Physiologic Control of Rotary Blood Pumps an in.1

Bioengineering

Physiologic Control of Rotary Blood Pumps: An In Vitro Study

GURUPRASAD A. GIRIDHARAN,* GEORGE M. PANTALOS, KEVIN J. GILLARS, STEVEN C. KOENIG, AND MIKHAIL SKLIAR*

Rotary blood pumps (RBPs) are currently being used as abridge to transplantation as well as for myocardial recoveryand destination therapy for patients with heart failure. Phys-iologic control systems for RBPs that can automatically andautonomously adjust the pump flow to match the physiologicrequirement of the patient are needed to reduce humanintervention and error, while improving the quality of life.Physiologic control systems for RBPs should ensure adequateperfusion while avoiding inflow occlusion via left ventricular(LV) suction for varying clinical and physical activity condi-tions. For RBPs used as left ventricular assist devices (LVADs),we hypothesize that maintaining a constant average pressuredifference between the pulmonary vein and the aorta (Pa)would give rise to a physiologically adequate perfusion whileavoiding LV suction. Using a mock circulatory system, wetested the performance of the control strategy of maintaininga constant average Pa and compared it with the resultsobtained when a constant average pump pressure head (P)and constant rpm are maintained. The comparison was madefor normal, failing, and asystolic left heart during rest and atlight exercise. The Pa was maintained at 95 1 mm Hg forall the scenarios. The results indicate that the Pa controlstrategy maintained or restored the total flow rate to that ofthe physiologically normal heart during rest (3.8 L/m) andlight exercise (5.4 L/m) conditions. The Pa approachadapted to changing exercise and clinical conditions betterthan the constant rpm and constant P control strategies. ThePa control strategy requires the implantation of two pres-sure sensors, which may not be clinically feasible. SensorlessRBP control using the Pa algorithm, which can eliminate thefailure prone pressure sensors, is being currently investigated.ASAIO Journal 2004; 50:403409.

Ventricular assist devices (VADs) have been used success-fully for many years as a bridge to transplantation1, and theyhold the potential to become long-term alternatives to donorheart transplantation (destination therapy). However, a controlsystem that automatically responds to physiologic cardiac de-mand for the continuous flow VAD does not exist. In hospitals,

the flow rate generated by continuous flow VADs is selectedmanually by physicians or trained support personnel. Mobilepatients operate the implanted continuous flow VADs by ad-justing the pump rpm or flow rate using guidelines provided bythe doctor or until a perceived comfort level of perfusion isachieved. No automatic feedback mechanism, directly basedupon physiologic indicators of cardiac demand, has beensuccessfully implemented.

Several physiologic indicators of cardiac demand, like atrialpressure, blood oxygen saturation, lactic acid concentration inblood, P wave activity of the atria, renal sympathetic nerveactivity, and aortic nerve activity, have been identified. Atrialpressure (AP) is correlated to the preload in a straight forwardfashion, which makes AP the most widely used input controlparameter for the VAD.24 However, AP is not a direct indi-cator of physiologic demand and is influenced by many irrel-evant factors. An excellent indication of tissue perfusion isgiven by blood oxygen saturation.59 Unfortunately, the re-sponse time of blood oxygen saturation to the physiologicdemand is relatively slow, and implantable oxygen saturationsensors capable of long-term, reliable operation are yet to bedeveloped. It was found that P wave activity decayed overtime10 once the natural heart was removed. With VAD, P wavedoes not decay; however, the problem of decreasing sensitivityof an electrical activity sensor over a long term still remains.The renal sympathetic nerve activity and aortic nerve activitysuffers from a similar problem of signal degradation and long-term sensor reliability. The monitoring of lactic acid usingcurrently available sensors is not specific, reducing the valueof obtained results in on-line control of the total artificial heart(TAH) and VAD. Moreover, physiologic indicators, which cur-rent control strategies (both in literature and in practice) relyupon, change with variation in cardiac demand. For example,if the control objective is to maintain a reference VAD rpm, anincrease in cardiac demand would necessitate an increase inthe desired rpm according to some expert rule or model pre-diction. Additionally, most of the discussed indicators areaffected by factors unrelated to cardiac demand. Conse-quently, it may be difficult to accurately correlate these indi-cators to the cardiac demand. In contrast, the average pressuredifference between pulmonary vein and aorta, Pa, is almostconstant for varying levels of cardiac demand, does not decaywith time, and can be reliably measured. Hence, we suggestthat maintaining an average reference Pa is an appropriatestrategy for controlling ventricular assist devices. The naturalregulatory system varies the vascular resistances to maintainthe required flow of blood11,12 with an almost constant aver-age Pa. By using a VAD to assist the failing heart in main-taining the prescribed average Pa, we, in effect, synchronize

