Congress Presidential Address

The Living Organism and Artificial Organs

Jean-Raoul Monties

Cardio-Thoracic Surgery, Laboratory for Surgical Research, Faculty of Medicine, University of Marseille,Marseille, France

Ever since man first used a stick to help himselfwalk, he has continued to develop devices to assist orreplace natural physiological functions. Orthetic de-vices such as crutches, dentures, and glasses havelong been used. Prosthetic devices result from morerecent technology that began with the introductionof implants such as plates for osteosynthesis anddentures and progressed to active systems such aspacemakers and cochlear implants. In keeping withthis long heritage, our society is dedicated to thedevelopment of blood pumps for total or partial re-placement of the failing human heart.

Our experience in this endeavor has taught usmuch. We all have learned that living organisms arecomplex and that the scope of any given function ororgan is difficult to evaluate and thus the conse-quences of artificial replacement are unpredictable.As we all know, experimentation and observation canlead to great rewards as well as great disappointment.

The goal of development of any artificial organ isto obtain long-term replacement of the function withadequate patient comfort. Attainment of this goaldepends on knowledge of the living organism in gen-eral and the function in particular, on available tech-nology, and on creating an interface between theliving organism and the artificial organ. Experimen-tal research and clinical trials have greatly improvedour physiological understanding. Technologicalbreakthroughs achieved by engineers and researchworkers in all fields of physics, chemistry, and elec-tronics have greatly improved available hardware.However, little progress has been made with regardto the interface between the living organism and ar-tificial organ.

My purpose here today is to try to describe mymain impressions after 40 years of research in thefields of cardiac surgery, heart transplantation, andcirculatory assistance with special focus on the topicof this meeting, circulatory assistance using rotaryblood pumps.

THE LIVING ORGANISM

Three general features of living organisms seemcrucial to the development of artificial organs. Thefirst is immune response. When a foreign body isintroduced into a living organism, the natural reac-tion of the organism is to detect, isolate, and destroyor otherwise neutralize the intruder. This rule ap-plies not only to germs and cells but also to implantsand prostheses whether they be active or passive.Although some degree of tolerance may be attained,the balance is always delicate and uncertain. De-struction and neutralization can be slowed down andeven temporarily controlled but can never be per-manently stopped.

Another fortunate characteristic of living organ-isms is adaptability to new conditions. There are nu-merous natural and clinical examples of adaptationincluding compensatory hypertrophy of an organ ormuscle group, development of collateral circulation,retraining of muscle cells by programmed progres-sive stimulation, and adaptation to nonpulsatile cir-culation.

The last and paramount feature of the living or-ganism is the interdependence of structures andfunctions. This is true not only for organs and organgroups but also within cells where each componentcan be considered almost as a system in its own right.Our understanding of the interdependence of vari-ous functions and organs and automatic control offeedback is limited, but one cannot help but beamazed by the ability of the living organism to com-pensate for pathological and environmental changesand to regenerate.

Received December 1997.Presented in part at the 5th Congress of the International So-

ciety of Rotary Blood Pumps, held September 10–12, 1997, inMarseille, France.

Address correspondence and reprint requests to Prof. J.-R.Monties, Cardio-Thoracic Surgery, C.H.U. Timone, Rue St-Pierre, 13385 Marseille Cedex 5, France.

Artificial Organs22(5):358–361, Blackwell Science, Inc.© 1998 International Society for Artificial Organs

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With regard to the function of the heart in par-ticular, it is important to stress that natural output ispulsatile. The heart rate is sufficient to maintainmean pressure between 80 and 100 mm Hg. Thispulsatile arrangement achieves circulation with op-timal efficiency by storing energy in the elastic vas-cular network during the systolic phase and reusingthat energy during the diastolic phase. Arterial pres-sure is regulated by peripheral resistance with eachorgan or muscle being able to regulate blood supplyin response to its own requirements. Although theunderlying physiological mechanisms are consider-ably more complex, this simple explanation providesthe basis for control algorithms depending mainly onpreload and afterload.

