Banister Heather R, Hammond Stephen T, Parr Shannon K, Sutterfield Shelbi L, Turpin Vanessa-Rose G, Treinen Scott, Bell Martin J, Ade Carl J
Clinical Integrative Physiology Laboratory, Department of Kinesiology, College of Health and Human Sciences, Kansas State University, Manhattan, KS, 66506, USA.
Central Kansas Cancer Center, Manhattan, KS, USA.
Cardiooncology. 2021 May 13;7(1):18. doi: 10.1186/s40959-021-00104-z.
Cancer patients with a history of radiotherapy are at an increased risk of ischemic heart disease. Preclinical animal studies demonstrate markedly impaired acetylcholine (ACh)-mediated endothelium-dependent vasorelaxation within days to weeks post-irradiation, however, whether microvascular function is affected in the intact human circulation during cancer radiation therapy has yet to be determined.
Using laser-Doppler flowmetry, microvascular endothelium-dependent and independent responses were evaluated through iontophoresis of acetylcholine (ACh) (part 1, n = 7) and sodium nitroprusside (SNP) (part 2, n = 8), respectively, in women currently receiving unilateral chest adjuvant radiation therapy for breast cancer. Measurements were performed at the site of radiation treatment and at a contralateral control, non-radiated site. Cutaneous vascular conductance (CVC) was calculated by normalizing for mean arterial pressure.
In part 1, patients received an average radiation dose of 2104 ± 236 cGy. A significantly lower peak ACh-mediated endothelium-dependent vasodilation was observed within the radiated microvasculature when compared to non-radiated (radiated: 532 ± 167%, non-radiated 1029 ± 263%; P = 0.02). In part 2, the average radiation dose received was 2251 ± 196 cGy. Iontophoresis of SNP elicited a similar peak endothelium-independent vasodilator response in radiated and non-radiated tissue (radiated: 179 ± 58%, non-radiated: 310 ± 158; P = 0.2). The time to 50% of the peak response for ACh and SNP was similar between radiated and non-radiated microvasculature (P < 0.05). These data provide evidence of early endothelium-dependent microvascular dysfunction in cancer patients currently receiving chest radiation and provide the scientific premise for future work evaluating coronary endothelial function and vasomotor reactivity using more detailed and invasive procedures.
有放疗史的癌症患者患缺血性心脏病的风险增加。临床前动物研究表明，在照射后数天至数周内，乙酰胆碱（ACh）介导的内皮依赖性血管舒张功能明显受损，然而，癌症放射治疗期间完整人体循环中的微血管功能是否受到影响尚未确定。
使用激光多普勒血流仪，分别通过乙酰胆碱（ACh）离子电渗疗法（第1部分，n = 7）和硝普钠（SNP）离子电渗疗法（第2部分，n = 8）评估目前正在接受单侧胸部辅助放疗的乳腺癌女性患者的微血管内皮依赖性和非依赖性反应。在放射治疗部位和对侧对照非放射部位进行测量。通过对平均动脉压进行归一化计算皮肤血管传导率（CVC）。
在第1部分中，患者接受的平均辐射剂量为2104±236 cGy。与未辐射的微血管相比，辐射的微血管内观察到ACh介导的内皮依赖性血管舒张峰值明显降低（辐射组：532±167%，未辐射组：1029±263%；P = 0.02）。在第2部分中，接受的平均辐射剂量为2251±196 cGy。SNP离子电渗疗法在辐射和未辐射组织中引起类似的内皮非依赖性血管舒张峰值反应（辐射组：179±58%，未辐射组：3±158；P = 0.2）。辐射和未辐射的微血管之间，ACh和SNP达到峰值反应50%的时间相似（P < 0.05）。这些数据证明了目前正在接受胸部放疗的癌症患者早期存在内皮依赖性微血管功能障碍，并为未来使用更详细和侵入性程序评估冠状动脉内皮功能和血管舒缩反应性的研究提供了科学依据。
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