From the *Department of Chemical Engineering, University of Utah,Salt Lake City, Utah; and the Jewish Hospital Heart and Lung Institute,University of Louisville, Department of Surgery, Louisville, Kentucky.

Submitted for consideration June 2003; accepted for publication inrevised form May 2004.

Presented at the 49th ASAIO Conference, June 1921, 2003, Wash-ington, DC.

Correspondence: Dr. Guruprasad A. Giridharan, Department ofChemical Engineering, 50 South Central Campus Dr., Rm 3290 MEB,University of Utah Salt Lake City, UT 84112.

DOI: 10.1097/01.MAT.0000136652.78197.58

ASAIO Journal 2004

403

the assisted and natural perfusion, thus indirectly incorporatingnatural cardiovascular regulation into the VAD control.

In this study, the hypothesis of maintaining a constant aver-age Pa to achieve physiologically motivated perfusion istested for a centrifugal blood pump using an in vitro mockcirculatory system13 for the following test conditions: normal,failing, and asystolic left heart during rest and light exercise.

Materials and Methods

Experimental Design

An adult mock circulation (consisting of a mock left ventri-cle, ventricular apical inflow cannulation, and mock systemicvasculature with aortic root outflow cannulation) along with acentrifugal continuous flow blood pump (BioMedicus,Medtronic, Eden Prairie, MN) was used to test the viability ofthe Pa control strategy and compare it with constant rpm andconstant pump pressure head control strategies.

To study the range of applicability of the proposed ap-proach, one normal and two different pathologic cases of theVAD assisted perfusion were simulated using the mock circu-latory system. In the first case, the left ventricular assist device(LVAD) was attached to the human equivalent of a normalhealthy heart, which is a realistic case when testing withanimals or when natural left heart (LH) function has com-pletely recovered after VAD implantation, as observed in sev-eral clinical cases.14,15 Equivalence of pathologic cases in-clude LVAD assistance of failing and asystolic left heart (Table1). Three scenarios were tested under rest and light exerciseconditions. Heart rate was 60 bpm during rest and 100 bpmduring light exercise. For all test conditions, 35% systole and65% diastole was maintained. A lower value of heart rate andthe resulting lower cardiac output during rest were chosen toincrease the variability in the cardiac demand as the maximumflow rate of the mock circulatory system is limited. The aorticinput impedance and vascular mechanical properties werecontrolled to simulate the flow and impedance of the normalhuman vasculature.16 The vascular resistance (total peripheralresistance) and the driveline pressure (which controls the con-tractility of the LV) were adjusted to match the pressure andflow waveform characteristics of the human circulatory systemunder the described scenarios. Once the resistance and thedriveline pressure are determined, they are used consistently totest different control strategies.