In keeping with what I have already said about theadaptive ability of the organism in general, clinicalfindings demonstrate that the circulatory system hasan extraordinary ability to adapt to pathologicalchanges such as increased peripheral resistance, lossof arterial elasticity, or slowing of heart rate. Thisadaptive ability also allows functional assistance us-ing biomedical techniques that are often far fromphysiologic (e.g., extracorporal circulation, pace-making, and circulatory assistance).

The reactivity and adaptability of the living organ-ism accounts for the fact that discoveries often raisemore questions than they answer. The practical con-sequences of these features for research are that newand unforeseen problems can and almost always doarise and that requirements can almost never be es-tablished in advance. These uncertainties make com-munication difficult between the cautious physicianwho has come to expect the unexpected and thepractical-minded engineer whose exact science de-mands facts and figures.

ARTIFICIAL ORGANS

Artificial ventricle technology currently repre-sents the cutting edge of active implant develop-ment. Regardless of whether output is pulsatile ornonpulsatile, an artificial ventricle consists of apump, motor, control system, and power supplywhich must work in unison to supply blood in re-sponse to the needs of the body. The shape, weight,and size of the system must be compatible with im-plantation. Operation must be reliable, durable, andtolerable (no noise, vibration, or heat). The designand development of any of the components of anartificial ventricle constitutes a gamble, a challenge,and a financial decision. It is a gamble because noone can be sure in advance that the choices made fordevelopment are right. It is a challenge because

development often requires cutting edge technology,and it is a financial decision because scarce resourcesspent on one project cannot be used for another.

One of the major problems in the development ofartificial ventricles is the choice of construction ma-terials. A list of the ideal specifications reveals anumber of seemingly incompatible physical andchemical properties including lightness, hardness,wear and corrosion resistance, inalterability, and ab-solute inertness. Materials used must not induce anychemical, magnetic, or electrical reaction. They mustbe easy to work with and exhibit optimal surfacesmoothness. The choice of material depends on theintended function of the component, its location inthe device, and the stress and constraints that will beapplied. Current materials include flexible polymersfor sacks or membranes, rigid polymers for impellersand housings, alumine ceramics for bearings, tita-nium alloys, and pyrolytic carbon.

With regard to materials, our research has led usto composite technology which can provide light, re-sistant, and smooth materials. We have used finegrain graphite coated with titanium nitride, dia-mond-like carbon, or crystalline diamond (1). Al-though production and use of these materials can bedifficult, especially because internal surfaces must beperfectly smooth, our experience indicates that theyprovide the best results in terms of physicochemicalperformance and tolerance by the organism.

Hydrodynamic design is a problem specific to thedevelopment of rotary pumps in which impellers canturn at high speeds ranging from 1,500 to 30,000rpms depending on the model. Studies are necessaryto optimize the shape of the impeller, design wing-lets, and screws; improve efficiency; avoid zones ofstagnation or depressions; and minimize shearingforces and turbulence. Unfortunately, the necessaryfacilities for these studies are not available at thepresent time. Studies with current equipment arecarried out under continuous and stable conditionsthat do not take into account the unpredictable pres-sure variations observed when the pump is used in apulsatile circuit (e.g., in association with a partiallyviable heart). Not even the supercomputers andcomplex software used by aeronautic firms to factorin variables such as incidence, slope, and turbulenceare powerful enough to evaluate the consequencesof these variations which can greatly affect the per-formance of a rotary pump.

Another daunting problem in the development ofthe artificial heart is nonstop operation. For a rotarydevice, this means continuous high-speed operation.In comparison with an automobile engine which isdesigned to run for 1,500 to 2,000 h, i.e., 83 days, the

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number of rotations that a rotary pump would makeover the same period of time is about 360 million. Inone year, a centrifugal pump performs 1,576 millioncycles, and an axial pump running at 20,000 rpmsperforms 10,512 million cycles. This is equivalent to30 car lifetimes. This is one of the reasons that wechose to develop the Cora rotary pump (2), whichoperates at a low speed ranging from 50 to 180 rpm.This is approximately the same as the natural heart,i.e., 40 million cycles a year. Although rotary pumpsdevelop much less power than automobile engines,the rotary pump must be more durable and reliable(absence of catastrophic failure).

