About Utopia and the Ephemeral

ABOUT UTOPIA AND THE EPHEMERAL

Marian Ion Ionescu

Lecture, given by invitation, at the Annual Scientific Meeting of the 'Society for Cardiothoracic Surgery in Great Britain and Ireland'. 13 - 16 March 2006, Dublin, Eire.

Mr Chairman, Ladies and Gentlemen,

You kindly invited me to participate in this scientific gathering and to talk about something of my experience. As I retired from surgery many years ago, I cannot contribute with anything new.All I could do, I thought, is to tell you something of my views on the long struggle towards progress and the way to interpret it now in a detached and critical manner.
Looking back at some attempts to create an artificial valve may be of some interest. It may help to understand the complicated and difficult decisions to be made and the pitfalls and solutions that lay ahead.

In order to present my viewpoint, I shall use my experience, merely because I find it easier to understand and to be critical of my own work than about that of others. In general, experience is the name we give to our mistakes and I must confess that I learned much more from my mistakes than from my few successes. Lillehei knew that "good judgement comes from experience and experience comes from bad judgement."

To describe my experience in this field, I shall rely on two notions: one is the dream of perfection, the creation of Thomas More who published in 1516 his UTOPIA, which has had a great impact on Western Europe ever since. The second one is related to observations made by Galileo Galilei around 1610 whereby the 4 moons or satellites of Jupiter orbit their mother planet with mathematical regularity. Based on this phenomenon, he established the tables of astronomical movement known as the EPHEMERIDES because of the short duration of their appearance on the visible side of Jupiter. What follws will be often related directly or in a subtle way to these two notions: UTOPIA and the EPHEMERAL. If the ephemeral is a reality, UTOPIA does not exist except in our imagination. It was probably created by the need to have a stimulus somewhere outside our conscience.

One does not need a great critical spirit to understand that, in general, progress in all fields of activity is the result of a subtle balance between two factors, one being the achievements which appear initially to be valid, even important, but become obsolete with the passage of time, and the other one, our persistent desire to make progress, to attain some UTOPIA, which by its own nature evades us, continually distancing itself as we approach it. It is the perfect perennial moving target.

The pictures I shall present are old stuff. They are meant to make a point, not an impression.

I was lucky to be part of that privileged generation who witnessed and participated in the great scientific adventure: the evolution of open-heart surgery. Few of the new developments in medicine were as dramatic as the beginnings of open-heart surgery. Few triumphs came at such tragic cost. It had to evolve through the bleeding, and the dying of numerous patients during those heroic years between the mid-nineteen fifties and the beginning of the sixties. In retrospect, C.W. Lillehei's writing on the origins of direct-vision intracardiac surgery may have best captured the sentiment of the early period: "there were innumerable failures, disappointments, frustrations and obstacles, nature's as well as man's; the only solution was a mixture of persistence and stubbornness"
And for those few who remember that period, it was indeed daring, naive, dangerous and difficult but full of promise.

For what I did or tried to do personally over the years, I do not seek any justification, it is too late anyhow. Oscar Wilde knew that "nobody is rich enough to redeem his past". But I thought that as an excuse for chasing Utopia, I could pretend that I tried to create for myself an alibi for the Last Judgement.

Wolfgang Goethe said somewhere that "daring ideas are like chessmen moved forward, they may be beaten but they may start a winning game". He encompassed in this sentence both the ephemeral and the aim it may serve.

My real contact with open-heart surgery during the late 1950s took place at the Mayo Clinic with D.C. McGoon and J.W. Kirklin in an austere and highly intellectual atmosphere. From there, I moved to the Cleveland Clinic, in 1958, where W. Kolff in the laboratory and D.B. Effler in the clinic maintained an ambience of continuous search for truth and progress. In Kolff's laboratory, I worked on my first artificial heart valve project and in February 1958 I created the single leaflet aortic valve out of polyurethane (Fig.1). Johnathan Swift would have said in such a circumstance: "Great was the courage of the man who first ate an oyster". This was probably my shortest and most ephemeral creation. The valve clotted in almost all our experimental animals. We learned from this venture that smooth plastic surfaces encourage thrombus formation.
As so often happens, this truism remained buried in an article only to be rediscovered many years later.