For different clinical and cardiac demand conditions, theVAD rpm is adjusted manually until the setpoint for Pa, P,or rpm is reached. The setpoint for Pa is selected as the Pavalue observed with normal unassisted heart (baseline case) atrest and is equal to approximately 95 mm Hg. Based upon the

result of the previous simulation study,17 the setpoint for P isselected as 75 mm Hg. The pump speed of approximately1,440 rpm, which was needed to restore the cardiac output tothe physiologic level of 3.8 L/m for the case of failing heart atrest, was selected as the rpm setpoint. Once the setpoint isreached, the limit cycle hemodynamic waveforms were re-corded with and without VAD assistance for each of the threecontrol strategies. Characterizing hemodynamic parameters,waveform morphology, and ventricular pressure-volume loopresponses were calculated to identify differences in the perfor-mance with different control strategies for each test condition.

Mock Circulation

The adult mock circulation consists of atrium, ventricle, andsystemic and coronary vasculature components as illustratedin Figure 1. In a previous study,13 the adult mock circulationwas shown to mimic human normal ventricle, failing ventricle,and partial cardiac recovery physiologic responses as definedby characterizing hemodynamic parameters, ventricular pres-sure-volume relationship, aortic input impedance, and vascu-lar mechanical properties. An artificial atrium,18 made of aflexible polymer sphere 50 mm in diameter, is connectedupstream of the inflow valve of a mock ventricle. The mockventricle consists of a flexing polymer sac inside a pressuriza-tion chamber.19 The ventricular sac is hemiellipsoid shapedand is 70 mm wide at the base and 83 mm long from base toapex. The base is covered by a semi-rigid polymer dome 20mm high, with mounts for inflow (mitral) and outflow (aortic)prosthetic valves. Metered pulses of compressed air (UtahHeart Controller, CardioWest, Tuscon, AZ) are delivered to thepressurization chamber during systole, compressing the ven-tricular sac to form coapting quadrants simulating contractionof the normal and dysfunctional ventricle and the delivery ofcardiac stroke volume. An artificial aorta (polyurethane tubesegment 25 mm diameter) is connected downstream of theoutflow valve of the ventricular sac to the mock systemicvasculature. The mock systemic vasculature consists of fourintegrated chambers that represent lumped proximal resis-tance, systemic compliance, peripheral resistance, and venouscompliance.13 Introduction ports for the VAD uptake cannulaare incorporated into the ventricular sac apex and VAD outputflow cannula at the aortic root.

Instrumentation

A high fidelity, pressure-volume conductance catheter (Mil-lar Instruments, Houston, TX) was inserted into an aortic in-troducer port and passed retrograde through the aortic valve

Table 1. Baseline Parameters of the Mock Circulatory System Used in Simulating the Human Equivalence of a Normal, Failing,and Asystolic LV

Parameter

Normal LV Failing LV Asystolic LV

Rest Exercise Rest Exercise Rest Exercise

Mean AoPr (mm Hg)a 96 100 68 75 CO (L/m)b 3.8 5.4 2.0 3.1 0 0DLP (mm Hg)c 210 300 100 150 0 0

LV, left ventricle; AoPr, aortic root pressure; CO, cardiac output; DLP, drive line pressure.

404 GIRIDHARAN ET AL.

and down to the ventricular apex for simultaneous ventricularpressure, root aortic pressure, and ventricular volume mea-surements. Single tip, high fidelity catheters (Millar Instru-ments, Houston, TX) were inserted into introducer ports formeasuring atrial pressure, distal aortic pressure, and drivelinepressures. Aortic root, aortic distal, and VAD output weremeasured with inline transit time flow probes (Transonics,Ithaca, NY). Pressure, flow, and volume transducers were pre-and postcalibrated, and transducer gains and offsets were cal-culated and applied to ensure measurement accuracy. Gainswere calculated for the LV volume data to match the strokevolume of the LV, as sensed by the aortic root flow probe.Offsets for the LV volume data were calculated taking intoconsideration the total flow and left ventricular end diastolicpressure (LVPed) data. Placement of instrumentation for hemo-dynamic measurements of pressures, flows, and volume isshown in Figure 1. Signal conditioning was accomplishedusing transducer amplifiers (Ectron, San Diego, CA), transit-time flow meters (Transonics, Ithaca, NY), a volume conduc-tance unit (Leycom, Sigma V, Netherlands), and other periph-eral conditioners integrated in an instrumentation systemcompliant with Good Laboratory Practice (GLP) guidelines.Signal conditioned data were low pass filtered at 60 Hz,analog to digitally converted (AT-MIO-16E-10 and LabVIEW,National Instruments) at a sampling rate of 400 Hz, and storedon a personal computer for postprocessing and analysis.20

