Bridging vascular physiology to vascular medicine: an integrative laboratory class

Abstract

Vascular diseases of the legs are highly prevalent and constitute an important part of medical curricula. The understanding of these diseases relies on strongly interwoven aspects of vascular physiology and vascular medicine. We aimed to connect these within a horizontally integrated laboratory class on vascular physiology of the leg that was designed in cooperation between the departments of physiology and vascular surgery. Conceptually, we applied examination techniques of vascular medicine to visualize physiological parameters that are altered by the most frequent diseases. This facilitates integrative discussions on malfunctions, trains diagnostic skills, and bridges to vascular medicine. In four experiments, we use oscillometry and impedance venous occlusion plethysmography to address key aspects of the arterial and venous system of the legs: 1) arterial pulse wave, 2) arterial systolic blood pressure, 3) venous capacitance and venous outflow, and 4) reactive hyperemia. After the experiments, physiological vascular function, the associated diseases, their impact on the recorded parameters, and diagnostic options are discussed. To allow reproduction, we describe the course structure and the experimental setup in detail. We present the experimental data of a cohort of medical students and document learning success and student satisfaction. All experiments were feasible and provided robust data on physiologically and clinically relevant vascular functions. The activity was perceived positively by the students and led to a substantial improvement of knowledge. With this work, we offer a template for reproduction or variation of a proven concept of horizontally integrated teaching of vascular physiology of the leg.

NEW & NOTEWORTHY This article presents an integrative laboratory class on vascular physiology bridging to vascular medicine. The four experiments rely on oscillometry and venous occlusion plethysmography. We describe in detail this new class regarding structure, experimental setup, and experimental procedure, and we give insight into the applied materials. Moreover, we present the experimental data of 74 students and a quantitative evaluation of the students’ learning success and acceptance.

INTRODUCTION

Objectives and Overview

Vascular diseases of the legs, e.g., arteriosclerosis (AS), peripheral artery disease (PAD), deep vein thrombosis (DVT), and varicose disease (VD), are highly prevalent and constitute an important part of medical curricula. The understanding of these diseases relies on strongly interwoven aspects of vascular physiology and vascular medicine. We aimed to connect these within a horizontally integrated laboratory class. The didactical concept of integrative teaching aims to connect students’ knowledge and skills on different levels. The term “horizontal integration” is used to describe the connection of knowledge and skills of basic science and clinical medicine (1–3). This accentuation of the clinical implications of basic sciences enhances students’ motivation and learning success. In cooperation between the departments of physiology and vascular surgery, we designed a horizontally integrated physiology laboratory class on the vascular system of the legs that bridges to vascular medicine. We used examination techniques of vascular medicine to assess relevant physiological parameters that are typically altered by the most frequent diseases. This concept allows the visualization of physiological key concepts, facilitates discussions and/or further experiments on the associated malfunctions and pathologies, trains diagnostic skills, and therefore bridges to vascular medicine. All experiments were designed for performance by untrained students to allow self-experience and foster experiential leaning (4). All experiments yield quantitative results to facilitate proper physiological interpretation. The created laboratory class is composed of four experiments that focus on different aspects of the arterial and venous system: 1) arterial pulse wave, 2) arterial systolic blood pressure, 3) venous capacitance and venous outflow, and 4) reactive hyperemia. All experiments assess parameters that visualize key aspects of vascular physiology and are sensitive to frequent vascular diseases. The respective contents of vascular physiology and vascular medicine are exemplarily given in Table 1. The experiments technically rely on oscillometry and impedance venous occlusion plethysmography (Table 1). Both techniques are well established in vascular medicine and vascular research, which ensures feasibility and standardization. The experimental phase of the class is followed by a group discussion. All experiments were designed to encourage considerations on the translational axis. The assessed parameters are discussed regarding their role in healthy vascular function and their role in pathophysiological processes that lead to malfunctions and the associated vascular diseases. We also discuss the manifestation of those diseases in the experimental data and the diagnostic options.

Table 1.

Physiological, diagnostic, and technical aspects of the four experiments

Contents of Vascular Physiology (Exemplary)	Evaluable Vascular Diseases (Exemplary)	Examination Technique
1) Arterial systolic blood pressure
Arterial compliance	AS	Oscillometry
Pressure changes with distance to heart	PAD (ABI)
Pathophysiology of stenoses
2) Arterial pulse wave
Formation + shape of pulse wave	AS	Oscillometry
Properties of arterial walls	PAD
3) Venous capacitance and venous outflow
Properties of venous walls	VD	Impedance venous occlusion plethysmography
Function as capacity vessels	DVT
4) Reactive hyperemia
Regulation of muscle perfusion	PAD	Impedence venous occlusion plethysmography
Perfusion reserve

For each experiment, examples of the comprised aspects of vascular physiology and of the diseases that can be evaluated are given as well as the applied examination technique. ABI, ankle brachial index; AS, arteriosclerosis; DVT, deep vein thrombosis; PAD, peripheral artery disease; VD, varicose disease.

In this work, we describe in detail this new class regarding the structure, the experimental setup, and the experimental procedure, and we give insight into the applied materials. Moreover, we present the experimental data that were generated from a cohort of medical students (n = 74). To give a realistic impression of the feasibility of the class and of the data that may be expected, erroneous data were not excluded. To demonstrate students’ learning success and acceptance of the class, we share the results of a comparative self-assessment of knowledge and skills and of a quantitative evaluation of the students’ satisfaction.

Background

Vascular diseases of the leg.

AS is a chronic and progressive vascular disease that is characterized by a thickening and stiffening of the arterial walls resulting in decreased arterial compliance and increased systolic pressure (5). One manifestation of AS is PAD, an obstruction of peripheral arteries that compromises the perfusion of the distal tissue, especially under muscular activity leading to pain and trophic disturbances (6, 7). DVT is caused by thrombi in the deep veins that impede the venous outflow. This leads to swelling and pain in the distal tissue and may also cause potentially lethal pulmonary embolisms (8). VD is characterized by increased venous pressure and remodeling of the venous walls that leads to a reduced elastic recoil and dilation (9). VD is associated with symptoms, e.g., pain and pruritus, and with complications, e.g., thrombosis, infections, and ulcers (10, 11).

Oscillometry.

