The fourth barrier

At the entrance of a new era, clinical xenotransplantations is a valued and auspicious option in tackling the problem of donor shortage. Because of et hical and anatomical issues, domestic farm animals are considered the most favourable species for organ donation, but transplantation of their organs leads to a complex process of rejection. Mechanistically, three immunologic al barriers, namely hyperacute rejection, delayed xenograft rejection and s ubsequent cellular rejection, are distinguished. A fifth (microbiological) barrier, is also being recognised. This review focuses on problems regardin g the fourth barrier i.e. physiology, in possible clinical settings and the ir corresponding animal models. Besides anatomical differences and posture, biochemical differences may have a severe impact on recipient survival. Di fferences in blood components and electrolyte and other biochemical concent rations are easily detected throughout the species considered for xenotrans plantation. Enzymes and hormones have complex routes of action, activation and inhibition, and their molecular differences can impede function. As inf usion or medicine may correct certain imbalances in electrolytes and protei ns, problems with complex interactions might be difficult to retrieve and s olve. Experimentally, survival of discordant xenografts show promising resu lts, but the first physiological problems have already been detected. So, b ased upon the few experimental data available and the comparison of veterin ary physiology, one might expect differences between the organs grafted, re garding the possible occurrence of physiological problems. Moreover, precau tions must be taken to extrapolate long-term survival, because of species s pecificity.