化疗引起的自噬功能障碍涉及由抗癌药物引起的心脏毒性。啮齿动物模型的不完善翻译和缺乏毒性的体外模型限制了对自噬通量失调的调查，阻止了基于自噬调控的新型心脏保护策略的设计。从翻译模型中开发成人心脏组织培养技术将改善心脏毒性的研究。我们旨在优化一种犬心脏切片培养系统，以探索癌症治疗对完整心脏组织的影响，创建一个在培养中保留自噬并易于进行自噬调节的可翻译模型。犬心脏组织切片（350μm）是从离体犬心左室游离壁中收集的，这些犬来自于塔夫茨大学福斯特小动物医院，不患心血管疾病（n = 7）。采用MTT试验和TUNEL染色量化细胞存活和细胞凋亡。心脏切片经过多柔比星和自噬激活剂（雷帕霉素）或抑制剂（氯喹）的挑战。自噬通量组分（LC3，p62）通过Western blot定量。心脏切片在培养中保持高细胞存活率> 7天，自噬标记的基础水平保持不变。多柔比星处理导致自噬通量紊乱和细胞死亡，而雷帕霉素联合治疗恢复了正常的自噬通量并维持了细胞存活。我们开发了一种成人犬心脏切片培养系统，适用于研究自噬通量效应，并可用于药物毒性评估。版权所有：©2023 Boukhalfa等人。本文是根据知识共享许可证发布的开放获取文章，只要原作者和出处被认可，任何人都可以在任何媒介上进行无限制的使用、分发和复制。

Chemotherapy-induced impairment of autophagy is implicated in cardiac toxicity induced by anti-cancer drugs. Imperfect translation from rodent models and lack of in vitro models of toxicity has limited investigation of autophagic flux dysregulation, preventing design of novel cardioprotective strategies based on autophagy control. Development of an adult heart tissue culture technique from a translational model will improve investigation of cardiac toxicity. We aimed to optimize a canine cardiac slice culture system for exploration of cancer therapy impact on intact cardiac tissue, creating a translatable model that maintains autophagy in culture and is amenable to autophagy modulation. Canine cardiac tissue slices (350 μm) were generated from left ventricular free wall collected from euthanized client-owned dogs (n = 7) free of cardiovascular disease at the Foster Hospital for Small Animals at Tufts University. Cell viability and apoptosis were quantified with MTT assay and TUNEL staining. Cardiac slices were challenged with doxorubicin and an autophagy activator (rapamycin) or inhibitor (chloroquine). Autophagic flux components (LC3, p62) were quantified by western blot. Cardiac slices retained high cell viability for >7 days in culture and basal levels of autophagic markers remained unchanged. Doxorubicin treatment resulted in perturbation of the autophagic flux and cell death, while rapamycin co-treatment restored normal autophagic flux and maintained cell survival. We developed an adult canine cardiac slice culture system appropriate for studying the effects of autophagic flux that may be applicable to drug toxicity evaluations.Copyright: © 2023 Boukhalfa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.