Data Analysis

Differences in characterizing hemodynamic parameter val-ues and ventricular pressure-volume loop response were cal-culated using a Hemodynamic Evaluation and AssessmentResearch Tool (HEART) program21 and supporting m-files de-veloped in Matlab (MathWorks, Natick, MA). Pressure, flow,and volume waveforms were used to calculate the followinghemodynamic parameters: mean pulmonary vein pressure,LVPed and VAD output flow, and the total flow. All hemody-namic parameters were calculated on a beat to beat basis, withall beats in each data set averaged to obtain a single represen-tative mean value for each parameter. Pressure-volume loops

were constructed by plotting ventricular pressure against ven-tricular volume, in which each loop represents one completecardiac cycle (one beat). Characterizing hemodynamic param-eters and pressure-volume loops were calculated for all exper-imental conditions.

Results

The hemodynamic parameters for a normal, failing, andasystolic LV with and without continuous assist for each of thethree control strategies during rest and light exercise are listedin Table 2. Without VAD assistance, the values of the total flowrate, P, and Pa decrease during ventricular failure at restand exercise in comparison with the normal LV at rest andexercise. The left ventricular end diastolic pressure for all thecontrol strategies remain within 3 mm Hg of the baselinenormal LV value. Because the left ventricular pressure andvolume sensor is introduced through the aortic valve (Figure1), there is a back flow through that valve for baseline and allVAD assist scenarios.

Table 2 indicates that all of the tested control strategiesincrease the total flow, P, and Pa with failing and asystolicLV. The Pa control strategy maintains or restores the totalflow rate to that of the physiologically normal heart during restand exercise and adapts best to the need for support. Forexample, in the case of the normal heart during rest andexercise, the average net VAD flow rate with this strategy isclose to zero, as expected, because the native LV provides allthe required cardiac output.

Figure 2 shows the comparison between the total flow rates(sum of VAD flow rate and cardiac output) at baseline andduring assistance using constant rpm, P, and Pa controlstrategies during rest and exercise scenarios for each clinicaltest condition. The baseline cardiac output of 3.8 L/m at restand 5.4 L/m during light exercise are considered to be physi-ologic flows for the corresponding physical activities. Thecomparison of total flow rates produced with different controlstrategies shows that the Pa approach best matched the phys-iologic flow rate. The comparison of rest and exercise casesshows that the control strategy of maintaining an average Pa

Figure 1. Schematic of the mockcirculatory system with the assistdevice.

405VAD COMPUTER SIMULATION

leads to the correct adaptation to changing cardiac demand.For a normal LV, the Pa control strategy best matches thephysiologic flow rates (Figure 2a). At the same time, the con-stant rpm and P control strategies result in higher than normalflow rate. The overpumping (highest when constant rpm ismaintained) increases the risk of LV suction.

Figure 2b indicates that when the failing LV is assisted by aVAD, all three control strategies restore the total cardiac outputto near physiologic level. The Pa approach best matches thephysiologic flow rate during rest and exercise. The P ap-proach leads to an output that is slightly higher than thephysiologic flow rate. The constant rpm strategy results in alower than normal flow rate during exercise, increasing thechances of under perfusion during higher cardiac demand.

With an asystolic LV (Figure 2c), the Pa strategy is the bestapproach at restoring the flow rates to near physiologic values,followed by constant rpm and P strategies. Overall, the Pastrategy consistently produced a total flow rate that is theclosest to the physiologic flow rate for all heart conditions andphysical activity scenarios.

