Haque Omar, Pendexter Casie A, Cronin Stephanie E J, Raigani Siavash, de Vries Reiner J, Yeh Heidi, Markmann James F, Uygun Korkut
Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Technology (Singap World Sci). 2020 Mar-Jun;8(1-2):27-36. doi: 10.1142/s2339547820500028. Epub 2020 Nov 5.
Ex-vivo liver perfusion (EVLP) is an ideal platform to study liver disease, therapeutic interventions, and pharmacokinetic properties of drugs without any patient risk. Rat livers are an ideal model for EVLP due to less organ quality variability, ease of hepatectomy, well-defined molecular pathways, and relatively low costs compared to large animal or human perfusions. However, the major limitation with rat liver normothermic machine perfusion (NMP) is maintaining physiologic liver function on an ex-vivo machine perfusion system. To address this need, our research demonstrates 24-hour EVLP in rats under normothermic conditions. Early (6 hour) perfusate transaminase levels and oxygen consumption of the liver graft are shown to be good markers of perfusion success and correlate with viable 24-hour post-perfusion histology. Finally, we address overcoming challenges in long-term rat liver perfusions such as rising intrahepatic pressures and contamination, and offer future directions necessary to build upon our work.
体外肝脏灌注(EVLP)是一个研究肝脏疾病、治疗干预措施以及药物药代动力学特性的理想平台,且不存在任何患者风险。大鼠肝脏是EVLP的理想模型,因为与大型动物或人体灌注相比,其器官质量变异性较小、肝切除术操作简便、分子途径明确且成本相对较低。然而,大鼠肝脏常温机器灌注(NMP)的主要局限性在于如何在体外机器灌注系统上维持肝脏的生理功能。为满足这一需求,我们的研究展示了在常温条件下对大鼠进行24小时的EVLP。早期(6小时)灌注液转氨酶水平和肝移植的氧消耗被证明是灌注成功的良好指标,并且与灌注后24小时的存活组织学相关。最后,我们探讨了如何克服长期大鼠肝脏灌注中的挑战,如肝内压力升高和污染问题,并为在我们工作基础上进一步开展研究提供了未来方向。