patients older than 70 years. similar conclusions about the relationship between age and valve related complications were published about porcine valves. the clear demonstration of this inverse relationship between the age of the patient and the rate of valve calcification 'sounded an alarm bell' and started to change the way in which tissue valves (porcine aortic and bovine pericardium) should be used in the future, and indicated the direction in which potential future research should be concentrated in order to make tissue valves universally acceptable by young and old patients without problems. at this moment in time,(2011), tissue valves are almost exclusively used in patients older than 65 years because in old age the process of calcification is considerably slowed down and also because the life of the valves may outlast the life of those patients who reach a 'respectable' age. several attempts have been made in order to abolish or at least to delay the occurrence of calcification. two chemical processes were put forward: the t6 by hancock laboratory and the pv2 by edwards laboratory. the two chemical interventions had been tested in animals and in humans with unconvincing results. subcutaneous implants, in rats, of cusps of porcine valves and strips of pericardium showed some positive results. however, care should be exercised in extrapolating such data obtained from subcutaneous implants to intracardiac location and function of valves in humans. jones and associates using the well known sheep model, which is a rapidly, universally and highly calcifying model, implanted porcine and pericardial valves either 'standard' or pre-treated with the hancock t6 or the edwards pv2 processes. the results showed that these processes mitigated the calcification of porcine valves but did not have any effect on the pericardial valves. gallo conducted similar experiments using the same model as jones and ferrans and implanted hancock porcine valves, with and without the t6 treatment, in the mitral and tricuspid positions of sheep. he found no significant difference in the amount of cusp calcification between the standard and the t6 treated valves, whether in the mitral or in the tricuspid position. although very little is known about the exact causes of this extremely complex process of calcification, attempts are made to treat it. macro and microscopic pathology studies of failed porcine bioprostheses by schoen and cohn showed in detail the process of tissue degeneration in valves with tears, calcification, or both. they consider that patients with porcine aortic bioprosthetic valves follow a clinically satisfactory course for around five years after operation. late deterioration of these valves frequently necessitates re-operation. they estimate the rate of failure at approximately 15 to 25%, 7 to 10 years after valve implantation. gallo and his associates describe in detail the rate of occurrence and timing of primary tissue failure with the hancock porcine valve, and show a similar percentage of failures. the actuarial freedom from valve failure in the mitral position at 10 years is 69%, and in the aortic position only 53%. the rate of tissue valve failure accelerated from the third post-operative year in the mitral position, and from the fifth year in the aortic position with a precipitous fall during the 8th and 9th years of follow-up. they believe that the patient can be told that he or she has a 30% chance of requiring re-operation because of the porcine valve degeneration within the next 10 years. this general calculation does not take into account the other causes of valve 'problems' which may lead to re-operation or some other morbidity during that period of time. goffin showed in a comparative histological study of explanted porcine and pericardial valves that the microscopic pathologic changes were similar in these two types of tissue. grabenwoger found similar pathologic changes in the failed sorin pericarbon pericardial valve. these long-term studies showed that both the tissue of pig valves and that of calf pericardium behave in a similar manner when used for valve replacement in humans. in a simplified way, the main difference between these two types of valves is the haemodynamic superiority of the pericardial valve and its smaller risk for embolisation. but the overwhelming advantage of the pericardial valve remains the fact that, being a man-made device, it lends itself to a variety of changes in order to improve its performance. in most published reports about tissue heart valve replacement, there are differences in the presentation of data and of the results in all aspects of a particular topic between the various publications. in almost all chapters of valve function, with the exception of haemodynamic and hydraulic measurements - which are scientifically obtained and mathematically expressed - there are differences from author to author. why in the hands of one surgeon, the same type of tissue valve fails in one patient at 24 months, and in another one it lasts 243 months? microscopic studies performed on porcine and pericardial valves, explanted because of failure between 12 months and 6 years, all showed gross histological changes in the structure of tissue. in view of these changes in those valves, how did some of the porcine and pericardial valves continue to function well beyond 10 years? why did the rate of occurrence of bacterial endocarditis differ from one hospital to another, and the embolic rate vary from surgeon to surgeon? an overview of the publications on this topic may lead to the formulation of some tentative answers. there are, generally speaking, several potential factors which may affect variously the durability of tissue valves, and which may explain the discrepancy among published results. carlos duran summarised some of them in the following way: variations at manufacturing level: selection of tissue according to age of animal, thickness of the material in relation to the size of the valve to be constructed. the handling of the tissue from harvesting to the finished product. the design, chemical treatment and technique of construction of the device. about the patient: complete information about the age and biological condition of the patient, history of other pathologies, heart rhythm, previous embolic episodes, anticoagulant treatment, etc. concerning the surgeon: correct rinsing of the bioprosthesis prior to implantation, maintaining the moistness of the valve throughout the time