EARLY RENAL MEDULLARY HYPOXIC INJURY FROM RADIOCONTRAST AND INDOMETHACIN

EARLY RENAL MEDULLARY HYPOXIC INJURY FROM RADIOCONTRAST AND INDOMETHACIN
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DOI:
10.1038/ki.1991.255
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发表时间:
1991-10-01
影响因子:
19.6
通讯作者:
ROSEN, S
ROSEN, S
中科院分区:
医学1区
文献类型:
--
作者:
HEYMAN, SN;BREZIS, M;ROSEN, S

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我们评估了麻醉的Sprague-Dawley大鼠给予吲哚美辛和碘酞酸盐后前90分钟内皮质和外髓氧分压的急性变化以及肾功能和形态学的改变。发现两种药物均产生明显和持久的外髓缺氧,平均值分别为12 +/- 4和9 +/- 2 mm Hg(平均值+/- SE)。同时给予去盐的单侧肾切除大鼠,它们产生了选择性地定位于外髓质的早期缺氧损伤。该病变从15分钟时的3 +/- 1%髓质厚升支(mTAL)进展至24小时时的22 +/- 7%。在15分钟时观察到浓缩的“暗”细胞,可能代表一种类型的早期损伤。在碘酞酸盐处理的大鼠中,在灌注固定肾脏的外髓血管中定量的残留红细胞量(可能反映停滞)显著增加。束间区的红细胞团与mTAL坏死相关。总之,这些结果显示了早期的髓质缺氧,伴随着对中央束间区mTAL的选择性损伤,具有明显的停滞。这些发现与肾损伤的缺血-再流模式形成鲜明对比,并强调了髓质缺氧在该模型中急性肾功能衰竭发生中的重要作用。
We evaluated the acute changes in cortical and outer medullary oxygen tension and the alterations in renal function and morphology within the first 90 minutes after the administration of indomethacin and iothalamate to anesthetized Sprague-Dawley rats. Both agents were found to produce marked and protracted outer medullary hypoxia averaging 12 +/- 4 and 9 +/- 2 mm Hg, respectively (mean +/- SE). Given together to salt depleted uninephrectomized rats they produced an early hypoxic injury localized selectively in the outer medulla. This lesion progressed from 3 +/- 1% of medullary thick ascending limbs (mTALs) at 15 minutes to 22 +/- 7% at 24 hours. Condensed "dark" cells were observed at 15 minutes, probably representing a type of early injury. Residual red cell mass, quantified in the outer medullary vasculature of perfusion-fixed kidneys and presumably reflecting stasis, was substantially increased in iothalamate treated rats. Red cells mass in the interbundle zone correlated with mTAL necrosis. Taken together, these results show an early period of medullary hypoxia, accompanied by a selective injury to mTALs in the central interbundle zone with apparent stasis. These findings contrast sharply with the ischemia-reflow pattern of renal damage and emphasize the important role of medullary hypoxia in the genesis of acute renal failure in this model.