The left ventricular pressure-volume relationships for a nor-mal and failing LV with and without assistance is shown inFigure 3. All of the tested control strategies cause a leftwardshift in the pressure volume loop for a failing ventricle duringrest and exercise (Figure 3,c and d) and a lowering of leftventricular end diastolic pressure, indicating a correct direc-tion of adaptation for all the control strategies. Except for theresult with Pa control, a leftward shift in the PV loop andlowering of LVPed was noticed for a normal heart assisted by

a VAD during rest and exercise (Figure 3, a and b), indicatingan increased likelihood for suction.

Discussion

The importance of adequate VAD control cannot be over-stated. Although the design of the VAD itself is critical to thelong-term success of the electromechanical implant, the con-trol of the VAD determines the confidence of doctors andpatients in the VAD as a permanent solution and an alternativeto donor heart transplantation. The key requirement of theautomatic control system is the adaptation of VAD generatedflow to the changing physiologic requirements of the patientwhile reliably avoiding suction.2224

Our in vitro results show that maintaining a constant averagePa is an effective way to the correct adaptation of the cardiacoutput to changing requirements of the patient irrespective ofthe type of rotary pump used to assist perfusion. The physio-logic explanation of this conclusion rests with the fact that thevascular bed resistance can increase or decrease by a factor oftwo to five in response to the changing cardiac demand25 andis the dominant factor in regulating perfusion. The blood flowis inversely proportional to the vascular bed resistance so thatmaintaining a constant Pa with changing resistance can in-crease or decrease the flow rate by the same factor of two tofive.

The desired (reference) Pa can be maintained by adjustingthe pump rpm within physiologically admissible limits despitethe changing vascular resistance, stroke volume, and heart

Table 2. Comparison of Assisted and Unassisted Perfusion Under Different Scenarios

VAD rate(rpm)

Total Flow(L/m)

P(mm Hg)

Pa(mm Hg)

VAD Flow(L/m)

LVPeda

(mm Hg)

Baseline valuesNormal LV, rest 0 3.8 54.3 94.4 0.0 0.0Failing LV, rest 0 2.0 30.5 51.5 0.0 17.2Asystolic LV, rest 0 0 Normal LV, exercise 0 5.4 54.4 98.4 0.0 6.7Failing LV, exercise 0 3.1 32.9 58.7 0.0 16.4Asystolic LV, exercise 0 0

Centrifugal VAD with Pa controlNormal LV, rest 800 3.6 55.3 95.0 0.2 1.0Failing LV, rest 1440 3.9 71.9 95.2 4.5 0.8Asystolic LV, rest 1490 3.9 96.4 94.9 4.5 1Normal LV, exercise 650 5.5 51.7 95.8 0.4 5.3Failing LV, exercise 1490 5.2 68.6 94.4 5.6 5.1Asystolic LV, exercise 1600 5.7 98.3 95.2 6.3 2.8

Centrifugal VAD with P controlNormal LV, rest 1300 4.6 75.3 115.4 3.2 1.3Failing LV, rest 1450 4.0 78.2 101.2 4.5 1.3Asystolic LV, rest 1320 3.3 75.6 74.5 3.9 0.0Normal LV, exercise 1280 6.4 74.6 117.5 3.5 7.6Failing LV, exercise 1600 5.7 76.6 101.5 6.2 6.2Asystolic LV, exercise 1400 4.8 74.1 71.6 5.4 0.1

Centrifugal VAD with rpm controlNormal LV, rest 1450 4.7 80.1 120.2 3.8 1.8Failing LV, rest 1440 3.9 71.9 95.2 4.5 0.8Asystolic LV, rest 1450 3.7 89.3 87.8 4.3 1Normal LV, exercise 1440 6.8 80.0 122.4 4.4 7.9Failing LV, exercise 1440 4.8 70.5 97.0 5.3 4.8Asystolic LV, exercise 1440 5.0 76.6 74.0 5.5 0.6

VAD, ventricular assist device; LVPed, left ventricular end diastolic pressure, LV, left ventricle.a LVP for the asystolic LV is a constant value


rate, which represent the response of the natural regulatorymechanisms to the changing physiologic cardiac output de-mand. The dominant role of the changing resistance in adap-tation to physiologic demand11,12 implies that by maintaining,on average, the prescribed Pa, we in effect synchronize theassisted and natural perfusion, thus indirectly incorporatingnatural cardiovascular regulation into VAD control.

