A rabbit cardiopulmonary bypass platform for modeling post-cardiopulmonary bypass coagulopathy and testing platelet-based hemostatic support

Post-cardiopulmonary bypass coagulopathy is a major contributor to bleeding after cardiovascular surgery, but mechanistic evaluation in patients is confounded by surgical complexity, transfusion, hemostatic interventions, and comorbidities. Practical in vivo platforms that permit controlled CPB exposure, multidimensional assessment of hemostatic dysfunction, and proof-of-concept testing of targeted interventions remain limited. We sought to establish a rabbit CPB platform for modeling post-CPB coagulopathy and evaluating platelet-based hemostatic support. Male New Zealand White rabbits (~ 3 kg) underwent cardiopulmonary bypass under general anesthesia via ascending aortic and right atrial appendage cannulation through median sternotomy. A commercially available neonatal CPB circuit was primed with donor rabbit red blood cells to achieve a priming hemoglobin concentration of 3.0 g/dL. CPB was maintained for 60 min. After CPB termination, residual circuit blood was recovered and returned to maintain post-bypass survival, followed by a 2-h observation period. Post-CPB coagulopathy was assessed using platelet count, clotting function, and platelet function analyses. As a proof-of-concept intervention study, donor rabbit platelet-poor plasma (PPP group, n = 4) or platelet-rich plasma (PRP group, n = 6) was administered after CPB. CPB produced a reproducible coagulopathic phenotype characterized by thrombocytopenia, impaired clotting function, and reduced platelet function. Compared with PPP administration, PRP administration was associated with numerically shorter coagulation function testing values (418 ± 190 vs. 228 ± 59 s) and higher platelet function testing values (13.0 ± 5.7 vs. 39.8 ± 22.7 AUC). We established a rabbit CPB platform that reproduces key features of post-CPB coagulopathy and enables multidimensional assessment of hemostatic dysfunction. This model provides a translational experimental platform for evaluating platelet-based and other targeted strategies to prevent or treat CPB-associated bleeding.