Department of Pulmonary Medicine, Medical College of Wisconsin, Milwaukee, WI.
Department of Physiology, Medical College of Wisconsin Milwaukee, WI.
Health Phys. 2019 Apr;116(4):558-565. doi: 10.1097/HP.0000000000000919.
Total-body irradiation causes acute and delayed toxicity to hematopoietic, pulmonary, cardiac, gastrointestinal, renal, and other organ systems. Angiotensin-converting enzyme inhibitors mitigate many of the delayed injuries to these systems. The purpose of this study was to define echocardiographic features in rats at two times after irradiation, the first before lethal radiation pneumonitis (50 d) and the second after recovery from pneumonitis but before lethal radiation nephropathy (100 d), and to determine the actions of the angiotensin-converting enzyme inhibitor lisinopril. Four groups of female WAG/RijCmcr rats at 11-12 wk of age were studied: nonirradiated, nonirradiated plus lisinopril, 13-Gy partial-body irradiation sparing one hind leg (leg-out partial-body irradiation), and 13-Gy leg-out partial-body irradiation plus lisinopril. Lisinopril was started 7 d after radiation. Echocardiograms were obtained at 50 and 100 d, and cardiac histology was assessed after 100 d. Irradiation without lisinopril demonstrated echocardiographic transient pulmonary hypertension by 50 d which was largely resolved by 100 d in survivors. Irradiated rats given lisinopril showed no increase in pulmonary artery pressures at 50 d but exhibited left ventricular remodeling. By 100 d these rats showed some signs of pulmonary hypertension. Lisinopril alone had no impact on echocardiographic end points at either time point in nonirradiated rats. Mild increases in mast cells and fibrosis in the heart were observed after 100 d following 13-Gy leg-out partial-body irradiation. These data demonstrate irradiation-induced pulmonary hypertension which was reversed in survivors of pneumonitis. Lisinopril modified cardiovascular remodeling to enhance survival in this model from 41% to 86% (p = 0.0013).
全身照射会导致造血、肺、心脏、胃肠道、肾脏和其他器官系统的急性和迟发性毒性。血管紧张素转换酶抑制剂减轻了这些系统的许多迟发性损伤。本研究的目的是在照射后两个时间点定义大鼠的超声心动图特征，第一个时间点在致死性放射性肺炎之前（50d），第二个时间点在肺炎恢复后但在致死性放射性肾病之前（100d），并确定血管紧张素转换酶抑制剂赖诺普利的作用。研究了四个组别的雌性 WAG/RijCmcr 大鼠，年龄为 11-12 周：未照射、未照射加赖诺普利、13Gy 半身照射（保留一条后腿的半身照射）和 13Gy 保留一条后腿的半身照射加赖诺普利。赖诺普利在照射后 7 天开始使用。在 50 和 100d 时获取超声心动图，在 100d 时评估心脏组织学。未用赖诺普利照射的大鼠在 50d 时出现超声心动图一过性肺动脉高压，幸存者在 100d 时基本恢复。接受赖诺普利照射的大鼠在 50d 时肺动脉压没有升高，但表现出左心室重构。到 100d 时，这些大鼠出现了一些肺动脉高压的迹象。赖诺普利单独使用对未照射大鼠在两个时间点的超声心动图终点均无影响。在 13Gy 保留一条后腿的半身照射后 100d 时，心脏中的肥大细胞和纤维化有轻度增加。这些数据表明，照射引起的肺动脉高压在肺炎幸存者中得到了逆转。赖诺普利改变了心血管重构，使该模型的存活率从 41%提高到 86%（p=0.0013）。
