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Ann Thorac Surg 1995;59:565-567
© 1995 The Society of Thoracic Surgeons
Harley Street Clinic, London, United Kingdom
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However, our attitudes are more deeply rooted than simple surgical fashion and are based on the premise that our entire physical makeup and body structures represent the end result of millions of years of evolutionary development. This makes it difficult to conceive of man-made equipment (ingenious though it often is) being more effective and efficient than the natural tissues. Nowhere is this more striking than when looking at the heart valves, which have been molded by millions of years of blood flow and pressure in the cardiac chambers. I believe it would be conceited of us to think we can improve on them.
In addition, my former chief (Lord Brock) had a positive revulsion for foreign bodies born of his early experience with these in relation to tuberculosis and surgical infections. It is not surprising, therefore, that the use of the body's natural tissues was deeply inculcated in me, and it still remains a guiding principle in my surgical practice to use natural tissues where possible.
This attitude is in direct contrast with perhaps the all-too-common mechanical approach embodying all manner of surgical prostheses. The choice between mechanical and biological is a decision we all have to make consciously or unconsciously in the course of our surgical development-a decision that I am afraid often is influenced unduly by subtle commercial incentives rather than objective appraisal.
My story begins in Guy's Hospital, London, before the days of open heart surgery when I was a surgical research fellow working primarily on hypothermia as a means of access to the heart. At that time I also had the task of studying and preserving arterial segments for use in coarctation and abdominal aneurysm. Ethylene oxide sterilization followed by freeze drying was the favored technique.
Meanwhile, in 1952 Conrad Lam [1] of Detroit had experimented with dog homograft aortic valves in the descending aorta. Most of the cusps fibrosed and stuck to the wall, but he correctly postulated that they would perform better in the presence of aortic regurgitation.
Lord Brock set up the task of repeating Lam's work in the laboratory, and we confirmed the functional persistence of the valve once we had established aortic regurgitation (the most difficult part). That was our introduction to the homograft valves, and together with our arterial segments we freeze-dried a number of human valves (and incredibly have been able to reconstitute them more than 25 years later).
Next on the scene was Gordon Murray [2] of Toronto, who put fresh human aortic valves in the descending aorta just as Hufnagel had done with a primitive ball. Murray's valves continued to function and were reported on by Kerwin and associates [3] at least 6 years later.
By 1962 Lillihei and Kirklin had given us practical open heart surgery and we were working regularly on heavily calcified aortic valves, decalcifying and sometimes repairing them when we were over-enthusiastic. At the same time we experimented with our freeze-dried valves in a pulse duplicator, and our colleagues Duran and Gunning [4] in Oxford worked on the possibility of sewing homografts into dogs in the subcoronary position.
At that stage one of my valve decalcifications turned into a disaster in that the whole valve disappeared down the sucker. We hurriedly reconstituted a freeze-dried valve and sewed it in with a single suture line [5] to tide us over until we could import one of the new-fangled Starr valves. The patient was discharged fit within 10 days and we adopted the homograft with enthusiasm and forgot about importing mechanical valves.
There was great excitement in the hospital, and naturally we expected a rejection phenomenon. Our Guy's Hospital immunologists [6, 7] were in fact able to demonstrate this unequivocally, and their animal studies confirmed it even to the point of demonstrating an accelerated second-set reaction. We used steroids as an immunosuppressive, and as the antibody titer tended to fall between 2 and 3 weeks, we used a 3-week course of immunosuppressives.
Because of the danger of infection and objections from our cardiologists we gradually gave them up without adverse effects. Of course we still recognize there is invariably an antibody reaction, usually with a slight fever, and we have come to terms with this in managing our patients.
However, it has both annoyed and amazed me over the years to see how the simple rules of immunology have been ignored, flouted, or rewritten by homograft surgeons, especially unthinking cryopreservation enthusiasts. They somehow believe that freezing imparts some magical properties on the valve although there is plenty of contrary evidence [8–10]. In fact cryopreserved valves are usually more immunologically reactive so that the cells and fibroblasts cannot possibly survive. However, it is encouraging to note a reawakening and a reappraisal of the immune reaction among homograft surgeons, particularly those dealing with the immunologically active infant age group.