Kolff often repeated that "no hope is needed to work, nor success to persevere", and so I did and soon thereafter, I constructed an entire three-cusp aortic valve, this time made of Dacron cloth (Fig.2). I left Cleveland at the end of my fellowship and that was also the end of another ephemeral creation. However, a similar type of valve made out of Teflon was used later with some success by Earl Kay and Akio Suzuki in Cleveland.

Contaminated by a lot of hope and a little knowledge, I returned to Bucharest where I started the programme of open-heart surgery in January 1960. As would be expected, the first case was an A.S.D.

A Chinese proverb says that "It is better to light even a small candle than to curse darkness".

During 1961 and 1962, I experimented - with some success - with a three-cusp valves made out of compressed polyurethane sponge and with calf dura mater.

Mitral valve replacement with reinforced mitral allografts, which I tried experimentally, proved to be, even in normal dogs hearts, too difficult to pursue, because of the adjustment of the length of the chordae (Fig.3).

But obsessed with the utopian idea of creating an artificial heart valve which would not require anticoagulants, I started at Leeds General Infirmary, experimenting, in 1966, with porcine aortic valves. In February 1967, I implanted in the mitral position the first pig valves attached to a flexible Dacron collar (Fig.4).

In June of that year, I used these valves mounted on titanium frames for all three cardiac valvular positions. These porcine valves were manufactured by ourselves in the hospital; Christina sewed the stents by hand and prepared them for tissue mounting (Fig.5)

At about the same time, Mark O'Brien in Australia and Alain Carpentier in France pursued a similar type of work with a slight variation but only for aortic valve replacement. It happens that history is interpreted and often rearranged depending on the prism through which interested parties look at events. For the sake of accuracy, I want to show the title page of our publication in THORAX in July 1967 on "Mitral Valve Replacement with Aortic Heterografts in Humans"(Fig.6). In this respect I want to remind you that you will always find a professor of astronomy at a major french university who believes that the earth is flat.

Initially our porcine xenografts were treated with formaldehyde as at that time nobody knew better. The early failures were due to tissue disintegration (Fig.7). The histology of failed valves showed lymphocyte infiltration and disorganisation of connective tissue, signs that the xenograft had become a mechanically vulnerable structure in a state of chronic rejection.

By this time, disappointed with the pig valve, I was attracted by the idea of constucting a tissue valve in its entirety, instead of using existing natural valves.

In April 1969, I started constructing and using, for the first time, three-cusp stented, autologous fascia lata valves, manufactured during the surgical procedure, for all 3 cardiac valvular positions (Fig.8).

The experience with fascia lata is an example of how the promised land always looks better from a distance. About 3 years after implantation, discrete signs of valve incompetence appeared and although most of these valves functioned correctly for up to 7 years, their use - which expanded considerably throughout the world - was discontinued.

The usual mechanism of valve failure was fibrosis and retraction of one or, rarely, two cusps (Fig.9). What in theory appeared correct proved only partly valid in practice.. By that time, it became obvious that what complicates the matter is the environment in which valves function. In general, the human spirit prefers a simple theory to a complicated truth - truth, in fact, is rarely pure and never simple.

At 14 years after implantation, some 40 percent of the fascia lata valves were still functioning. In comparison, the durability of aortic allografts in the aortic position did not fare any better, although they were considered at the time - especially in London - to be the tissue valve of choice for aortic replacement (Fig.10).

The experience gained with fascia lata was extremely useful. We learned how to build 3-cusp stented tissue valves, how to obtain improved haemodynamic performance by trying different profiles and models and, most importantly, the fact that such tissue valves could be used in all cardiac positions without anticoagulant treatment and with a minimal risk of embolisation. The limited success with fascia lata gave us the confidence to put into practice what failure had taught us.

