Cryopreserved Cardiac Valves: Initial Experiences and Theories

Abstract

were realized with the use of “fresh” wet-stored antibiotic-sterilized human homograft valves for the reconstruction of left and right ventricular outflow tracts. However, problems with availability and lack of certainty concerning preservation and storage techniques limited their widespread use. The combination of their apparent resistance to infection, excellent hydraulic function, absence of need for anticoagulation, and versatility in difficult outflow reconstructions made them optimal choices for many categories of patients, beyond the single issue of durability. The durability of the nonviable but gently preserved homografts was certainly as good as xenografts in adults and even better than xenografts in children. For the past 15 to 20 years, the theoretical hope has been that, if durability could be improved, a homograft would combine the superior attributes of xenografts with the superior attributes of mechanical prostheses and thus be the valve of choice for large numbers of patients. Evaluation of data from the fresh, wet-stored series suggested that tissue viability at the time of transplantation was associated with increased durability. This impression that short, warm ischemia times and shorter, cold storage periods contributed to prolonged graft durability has been difficult to prove with retrospective analyses. Attention to such issues was not what it is today in the era of multipleorgan donor retrievals. Nevertheless, there does appear to be some suggestion that it has indeed been the case when looking at the larger series from the 1960s and 1970s. For example, many of the original recipients of homografts had prolonged durability of their prostheses, and these patients were the very ones in whom prolonged cold storage did not precede the implant. Also, comparing the Harefield series with the National Heart Hospital series of Ross suggested better durability in the former series. The techniques of preservation and harvesting were essentially the same, with the primary difference being that the Harefield group tended to use homografts sooner following procurement; they reported their 8-year actuarial patient survival at 72%, with homograft valve failure occurring in only 19.3% of their patients by 13 years. The Harefield group suggested by logistic analysis a significant negative contribution (p < 0.01) of warm ischemia time (defined by them as the death-todissection interval) to valve durability. Thus these intriguing tidbits plus the teleological thinking that transplanting a viable fibroblast that can remodel and repair by synthesizing structural proteins would confer greater durability led to cryopreservation techniques and alterations in retrieval protocols designed to enhance cellular viability. Beginning in June 1975, O’Brien from Brisbane, Australia began a series of valve replacements utilizing allograft valves that had undergone gentle antibiotic sterilization after retrieval, with attention to short, warm ischemia times; these were then cryopreserved with a dimethylsulfoxide (DMSO) controlledrate freezing technique with storage in liquid 8 Cryopreserved Cardiac Valves: Initial Experiences and Theories