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Background Cardiopulmonary bypass (CPB) has been shown to be associated with systemic inflammatory response leading to postoperative organ dysfunction.Elucidating the underlying mechanisms and developing protective strategies for the pathophysiological consequences of CPB have been hampered due to the absence of a satisfactory recovery animal model.The purpose of this study was to establish a novel,minimally invasive rat model of normothermic CPB model without blood priming.Methods Twenty adult male Sprague-Dawley rats weighing 450-560 g were randomly divided into CPB group (n=10) and control group (n=10).All rats were anaesthetized and mechanically ventilated.The carotid artery and jugular vein were cannulated.The blood was drained from the right atrium via the right jugular and further transferred by a miniaturized roller pump to a hollow fiber oxygenator and back to the rat via the left carotid artery.The volume of the priming solution,composed of 6％ HES130/0.4 and 125 IU heparin,was less than 12 ml.The surface of the hollow fiber oxygenator was 0.075 m2.CPB was conducted for 60 minutes at a flow rat of 100-120 ml· kg-1· min-1 in CPB group.Oxygen flow/perfusion flow was 0.8 to 1.0,and the mean arterial pressure remained 60-80 mmHg.Results All CPB processes were successfully achieved.Blood gas analysis and hemodynamic parameters of each time point were in accordance with normal ranges.The vital signs of all rats were stable.Conclusions The establishment of CPB without blood priming in rats can be achieved successfully.The nontransthoracic model should facilitate the investigation of pathophysiological processes concing CPB-related multiple organ dysfunction and possible protective interventions.This novel,recovery,and reproducible minimally invasive CPB model may open the field for various studies on the pathophysiological process of CPB and systemic ischemia-reperfusion injury in vivo.