Department of Radiology, University of Wisconsin, Madison, Wisconsin.
Department of Medicine, University of Wisconsin, Madison, Wisconsin.
J Vasc Interv Radiol. 2023 Mar;34(3):386-394.e2. doi: 10.1016/j.jvir.2022.11.034. Epub 2022 Dec 9.
To determine the risk of mechanical vessel wall damage resulting in hemorrhage during and after hepatic and renal histotripsy in an anticoagulated in vivo porcine model.
Non-tumor-bearing pigs (n = 8; mean weight, 52.5 kg) were anticoagulated with warfarin (initial dose, 0.08 mg/kg) to a target prothrombin time (PT) of 30%-50% above baseline. A total of 15 histotripsy procedures were performed (kidney: n = 8, 2.0-cm sphere; liver: n = 7, 2.5-cm sphere). Treatments were immediately followed by computed tomography (CT) imaging. Animals were observed for 7 days while continuing anticoagulation, followed by repeat CT and necropsy.
All animals survived to complete the entire protocol with no signs of disability or distress. Three animals had hematuria (pink urine without clots). Baseline PT values (mean, 16.0 seconds) were elevated to 22.0 seconds (37.5% above baseline, P = .003) on the day of treatment and to 28.8 seconds (77.8% above baseline, P < .001) on the day of necropsy. At the time of treatment, 5 of 8 (63%) animals were at a therapeutic anticoagulation level, and all 8 animals (100%) reached therapeutic levels by the time of necropsy. There were no cases of intraparenchymal, peritoneal, or retroperitoneal hemorrhage associated with any treatments despite 5 of 7 (71%) liver and all 8 (100%) kidney treatments extending to the organ surface.
Liver and kidney histotripsy seems safe with no elevated bleeding risk in this anticoagulated animal model, supporting the possibility of histotripsy treatments in patients on anticoagulation.
在抗凝的活体猪模型中，确定肝、肾组织粉碎术期间和之后机械性血管壁损伤导致出血的风险。
非肿瘤猪（n=8；平均体重 52.5kg）接受华法林抗凝（初始剂量 0.08mg/kg），使凝血酶原时间（PT）延长至基线水平的 30%-50%。共进行 15 次组织粉碎术（肾：n=8，2.0cm 球；肝：n=7，2.5cm 球）。治疗后立即进行计算机断层扫描（CT）成像。动物继续抗凝 7 天，然后进行重复 CT 和尸检。
所有动物均完成了整个方案，没有残疾或不适的迹象。3 只动物出现血尿（无凝块的粉红色尿液）。基线 PT 值（平均值 16.0 秒）在治疗当天升高至 22.0 秒（比基线高 37.5%，P=0.003），在尸检当天升高至 28.8 秒（比基线高 77.8%，P<0.001）。治疗时，5/8（63%）的动物处于治疗性抗凝水平，所有 8 只动物（100%）在尸检时达到治疗水平。尽管 7/8（88%）的肝脏和 8/8（100%）的肾脏治疗都延伸到器官表面，但没有一例与任何治疗相关的实质内、腹膜或腹膜后出血。
在这种抗凝动物模型中，肝、肾组织粉碎术似乎是安全的，没有增加出血风险，这支持了在抗凝患者中进行组织粉碎术治疗的可能性。