Because of the need to maintain continuous op-eration, development of bearings is a key issue forrotary pumps as demonstrated by the number andquality of presentations on this topic at this meeting.Ball bearings and hydraulic or wet bearings appearto be losing ground to magnetic bearings. The driveunit is subject to the same requirements in terms ofreliability and longevity. Motor efficiency must beoptimal to avoid overheating and hot spots. Brush-less DC electric motors have a good reputation forreliability and durability. Magnetic drive transmis-sion is often used.

Conventional control systems rely on sensors togather the physiological feedback necessary to adaptpump output to the needs of the organism. However,the use of sensors poses a number of disadvantagesincluding need for frequent calibration, lack of reli-ability, and susceptibility to interference from out-side factors such as acceleration, variation in atmo-spheric pressure, etc. We have developed analternative method using the current intensity curveas an indicator of pressure at the pump inlet. Severalgroups will present the results of their research inthis area during this meeting.

Electronic circuitry is needed to ensure powersupply and motor control. Despite the proven reli-ability of electronic circuits, back-up systems, mal-function detectors, and automatic switching devicesmust be included. In addition, the control systemmust be equipped with a memory unit to allow veri-fication and programming of pump performancefrom the outside. In this regard, use of fuzzy logicseems well suited to biomedical applications.

With current technology, a battery can be im-planted as a back-up, but the main power supplymust remain outside the body. However, wirelesstransmission can be ensured by high frequency trans-cutaneous induction thus avoiding any contact be-tween the prosthesis and exterior. This is also pos-sible because rotary pumps do not require venting.

After several years of intense research and devel-

opment, the technology to produce all these compo-nents is available, i.e., materials, hydrodynamic de-sign, motor, control unit, electronic circuitry, andpower supply. Permanent implantation is possible,but questions remain about the durability of the sys-tem.

THE INTERFACE BETWEEN THE LIVINGORGANISM AND ARTIFICIAL ORGAN

As previously stated, physicians and researchworkers have demonstrated over and over the re-markable ability of the living organism to adapt tonew conditions. Using new technologies, engineershave developed more and more reliable and durablesystems. However, unsuspected problems probablylurk at the interface between the living organism andthe artificial organ. Problems can arise due to per-manent contact of the prosthesis with surroundingtissue and blood due to mismatching between pumpoutput and the needs of the patient and due to poorquality of life.

BiocompatibilityThe biocompatibility of a material depends on the

aggressiveness of the material toward the body andthe degree of tolerance or acceptance of that mate-rial by the body. The characteristics of different ma-terials are well known. No material is completelyinert. A fibrous capsule always develops around theprosthesis. This encapsulation has the advantage ofholding the device in place, but with time this pro-cess can lead to narrowing or kinking of tubing. In-teraction with the organism can also lead to prema-ture aging of materials as observed with polymers.

Another problem is that no material is completelyleakproof. Gas leaks and seepage of fluids have beenmajor problems in the development of implantablecompliance chambers. Experience with pacemakershas shown that titanium cases are almost completelyimpervious to steam.

We have studied the biocompatibility of a numberof materials. Our results show that only graphitecoated with pyrolytic carbon (Societe Europeannede Propulsion, Bordeaux, France) did not induce anyreaction (3). There was no sign of fibrosis in sur-rounding tissue (peritoneum, muscle, or endothe-lium).

HemocompatibilityThis is not the time or place for an exhaustive

review of the complex topic of hemocompatibility.However, I would like to mention several points.

Because a thin protein layer develops on all ma-terials, direct contact between the implant and blooddoes not appear to occur. Formation of this layer can

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be accelerated by ‘‘biolisation’’ with albumin (Nose)prior to implantation. Our tests with several testedporous materials confirmed the formation of a coat-ing layer including fibrocytes and new vessels. Thissubstrate served as the foundation for neoendothe-lium that began in patches and became confluentwith development of giant cells (probably macro-phages) which attached to the substrate. The samelining has been observed in Heartmate ventricles.Unfortunately, this lining cannot form inside rotarypumps because the flow is too rapid. For this reasonwe abandoned porous materials in the Cora pumpand adopted smooth surfaces. However, it should beemphasized that surfaces inside the rotary pumpmust be highly polished and as close to perfect aspossible; the slightest scratch can lead to extensivehemolysis. The condition of connections is as impor-tant as that of the pump itself. Tubing and jointsmust be carefully studied. Severe dysfunction,thrombosis, pannus, and infection are often due todefects in connecting tubes.