And again, attracted by Utopia and strongly believing that a better tissue valve could be created, I decided to look sideways and started to work with an entirely novel material - bovine pericardium. I used this to consruct the first glutaraldehyde-treated, stent-mounted, pericardial xenograft valve, which I started implanting in patients in February 1971 (Figs. 11, 12, 13).



The premises on which the pericardial valve programme was based were: the availability of the material, the ease of handling it, its pliability and the fact that it is impervious to blood. The calf pericardium becomes biocompatible following chemical treatment and it proved to be "nonthrombogenic".

The pericardial valve being entirely a man-made structure, it lends itself to an infinate diversity of permutations of shape in order to obtain the optimal functional results. This concept sets aside the pericardial valve from all other tissue valves.
I implanted more than 1200 of these valves between 1971 and 1987 and I systematically and rigorously monitored all patients until my retirement and I reached some interesting conclusions.

In vitro, we demonstrated that the pericardial valves open in a smooth and synchronous manner and provide a larger surface area to central flow when compared with porcine valves (Fig.14).

Multiple, and in some patients, sequential, haemodynamic studies - performed by Dr. A.P. Tandon and his cardiological team - have shown, as in-vitro, the same pattern of hydraulic performance with small trans-valvular pressure gradients and large calculated surface areas even for small valve sizes (Fig.15.)


As far as thrombosis is concerned, it has been completely absent from our series. Embolism (whilst the great majority of patients did not receive long-term anticoagulation) has been very low indeed and anticoagulant-related bleeding did not occur.

Concerning the propensity of tissue valves to thrombosis and embolism or their resistance to these phenomena, I consider that our knowledge is still in the Middle Ages of science.
Exactly as Claude Bernard said: "It is what we believe we already know which prevents us from learning."

We compared 2 groups of patients with pericardial xenografts in the mitral position, one of them treated for six weeks with either warfarin or Persantin and another one without any such medication. There was a marginal advantage for those who received short-term treatment. Beyond this period of six weeks, the benifit of anticoagulation was very limited. We therefore decided to use warfarin just for six weeks in all patients following mitral or multiple valve replacements.

Because the importance of these facts seems to be ignored by some and disputed by others, I should like to remind you that almost every scientific truth goes through 3 stages: first people say it conflicts with the Bible; next they say it has been dicovered before; lastly they say they always believed it.

We realised that there are some patients (probably 5 percent) who have a propensity to embolise, independent of the known predisposing factors and sometimes almost irrespective of the use of anticoagulants. These patients will manifest themselves, unfortunately, by throwing an embolus and they will have to be anticoagulted and maintained on warfarin indefinately. The problem is that there is no way of identifying these patients beforehand.

For the great majority of patients with pericardial xenografts (about 95 percent), long-term anticoagulation did not seem to be necessary; conversely, it carries the risk of bleeding and it is also cumbersome for both patient and physician. However, one is not at liberty to make statements except perhaps in geometry as Voltaire said. Much more research is needed to validate these impressions. Statistics are no substitute for common sense. In this respect, some people prefer to believe in what they see, while others like to see what they believe in, which is a cardinal fallacy in science. However, in general, people would rather live with a problem they cannot solve than to accept a solution they do not understand.

As far as valve durability is concerned, I want to tell you, right from the start, that "it takes time to ruin a valve but time is all it takes." The important thing, however, is to be able to predict the length of time a valve would last, exactly as Montesquieu put it: "success generally depends on knowing how long it will take to succeed."
In-vitro accelerated testing gives us a general indication about the mode of valve failure and some vague information concerning durability in the clinical setting. It may also help to improve the configuration and construction of tissue valves. Even with sophisticated testing machines, it is "difficult to look further ahead than you can see" as Churchill used to say.