The proposed approach to the control of RBP requires thatthe natural regulatory mechanism functions properly in re-sponse to changing cardiac demand, which may not always bethe case. For example, medical intervention may be necessaryin the case of severe hypertension (often seen in the VADrecipients after initial recovery), which could lead to higherthan normal arterial pressures, resulting in lung edema. Notethat neither the alternative VAD control strategies nor thenatural heart can directly mitigate arterial hypertension and theresulting lung edema. Consequently, the long-term goal mayhave to include the development of an automatic, autono-mous, portable health monitoring and management system forpatients with the permanent VAD or TAH, which would com-bine real time control of the blood pump with the automaticmonitoring of the cardiac function and, if necessary, emer-gency drug administration and other advanced functionalities.

The primary advantage of the Pa control strategy is itsability to autonomously adjust the total output, defined as thesum of cardiac and pump outputs, to match the cardiac de-

mand better than any alternative strategies. The Pa, being thedifference between the aortic and the pulmonary venous pres-sure (equal to left atrial pressure), is sensitive to changes bothin preload and afterload. The current in vitro study shows thatthe proposed strategy of maintaining the desired average Paleads to an adequate adaptation for widely changing cardiacdemand and clinical conditions in a completely autonomousway. The results show that, although some degree of physio-logic adaptation is achieved with constant rpm and constantP, these alternatives are less effective for a wide range ofphysical activities and rapidly changing status of cardiac func-tion (such as a sudden transition from failing to asystolic heart).With the constant rpm control strategy, a broad range ofphysical and clinical conditions would require an externalintervention to change the rpm setpoint according to someexpert rule, model prediction, or operator input. The constantP approach does not perform well for a broad range ofclinical conditions of the native heart, which changed fromnormal to asystolic LV in this study, but adapts well to thechanging cardiac demand due to different exercise levels. Thein vitro study is consistent with the results of computer simu-lations,17,2628 which showed that the P control strategyadapts better to widely varying cardiac output requirementswhen compared with the traditional constant rpm controlapproach. Because of the limitations of the mock circulatorysystem, we were unable to test the higher cardiac demandconditions to make an in vitro comparison between the differ-ent control strategies. In the limited range of cardiac demandsthat could be tested in vitro, the performance of the Pacontrol strategy is superior to P and constant rpm controlalternatives.

Using the proposed approach, both the natural heart and theassist device are contributing to the pumping action of main-taining an average Pa. If cardiac function improves, thenative heart will increase its contribution to maintaining thereference pressure difference, with the VAD controller auton-omously and automatically responding to the decreased needfor assisted perfusion, as evidenced by the near zero net VADflow rate with the normal heart during rest and exercise. Whenthe net flow rate through the VAD is close to zero, blood doesnot stagnate inside the VAD, although the residence time ofblood in the pump is higher, increasing the probability ofhemolysis. Because this scenario occurs only with a normal ornear normal heart, the patient could be weaned from the pumpat this stage.

The ability of the proposed control strategy to automaticallyadjust its contribution towards maintaining Pa may prove tobe well suited to the application of the ventricular assist de-vices in cardiac recovery therapy14,15,29 of end-stage heartfailure (alone or in combination therapy), as well as in thedestination therapy.

