对一家机构的九项研究进行汇总分析,以评估大鼠模型全心辐照的影响。

IF 2.1 4区 医学 Q2 BIOLOGY International Journal of Radiation Biology Pub Date : 2024-01-01 Epub Date: 2023-08-21 DOI:10.1080/09553002.2023.2242937
Reid D Landes, Chenghui Li, Vijayalakshmi Sridharan, Carmen Bergom, Marjan Boerma
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引用次数: 0

摘要

目的:多年来,局部心脏辐照动物模型为人类了解辐射诱发心脏病的机制和治疗方法提供了启示。然而,目前还不完全清楚全心辐照后最常见的辐射损伤表现是什么,以及某些生物因素是否会影响实验结果。结合一个实验室对全心照射大鼠模型进行的 9 项同类研究,我们试图找出影响心脏结果的实验和/或生物学因素。我们评估了在分析生物参数时将(1)心率和(2)体重作为协变量的有用性,(3)我们确定了哪些超声心动图、组织学和免疫组化参数最易受辐射影响。最后,(4) 作为一个教育实例,我们仅使用 9 项大鼠研究的汇总估计值作为背景,说明了评估辐射改良剂时常用的研究设计的假设样本量计算方法。这些结果可能有助于研究人员设计和分析全心辐照的临床前研究:我们使用了来自我们实验室的 9 项大鼠研究数据、2008-2017 年在其他地方发表的 8 项研究数据和一项未发表的研究数据。这些研究收集了超声心动图、组织学和免疫组化参数。利用混合效应协方差分析模型,我们估算了心率和体重的斜率,并估算了辐射对每个参数的影响:结果:体重与大多数超声心动图参数有关,心率对与左心室直径有关的超声心动图参数有影响。有证据表明,心率和体重与某些参数的关系取决于大鼠是否受到辐射。在与左心室直径相关的收缩期超声心动图参数、射血分数和分数缩短、心房壁厚度以及心脏毛细血管密度、胶原沉积和肥大细胞浸润的组织学测量中,都发现了辐射影响:结论:在分析超声心动图参数时考虑体重和心率,可减少辐射效应估计值的变化。一些超声心动图和组织学参数特别容易受到全心辐照的影响,与假辐照相比,这些参数显示出强大的效应。最后,我们提供了一个样本大小计算的示例方法,这将有助于在研究辐射改变因子的实验中进行严格的研究设计和可重复性。
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A pooled analysis of nine studies in one institution to assess effects of whole heart irradiation in rat models.

Purpose: Over the years, animal models of local heart irradiation have provided insight into mechanisms of and treatments for radiation-induced heart disease in human populations. However, it is not completely clear which manifestations of radiation injury are most commonly seen after whole heart irradiation, and whether certain biological factors impact experimental results. Combining 9 homogeneous studies in rat models of whole heart irradiation from one laboratory, we sought to identify experimental and/or biological factors that impact heart outcomes. We evaluated the usefulness of including (1) heart rate and (2) bodyweight as covariates when analyzing biological parameters, and (3) we determined which echocardiography, histological, and immunohistochemistry parameters are most susceptible to radiation effects. Finally, (4) as an educational example, we illustrate a hypothetical sample size calculation for a study design commonly used in evaluating radiation modifiers, using the pooled estimates from the 9 rat studies only for context. The results may assist investigators in the design and analyses of pre-clinical studies of whole heart irradiation.

Materials and methods: We made use of data from 9 rat studies from our labs, 8 published elsewhere in 2008-2017, and one unpublished study. Echocardiography, histological, and immunohistochemical parameters were collected from these studies. Using mixed effects analysis of covariance models, we estimated slopes for heart rate and bodyweight and estimated the radiation effect on each of the parameters.

Results: Bodyweight was related to most echocardiography parameters, and heart rate had an effect on echocardiography parameters related to the diameter of the left ventricle. For some parameters, there was evidence that heart rate and bodyweight relationships with the parameter depended on whether the rats were irradiated. Radiation effects were found in systolic measures of echocardiography parameters related to the diameter of the left ventricle, with ejection fraction and fractional shortening, with atrial wall thickness, and with histological measures of capillary density, collagen deposition, and mast cells infiltration in the heart.

Conclusion: Accounting for bodyweight, as well as heart rate, in analyses of echocardiography parameters should reduce variability in estimated radiation effects. Several echocardiography and histological parameters were particularly susceptible to whole heart irradiation, showing robust effects compared to sham-irradiation. Lastly, we provide an example approach for a sample size calculation that will contribute to a rigorous study design and reproducibility in experiments studying radiation modifiers.

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来源期刊
CiteScore
5.00
自引率
11.50%
发文量
142
审稿时长
3 months
期刊介绍: The International Journal of Radiation Biology publishes original papers, reviews, current topic articles, technical notes/reports, and meeting reports on the effects of ionizing, UV and visible radiation, accelerated particles, electromagnetic fields, ultrasound, heat and related modalities. The focus is on the biological effects of such radiations: from radiation chemistry to the spectrum of responses of living organisms and underlying mechanisms, including genetic abnormalities, repair phenomena, cell death, dose modifying agents and tissue responses. Application of basic studies to medical uses of radiation extends the coverage to practical problems such as physical and chemical adjuvants which improve the effectiveness of radiation in cancer therapy. Assessment of the hazards of low doses of radiation is also considered.
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