Wan Yixuan, Zhu Dongyong, He Bo, Guo Yong, Wang Lei, Dingda Duojie, Laji Angwen, Wang Chunhua, Zhang Yonghai, Gao Fabao
Department of Radiology, West China Hospital, Sichuan University, Chengdu, China.
Department of Radiology, Yushu People's Hospital, Qinghai, China.
Quant Imaging Med Surg. 2022 Jan;12(1):711-725. doi: 10.21037/qims-21-360.
Doxorubicin (DOX)-induced cardiotoxicity (DIC), a major clinical problem, has no effective preventive therapies. We hypothesized that left ventricular (LV) systolic function would be improved in a chronic hypobaric hypoxia environment at high altitude. The purpose of this study was to investigate whether cardiovascular magnetic resonance could reveal the cardioprotective effect of chronic hypobaric hypoxia on DIC.
In total, 60 rats were randomly assigned to 1 of 6 groups (n=10 per group): the P group (plain), PD group (plain + DOX), HH group (high altitude), HHD4 group (high altitude + DOX for 4 weeks), HHD8 group (high altitude + DOX for 8 weeks), and HHD12 group (high altitude + DOX for 12 weeks). The rats were transported to either Yushu (altitude: 4,250 m) or Chengdu (altitude: 500 m) where they underwent intraperitoneal injection of DOX (5 mg/kg/week for 3 weeks) or saline. Preclinical 7 T cardiovascular magnetic resonance was performed at weeks 4, 8, and 12. Tissue tracking was used to measure LV cardiac function and to analyze global and segmental strains. Subsequently, histological and oxidative stress tests were performed to evaluate the protective effect of a high-altitude environment on DIC.
The left ventricular ejection fraction (LVEF) and global and regional strains in the middle, apical, anterior, septal, inferior, and lateral segments (all P<0.05) were improved in the HHD4 group compared with the PD group. The global strain was significantly greater in absolute value in the HHD8 and HHD12 groups than in the HHD4 group (all P<0.05). Additionally, histological and enzyme-linked immunosorbent assay evaluations supported the results.
A chronic hypobaric and hypoxic environment at high altitude partially prevented cardiac dysfunction and increased global and regional strain in DIC rat models, thereby minimizing myocardial injury and fibrosis. In addition, by increasing the total duration of chronic hypobaric hypoxia, the global strain was further increased, which was likely due to reduced oxidative stress.
阿霉素（DOX）诱导的心脏毒性（DIC）是一个主要的临床问题，目前尚无有效的预防治疗方法。我们假设在高海拔慢性低压低氧环境中左心室（LV）收缩功能会得到改善。本研究的目的是调查心血管磁共振是否能揭示慢性低压低氧对DIC的心脏保护作用。
总共60只大鼠被随机分为6组中的1组（每组n = 10）：P组（平原组）、PD组（平原 + DOX组）、HH组（高海拔组）、HHD4组（高海拔 + DOX 4周组）、HHD8组（高海拔 + DOX 8周组）和HHD12组（高海拔 + DOX 12周组）。将大鼠转运至玉树（海拔：4250米）或成都（海拔：500米），在那里它们接受腹腔注射DOX（5毫克/千克/周，共3周）或生理盐水。在第4、8和12周进行临床前7T心血管磁共振检查。使用组织追踪测量左心室心脏功能并分析整体和节段应变。随后，进行组织学和氧化应激测试以评估高海拔环境对DIC的保护作用。
与PD组相比，HHD4组的左心室射血分数（LVEF）以及中间、心尖、前壁、间隔、下壁和侧壁节段的整体和区域应变均有所改善（所有P<0.05）。HHD8组和HHD12组的整体应变绝对值明显大于HHD4组（所有P<0.05）。此外，组织学和酶联免疫吸附测定评估支持了这些结果。
高海拔慢性低压低氧环境部分预防了DIC大鼠模型中的心脏功能障碍，并增加了整体和区域应变，从而使心肌损伤和纤维化最小化。此外，通过增加慢性低压低氧的总持续时间，整体应变进一步增加，这可能是由于氧化应激降低所致。