Oscillometry allows indirect automatic measurements of systolic, diastolic, and mean arterial pressure. Oscillometric devices are composed of an air cuff with an electric pump for inflation, a valve for controlled deflation, and a highly sensitive pressure transducer. The air cuff is placed tightly around the extremity of interest and inflated. The pressure in the air cuff is constantly recorded by the transducer. The automatic procedure begins with an inflation of the air cuff beyond systolic pressure followed by a slow deflation (Fig. 1). As long as the cuff pressure exceeds systolic pressure, the transmural pressure (net pressure on the vessel wall) of the arteries is constantly negative. The arteries are occluded. When the cuff pressure falls below systolic pressure, transmural pressure becomes temporarily positive during each systolic pressure peak, which causes a pulsation of the artery. The volume change of this pulsation is transduced to the air cuff and causes a gentle oscillation of cuff pressure. With continuous deflation of the air cuff, the difference between systolic pressure and cuff pressure increases. Consequently, the amplitude of the oscillations rises and eventually reaches a maximum. Thereafter, the oscillation drops and finally disappears. The remaining cuff pressure is released. The cuff pressure during the maximal oscillation, together with other supporting parameters, is used for automatic calculation of the systolic, diastolic, and mean arterial pressure. The available oscillometric devices are heterogeneous regarding several details, e.g., the technical components, the measuring procedure, or the calculation of the blood pressure parameters. Consequently, the accuracy of the oscillometric estimation of blood pressure, in comparison to auscultatory measurement, varies between different devices. Many of them could be validated as accurate (12). Because of their easy handling, which allows use by nonprofessionals, oscillometric measurements are widely established for blood pressure measurements (13, 14).

Figure 1.

Exemplary and simplified course of the cuff pressure during an oscillometric measurement. The axes are nondimensional.

Moreover, oscillometric devices allow an indirect measurement of the pulse wave morphology. For this measurement, the cuff is inflated to the diastolic pressure and the oscillations of the cuff pressure are recorded by the pressure transducers. The recorded pressure changes are inversely proportional to the underlying arterial pulse wave and, therefore, depict in detail the pulse wave morphology (15, 16).

Impedance venous occlusion plethysmography.

Venous occlusion plethysmography characterizes a continuous measurement of blood volume changes within a specified tissue of an extremity during a temporal occlusion of the proximal veins. The measurement of blood volume changes (plethysmography) can be achieved by heterogeneous techniques, e.g., water, strain gauge, or impedance plethysmography (16–19). In the experiments presented here we use impedance plethysmography.

Impedance plethysmography was first described by Nyboer et al. in 1950 (20). Two electrodes are placed proximally and distally of the tissue of interest to apply a nonperceptible low-voltage alternating current (Fig. 2). Two further electrodes are positioned over the tissue of interest for a continuous measurement of the voltage. The bioelectrical impedance is calculated on the base of Ohm’s law. Because blood has a lower impedance than the surrounding connective tissue, changes of blood volume are inversely proportional to changes of the tissue’s impedance (19–21).

Figure 2.

Schematic illustration of the principle of impedance-based venous occlusion plethysmography (IVOP) on the example of the right calf. The leg position depends on the experimental intention. Here we present an elevated leg position as used in our experiments. Electrodes for the application of an alternating current are placed proximally and distally to the calf. Electrodes for voltage measurements are placed over the muscle tissue of the calf. The air cuff for venous occlusion is placed around the thigh. Changes of the impedance and blood volume are calculated.

For impedance-based venous occlusion plethysmography (IVOP), the devices for impedance plethysmography are placed as described. Additionally, an air cuff is placed proximal to the tissue of interest (Fig. 2) and inflated to 60–80 mmHg. At this pressure veins are occluded, whereas arterial inflow is scarcely affected. The blood volume within the tissue rises and the arterial inflow (“perfusion”) can be quantified. With increasing filling of the tissue, the arterial inflow decelerates, and the blood volume eventually reaches a maximum. The difference of this maximal blood volume and the minimal blood volume before or after the venous occlusion informs as to the maximal blood volume that the tissue (mostly the veins) can accommodate. After the maximum is reached, the air cuff is deflated, and the blood drains through the veins. The decrease of blood volume informs as to the venous outflow (16–18, 22, 23).

IVOP allows a noninvasive, precise, and quantitative assessment of physiologically and diagnostically relevant arterial and venous parameters and the evaluation of the effects of a variety of interventions (e.g., pharmaceutics, ischemia, positioning). It is widely used in basic research and clinical diagnostics of, e.g., PAD, DVT, and VD (19, 22, 23).

Experiment 1: Arterial Systolic Blood Pressure

The experiment.

An oscillometric air cuff is placed around each ankle and upper arm to measure the arterial systolic pressure of all locations by an automatic computer-controlled procedure (Fig. 3). The test person is positioned horizontally to avoid hydrostatic pressure differences. After the experiment, students compare the systolic pressures of all four locations and calculate the ankle brachial index (ABI) for each leg according to the following formula:

$$\mathrm{ABI=}\frac{\text{systolic pressure }\left(\text{ankle}\right)}{\text{systolic pressure }\left(\text{upper arm with the higher pressure}\right)}$$

Figure 3.

Placement of the oscillometric air cuffs for experiments 1 and 2. Oscillometric air cuffs are placed around both upper arms and ankles. All air cuffs are connected to an air pump (air) and a pressure transducer (P).

Physiology aspects.

In people with a healthy vasculature, the arterial systolic pressure increases with the distance to the heart because of changes of the arterial compliance and of the impedance and because of reflections of the pulse wave (24–27). This can be visualized by the experimental data when comparing the blood pressure of the relatively proximal upper arms and the relatively distal ankles. The phenomenon is also represented by the ABI, which is >1 in most persons with a healthy vasculature (28).

Vascular medicine aspects.

The ABI is a highly relevant screening test for PAD that can even detect asymptomatic patients (29–31). Moreover, it is an independent predictor of total and cardiovascular mortality (27, 31, 32). The ABI can be assessed by oscillometry, which is easy to use because of the automatic procedure. It has been validated against the gold standard, the doppler-based ABI (30, 32, 33). In the case of an arterial stenosis, following the laws of hemodynamics, systolic blood pressure drops distally, which results in a decreased ABI of the affected leg (27, 29, 30, 32). For ABI calculation, the use of the higher systolic pressure of both arms is recommended (27). Otherwise, a unilateral manifestation of a subclavian artery stenosis would reduce the affected arm’s systolic pressure and might cause a false negative ABI. Moreover, the ABI measurements can be compromised by Mönckeberg’s arteriosclerosis. It is characterized by a calcification of the tunica media, especially of the lower body’s arteries, which decreases the arterial compliance. The compression of these calcified vessels by the air cuffs requires a higher pressure, which leads to artificially high systolic pressures and ABIs (7, 31, 34).

Experiment 2: Arterial Pulse Wave

The experiment.

The oscillometric air cuffs are placed as in experiment 1. Another automatic program is used to simultaneously record the arterial pulse waves (pressure course) of both ankles (Fig. 2). The air cuffs are inflated to the diastolic pressure. Both sides’ pulse waves are recorded and plotted (Fig. 4). Several parameters are established to quantify the time course of the pulse wave. The program used for this experiment reports three parameters: crest time, crest width, and propagation time difference (Δ propagation time). Crest time (ms) is a measure of the duration of the ascent of the pulse wave (Fig. 4). It is defined as the time difference between the pressure minimum and maximum. Crest width (ms) describes the width of the pressure maximum. It is defined as the time interval between both moments when pressure is at 95% of the maximum. Δ Propagation time (ms) quantifies the time difference between the pressure maxima of the right and left sides.