Although not directly addressed in this study, the overarch-ing principle behind the proposed approach of maintainingkey pressure differences with mechanical blood pumps, whilerelying on the natural regulation to adjust the resistances to theblood flow to meet the physiologic demand, is also applicableto the case of pulsatile ventricular assist devices, as well as thetotal artificial heart. In the case of the TAH, the blood pumpshould be controlled to maintain key pressure differences atthe average reference values, which, in the case of pulmonary

Figure 2. Comparison of total flow generated with Pa, P, andconstant rpm strategies with and without the VAD: (a) Normal LV, (b)Failing LV, and (c) Asystolic LV. VAD, ventricular assist device; LV,left ventricle.


circulation, is the difference between pulmonary arterial andvena cava pressures. The proposed approach for VAD control,in its current form, requires the implantation of two pressuresensors. Long-term clinical implantation of pressure sensorsmay not be feasible because of decreasing sensitivity overtime, sensor drift, and the risk of thrombus formation. How-ever, for different types of blood pumps, it may be possible toestimate Pa using only the pump model and readily measur-able intrinsic pump parameters (such as pump rpm, voltage,and current), eliminating the need for implantable pressuresensors. The approach that uses a blood pump as both theactuator and the flow or pressure sensor can be viewed as asensorless control.27 Sensorless estimation of Pa is cur-rently being pursued as a follow-up investigation.

Limitations

The performance of the mock circulation during normal,failing, and asystolic heart test conditions is representativeof clinical observations from a purely hemodynamic/hydro-dynamic viewpoint. Clearly, mock circulation experimentsare limited in replicating clinical conditions. For instance,mock circulation cannot mimic neurohumoral responses,tissue remodeling, or activation of regulatory proteins. Theparticular mock circulatory system used in the experiment isa single sided mock and can simulate the systemic (left side)circulation only. In this mock system, the uptake cannulainflow occlusion is physically impossible, and the reducedLV pressure and volume are the only indications of suction.

Figure 3. PV loops with and with-out VAD assistance using constantrpm, P, and Pa control strate-gies for the following test condi-tions: (a) Normal LV during rest; (b)Normal LV during exercise; (c) Fail-ing LV during rest; and (d) Failing LVduring exercise. VAD, ventricularassist device; LV, left ventricle; PV,pressure volume.


The instrumentation used to record hemodynamic wave-forms in the present study has inherent measurement errorsassociated with each technique (i.e., pressure error 1mm Hg, flow error 0.5 L/min), which we have at-tempted to minimize by using GLP compliant test equip-ment, calibration procedures, and documentation practices.The gains and offsets assigned for the LV volume data mayhave inherent errors associated with it, as it is based uponthe aortic root stroke volume, LVPed, and total flowsproduced.

Despite these limitations, these results provide valuable in-sight into the differences of each control algorithm, which aidsin further development of control algorithms and experimentalprotocols to identify optimal ventricular assist therapies thatcan subsequently be validated in in vivo models.

Conclusions

The in vitro results show that maintaining an average pres-sure difference between the pulmonary vein and aorta (Pa)provides an effective way to control a continuous flow LVADover a wide range of physiologic and cardiac demand condi-tions while reducing the probability of suction. Change invascular resistance is the dominant regulatory mechanism inmeeting the physiologic requirements for blood perfusion.Maintaining the desired average Pa by adjusting the pumprpm during changing cardiac demand, in effect, synchronizesthe assisted and natural perfusion. Therefore, the proposedcontrol strategy indirectly incorporates natural cardiovascularregulation, which changes vascular resistance into VAD con-trol. The comparison with the VAD control systems, whichmaintain either constant reference pump rpm or constantpump pressure head (P), shows that the proposed approach issuperior in autonomously maintaining an adequate perfusionduring changing cardiac demand for the test conditions simu-lated in vitro. Because the Pa control strategy automaticallyadjusts its contribution to the total flow based upon the func-tion of the native ventricle, the proposed approach may proveto be well suited to the application of the ventricular assistdevices in recovery therapy.

Acknowledgment

This study was supported by the Established Investigator Award fromthe American Heart Association.

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Physiologic Control of Rotary Blood Pumps an in.1