152 ASAIO Journal 2013 The utilization of a heart–lung machine (HLM) for the correc- tion of congenital heart defects can lead to various complica- tions, which can culminate in multiorgan failure and death. To reduce the considerable risk of complications, we developed a miniaturized, highly integrated HLM (MiniHLM) for use in infants and children. For the purpose of testing the MiniHLM, we developed a new rabbit animal model. In all, surgery was performed on 32 rabbits. In the first series, 13 New Zealand white rabbits were placed on cardiopulmonary bypass (CPB) for 1 hour with the use of an initial version of the MiniHLM. In the second series, we operated on 19 Chinchilla Bastard rabbits using the further developed MiniHLM 02 or the Dideco Kids D100 system. While several adjustments had to be made to the operating protocol in the first series in order to lower the mortality rate, 15 of the 19 rabbits were suc- cessfully weaned from the HLM in the second series. Blood tests pertaining to hemolysis and the expression of inflamma- tion were performed. In addition, tissue samples were taken from the right atrial auricle for the purpose of investigating the expression of inflammatory parameters. The newly devel- oped MiniHLM prototype was tested successfully in an ani- mal model in terms of technical function, hemolysis, and the expression of inflammation. On account of the comparabil- ity of their blood values, as well as their anatomy, Chinchilla Bastard rabbits serve as excellent models for the testing of CPB and support systems for infants and children that do not require the administration of foreign blood. ASAIO Journal 2013;59:152–156 Key Words: small animal model, extracorporeal circulation, rabbit Congenital heart defects occur in 0.8% of all newborns. 1 The correction of these defects often requires the implementation of a heart–lung machine (HLM). However, the use of a HLM involves inherent risks. Partly due to the disparity between the small blood volume of newborns and the comparatively huge foreign body surface area of a HLM, severe complications can ensue, which can culminate in multiorgan failure and death. For this reason, recent endeavors have been made to minia- turize the HLM, with the aim of reducing the filling volume and foreign body surface area, thereby lessening the compli- cations. A further objective is complete avoidance of foreign blood administration. Following the design and construction of our miniaturized HLM (MiniHLM) and preliminary in vitro testing, testing by means of an animal model was necessary. Although a suitable animal model does not exist for every disease and applica- tion, adequate testing through the use of an animal model has become indispensible to modern medical research. 2 We designed a rabbit animal model to test our newly developed MiniHLM. 3–5 For this purpose, we had many stipulations pertaining to anatomy, including size, weight, and also the blood volume, which should reflect the new- born patients for whom the MiniHLM was constructed. These specifications are multifactorial. 6 Furthermore, as several of the complications of HLMs are induced by a rise in inflam- matory parameters, 5,7 the tested animals should demonstrate an expression of inflammatory parameters that is similar to humans. Further blood testing with reference to hemolysis and fibrinolysis 4 should also be feasible. To prevent falsifica- tion of the results through foreign blood administration, it should be possible to complete the trials completely without foreign blood. In relation to the aforementioned stipulations, the rabbit fulfills the requirements for serving as the small animal model. It is similar with regard to its anatomy, including blood volume, to newborn children. Although the rabbit possesses a persistent left-sided superior vena cava, this plays only a subordinate role for cannulation and connection to the HLM. The blood volume of infants is approximately 75 ml/kg body weight, and the blood volume of rabbits is 58 ml/kg. Thus, testing of the HLM using a rabbit model would mean testing under more strict and difficult conditions. In contrast to the rat model, 8–10 the ascending aorta and the right atrium can be cannulated after sternotomy exactly as done in the case of a newborn, and it is possible to sustain adequate flows. Also, comparability of hemolysis, 4,11 as well as inflammatory 5,12,13 parameters between rabbits and humans has been reported. Development of a Rabbit Animal Model for Miniaturized Heart–Lung Machines HEIKE SCHNOERING,* JUTTA ARENS,† SABINE M. DETERING,* TADEK STOPINSKI,‡ TARAH J. KUSCHEL,* RENE TOLBA,‡ ULRICH STEINSEIFER,† AND JAIME F. VAZQUEZ-JIMENEZ* Copyright © 2013 by the American Society for Artificial Internal Organs DOI: 10.1097/MAT.0b013e3182857990 From the *Department of Pediatric Cardiac Surgery, Medical Faculty, RWTH Aachen University, Germany; †Department of Cardiovascular Engineering, Institute of Applied Medical Engineering, Helmholtz Insti- tute, RWTH Aachen University, Germany; and ‡Institute for Laboratory Animal Science and Experimental Surgery, Medical Faculty, RWTH Aachen University, Germany. Submitted for consideration September 2012; accepted for publica- tion in revised form December 2012. Heike Schnoering and Jutta Arens contributed equally to the article. Disclosure: The authors have no conflicts of interest to report. Supported by Foerdergemeinschaft Deutsche Kinderherzzentren. Reprint Requests: Heike Schnoering, MD, Department of Pediatric Cardiac Surgery, University Hospital, RWTH Aachen University, Pau- welsstr. 30, 52057 Aachen, Germany. Email: hschnoering@ukaachen.de.