Figure 4.

Sketch of a typical pulse wave recording from the left and right ankle as generated in experiment 2. The pressure maximum, the pressure minimum, the dicrotic wave, and all parameters taken are labeled. The axes are nondimensional. Relative changes of pressure (Δ pressure) are given.

Physiology aspects.

The visualization of the pulse wave allows discussions on the formation, propagation, and morphology of the pulse wave. For example, the pulsatile heartbeat and the associated periodic rise and decrease of pressure may be discussed or the propagation of this pressure course as a pressure wave. Also, the physiology behind details of the pulse wave morphology (e.g., the dicrotic wave or the height of the pressure maximum) may be considered. This may include the role of the arterial compliance, the impedance, and pulse wave reflections.

Vascular medicine aspects.

Specific arterial diseases have characteristic effects on the pulse wave. This allows visual diagnostics of the pulse wave morphology and the interpretation of quantitative pulse wave parameters that are sensitive to the different diseases. AS decreases the arterial compliance, which increases the pulse wave velocity. The reflected wave returns earlier and adds to the pressure maximum, whereas the dicrotic wave vanishes (15). PAD-associated stenoses are associated with a lowered ascent of the pulse wave (increased crest time), a flattened pressure maximum (increased crest width), and the absence of a dicrotic wave (16, 31, 35) in distal arteries. Moreover, stenoses diminish the pulse wave velocity. Therefore, a unilateral manifestation provokes an increased Δ propagation time (36).

Experiment 3: Venous Capacitance and Venous Outflow

The experiment.

An automatic IVOP procedure is used to simultaneously assess the venous properties of both calves. For this experiment, the legs are positioned over heart level to create a hydrostatic pressure difference, which increases the venous outflow. One air cuff is placed around each thigh (Fig. 5A). One electrode for current application is positioned on each ankle. Two measuring electrodes are positioned on each calf. Volume-time curves of both calves are displayed in real time during the procedure (Fig. 5B). Before the start of the procedure, the hydrostatic pressure gradient is used to achieve a venous emptying until a steady state is reached. The minimally reached blood volume (V_pre) is set as a reference level for further filling. Then, both air cuffs are inflated stepwise to 80 mmHg. This pressure is maintained for a predefined and standardized time that must be long enough to ensure that the rise of blood volume decelerates and a maximum or even a plateau is reached in the volume-time curve. When the cuff pressure is released, the venous drainage is enhanced by the hydrostatic pressure gradient. This allows an approximation of the maximal possible venous outflow. The blood volume measurements are continued, and a further steady state of minimal blood volume (V_post) is reached. At the end of the procedure, the volume-time curves of both sides and the parameters venous capacitance and venous outflow are displayed. The venous capacitance (mL/100 mL tissue) is defined by the height of the maximum. It is calculated by the difference of the maximal blood volume during venous occlusion (V_max) and the lower blood volume of V_pre and V_post (Fig. 5B). The venous outflow (mL/min/100 mL tissue) is calculated by the slope (ΔV/Δt) of the steepest descent during the first 2 s following cuff deflation.

Figure 5.

A: experimental setup for the impedance-based venous occlusion plethysmography (IVOP) measurements as used in experiments 3 and 4. Legs are positioned over heart level in a standardized position (details are given in methods). B: sketch of a typical IVOP volume-time curve of 1 leg as generated during experiment 3. The axes are nondimensional. Δ volume = V(time) − V_pre. The parameters taken are labeled. The phase of venous emptying before the venous occlusion is not plotted. The minimal blood volumes during the steady states before and after venous occlusion are indicated by the beginning and ending of the curve (V_pre and V_post). V_max is the maximally reached blood volume during venous occlusion.

Physiology aspects.

On the ascending part of the curve, the venous compliance and the veins’ function as capacitance vessels can be demonstrated. The venous compliance is defined as C = ΔV/ΔP_TM, where P_TM is transmural pressure. Because the blood volume changes are proportional to the transmural pressure, the venous compliance is proportional to the slope of the volume-time curve. At the beginning of the venous filling, the veins are almost empty and almost collapsed (37). With further filling they expand, and the wall becomes distended. The compliance gradually decreases. This observation can be used to demonstrate that under physiological pressure conditions the veins can take up large amounts of blood volume (capacitance vessels) and that the maximal venous filling is limited (venous capacitance). On the basis of the descending part of the curve and the parameter venous outflow, the basic laws of hemodynamics can be discussed. This includes reflections on the vessel radius, the driving pressure, the hydrostatic pressure (and the height of leg positioning), or the venous capacitance.

Vascular medicine aspects.

The quantitative assessment of venous capacitance and venous outflow allows graduated diagnostics on venous diseases, e.g., VD or DVT. The dilated veins of VD patients take up an increased blood volume during venous filling. The venous capacitance is increased (23). The high capacitance and the reduced elastic recoil (and venous compliance) increase venous pressure and consequently the driving pressure. The venous outflow is increased (23). In DVT, a clot reduces the radius of one or more draining veins. In obstructed veins, the venous emptying at the beginning of the procedure remains incomplete. Further filling during venous occlusion is limited; the venous capacitance is reduced. The venous outflow after cuff deflation is decreased (16, 23).

Experiment 4: Reactive Hyperemia

The experiment.

An automatic IVOP protocol is used to assess the arterial inflow (perfusion) of both calves before and after a temporary ischemia. The technical setup is the same as in experiment 3, but another protocol is used. It consists of three measurements of arterial inflow before and seven measurements after a temporary ischemia that is induced by the inflation of both air cuffs to 220 mmHg for 180 s. For each measurement, both air cuffs are inflated to 60 mmHg for ∼10 s and then deflated quickly. This induces a brief rise and fall of the volume-time curves (Fig. 6). At the end of the procedure, the volume-time curves and the arterial inflow measurements of both sides are reported. The parameter arterial inflow (mL/min/100 mL tissue) is calculated by the slope (ΔV/Δt) of the steepest ascent of each peak following venous occlusion (Fig. 6). Baseline arterial inflow is reported as the mean of the three preischemic measurements. The postischemic arterial inflow measurements are reported as individual values. On the basis of these data, the students calculate the parameter perfusion reserve. It is defined as the quotient of the maximal postischemic arterial inflow and the baseline arterial inflow. Therefore, it describes the factor by which the perfusion can maximally rise from a baseline perfusion under the standardized conditions of this experiment.

Figure 6.

Sketch of a typical impedance-based venous occlusion plethysmography (IVOP) volume-time curve for the left and right calf as generated during experiment 4. The parameters taken are labeled. The axes are nondimensional.

Physiology aspects.

