Table_1_Comparison of Experimental Rat Models in Donation After Circulatory Death (DCD): in-situ vs. ex-situ Ischemia.DOCX

Introduction: Donation after circulatory death (DCD) could substantially improve donor heart availability. However, warm ischemia prior to procurement is of particular concern for cardiac graft quality. We describe a rat model of DCD with in-situ ischemia in order to characterize the physiologic changes during the withdrawal period before graft procurement, to determine effects of cardioplegic graft storage, and to evaluate the post-ischemic cardiac recovery in comparison with an established ex-situ ischemia model.
Methods: Following general anesthesia in male, Wistar rats (404 ± 24 g, n = 25), withdrawal of life-sustaining therapy was simulated by diaphragm transection. Hearts underwent no ischemia or 27 min in-situ ischemia and were explanted. Ex situ, hearts were subjected to a cardioplegic flush and 15 min cold storage or not, and 60 min reperfusion. Cardiac recovery was determined and compared to published results of an entirely ex-situ ischemia model (n = 18).
Results: In donors, hearts were subjected to hypoxia and hemodynamic changes, as well as increased levels of circulating catecholamines and free fatty acids prior to circulatory arrest. Post-ischemic contractile recovery was significantly lower in the in-situ ischemia model compared to the ex-situ model, and the addition of cardioplegic storage improved developed pressure-heart rate product, but not cardiac output.
Conclusion: The in-situ model provides insight into conditions to which the heart is exposed before procurement. Compared to an entirely ex-situ ischemia model, hearts of the in-situ model demonstrated a lower post-ischemic functional recovery, potentially due to systemic changes prior to ischemia, which are partially abrogated by cardioplegic graft storage.

引言：循环死亡后捐献（Donation after circulatory death, DCD）可显著提升供心来源。然而，获取术前的热缺血问题对心脏移植物质量存在显著不良影响。本研究构建了一种带原位缺血的DCD大鼠模型，旨在明确移植物获取前撤除阶段的生理变化，评估心脏停搏液移植物保存的效果，并与已建立的离体缺血模型对比，评价缺血后心脏功能恢复情况。
方法：选取体重为404±24g的雄性Wistar大鼠共25只，予以全身麻醉后，通过横断膈肌模拟撤除生命支持治疗。将大鼠心脏分为两组：无缺血组及27分钟原位缺血组，随后完成心脏摘取。离体阶段，对心脏行心脏停搏液灌注并予以15分钟冷保存（或不保存），随后进行60分钟再灌注。检测心脏功能恢复情况，并与已发表的完全离体缺血模型（n=18）的结果进行对比。
结果：在循环骤停前，供心已暴露于缺氧环境并出现血流动力学改变，同时循环中儿茶酚胺与游离脂肪酸水平升高。与离体缺血模型相比，原位缺血模型的缺血后收缩功能恢复显著降低；采用心脏停搏液保存可提升压力-心率乘积，但无法改善心输出量。
结论：本研究所构建的原位缺血模型可阐明供心在获取前所处的病理生理状态。与完全离体缺血模型相比，原位缺血模型的心脏缺血后功能恢复更差，这可能与缺血前的全身系统性改变有关，而心脏停搏液移植物保存可部分逆转该不良影响。