猪DCD模型撤除呼吸机后肝脏生理和病理变化

Physiological and pathological changes after ventilation withdrawal in a porcine DCD model

目的心脏死亡后器官捐献(donation after circulatory death,DCD)被认为是缓解器官资源短缺的一种方法,器官短缺增加了等待器官移植患者的病死率。在停止生命维持治疗后,供体器官的一系列病理改变可能会影响移植结果。本研究旨在探讨猪心脏死亡后供肝缺血的病理生理机制。方法本试验选用巴马小型猪16只(8只雌猪,8只雄猪,体重为45~55 kg)。采用窒息法建立猪DCD模型。记录撤除呼吸机后实验动物的血流动力学变化,评价供体肝脏热缺血时间(warm ischemia time,WIT)的病理变化。结果实验动物的平均存活时间为17.94 min。撤除呼吸机之后,收缩压和舒张压均在前5 min内升高,之后持续下降。中心静脉压在开始前10 min内升高,之后持续下降同时,PaO_(2)在前10 min内急剧降至零,PaCO_(2)逐渐升至100 mmHg(1 mmHg=0.133 kPa)的稳定水平。组织学评价显示,肝组织损伤程度会随着WIT的延长逐渐加重。亚细胞结构观察结果显示,肝细胞在30 min内的缺血损伤是可逆的,但超过30 min肝细胞则会出现不可逆的变性。结论通过建立猪窒息模型模拟临床环境下的供者心脏死亡;猪模型供肝损伤程度与WIT呈正相关。通过窒息方式建立猪心脏死亡模型的结果显示,30 min的WIT是获取理想质量器官的限制因素。

Objective Donation after circulatory death(DCD)is considered a way to alleviate organ shortage,which increases the mortality of patients waiting for organ transplantation.After the withdrawal of life-sustained therapy,a series of pathological changes in the donor organ may impact graft outcome.This study is to investigate the ischemic pathophysiology of donor's liver after circulatory death in porcine model.Methods Sixteen Bama minipigs(8 females,8 males,45~55 kg)were used in this study.A porcine DCD model was created by the asphyxia method.Hemodynamic changes after ventilation withdrawal were recorded,and pathological changes in the donor's liver during warm ischemia time(WIT)were assessed.Results The average survival duration was 17.94 min.Systolic and diastolic blood pressures increased in the first 5 minutes,then decreased continuously afterward.Central venous pressure increased in the first 10 minutes and then decreased continuously afterward.Simultaneously,PaO_(2) dropped sharply to 0 in the first 10 minutes,and PaCO_(2) gradually rose to a stable level of 100 mmHg(1 mmHg=0.133 kPa).The histological assessment indicated that warm ischemic injury on liver tissue aggravated gradually as time progressed.In subcellular observation,ischemic injury within 30 minutes of WIT seemed to be reversible,but longer WIT caused irreversible degeneration.Conclusion Through the porcine ventilation withdrawal model,the circulatory death in the clinical setting could be simulated.Damage to graft tissues was positively correlated with WIT.30 minute WIT after confirmation of circulatory death with the asphyxia method appeared to be a limit for a desirable organ quality.