This experiment illustrates the rise and successive decrease of perfusion of the calves following an interrupted blood flow (reactive hyperemia). This allows discussions on the involved mechanisms regulating arteriolar diameter according to the current demands of the tissue. The stopping of the blood flow, e.g., leads to a deficiency of oxygen and accumulation of metabolites (e.g., CO₂, H⁺, adenosine) in the legs that induce arteriolar dilation (38). Additionally, when releasing the arterial occlusion, a quick ascending vasodilation occurs. It is mediated, e.g., by the Bayliss effect and by a nitric oxide release caused by endothelial shear stress. Consequently, when releasing the arterial occlusion, the reduction of arteriolar resistance causes an increase of perfusion (reactive hyperemia). The increased blood flow removes the metabolites and reconstitutes oxygen supply, which contributes to a decrease of perfusion. The parameter perfusion reserve provides the students with an impression of the extent to which the blood volume of a skeletal muscle can be maximally raised.

Vascular medicine aspects.

At rest, PAD patients with moderate stenoses may have a normal perfusion of the distal tissue and be without pain because of a compensatory collateralization and vasodilation. However, a further dilation and rise of perfusion are limited. Under muscular activity, this can cause a transient ischemic pain limiting walking distance (intermittent claudication). In the case of more severe stenoses, the resting perfusion may be reduced, which can cause constant ischemic pain and trophic disturbances (6, 39). In IVOP, moderate stenoses are characterized by a normal baseline perfusion and a decreased perfusion reserve of the distal tissue. Moreover, as the washout effect is reduced, the duration of reactive hyperemia is prolonged. Severe stenoses are characterized by a reduced baseline perfusion and perfusion reserve (22). IVOP measurements of baseline perfusion, reactive hyperemia, and perfusion reserve can be used to quantify the endothelial dysfunction in PAD patients, to estimate the long-term prognosis, and to evaluate the effect of therapeutic efforts (22, 38).

Learning Objectives

After this activity, students will be able to

• 1) explain conceptual aspects of the oscillometric pulse wave analysis and IVOP
• 2) perform oscillometric measurements of the

  • ABI (including correct calculation of the index)

  • pulse wave

• 3) perform IVOP to assess the

  • venous capacitance and venous outflow

  • perfusion reserve with a controlled ischemic stimulus

• 4) explain key aspects of hemodynamics (e.g., Hagen–Poiseuille’s law, Darcy’s law)
• 5) explain the differences of systolic blood pressure between proximal and distal arteries
• 6) explain the formation and propagation of the arterial pulse wave
• 7) explain the principles of venous compliance, venous capacitance, and venous outflow
• 8) explain the regulation of arterial perfusion and the concept of perfusion reserve
• 9) explain the influence of AS and PAD on the systolic blood pressure and the ABI
• 10) explain the influence of AS and PAD on the pulse wave morphology and pulse wave parameters
• 11) explain the influence of DVT and VD on the venous outflow and venous capacitance and, on that basis, explain typical symptoms
• 12) explain how PAD affects the baseline perfusion, reduces the perfusion reserve, and causes an intermittent claudication

Activity Level

This laboratory class aims for a horizontal integration between vascular physiology and vascular medicine. Therefore, it is especially (but not exclusively) relevant for integrated curricula. If possible, we recommend placing this class in an intermediate curricular position between both disciplines’ lectures. However, other placements might also be reasonable.

Prerequisite Student Knowledge or Skills

Before performing this activity, students should possess a basic knowledge about vascular physiology and ideally, but not necessarily, a modest knowledge about the pathophysiology and the symptoms of AS, PAD, DVT, and VD and about the corresponding diagnostic approaches of vascular medicine. A brief theoretical and practical introduction to the devices at the beginning of the class is necessary to achieve an understanding of the procedures and the results.

Time Required

As performed at our faculty, the laboratory class has an overall duration of ∼200 min (Fig. 7). It is composed of four parts: 1) introduction to the theoretical background and technical instruction (entire group), 2) performance of the four experiments (subgroups of 3–5 students), 3) analysis of the experimental data (subgroups), and 4) discussion of the subgroup results and the underlying aspects of vascular physiology and vascular medicine (entire group). Also, other compositions are conceivable. The course can be split into two shorter classes, with one of them addressing the oscillometric measurements (experiments 1 and 2) and one the IVOP measurements (experiments 3 and 4). This might be especially helpful when the curriculum does not provide sufficient time slots for a single class with a duration of ∼200 min, or when the course should be embedded into specific learning concepts, e.g., problem-based learning.

Figure 7.

Composition of the current form of the presented class and estimated duration of the single steps.

METHODS

In this section, we describe the technical equipment and the experimental procedures of this laboratory class. As the technical equipment is available from several manufacturers, this description is given independently of brands to allow a flexible technical reproduction. Additionally, as a specific example, we illustrate the approach we used in our classes at the University Medical Center Hamburg-Eppendorf. Furthermore, we point out relevant considerations for the decision making process upon a specific technical solution, and we indicate alternative technical approaches.

Equipment and Supplies

For all experiments, a horizontal examination table with a height-adjustable backrest and software for controlling the automatic procedures are required.

Experiments 1 and 2 additionally rely on a setup for oscillometric blood pressure measurements that typically consists of

• central control unit

• air compressor

• pressure transducer

• 4 oscillometric air cuffs

• 4 cables for connecting the air cuffs with the control unit (ideally color coded)

Experiments 3 and 4 are performed with a setup for IVOP that typically includes

• central control unit

• 6 skin electrodes per test person (e.g., spot electrodes as used for ECG monitoring)

• 6 cables for connecting the control unit with the electrodes (ideally color coded)

• air compressor for venous and arterial occlusion

• 2 air cuffs for venous and arterial occlusion

• 2 cables for connecting the air cuffs with the air compressor.

• pillows for standardization of leg position

At our faculty, the laboratory class was realized with a modular setup by medis–Medizinische Messtechnik GmbH (Ilmenau, Germany; Fig. 8). All data presented in this work were generated with these devices. Oscillometric blood pressure measurements were performed with a VasoScreen 2000. For IVOP, the impedance plethysmographic measurements were performed with a VasoScreen 1000; the venous and arterial occlusion was performed with a VasoScreen 4000. All devices were controlled with the modular software CardioVascular Lab, which follows a one-software concept for all experiments in this course.

Figure 8.

Technical equipment for oscillometry (experiments 1 and 2) and impedance-based venous occlusion plethysmography (IVOP) (experiments 3 and 4) as used in our classes. The devices were manufactured by medis–Medizinische Messtechnik GmbH: 1) computer; 2) VasoScreen 2000: central control unit for oscillometric blood pressure measurements with included air compressor and pressure transducer; 3) color-coded cables connecting the air cuffs with VasoScreen 2000; 4) oscillometric air cuffs; 5) VasoScreen 4000: central control unit for venous and arterial occlusion with included air compressor; 6) air cuffs for venous and arterial occlusion (with included cables connecting to VasoScreen 4000; 7) VasoScreen 1000: device for impedance plethysmographic measurements (with included cables ending in color-coded click-connections to the electrodes); 8) spot-electrodes. A: overview of the technical devices used and the cable connections. B: color-coded cables for the connection of the oscillometric air cuffs with VasoScreen 2000. C: pictograms on VasoScreen 2000 indicating the correct cable connections. D: VasoScreen 1000 (with imprinted pictogram indicating the correct electrode placement) and connection cables that end in color-coded click connections for the electrodes.