To return to my story after that digression, we continued to use freeze-dried homograft valves for about 7 years and then because of an increasing incidence of calcification switched to freshly procured autopsy valves sterilized in antibiotics and stored in a nutrient medium in a commercial refrigerator for 3 to 6 weeks. This decision rested on our early viability studies-carried out by a clever Iraqi lady who worked in my laboratory in the 1970s [11]. She introduced the use of tritiated thymidine, which is now the recognized method of assessing fibroblast viability. She also showed that tissue culture is worthless in this respect and as such is no guide to quantitative assessment of viability. We regard the presence of viable cells simply as an indication of retained structural integrity of the cusp, but of course they do not persist when they are in the body.
Antibiotic-preserved autopsy valves or homovital valves removed at transplantation and stored in tissue culture medium at 4°C are still our preferred form of stored homografts [12]. These generally show 60% to 70% viable cells just as with cryopreserved valves. This figure tails off at 3 weeks, but the valves can be used for up to 6 weeks. These so-called fresh valves have the great advantage of being rapidly accessible at operation and with no laborious reconstitution procedures. However, unless your valve throughput is rapid, there is the risk of wasted valves, and where supply is in excess of use the valves are cryopreserved and stockpiled.
Although switching from freeze drying reduced the incidence of calcification in the valve, the subsequent use of cryopreservation has in our hands made no difference to the end result. We can still predict confidently primary tissue failure or wearing out of the accellular cusps exposed to the stress of repeated flexion and without any means of repopulating and restoring the degenerating collagen.
Studies of the onset of tissue failure over the years show an average onset of failure at about 7 years, after which it is relentlessly progressive. For example, if we now superimpose clinical features on the tissue failure curve there is unlikely to be any overt clinical evidence of this until about 10 years. At that stage a diastolic murmur or changing murmur usually presages the onset of cusp degeneration. Replacement is likely to be needed within 4 to 5 years, making the effective life of the average aortic homograft in an adult about 15 years.
About 2,000 of these valves have been inserted, the majority in a subcoronary position, but since 1972 an increasing proportion have been root replacements particularly in reoperations and infective endocarditis.
Although the homograft valve offers a trouble-free and embolism-free replacement, it is clearly not a permanent solution and this was evident within 5 years of our earliest homograft replacements. Only two alternatives presented: either the use of truly living homovital valves plus immunosuppression as with organ transplants or the use of a living autotransplant of the pulmonary valves.
Although immunosuppression seems to negate many of the advantages of the homograft, the newly developed less toxic immunosuppressives may well offer an extended life to the homograft and may be needed for only a limited period of time after the operation. On the other hand, the pulmonary autograft valve has the advantage of perfect design with living metabolizing tissue able to maintain and replace its structural components. The first autograft valve was in 1967 [13], and that patient is still alive as are an increasing number of patients still active and asymptomatic after 25 years. This makes the autograft unique among valve replacements, and it becomes justifiable at least to talk of a permanent or even ideal form of valve replacement.
Returning to the homograft, we were proud back in 1966 to perform the first-ever pulmonary atresia reconstruction with a valved homograft [14]. The technique quickly was taken up by McGoon and Rastelli in the correction of truncus arteriosus. Now I think there is worldwide acceptance of the homograft for right ventricular outflow reconstruction; not surprisingly, this takes us back once more to fundamental immunologic principles in that the immunologically reactive infant around 3 years and under may reject the cell-rich cryopreserved homograft quite vigorously.
Because pulmonary autografts are being done in much younger patients even down to 1-day-old infants, the choice of a pulmonary valve replacement on the right side becomes critical. Either some inert substitute must be used or a homograft plus immunosuppression or the solution we favor, which is a nonreacting nonviable homograft stored in antibiotics.
Looking further afield, I am delighted that the principle of using the anatomically correct homograft to replace all or part of the diseased mitral and tricuspid valves is being reintroduced [15, 16]. In the early days of homografts we and one or two other European surgeons tried mitral valve homografts, but these failed largely because of chordal rupture. However, the principle is correct, and with persistence and the fresh trials under way I am sure we will overcome any remaining difficulties that lie ahead.
Footnotes
Presented at the Forty-first Annual Meeting of the Southern Thoracic Surgical Association, Marco Island, FL, Nov 10–12, 1994.
Address reprint requests to Mr Ross, 25 Upper Wimpole St, London, W1A 7TA, United Kingdom.
References
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