answers for subsequent use. This file can then be retrieved for additional studies or corrections at a later date. The saved file can be printed or submitted to the instructor. The key elements in the meaningful learning process include:
1) discussion to specify the predictions to be made,
2) comparisons between the predictions and the Model results,
3) deciding what "experimental evidence" is needed to understand the system, and
4) development of cause-and-effect chains of logic to explain the results.
The discussion of each experiment in the Information File is designed to reinforce (or help correct) the learner’s progress in learning about the cardiovascular interactions.
Each experiment will require 10–30 minutes to complete. The instructor may want to assign only a few experiments if time is limited. For example, assign Experiments 1, 3, 8, 11, 12, 14, and 17 as described in Table 1. Using the "explore" version of the Lab Book (instead of saving their own copy of the Lab Book with predictions and answers to questions) provides a quick review or update of understanding of the cardiovascular system.
Please note that these simulated experiments do not provide real data. Only well designed experiments with living subjects can provide the basic knowledge needed to substantiate the equations and parameters employed.
History of development of CVI project.
Mechanical models have been used to help learners understand the cardiovascular system (15), but they are limited. One of the first detailed mathematical analyses of cardiac and blood vessel hemodynamics was by Grodins (5). However, it involved the solution of complex algebraic equations and provided no dynamic patterns. Coleman, et al. (2) in 1974 pioneered an alternative approach based on numerical integration, which was subsequently used for our cardiovascular simulation (9). This was combined with a paper-and-pencil tutorial to help our medical and graduate learners understand the overall function of the cardiovascular system. The model was implemented on a group of personal computers with the support of an IBM grant to the Department of Physiology. (The PCs had 256 kilobytes of RAM and a 2-MHz CPU.) A description and evaluation of the project was published (10).
Because of the subsequent availability of much more powerful computers and computer software, the possibility of converting the pencil-and-paper tutorial into a Windows-based package was explored. Using Microsoft Visual Studios (version 5 and then 6) and Bennet-Tec ALLText software, we developed a functioning Lab Book that used an interactive hypertext format. The concept was presented at the Computer-Based Resources in Teaching and Research session of the Experimental Biology meeting in 1999, and a functioning version running from a CD was displayed at the Experimental Biology 2000 meeting.
The Model provides a summarization of over 32 years of research support by National Institutes of Health Grant HL-07723 titled: "Reflex Control of Vascular Capacitance" (see for example Refs. 12, 13, 15).
Are classroom faculty needed?
The present self-paced CVI project does not need the on-site presence of a faculty member. However, our experience at the Indiana University School of Medicine at Indianapolis with the pencil-and-paper version of the CVI package in the 1980s demonstrated that a knowledgeable faculty member present in the room with six to eight computers and groups with two to four students each was helpful. After a few years, however, the lack of faculty with a working knowledge of cardiovascular physiology led to the computer projects being assigned (we had about five) to the students to do in their "free time." No faculty member was present, and there were no specific cardiovascular interactions questions on the examinations. There is no good substitute for a live, knowledgeable, friendly, computer-skilled faculty member. Without a faculty member present, and without having specific questions on exams related to the computer labs, the students soon learned that the computer labs were optional and so quit using them. Use of computer-assisted instruction in our curriculum was thus abandoned.
The questions in the Lab Book and the Information File are designed to encourage and help the student, but there is no substitute for related questions on the examinations to encourage students to use the project. If these questions cover important concepts, then the use of the self-paced project (and similar ones) can be assessed and, if positive, justify their use.
The reality of current medical school funding and priorities and the press of limited scheduled time for students justifies the attempt to use a learning environment that is "asynchronous" (i.e., "distributed learning," "distance education"). Continuing education for physicians and other professionals also benefits from the use of modern information technology approaches. It is not easily accomplished, quickly done, or inexpensive. Furthermore, packages put together by computer experts without major direction and help from people skilled in both the discipline and teaching will be a waste of time and money.
Assessment of the learning project.
Evaluating the quality of a learning tool is a challenge. Surveys are helpful but are not definitive. Pre- and posttesting are feasible (7), but simple multiple-choice questions about the interactive aspects of the system are difficult to develop. A statistically valid assessment would require random assignment of students to the project or to the lecture-only, animal lab, or research paper-writing formats. In the current climate in American medical schools with their emphasis on molecular biology and the proliferation of many other important subjects that crowd the curriculum, this is rarely feasible.