Technical Alternatives

Devices that correspond to the above-described measuring techniques and experimental setup are available from several manufacturers. Even though relying on the same techniques, they may differ regarding several aspects, e.g., the reported parameters or the specific handling. As an alternative to the described approach, all experiments can also be performed with devices relying on other measuring techniques. In either case, the characteristics of each specific technical solution have impact on the overall feasibility of the course. Therefore, the following aspects should be considered before choosing one specific technical solution:

• degree of automatization during data acquisition and data analysis

• definition of the recorded parameters (e.g., absolute vs. normalized values, didactical relevance for integrative teaching)

• availability of raw data for further analysis

• adaptability of the procedure (e.g., software interface, timing, cuff pressure, sequence of measurements)

• user-friendliness of the software and the equipment

• technical training and supervision necessary for students and tutors

• expected sources and rates of technical errors

• time effectiveness, especially when performing the experiments in sequence

• support by the manufacturer (e.g., for technical modifications for a student course)

• cost effectiveness

In the following, technical alternatives to oscillometry and IVOP are given. Some may be associated with a more favorable cost profile. However, they may have limitations, e.g., regarding the feasibility for untrained students or due to the associated multidevice approach, which may require more time for technical instruction and hamper a smooth sequence of the experiments. This would entail a temporal restructuration of the class. Also, the quality of the experimental results or the students’ satisfaction may be affected.

Oscillometry.

For the assessment of the ABI, alternative investigation techniques are well established, e.g., sphygmomanometry or Doppler sonography. The pulse wave can be recorded by, e.g., tonometry. In contrast, oscillometry, allows a measurement of the ABI and the pulse wave by a single device. Moreover, it relies on automatic measurements and is easy to perform by unexperienced operators.

IVOP.

Changes of the legs’ blood volume can be measured by other plethysmographic techniques, e.g., strain gauge plethysmography. In our experience, strain gauges are critical in students’ hands as they are fragile and the selection of a correct length is essential. An interesting low-price option to impedance and strain gauge plethysmography is a self-made water plethysmograph as described by Raine and Sneddon (18). Alternatively, the arterial inflow and the venous outflow of individual vessels can be measured with duplex sonography. Because of its high clinical relevance this technique is interesting for the students. However, a proper performance requires training.

Human Subjects

The Ethics Committee of the Chamber of Physicians (Ethik-Kommission der Ärztekammer Hamburg) has determined that this research project complies with ethical guidelines and does not require a positive ethics statement because the data collection was anonymized and data could not be tracked to individuals (application number 2021–300117-WF). Since the data were anonymized, according to the national jurisdiction, a written consent of the participants was not necessary.

Adopters of this activity are responsible for obtaining permission for human research from their home institution. For a summary of the Guiding Principles for Research Involving Human Beings, please see https://journals.physiology.org/author-info.animal-and-human-research.

Instructions

Based on our experience with the devices we used in our classes, the experiments can be performed in subgroups of at least two persons with one student assigned as test person and one student operating the technical equipment. However, we experienced that a group size of at least three persons tends to improve the process quality and efficiency, as it allows a sharing of the operator’s tasks. The test person should wear clothes that allow an easy placement of all electrodes and air cuffs on the skin (e.g., t-shirt and shorts).

The following instructions are given without specificity of manufacturer. Additionally, to achieve a visual representation of the experimental steps, we exemplarily provide photographic material of the experimental setup we used in our classes.

Experiment 1.

• 1) Adjust the backrest of the treatment table in a horizontal position (Fig. 9A). Do not use positioning pillows during this experiment.
• 2) Place the test person in a recumbent, comfortable position (Fig. 9, A and C).
• 3) Place the oscillometric air cuffs tightly on both upper arms (∼2 cm proximal to the crook of the arm; Fig. 9, A and C).
• 4) Place the oscillometric air cuffs tightly on both calves proximally to the ankles (Fig. 9, A and C).
• 5) Use the cables to connect the oscillometric air cuffs with the oscillometric device (Fig. 9B).
• 6) Ensure that the test person was in a recumbent position for ∼10 min before starting the measurements to eliminate a bias by orthostatic volume shifts.
• 7) Advise the test person to remain motionless throughout the entire measurement and not to talk.
• 8) Start the automatic blood pressure measurements at all four locations.
• 9) At the end of the procedure, the systolic blood pressure data are reported.
• 10) Do not remove the experimental setup. It is required for experiment 2.

Figure 9.

Experimental setup for experiments 1 and 2 with the devices from medis–Medizinische Messtechnik GmbH. A: lateral view. B: pictograms on VasoScreen 2000 and color code of the connecting cables. C: frontal view.

Experiment 2.

• 1) Use the same experimental setup as in experiment 1 (Fig. 9).
• 2) Advise the test person to remain motionless throughout the entire measurement and not to talk.
• 3) Start the automatic procedure for continuous blood pressure measurements at both ankles.
• 4) At the end of the procedure, the arterial pulse waves and the parameters crest time, crest width, and Δ propagation time are displayed.
• 5) Remove the oscillometric air cuffs.

Experiment 3.

• 1) Slightly elevate the backrest of the treatment table until the test person feels comfortable and the leg muscles are totally relaxed (Fig. 10A).
• 2) 
  Place the legs on the positioning pillows as indicated by the manufacturer (Fig. 10, A and B). Take care that…

  • the calves are positioned in the air and are not compressed (e.g., by positioning pillows; Fig. 10C).
  • the popliteal space is positioned in the air and is slightly flexed (Fig. 10A). This can be eased by a slight outward rotation in the hips (Fig. 10B).
  • positioning of both legs (and the whole body) is symmetrical (Fig. 10B).
• 3) Symmetrically place two electrodes for the application of the alternating current on the distal legs as specified by the manufacturer (e.g., proximal to the medial malleoli; Fig. 10, B and C).
• 4) Precisely place two electrodes for voltage measurement on the broadest part of each calf exactly at the position and within the distance that are indicated by the manufacturer (Fig. 10, B and C). Ensure a side-symmetrical electrode position and a good electrode contact.
• 5) Use the cables to connect all electrodes with the central control unit as indicated by the manufacturer (Fig. 10B).
• 6) 
  Place the air cuffs for venous and arterial occlusion on a middle height of both thighs (Fig. 10, A and B). Make sure that….

