van der Veen Sonja J, Ghobadi Ghazaleh, de Boer Rudolf A, Faber Hette, Cannon Megan V, Nagle Peter W, Brandenburg Sytze, Langendijk Johannes A, van Luijk Peter, Coppes Robert P
Department of Cell Biology, University Medical Center Groningen, University of Groningen, The Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, The Netherlands.
Department of Experimental Cardiology, University Medical Center Groningen, University of Groningen, The Netherlands.
Radiother Oncol. 2015 Jan;114(1):96-103. doi: 10.1016/j.radonc.2014.11.017. Epub 2014 Nov 25.
In thoracic irradiation, the maximum radiation dose is restricted by the risk of radiation-induced cardiopulmonary damage and dysfunction limiting tumor control. We showed that radiation-induced sub-clinical cardiac damage and lung damage in rats mutually interact and that combined irradiation intensifies cardiopulmonary toxicity. Unfortunately, current clinical practice does not include preventative measures to attenuate radiation-induced lung or cardiac toxicity. Here, we investigate the effects of the ACE inhibitor captopril on radiation-induced cardiopulmonary damage.
After local irradiation of rat heart and/or lungs captopril was administered orally. Cardiopulmonary performance was assessed using biweekly breathing rate measurements. At 8 weeks post-irradiation, cardiac hemodynamics were measured, CT scans and histopathology were analyzed.
Captopril significantly improved breathing rate and cardiopulmonary density/structure, but only when the heart was included in the radiation field. Consistently, captopril reduced radiation-induced pleural and pericardial effusion and cardiac fibrosis, resulting in an improved left ventricular end-diastolic pressure only in the heart-irradiated groups.
Captopril improves cardiopulmonary morphology and function by reducing acute cardiac damage, a risk factor in the development of radiation-induced cardiopulmonary toxicity. ACE inhibition should be evaluated as a strategy to reduce cardiopulmonary complications induced by radiotherapy to the thoracic area.
在胸部放疗中，最大辐射剂量受到辐射诱发的心肺损伤及功能障碍风险的限制，这会影响肿瘤控制。我们发现，辐射诱发的大鼠亚临床心脏损伤和肺损伤相互作用，联合照射会加剧心肺毒性。遗憾的是，目前的临床实践中并未包含减轻辐射诱发的肺或心脏毒性的预防措施。在此，我们研究血管紧张素转换酶（ACE）抑制剂卡托普利对辐射诱发的心肺损伤的影响。
对大鼠心脏和/或肺部进行局部照射后，口服卡托普利。每两周测量呼吸频率以评估心肺功能。在照射后8周，测量心脏血流动力学，分析CT扫描结果和组织病理学。
卡托普利显著改善了呼吸频率以及心肺密度/结构，但仅在心脏被纳入辐射野时如此。一致地，卡托普利减少了辐射诱发的胸腔和心包积液以及心脏纤维化，仅在心脏受照射的组中使左心室舒张末期压力得到改善。
卡托普利通过减轻急性心脏损伤来改善心肺形态和功能，急性心脏损伤是辐射诱发的心肺毒性发展过程中的一个风险因素。应评估ACE抑制作为一种减少胸部放疗诱发的心肺并发症的策略。