The data in the actuarial curves shows freedom from valve dysfunction of around 70percent at ten years of follow-up. (Fig.16)

The durability of the Ionescu-Shiley pericardial Xenograft reported by other surgeons was very similar to that observed in our series at about the same post-operative duration. (Fig.17)

In the tricuspid position where the majority of artificial valves have produced unsatisfactory results, the pericardial xenograft proved, at least up to 18 post-operative years, to have performed extremely well.(Fig.18)


Although not up-to-date, the figures presented are important as they show that firstly, the pericardial valves performed initially in an acceptable manner and secondly, that this time, with this valve, we are further away from the ephemeral.


It is said that imitation is a pleasant form of flattery. Some seven years after I created and started using the pericardial valve, no less than 6 types of such valves appeared. All these so-called pericardial valves sprang up through the principle of "spontaneous generation" without any declared connection with the original "Leeds" pericardial valve. What distinguishes these valves is, in my opinion, more a likeness in pretensions than a difference in ideas. (Fig. 19)

The mode of failure of these valves became known with the passage of time. Rupture of cusps by abrasion occured within the first 10 years of implantation, while metabolic failure - fibrosis and calcification - came into being much later, more than 10 years later in valves which "survived" abrasion due to neo-intima formation on the Dacron covering the frame. It is interesting to note that a few of our original pericardial valves functioned well for very long periods of time, some of them up to 30 years.

Why endothelialisation occurs in some cases and not in others remains to be elucidated. Knowing this may help to create an even more durable valve. The conclusion of these findings seems logical: reduce the abrasiveness of the cloth covering the support frame by either induced neo-endothelium formation or cover the cloth with a smooth, non-thrombogenic material like pericardium. This we have done in a limited number of cases, too small to draw any conclusions. Lucian Blaga told us a long time ago that "most of the aspects of the present are accessible to prophecies only." As for the future, we will have to wait a little longer.

Today it is known that tissue valves calcify at an accelerated rate in young individuals and consequently, they should not be used in patients younger than approximately 65 years of age.

If we would now apply this knowledge to the evaluation of our results in patients operated upon in the past and only analyse the durability of valves implanted in patients older than 65 years at the time of operation, we shall certainly obtain a completely different picture and of course, a much more realistic one.

For many surgeons, this evidence influenced heavily their more recent choice for a valve substitute.

Among my trials and tribulations, attempts, failures and small successes, the creation of the pericardial valve was probably the least ephemeral. It changed direction, away from the immutable pig valve and opened a door towards further potential improvements as this valve, being entirely man-made, lends itself to a multitude of permutations of shape in order to further improve its long-term performance. The successive generations of pericardial valves produced are proof of the validity of this concept. But we should not forget that artificial valves are like clocks, the worst type is better than none and the best cannot be expected to function perfectly forever.

The record of predictions on artificial valves instils caution if not humility. Even now, after many years of research in this field, we do not really know what is crucial and what is not as regards the palpable problems of what was considered utopia only 40 years ago. The essential points still elude us. We continue to complain about the embolic complications of mechanical prostheses and about the durability of tissue valves. It is hard to accept that we live in an imperfect world, superbly described by Khalil Gibran in his Prophet when he says that: "Life, and all that lives, is conceived in the mist and not in the crystal and who knows but crystal is mist in decay". We probably forget all too often that science has promised us truth. It has never promised us either peace or happiness; these we should search for elsewhere in life, at the right time, certainly before sunset.

For me, the crepuscule of one activity became the beginning of another one, just as attractive, captivating and uplifting as surgery used to be, demanding the same technical precision and unfailing concentration, harnessing all the mental and physical energy in order to practice it safely, requiring the same attachment, the same perseverence and passion, the same sacrifices but carrying different risks, other privations.