  • they are fastened tightly.
  • they are not placed inside out.
  • they are placed symmetrically on both sides.
  • they are not placed over clothes.
• 7) Use the tubes to connect the air cuffs to the air compressor (Fig. 10, A and B).
• 8) Advise the test person to remain motionless throughout the entire measurement and not to talk.
• 9) Start the automatic IVOP procedure for the assessment of the venous properties.
• 10) A volume-time curve for each calf is displayed in real time on the computer. The air cuffs are automatically inflated and deflated in accordance with the predefined experimental protocol.
• 11) At the end of the procedure, the parameters venous capacitance and venous outflow are displayed for both calves.
• 12) Do not remove the experimental setup. It is required for experiment 4.

Figure 10.

Experimental setup for experiments 3 and 4 with the devices from medis–Medizinische Messtechnik GmbH. A: lateral view. B: frontal view of the placed air cuffs and electrodes. C: medial view of the electrodes placed on the left leg.

Experiment 4.

• 1) Use the same experimental setup as in experiment 3 (Fig. 10).
• 2) Inform the test person that the arterial occlusion can cause a slight pressure-associated pain in the thighs and a slight ischemic pain in the distal legs. Inform the test person that the measurement can be canceled with the software at any time.
• 3) Start the automatic IVOP procedure for the assessment of reactive hyperemia.
• 4) The volume-time curves for the left and right calf are displayed in real time on the computer.
• 5) The air cuffs are inflated and deflated in accordance with the predefined experimental protocol.
• 6) You can call the students’ attention to the changes of skin color during and after ischemia and to the sensory impressions of the test person.
• 7) At the end of the procedure, all eight measurements of arterial perfusion are displayed for each calf.

Troubleshooting

Most errors we observed were caused by movement of the test person or by an incorrect application of the technical devices. It is essential that the students follow the instructions with a particularly high accuracy when positioning the test person, when placing the air cuffs, and especially when applying the IVOP electrodes and cables. This may be ensured by a detailed technical introduction and close supervision. It is reasonable to advise the students to call a supervisor before starting each of the techniques for the first time to check for a proper setup.

Safety Considerations

The manufacturer of our devices indicated absolute and relative contraindications for oscillometry and IVOP. Absolute contraindications are thrombocytopenia and phlegmasia cerulea dolens. Relative contraindications are an age under 18 yr and a placement of the air cuffs on extremities with peripheral venous catheters.

RESULTS

Expected Results

To provide an impression of the expected results, we give a structured report on the experimental data we collected from a cohort of students of human medicine (n = 72–76) with the above-described experimental setup from medis-Medizinische Messtechnik GmbH. For each experiment, we first present a representative example of experimental data from an individual student. Based on that impression, we summarize a selection of the most important aspects of vascular physiology and vascular medicine that are illustrated by the experiments and thereby create a link back to the detailed descriptions given in Background. We provide the normal values as specified by the manufacturer, which may help the reader to interpret the subsequently presented cumulative data of the entire cohort. We deliberately did not exclude artificial or erroneous measurements, to give a realistic impression of student-generated data. Finally, for each experiment, we point out the most frequent sources of errors and, if applicable, we give examples from the collected data.

Experiment 1: Arterial systolic blood pressure.

For exemplary individual data, see Table 2.

Table 2.

Exemplary data for experiment 1

	Systolic Pressure, mmHg	ABI
Right arm	124
Left arm	128
Right leg	155	1.21
Left leg	155	1.21

Exemplary systolic blood pressure data of 1 student that were generated during experiment 1. ABI, ankle brachial index.

Aspects of vascular physiology.

This experiment demonstrates the increase of arterial systolic pressure with distance to the heart. This allows discussions on the underlying physiological phenomena, e.g., the decreasing arterial compliance.

Aspects of vascular pathophysiology and medicine.

Students learn to use oscillometers and to measure and calculate the ABI. The high clinical relevance of the ABI can be emphasized and explained. The experimental data form a basis for discussions on the pathophysiology of AS and PAD-associated stenoses and their manifestation in blood pressure and ABI measurements. It can be discussed how Mönckeberg’s arteriosclerosis and subclavian artery stenosis comprise the ABI measurements.

Normal values.

Normal values for the ABI are 0.9–1.3.

Results of the cohort.

The cohort’s mean systolic pressure of the upper arms was ∼125 mmHg, the ankle systolic pressure was relevantly higher at ∼145 mmHg, and the variances were relatively low (SD: ∼13 mmHg, n = 74; Fig. 11A). The resulting mean ABIs of both sides were ∼1.13 (SD: ∼0.07) and lay within the normal range for all students (Fig. 11B).

Figure 11.

Aggregated cohort data of experiment 1 (n = 74). The bars indicate mean and SD. A: arterial systolic pressure of all extremities. B: ankle brachial indexes (ABIs) of the left and right leg. LRL, lower reference limit; URL, upper reference limit.

Examples of typical errors.

Oscillometry is technically very robust. Significant errors are rare. Sometimes we observed a too-loose placement of the air cuffs. This can cause false high measurements of pressure, as a higher cuff pressure is needed to compress the arteries. This may cause side differences and inaccurate ABIs (Table 3).

Table 3.

Example of a relevant side difference

	Systolic Pressure, mmHg	ABI
Right arm	150
Left arm	124
Right leg	154	1.03
Left leg	154	1.03

In this test person, the systolic pressure of the right arm is remarkably high. In the case of a person with a healthy vasculature, an erroneous measurement may be assumed. As the ankle brachial index (ABI) is calculated from the arm with the higher systolic pressure, the ABIs of both legs are falsely low.

Experiment 2: Arterial pulse wave.

Exemplary individual data.

Exemplary data from one individual in experiment 2 are shown in Fig. 12.

Figure 12.

Exemplary curves and data from experiment 2 of one student. Δ Propagation time was calculated as the difference of the propagation time right and the propagation time left.

Aspects of vascular physiology.

The recorded pulse wave allows discussions on its formation, propagation, and morphology. This implies fundamental aspects of vascular physiology, e.g., the transmural pressure, the arterial compliance, and the physics of pressure waves.

Aspects of vascular pathophysiology and medicine.

The reduction of the arterial compliance by AS, the reduction of the vessel radius by PAD-associated stenosis, and its possible collaterals provoke specific changes of the propagation and shape of the pulse wave and the quantifying parameters. The pathophysiology behind these changes can be discussed.

Normal values.

Normal values are as follows: crest time, ≤230 ms; crest width, ≤90 ms; Δ propagation time, ≥ −60 ms and ≤60 ms. The dicrotic wave should be clearly visible.

Results of the cohort.

For both ankles, the mean crest time was ∼172 ms (Fig. 13A), crest width was ∼73 ms (Fig. 13B), and Δ propagation time was ∼1 ms (Fig. 13C). The variances were relatively low (SD: ∼14, 7, and 7, respectively). Almost all parameters were within the normal range.

Figure 13.