of implantation, careful handling of the device, extra care for the sterility and against possible contamination, correct positioning of the valve within the heart, especially in the mitral position, to avoid 'asymmetrical opening of the cusps'. the avoidance of trying to implant the largest possible valve in the respective heart annulus. all pericardial valves are large enough for the corresponding orifice in which they are supposed to be fitted comfortably. great damage can be inflicted on a bioprosthesis at the time of its implantation. one of the not so rare causes is allowing the cusps of the valve to become dry – to look like parchment - during the time of placement of sutures. some errors occurred exceptionally: the plastic identification tag remained attached to the valve and became stuck to the left ventricle wall; the sutures meant to secure the introducer were not removed and all three cusps of a valve were limited in their movement; entangling sutures around the stent struts, sometimes around two struts: (one of the incidents was published under the title of 'fatal bioprosthetic regurgitation immediately after mitral and tricuspid valve replacement with ionescu-shiley bioprosthesis'). during 1986, shiley made a substantial and original modification to the pericardial valve. the stent was redesigned. it was made of two wafer-thin, unequal, flexible delrin components: an outside, standard-shaped frame and an inner, smaller structure. the pericardial cusps were mounted inside the outer frame and were kept in position by the inner frame which is smaller and much thinner than the outer one. through this arrangement, the lower parts of the pericardial cusps exit from the supporting frame at its bottom, and therefore the pericardium does not bend over the upper margin of the stent, eliminating the possibility of abrasion during the closure phase of the valve. as it was learned from clinical and from in-vitro studies, abrasion of the pericardium was a cause of valve failure when the tissue was attached on the outside of the stent. the in-vitro testing of this modified pericardial valve showed almost identical hydrodynamic results when compared with the existing pericardial valve. accelerated life-testing showed that failure of this new valve occurred some 3 to 4 times later than that of existing valves. when valve failure occurred, it was not due to abrasion but through progressive fraying of the pericardium. encouraged by these results, shiley decided to start manufacturing this modified, improved valve called the 'ionescu-shiley pericardial optimograft'. at about that time, grave problems were encountered by shiley with the increasing number of sudden failure of the bjork-shiley mechanical disc valve. pfizer laboratories, the drug manufacturer and owner of shiley, stopped all manufacturing activities of shiley laboratory, with a view to liquidate the company. consequently, not only was the bjork-shiley valve (the culprit) affected by this action, but all other products – valves, oxygenators, catheters, etc. - went out of production. it was said (by mr larry wettlaufer: vice-president at shiley inc. 1987) that ionescu did not want to go to another valve manufacturer with his 'optimograft' and that he preferred his himalayan climbing expeditions instead. a careful appraisal of the results and the evolution of the two types of tissue valves created and used during the past four decades brings into focus the similarities but mainly the discrepancies which set them apart as structures and as functioning valves. the porcine valve was subjected to several modifications which reached the limits imposed by the fixed geometry of the pig's aortic valve. the pericardial valve, the embodiment of the concept of 'man-made' devices, lends itself to an infinite permutation of changes of shape and physico-chemical interventions in order to improve its function, and indeed this is what happened. almost 10 years after the creation, by ionescu, of the pericardial valve, the concept behind it attracted several specialised laboratories to study this valve, to modify and improve it and bring it anew in the clinical field of usage, under different shapes and names, but always following the same general concept: glutaraldehyde-treated bovine pericardium mounted on a flexible frame as a three-cusp valve. the second generation of pericardial valves building the second generation of pericardial valves was possible, first of all, because there existed a first generation. the originality of the concept, the successes and failures, the flaws and positive aspects of the original pericardial valve and the experience accumulated with its use over the first 10 to 15 years created the incentive and showed the way for changes, modifications and potential improvements in building the valves of a second generation. of the several pericardial valves built since 1980, some have been abandoned early and only three have stood the test of time. these three modified and improved pericardial valves were made respectively by mitral medical inc. (now part of the sorin group), edwards laboratories (now edwards lifesciences) and the sorin group. all three laboratories have devised different techniques of valve construction with the aim of reducing or abolishing the risk of tissue abrasion. the specialists at mitral medical inc. retained the technique of mounting the pericardium outside the stent as in the original ionescu valve, but found other ways of reducing abrasion. the edwards engineers used an ingenious way of mounting the pericardium inside the stent albeit with a minimum loss of useful opening flow area. the sorin technicians devised yet another way of mounting the pericardium in a double layer so as to have the stent margin padded with a pericardial sheet (similar to one of shiley's modifications). the edwards valve became available in 1980. the device made in the configuration for mitral replacement had to be withdrawn, after implantation in a small number of patients, because of excessive flexibility of the stent causing mitral incompetence. a new redesigned version of this valve was reintroduced in 1984. the mitroflow valve, as first manufactured by mitral medical in 1982, had to be redesigned because it showed a failure mode similar to the first generation of pericardial valves. since 1991 a modified version of this valve was introduced and has been used in a large number of patients. the additional changes made in the configuration of these two