This extravagance is called mountain climbing.
When the passion of mountaineering is rewarded by the success of the climb, the satisfaction has the same intensity, the joy is just as great, everything becomes an ecstacy like a flight above the clouds, an overwhelming explosion of light, splinters of rainbow, a kaleidoscope of colourful dreams. High up, in that world between rock, snow and the azure, one perceives vibrations inaccessible to the people of the flat land below.

In climbing it happens, as during a complex surgical peocedure, that sometimes you get into a tight squeeze from where you have to fight hard to come out on top (Fig.20).

Some other times, you may find yourself in a precarious position, (Fig.21) undecided on which side to take your chances, (Fig.22) especially when you and everything else are hanging by a thin thread (Fig 23).

For once you become the "patient" and therefore you are now the one taking the risks.

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As some of you may not be aquainted with the high mountains, I should like to ask you to join me in an imaginary adventure at altitude to discover together the magic and the majesty of that world of pure beauty, of light, of difficulties, of happiness and sometimes of tragedy.

We should start from down in the valley, leaving behind the colourful chalet as a landmark of stability and as a place to return to, at the end of the climb (Fig.24).

Under the slanting rays of the afternoon sun, we traverse lovely meadows where banks of rhododendrons, intermingled with clumps of primulas and campanulas are set ablaze in the warm light at the end of the day (Fig.25).

 

Dense larch and pine woods climb higher above the valley floor alongside glaciers before dying out on the steeper slopes of rock in the distance (Fig.26).



Slowly, without even noticing it, the shadows grow longer and the landscape becomes indistinct in the gathering shades of evening while the last rays of sun reflect their incandescent glow on the snow-covered high summits.

An enormous, moribund sun slides behind a ridge, announcing the beginning of the end of a most beautiful afternoon (Fig.27).







Just as in dreams, where everything is jumbled together, the play of the clouds and the azure form strange shapes at crepuscule and the ever-changing and fading colours of light give the impression that the entire horizon is an enormous gothic stained-glass window beyond which the agony of another world unfolds (Fig.28).

Now, above a sea of clouds, above the world of evening shadows, the sunset fades into the last shades of pink (Fig.29).







The rising moon floods the sky with an astonishing bright light that prevents the night from growing dark but not from spreading its intimate calm. Everything is stilled by the sharp night's frost and the silence remains unbroken (Fig.30).




One can breathe in the magic of a night that seems to come from another world. One gets drunk with solitude in a reverie that at times lifts us out of ourselves and takes us from where we are to where we would most want to be.

As the day always follows the night, the sky begins to lighten in the east. Gradually, the atmosphere becomes clearer, more transparent. The sky announces the dawn by a profusion of colours and shades in a grandiose spectacle (Fig.31).

The sun appears in glory and floods the higher peaks and the entire mountain with dazzling light (Fig.32).

In the light of dawn, great rock fortresses begin to appear; pinnacles soar vertically upward, pitiless, imposing, indifferent to the tiny, fragile human presence (Fig.33).








And to render the enchantment of the view even more intense, an immense glacier appears at our feet, stretched out like a tapestry right down to the valley and suspended between the rocky needles of the summits, embroidered with silver and emerald (Fig.34).

Yet, above the glacier, the spell is in no way lessened. There are promontories suspended in space, endless crests and rampant pinnacles and, on all sides, overhanging cornices like ocean waves frozen as though they were about to break (Fig.35).

Further down in the intricate world of ice, in continuous transformation, there is a creaking conglomerate of jagged ridges and decayed spires, grim-looking chasms and hidden crevasses of sinister reputation (Fig.36).

There are monstrous tangles of seracs, veritable frost palaces overhanging the void. For these enormous masses of ice in precarious balance, the maze of crevasses, the vertiginous outcrops, the innumerable treacherous snow bridges suspended across chasms, there is no better definition than "the zone of death" (Fig.37).






By mid-morning, the heat produces a thick woolly blanket of cloud which approaches the heights. Before long, the higher summits have already disappeared under the fog layer. Where a few minutes earlier the sun had shone in a blue sky, great waves of cloud appear and circle over the glaciers (Fig.38).