Cleaning the inner surfaces of the pump aftermanufacture and assembly is another important is-sue for avoiding complications. In one test we in-spected a pump that we thought had been properlymanufactured and cleaned and found that the devicewas literally covered with impurities (more than 30different substances) and manufacturing residues.To ensure complete removal of all impurities andresidues, we developed a specific cleaning processthat takes 10 days.

Functional assistanceRotary pumps provide a continuous nonpulsatile

flow. The animal experiments of Nose and Goldingshowed that an organism can adapt to nonpulsatileflow. In our clinical experience, we have observedpatients who have remained pulseless for over 20days (total centrifugal pump assistance) with no ad-verse effects. Because the natural heart often pro-vides some pulsatility, it is difficult to evaluate theeffects of long-term nonpulsatile circulation fromclinical experience. However the organism has greatadaptive potential. In long-term experiments Nosereported the appearance of peripheral pulsatility.The Cora is a partially pulsatile pump.

A control system is needed to continuously adjustpump output to meet circulatory requirements. Theorganism maintains constant mean arterial pressureby controlling peripheral vascular resistance, re-gional circulation rate, blood volume, and heart rate.The output of an artificial ventricle depends mainlyon venous return to keep the preload constant andavoid negative pressure. Because sensor devices are

unreliable, most groups have adopted a feedbacksystem based on the power intensity and waveformfor implantable devices. This is the choice that wehave made for the Cora pump (4).

Quality of lifeThe weight, size, and shape of the prosthesis are

important factors in patient comfort. The prosthesisshould be designed to fit the site of placement. Mostimplantable rotary pumps, especially axial pumps,are small and light. The main additional advantageof rotary pumps is low noise and vibration levelsduring operation.

Autonomy is a crucial factor in allowing normalactivity. The overall efficiency of the system must beoptimized to maximize the duration of autonomy. Inthis regard it should be restated that because rotarypumps do not require an expansion chamber for ex-ternal venting, power can be transmitted by transcu-taneous induction.

Our knowledge of physiology and pathophysiol-ogy has profited greatly from research in the field ofcirculatory assistance. New technology brings newinnovations in available hardware every day, andtechnical problems are now solvable. The main ob-stacle remains the interface between the living or-ganism and artificial organ. To understand and re-solve these problems, close collaboration is neededbetween physicians, research workers, and engineersand between the medical and industrial sectors.

In 1962 I had a dream to do heart transplantation.In November 1968 we performed our first procedureon a patient who lived for 181⁄2 years with his newheart and who was the longest surviving heart pa-tient for many years.

In 1974 I had another dream; the development ofan artificial heart. In 1997 the Cora is on the brink ofsuccess. As Antoine de Saint-Exupery wrote, ‘‘Vic-tory and defeat are meaningless words: only theevents of the moment count.’’

REFERENCES

1. Monties J-R, Dion I, Havlik P, Rouais F, Trinkl J, Baquey C.‘‘Cora’’ Rotary pump for Implantable LVAD: Biomaterialaspects. Artif Organs 1997;21(7):730–4.

2. Monties J-R, Trinkl J, Mesana T, Havlik P, Demunck JL.Cora valveless pulsatile rotary pump: New design and control.Ann Thorac Surg 1996;61(1):463–8.

3. Monties J-R, Chignier E, Havlik P, Buttazzoni B, Eloy R.Hemocompatibility and biological behaviour of pyrolytic car-bon for use as material for artificial heart. 9th Annual Meet-ing of European Society for Artificial Organs, Brussels, Sept1–3, 1982, in Life Support Systems-Proceedings ESAO1982:273–6.

4. Trinkl J, Mesana T, Havlik P, Mitsui N, Demunck JL, Dion I,Candelon B, Monties J-R. Control of pulsatile rotary pumpswithout pressure sensors. ASAIO Trans 1991;37(3):M208–10.

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