Electrophysiological and Pathological Impact of Medium-Dose External Carbon Ion and Proton Beam Radiation on the Left Ventricle in an Animal Model.

Electrophysiological and Pathological Impact of Medium-Dose External Carbon Ion and Proton Beam Radiation on the Left Ventricle in an Animal Model.
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DOI:
10.1161/jaha.120.019687
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发表时间:
2021-04-06
影响因子:
5.4
通讯作者:
Hirata KI
Hirata KI
中科院分区:
医学2区
文献类型:
--
作者:
Takami M;Hara T;Okimoto T;Suga M;Fukuzawa K;Kiuchi K;Suehiro H;Akita T;Takemoto M;Nakamura T;Sakai J;Yatomi A;Nakasone K;Sonoda Y;Yamamoto K;Takahara H;Hirata KI

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最近对难治性室性快速性心律失常患者进行了中等剂量(25灰色)的X射线放射治疗。与X射线不同,碳离子和质子束辐射可以将它们的大部分能量传递到目标组织。本研究观察了中等剂量碳离子和质子束照射对大鼠左心室(LV)电生理和病理的影响。对32只兔进行了全心外照射。未照射组(对照组)共9只。在3个月或6个月的随访中,动物接受开胸电生理检查,并安乐死进行组织学分析。无急性死亡病例发生。未见明显的左心室功能障碍。体表心电图显示放射组的P波和QRS波电压显著降低。电生理检查显示,照射组各部位局部传导时间明显长于对照组,局部双极电压明显低于对照组。组织学上可见左室心肌细胞凋亡、纤维化改变和连接蛋白43蛋白表达减少。这些变化在3个月时明显,并在辐射后6个月持续。冠状动脉和食道未见组织学改变,但可见部分放射性肺炎。中剂量碳离子和质子束照射全心可引起明显的电生理紊乱和心肌病理改变。致心律失常底物的辐射将改变电状态,并潜在地诱导抗心律失常的作用。
Medium‐dose (25 gray) x‐ray radiation therapy has recently been performed on patients with refractory ventricular tachyarrhythmias. Unlike x‐ray, carbon ion and proton beam radiation can deliver most of their energy to the target tissues. This study investigated the electrophysiological and pathological changes caused by medium‐dose carbon ion and proton beam radiation in the left ventricle (LV). External beam radiation in the whole LV was performed in 32 rabbits. A total of 9 rabbits were not irradiated (control). At the 3‐month or 6‐month follow‐up, the animals underwent an open‐chest electrophysiological study and were euthanized for histological analyses. No acute death occurred. Significant LV dysfunction was not seen. The surface ECG revealed a significant reduction in the P and QRS wave voltages in the radiation groups. The electrophysiological study showed that the local conduction times in each LV site were significantly longer and that the local LV bipolar voltages were significantly lower in the radiation groups than in the control rabbits. Histologically, apoptosis, fibrotic changes, and a decrease in the expression of the connexin 43 protein were seen in the LV myocardium. These changes were obvious at 3 months, and the effects were sustained 6 months after radiation. No histological changes were seen in the coronary artery and esophagus, but partial radiation pneumonitis was observed. Medium‐dose carbon ion and proton beam radiation in the whole LV resulted in a significant electrophysiological disturbance and pathological changes in the myocardium. Radiation of the arrhythmogenic substrate would modify the electrical status and potentially induce the antiarrhythmic effect.