Progressively, the cloud layer reaches the high crests, first light and transparent then thickening, it obscures the landscape. Suddenly, all pleasure goes out of climbing; the mountain has grown hostile and once again it becomes apparent how insignificant and feeble man is face-to-face with the implacable forces of nature (Fig.39).

Luckily, this menacing interlude does not last for long. The clouds around begin to thin out and, through openings in the fog banks, the snow-covered summit of the mountain appears in all its majesty.
But most impressive of all, because it is nearer, the proud, isolated pinnacle of granite lifts its colossal needle point to stab at the sky 'Fig.40).

Our imaginary climb continues towards even higher and more difficult summits. The warm tints of light begin to slide across peaks, faces, ridges and gullies, creating a kaleidoscopic movement of light and contrast (Fig.41).

We encounter all around rows of white peaks, sharp as shark"s teeth, sheer-sided towers, jutting sculptures of ice or rock, all looking like the true cathedrals of the earth built for the unknown gods of the azure or of the abyss (Fig.42).



In the middle of these impressive architectural structures appears a steep, unending couloir capped by ominous overhangs of ice, a giant, menacing funnel radiating dangers and fear (Fig.43).

Among many a superb structure stand bare rocks emerging from the snow in huge columns dressed in a multitude of colours (Fig.44).







Here to our amazement appears this proud pink granite pinnacle almost defying the laws of gravity and equilibrium (Fig.45).
On this immaculate dome of snow, we could imagine our arrival at the summit. Up there, the air is utterly pure, sparkling, as if from another planet, breathing it feels like filling your lungs with sky.

On the summit, there is nothing but light and space. What happens up there belongs more to the world of feelings than to physical things. While in contact with nature, in solitude one prefers the intimacy of one's emotions from which one would emerge as from a dream and happy to have dreamt (Fig.46).

Back to reality, a final "tour d'horizon" embraces vistas that weary the eyes; mountain ranges upon mountain ranges overlapping, merging and seperating again for no apparent reason (Fig 47).

During the return to the valley, the dream begins to unravel and we rejoin safe and sound the flowery chalet. (Fig. 48 )

Inside the imaginary chalet, we may find this inscription which summarises in four lines the essence of our communion with nature, with the mountains, with the magic and the majesty of the mountains:

To see a world in a grain of sand,
And a heaven in a wild flower;
Hold infinity in the palm of your hand,
And eternity in one hour.

William Blake

Now, I should like to remind you of what, in a light-hearted way, I said at the beginning, that whatever I did was in order to create for myself an alibi for the last judgement. What a disappointment it was when I learned recently from Emil Cioran that only tears are weighed in the balance at the last judgement. One does not know if he meant tears of sorrow or tears of joy. Now it does not matter anymore. When you are over the hill, you pick up speed and try to transfer your dreams, your utopian dreams, to your younger fellows.

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The ancient Greeks considered that man should accomplish deeds which approach the nobility, the beauty and the permanence of nature and that success would guarantee a form of immortality in the memory of fellow men, outside space and outside time.

In the Judeo-Christian philosophy, to abide by the precepts of the Bible and cultivate virtue and justice was the way to obtain salvation and immortality in the next life, beyond time, beyond history.
The Renaissance and later on the Enlightenment changed all this.
Man, with his knowledge and know-how, is capable of taking charge of his own destiny. History became a science, it has a sense, it has direction. Man, society, with reason, logic, imagination and through intelligent action, can reach perfection inside historical time. This modern point of view concerning the role of man in history, placing the aim inside historical time, considers that our accomplishments are within our creative power and probably could be manipulated in such a way as to occur earlier rather than later.

The post-modern era which is almost visible over the horizon appears even more intimidating. Progress and scientific developments occur at such a speed that there is hardly time to understand them, not to mention the chance to critically evaluate the change.
As we well know, progress in all fields of activity is not a linear, evolutionary process, but rather a succession of chaotic bursts of activity and creativity related to a multitude of factors.