In the 1980s, two half-day sessions involving three to four students with each computer and a 16-page paper-and-pencil lab book provided an effective learning experience. About 80% of the 98 medical and graduate students of the 1985 class who responded to a survey agreed or strongly agreed that the cardiovascular simulation package was helpful. Only about half were satisfied with the printed instructional material, however (10). In January 2001, 87 freshman medical students returned a survey evaluating their experience with the project. Although over 75% felt that their understanding was improved, most considered the project difficult to use in the form then available. Many useful suggestions were made. Unfortunately, not all of the students who used the project attended the 15-minute demonstration, nor did they use the video clips then available. The presentation of the project was radically revised, including a major revision of the Lab Book, a strong recommendation to use the audio-video clips, and a more familiar and clearer method for saving the Lab Book on a floppy and retrieving it for later use.
Availability.
A CD with the Model, Lab Book, Information File, and audio-video clips is available from the author (C. F. Rothe) for a nominal fee to cover the cost of reproduction, handling, and postage. The project can be run from the CD without installing it on the computer. The authors own the copyright to the project but grant permission to reproduce and distribute copies of this work for not-for-profit educational purposes. For a Cardiovascular Interactions CD, please send an e-mail request to the author (crothe{at}iupui.edu). It is also available as a supplement to this article at Advances in Physiology Education Online (URL: http://advan.physiology.org/cgi/content/full/26/2/98/DC1).
In summary, this Cardiovascular Interactions project was designed to help the learner gain a comprehensive understanding of the quantitative aspects of cardiovascular dynamics in a manner that is relatively easy to use. It also provides much relevant background information in a readily accessible format.
Acknowledgments
We are grateful for the comments and helpful suggestions of many students. The critique and encouragement of colleagues, including James Randall, Glenn Bohlen, Judith Tanner, Phillip Andrew, and Thomas Lloyd, are gratefully acknowledged.
The model and tutorial were developed in Microsoft Visual Basic (versions 5 and 6). It includes hypertext and data links using ALLText 4 HT/Pro (Bennet-Tec Information Systems, Jericho, NY). Computer screen images were captured with HyperSnap for the figures for this paper, and Hypercam was used to capture the action from the computer screen and saved to AVI [audio-video interleaved movie files (http://www.Hyperionics.com)].
This project was displayed in early development form at Experimental Biology 1999 and 2000.
Address for CD requests and other correspondence: C. F. Rothe, Dept. of Physiology (Med. Science, Rm. 374), Indiana Univ. School of Medicine, 635 Barnhill Dr., Indianapolis, IN 46202 (E-mail: crothe{at}iupui.edu).
Received for publication July 26, 2001. Accepted for publication February 26, 2002.
References
This article has been cited by other articles:
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  G. L. Brengelmann The classical Guyton view that mean systemic pressure, right atrial pressure, and venous resistance govern venous return is/is not correct J Appl Physiol, November 1, 2006; 101(5): 1532 - 1532. [Full Text] [PDF]
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M. R. Pinsky, S. Permutt, Y.-Y. L. Wang, W.-K. Wang, R. D. Baker, C. Rothe, and W. Mitzner The classical Guyton view that mean systemic pressure, right atrial pressure, and venous resistance govern venous return is/is not correct J Appl Physiol, November 1, 2006; 101(5): 1528 - 1530. [Full Text] [PDF]
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C. F. Rothe Last Word: Point:Counterpoint author responds to commentaries on "Active venoconstriction is/is not important in maintaining or raising end-diastolic volume and stroke volume during exercise and orthostasis" J Appl Physiol, October 1, 2006; 101(4): 1270 - 1270. [Full Text] [PDF]
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 A. W. Ra'anan The evolving role of animal laboratories in physiology instruction Advan Physiol Educ, September 1, 2005; 29(3): 144 - 150. [Abstract] [Full Text] [PDF]
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C. F. Rothe The muscle pump indeed raises muscle blood flow during locomotion. J Appl Physiol, August 1, 2005; 99(2): 773 - 773. [Full Text] [PDF]
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B. A. J. Reddi and R. H. S. Carpenter Venous excess: a new approach to cardiovascular control and its teaching J Appl Physiol, January 1, 2005; 98(1): 356 - 364. [Abstract] [Full Text] [PDF]
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