Aggregated cohort data of experiment 2 (n = 74). The bars indicate mean and SD. A: crest time of the pulse wave. B: crest width of the pulse wave. C: Δ propagation time between both ankles (right − left). LRL, lower reference limit; URL, upper reference limit.

Examples of typical errors.

A too-loose placement of the air cuffs should be avoided. It may affect the propagation of the pressure changes from the arteries to the air cuff and hamper a precise measurement of the pulse wave and the calculated parameters. According to our experience, these artifacts are hard to identify in the experimental data as they do not yield a typical waveform or alteration of the parameters. Therefore, preventive measures during the introduction and supervision are relevant.

Experiment 3: Venous capacitance and venous outflow.

Exemplary individual data.

Exemplary data from one individual in experiment 3 are shown in Fig. 14.

Figure 14.

Exemplary curves and data from experiment 3 of one student. LRL, lower reference limit; URL, upper reference limit.

Aspects of vascular physiology.

The volume-time curve illustrates changes of the compliance during venous filling, the venous capacitance, and the venous outflow. On this basis, properties of the venous wall, their role in the venous function as capacitance vessels, or the laws of hemodynamics can be discussed.

Aspects of vascular pathophysiology and medicine.

Based on the students’ normal curves and parameters, the typical aberrations that are caused by DVT, VD, and the underlying pathophysiology can be discussed.

Normal values.

Normal values for the venous capacitance are 2–7 mL/100 mL. Normal values for the venous outflow are >$\frac{7}{3}$ · venous capacitance + 15 mL/min/100 mL (cf. LRL in Fig. 15).

Figure 15.

Aggregated cohort data of experiment 3 (left: n = 76, right: n = 75). LRL, lower reference limit; URL, upper reference limit.

Results of the cohort.

The mean venous capacitance of both calves was ∼4 mL/100 mL (SD: ∼1 mL/100 mL; n left =76, n right =75), the venous outflow was ∼40 mL/min/100 mL (SD: ∼20 mL/min/100 mL) (Fig. 15). The majority of the students lay well within the normal range. However, as no data were excluded and the IVOP measurements are technically more challenging than oscillometry, more results were outside the normal range (see Examples of typical errors).

Examples of typical errors.

Movement artifacts or sudden traction on a cable cause typical sharp spikes in the volume-time curve (Fig. 16A). When they occur during a critical moment for the calculation of a parameter, the parameter may be strongly biased (Fig. 16A). Continuous cable tension and bad electrode contact to the skin or to the connected cable may provoke a trembling of the curve (Fig. 16B). When the measuring electrodes are not placed side-symmetrically, different regions of both calves with physiologically differing venous systems are compared, which results in artificial side differences (Fig. 16C). Loosely placed air cuffs may cause insufficient venous occlusion and submaximal filling. This is characterized by a low venous capacitance, which in turn reduces the venous outflow (Fig. 16, C and D). Both parameters may also be reduced when the venous occlusion is ended prematurely (Fig. 16D).

Figure 16.

Examples of typical errors from the cohort. A: the sharp spikes are typical for leg movements or sudden cable traction. Here, they potentially falsify venous outflow measurements. B: the left curve is characterized by a strong trembling. This might be caused by a bad contact of the electrodes to the skin or to the connected cables or by continuous cable tension. C: the venous capacitance and outflow of the left side are considerably lower than on the right side. This side difference might be caused by asymmetrically positioned measuring electrodes or by an insufficient venous occlusion on the right side. D: both sides’ venous capacitance and outflow are relatively low, and a deceleration of the rise of blood volume is not detectable. This might be caused by a prematurely ended venous occlusion and/or by loosely placed air cuffs on both sides. LRL, lower reference limit; URL, upper reference limit.

Experiment 4: Reactive hyperemia.

Exemplary individual data.

Exemplary data from one individual in experiment 4 are shown in Fig. 17.

Figure 17.

Exemplary curves and data from experiment 4 of one student. Left: volume-time curve. The measurements are paused during the arterial occlusion; the time axis is interrupted. Right: measurements of the arterial inflow for the baseline measurement (bl) and for the 7 postischemic measurements (1–7).

Aspects of vascular physiology.

This experiment visualizes the adaptation of muscle perfusion to a temporary ischemia. The involved mechanisms regulating the arteriolar radius (e.g., metabolites, nitric oxide) and the concept of the perfusion reserve can be discussed. Moreover, the sensory and visual impressions of ischemia provide an activating experience.

Aspects of vascular pathophysiology and medicine.

On the basis of the normal curves, students can discuss how a PAD would affect the measurements. This includes considerations of the compensatory mechanisms to a stenosis that may constitute a normal resting perfusion in patients with moderate PAD manifestations or the pathomechanisms behind the reduced perfusion reserve, the prolonged reactive hyperemia, and the intermittent claudication. Also, the diagnostic value of this experiment for the assessment of an endothelial dysfunction can be thematized.

Normal values.

A normal course of arterial inflow is characterized by a maximum at the 1st postischemic measurement, a return to the baseline level at the 3rd or 4th postischemic measurement. A subsequent decrease below baseline level can occur. Normal values for perfusion reserve are 2–10.

Results of the cohort.

The cohort’s mean baseline arterial inflow was ∼5 mL/min/100 mL (SD: ∼2 mL/min/100 mL; Fig. 18A). During the first postischemic measurement it increased to ∼28 mL/min/100 mL, with a relatively high variance (SD: ∼20 mL/min/100 mL). The mean arterial inflow returned to the baseline level at the 4th postischemic measurement and remained constant during the following measurements. The resulting perfusion reserve was ∼6 (SD: ∼4; Fig. 18B). These data comply well with the expectations.

Figure 18.

Aggregated cohort data of experiment 4 (n = 72). The bars indicate mean and SD. A: individual measurements of arterial inflow for the baseline measurement (bl) and the 7 postischemic measurements (1–7). *Eight data points are outside the axis limit: left: 91, 105, 120, and 124 mL/min/100 mL; right: 73, 75, and 157 mL/min/100 mL. #One data point is outside the axis limit: 61 mL/min/100 mL. B: individual measurements of the perfusion reserve. §Two data points are outside the reference limit: 41 and 26 mL/min/100 mL. LRL, lower reference limit; URL, upper reference limit.

Examples of typical errors.

The typical errors are similar to experiment 3. We often observed artifacts due to movement or cable tension, which may impair the automatic measurements of arterial inflow (Fig. 19, A and B). An insufficient arterial occlusion (e.g., due to a air cuff placed too loosely or a leaking cable connection) causes an abnormal low reactive hyperemia (Fig. 19C). The same may occur when the cuffs are placed inside out and open during inflation. In a very few cases, the course of the curve did not meet the expectations at all (Fig. 19D). This may be caused, e.g., by air cuffs that are placed too loosely to achieve a relevant venous occlusion and/or by very inaccurately placed measuring electrodes.

Figure 19.

