Chung Wen Yuan, Eltweri Amar M, Isherwood John, Haqq Jonathan, Ong Seok Ling, Gravante Gianpiero, Lloyd David M, Metcalfe Matthew S, Dennison Ashley R
Department of Hepatobiliary and Pancreatic Surgery, University Hospitals of Leicester.
J Vis Exp. 2013 Dec 18(82):e50567. doi: 10.3791/50567.
The use of ex vivo perfused models can mimic the physiological conditions of the liver for short periods, but to maintain normal homeostasis for an extended perfusion period is challenging. We have added the kidney to our previous ex vivo perfused liver experiment model to reproduce a more accurate physiological state for prolonged experiments without using live animals. Five intact livers and kidneys were retrieved post-mortem from sacrificed pigs on different days and perfused for a minimum of 6 hr. Hourly arterial blood gases were obtained to analyze pH, lactate, glucose and renal parameters. The primary endpoint was to investigate the effect of adding one kidney to the model on the acid base balance, glucose, and electrolyte levels. The result of this liver-kidney experiment was compared to the results of five previous liver only perfusion models. In summary, with the addition of one kidney to the ex vivo liver circuit, hyperglycemia and metabolic acidosis were improved. In addition this model reproduces the physiological and metabolic responses of the liver sufficiently accurately to obviate the need for the use of live animals. The ex vivo liver-kidney perfusion model can be used as an alternative method in organ specific studies. It provides a disconnection from numerous systemic influences and allows specific and accurate adjustments of arterial and venous pressures and flow.
使用体外灌注模型可以在短时间内模拟肝脏的生理状况，但要在延长的灌注期内维持正常的内环境稳定具有挑战性。我们在之前的体外灌注肝脏实验模型中加入了肾脏，以便在不使用活体动物的情况下，为长时间实验重现更准确的生理状态。从不同日期处死后的猪身上取出五个完整的肝脏和肾脏，进行至少6小时的灌注。每小时采集动脉血气以分析pH值、乳酸、葡萄糖和肾脏参数。主要终点是研究向模型中添加一个肾脏对酸碱平衡、葡萄糖和电解质水平的影响。将该肝肾实验的结果与之前五个仅肝脏灌注模型的结果进行比较。总之，在体外肝脏循环中添加一个肾脏后，高血糖和代谢性酸中毒得到改善。此外，该模型能够足够准确地重现肝脏的生理和代谢反应，从而无需使用活体动物。体外肝肾灌注模型可作为器官特异性研究中的一种替代方法。它与众多全身影响因素相分离，并允许对动脉和静脉压力及流量进行特定且准确的调整。