During the nineteen fifties, the cardiac surgical world was populated by giants. It was a unique period bristling with discoveries, innovations, inventions and fierce competition. During those years, pioneers established the foundations of open-heart surgery, quite often fighting through rivers of blood and hecatombs of young patients. A little later, during the time of my generation in the sixties and early seventies, there was in these islands a period of great activity, an atmosphere of great excitement, a continuous effervescence, that sense of exhileration which springs from self-confidence and achievement and I recall with pride and admiration the names of some of my contemporaries -- Andrew Logan, Donald Ross, Geoffrey Wooller, Denis Melrose, Eion O'Malley, Terence English, Magdy Yacoub, Iarostav Stark and many others who tried to look at the hidden face of the moon and who gave so much to our speciality.

One may ask now what happened to that sense of emulation, to that atmosphere of intense activity in these islands? The passion to look, to search, to discover, to create?
The enduring possibilities in these lands may still be here but only for those with true grit, those who love to be on the road to the unknown, those with a sense of adventure and of living at the frontier never quite effaced, those who believe in freedom of thought and who get away with living it, those who can strike sparks anywhere, as I said before, those who want to look at the hidden face of the moon.

During the sixties and seventies, there was a fantastic, almost universal feeling that whatever we were doing was right, that we were advancing, almost winning, we had that sense of inevitable victory over the old and the unknown; our energy, our ideas would simply have to prevail. I think that we develped the self-confident belief that life should be conducted according to our own rules rather than anyone else's. We had all the momentum, we were riding the crest of a high and beautiful wave.                                                                              

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Years have passed.
Now you can go up a steep hill anywhere in these islands and look around. With the right kind of eyes you may almost see the high water mark, that place where the wave finally broke and rolled back. This perhaps shows us that these possibilities may still be here, the possibility of awakening the wild,indomitable spirit to fight again for the initial, primitive dreams ... to look, to search, to discover, to create.
Without apologising, I feel the impulse to scream: What the hell, let's try again, let's give it a roll, let's go for the hidden side of the moon.

The ephemeral certainty does exist and you may encounter it often but, in a way, utopia may well exist at the end of a rainbow too or in the secret corner of your dreams and aspirations. As you well know, we really start to act under the fascination of the impossible. And this is the main message to be conveyed - act now, start to challange the 'impossible', push on that pain in the soul which makes us go beyond ourselves.

Get started and keep going, the road from NADIR to ZENITH is long and arduous, the essential is to be continually on the move, whether you reach the summit or not becomes almost secondary. And do not forget that if it works right the first time, you might have done something wrong. Perseverance to the point of stubbornness and hope will help on the way.
If you are convinced in your conscience that what you are doing is right, do not let yourselves be discouraged by the uninvited, armchair critics of your heterodoxy and do not seek immediate approval either. Hazlitt says that everthing which ceases to be a subject of controversy ceases to be a subject of interest. Great discoveries always have a lag period, they need time to mature.
But do not forget either the petty adversities that the world often flung in Paganini's face as a punishment for his "diabolically sublime" genius.

It appears to me that the Greek philosophy built on the desire for truth and the sense of tragedy, dealing with existence in terms of the myths of Prometheus, the stealer of fire, and Sisyphus - whose efforts are never rewarded - is not far from the condition of the scientist who is not satisfied with half measures. This may be a better answer to today's problems than a lot of fancy theories.

Man has the capacity to create change, to make progress, and this is all that matters in this imperfect world about which we know so little but often pretend the opposite.

For the future, I want to leave you with a simple exquisite thought written by Emily Dickinson: "Hope is that thing with feathers that perches in your soul."

Now, I want to thank you for your patience in listening to me and to wish you all, to reach the promised land which you hold in your own hearts.


For further information about the pericardial heart valve  see the following:

http://en.wikipedia.org/wiki/Pericardial_heart_valves