Characterization of an In Vitro Model of Extracorporeal Circulation: A New Tool for Investigating the Pathophysiological and Therapeutic Strategies in Whole Blood

A clinically relevant extracorporeal circulation model would be a valuable tool for investigating the pathophysiological and therapeutic strategies in whole blood. Previous models were limited by issues such as large circuit area; the inability to achieve full bypass; and donor blood requirement for prime. Here we established a miniature circuit to overcome these limitations consisting of a peristaltic pump, a test cell, a blood reservoir, and an oxygenator connected via polyvinylchloride and porous platinum silicon tubing. A heparinised (10？U/mL) saline solution at pH 7.4 was used to prime the circuit and the test cell was incubated in a water bath to maintain the temperature at 37°C. Blood flow through the circuit was at 5？mL/minute rate. Haemodynamics, haemoglobin concentration, and blood gases were analysed and the circuit performance was optimised according to the levels of haemolysis at three circulation time intervals: before the start, 30 minutes, and 60 minutes. No statistically significant haemodynamics and blood gases differences were observed. We have established a miniature extracorporeal circuit consisting of asanguineous prime for CPB model that maintains clinically acceptable results regarding hemodynamic parameters, blood gases, and haemodilution. This surrogate model would be important for further use in clinically pertinent research. 1. Overview Cardiopulmonary bypass (CPB) is one of the major technological advances in medicine that allows operating in controlled conditions. Since its introduction in the 1950s, there has been a rapid growth in the number of cardiac surgical operations performed throughout the world. Though the mortality for many of these operations has fallen, CPB is still associated with a significant morbidity [1]. CPB is known to activate inflammatory processes that may result in respiratory failure, bleeding disorders, neurologic dysfunction, and transient renal impairment [2]. Furthermore, CPB increases the production of inflammatory cytokines [1] and that cytokines are known to depress cardiac efficiency by mechanisms that are still unclear [3]. Increasing evidence also supports that oxidative stress occurs before the occurrence of proinflammatory factors during cardiopulmonary bypass [4]. This relationship may suggest a direct effect of free radicals on the inflammatory reaction induced by CPB; however, the underlying mechanism of these effects in blood remains elusive. There is a need, therefore, for a preclinical bypass model that could be used to study all aspects of extracorporeal circulating blood