Examples of typical errors from the cohort. A: typical artifacts probably caused by movement or cable tension between the first and second baseline (bl) measurement of both sides and during the seventh postischemic measurement of the left side. The latter artifact caused a false high arterial inflow. B: strong movement artifacts during the first and second postischemic measurement. The corresponding parameters of arterial inflow must be considered as artificial. C: the postischemic measurements of the left leg are abnormally low. An insufficient arterial occlusion may be suspected. D: example of a failed experiment. The course of the curves differs completely from the expectations. For example, the 10 spikes of the arterial inflow measurements are sparsely distinguishable.

Evaluation of student work.

The experimental phase of the class presented here is followed by a phase of data analysis (Fig. 7). Students aggregate their measured data, calculate the ABIs and the perfusion reserves, and create graphs. This is followed by a structured group discussion based on predefined questions and tasks that refer to the students’ data. These questions and tasks focus on a main field on the translational axis (technical aspects, vascular physiology, or vascular pathophysiology/medicine) with a deliberate overlap with one or both other fields [subsidiary field(s)]. In our experience, the blurred lines and the mixed sequence of the questions’ fields encourage integrative discussions and train integrative thinking. Table 4 provides an overview of exemplary questions and tasks and the respective main and subsidiary fields.

Table 4.

Exemplary questions of the group discussion

Question and Tasks	Main Field	Subsidiary Field(s)
Experiment 1: arterial systolic blood pressure
What are the principles of oscillometric blood pressure measurements?	A	B, C
What is the arterial compliance?	B	C
How and why does the arterial systolic pressure change with the distance to the heart?	B
How does an arterial stenosis affect the distal systolic pressure?	C	B
Why is the ABI formula based on the higher systolic pressure of both arms?	A	C
Which diseases are indicated by pathologically high/low ABIs?	C	A, B
Which disease typically impedes ABI-based PAD diagnostics? (Mönckeberg’s arteriosclerosis)	C	A
Name technical alternatives to oscillometry for the blood pressure and ABI assessment. (e.g., duplex sonography, sphygmomanometry)	A	C
What are the advantages and disadvantages of oscillometry and of the other techniques for blood pressure and ABI assessment?	A	C
Experiment 2: arterial pulse wave
Explain the mechanism of the oscillatory pulse wave measurement.	A	B
Explain the formation and propagation of the peripheral arterial pulse wave.	B	C
What is the origin of the dicrotic wave?	B	C
In which way does a decreased arterial compliance (AS) affect the pulse wave morphology?	C	B
How does an AS alter the pulse wave of the distal arteries?	C	B
How is the pulse wave velocity influenced by AS and PAD?	C	B
What is the additional benefit of a segmental pulse wave analysis?	A	C
Experiment 3: venous capacitance and venous outflow
Explain the principles of IVOP.	A	B
What are the definitions of the venous compliance and the venous capacitance?	B	A, C
Explain the role of the venous compliance and the venous capacitance for the venous function.	B	C
Which physiological/physical parameters have influence on the venous outflow?	B	C
How do DVT and VD affect the venous capacitance and the venous outflow?	C	A, B
Explain the influence of the height of the leg position on the parameters.	A	B, C
What are the standard diagnostic procedures for a patient with a suspected acute DVT?	C	A
Experiment 4: reactive hyperemia
Explain why a reduced vessel radius decreases the blood flow.	B	C
Describe the compensating mechanisms of an arterial stenosis.	C	A, B
Explain the molecular events leading to a reactive hyperemia and the following normalization.	B	A, C
Define the perfusion reserve.	B	A, C
Which resting perfusion would you expect in PAD patients and why?	C	A, B
Explain the effects of a PAD on the further parameters.	C	A, B
What are the symptoms of a PAD?	C
Name alternatives to assess the perfusion reserve.	A	C

The mainly addressed fields on the translational axis of each item and the subsidiary field(s) are indicated: A, technical aspects; B, vascular physiology; C, vascular pathophysiology/medicine. The assignment of the fields is not clear-cut. ABI, ankle brachial index; AS, arteriosclerosis; IVOP, impedance-based venous occlusion plethysmography; DVT, deep vein thrombosis; PAD, peripheral artery disease; VD, varicose disease.

Additional Information

Students’ evaluation.

At the end of each class, we evaluated the students’ learning success by a comparative self-assessment. Furthermore, to receive an impression of the students’ acceptance of the class, we performed a quantitative assessment on the students’ satisfaction. Two hundred seventy-eight students participated, a participation rate of 93%.

The comparative self-assessment was composed of four distinct skills/knowledges that were orientated on national and local learning objectives (Fig. 20A). On a six-point Likert scale, students rated their individual level of each skill or knowledge before and after the class, with high scores indicating a high level. For each skill and knowledge, the cohort’s mean levels before (μ_pre) and after the class (μ_post) as well as the mean absolute improvement (μ_post − μ_pre) are reported (Fig. 20A). For all items, the mean level of skills and knowledges improved significantly (2-way ANOVA, P < 0.005) by ∼3 points (SD ranging from 1 to 2 points). Additionally, in accordance with Raupach et al. (40), we calculated a weighted relative increase of skills and knowledge (“CSA-gain”). It ranged from 69% (SD 27%) to 81% (SD 28%). Overall, the comparative self-assessment indicated a high learning success (Fig. 20A).

Figure 20.

All data (n = 278) of the students’ evaluation are given as mean and SD. A: comparative self-assessment: the mean levels of skills and knowledge before (μ_pre) and after (μ_post) the class are reported as well as the absolute rise and the weighted relative rise (CSA-gain). B: quantitative assessment. Mean ratings on the Likert scales are given. For the first 4 items, high scores indicate a high level of approval.

The quantitative assessment (Fig. 20B) included four statements on different aspects of the students’ satisfaction. For each of them, students rated their grade of approval on a 6-point Likert scale, with high values indicating a high approval and satisfaction. Additionally, two further items aimed for a quantification of the individually perceived complexity and effort of the class, which were answered on a 5-point Likert scale. The results are given in Fig. 20B. Overall, the quantitative assessment indicated a high level of student satisfaction.

DATA AVAILABILITY

Data will be made available upon reasonable request.

DISCLOSURES

J.Q. and O.S. are employed by medis–Medizinische Messtechnik GmbH, Ilmenau, Germany. None of the other authors has any conflicts of interest, financial or otherwise, to disclose.

AUTHOR CONTRIBUTIONS

T.H., R.B., A.L.-A., H.E., and A.P.S. conceived and designed research; T.H., R.B., and A.P.S. performed experiments; analyzed data; T.H., R.B., J.Q., O.S., and A.P.S. interpreted results of experiments; T.H., R.B., and A.P.S. prepared figures; T.H., R.B., and A.P.S. drafted manuscript; T.H., R.B., A.L.-A., J.Q., O.S., H.E., and A.P.S. edited and revised manuscript; T.H., R.B., A.L.-A., J.Q., O.S., H.E., and A.P.S. approved final version of manuscript.