Baa Baa Blood Sheep (2015)

Background: Animal models have been a valuable tool for research into bloodproducts as well, as the effects of blood transfusions. Small animal models havebeen applied extensively and large animal model less frequently. This sessiondescribes the experience and details the ﬁndings from a recent series of in vivosheep transfusion models.Aims and method: To discuss the beneﬁts of sheep as a large animal transfusionmodel and to review conclusions from a series of sheep transfusion models.Results and discussion: Similarities in size, anatomy and physiology of sheep com-pared to humans have supported its use to model a wide range of human diseases.The large size of the sheep enables continuous physiological monitoring using stan-dard human techniques. Its size also equates to a higher total blood volume whichpermits the collection of multiple and serial samples.In this series the ﬁrst sheep model involved transfusion of supernatant (SN) fromhuman blood products. These studies conﬁrmed the two-hit TRALI mechanism, asboth host factors (lipopolysaccharide modelling bacterial infection) and blood pro-duct factors (storage duration of either platelet or packed red blood cell (PRBC)units) contributed to the development of TRALI. The ability to control interventionsin an animal model also enabled demonstration that pathophysiological changeswere more severe in TRALI induced by stored PRBC-SN than in TRALI induced bystored platelet-SN.Subsequent sheep transfusion models were more sophisticated with the collection anduse of homologous sheep blood products, and pre-transfusion cross-matching. Inaddition, similarities in the storage lesions of sheep and human PRBC units across42 days storage, supported the use of these models to investigate the effects of storedPRBC transfusion. In a haemorrhage model, transfusion of stored sheep PRBC affectedpulmonary function, even in the absence of overt tissue injury (ﬁrst hit), highlightingthe sensitivity and vulnerability of the pulmonary system to transfusions.Like human PRBC, sheep PRBC have negligible levels of selenium (trace elementinvolved with antioxidant function). The sheep haemorrhage model demonstratedthat the transfusion of sheep PRBC diluted selenium levels and compromised glu-tathione peroxidase antioxidant activity, which in turn allowed lipid peroxidation.Their large size also enabled development of a sheep model of extracorporeal mem-brane oxygenation (ECMO). In these studies the insults of lung injury and ECMOreduced selenium levels but transfusion with two units PRBC did not alter the mea-sured oxidative stress markers. A recent study has delineated the similarities and differences between ovine andhuman haemostasis. The study revealed the sheep had similar primary haemostasisresponse, however differences were detected in its secondary haemostasis response.For examples sheep platelets had reduced ADP and collagen response.Summary: These ﬁndings demonstrate the value of large animal models for transfu-sion research and reveal the sophistication of current sheep transfusion models. Conversely these studies have also identiﬁed where sheep differ (e.g. platelet response),and this information is useful in the design of future sheep transfusion models.