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具有心脏保护特性的肾保护碘造影剂:一项初步研究。

A nephroprotective iodinated contrast agent with cardioprotective properties: A pilot study.

机构信息

Neurrow Pharmaceuticals, Inc, Shawnee, Kansas, USA.

CorDynamics, Inc, Chicago, Illinois, USA.

出版信息

J Neuroimaging. 2021 Jul;31(4):706-713. doi: 10.1111/jon.12873. Epub 2021 May 12.

Abstract

BACKGROUND AND PURPOSE

Evaluation and treatment of acute ischemic syndromes, in the heart and brain, require vessel visualization by iodinated X-ray contrast agents. However, these contrast agents can induce injury, in both the kidneys and target organs themselves. Sulfobutylether beta cyclodextrin (SBECD) added to iohexol (SBECD-iohexol) (Captisol Enabled-iohexol, Ligand Pharmaceuticals, Inc, San Diego, CA) is currently in clinical trials in cardiovascular procedures, to determine its relative renal safety in high-risk patients. Preclinical studies showed that SBECD-iohexol reduced contrast-induced acute kidney injury in rodent models by blocking apoptosis. The current study was undertaken to determine whether SBECD-iohexol is also cardioprotective, in the male rat ischemia-reperfusion model, compared to iohexol alone.

METHODS

After anesthesia, the left coronary artery was ligated for 30 min and the ligation released and reperfusion followed for 2 h prior to sacrifice. Groups 1-4 were injected in the tail vein 10 min prior to ischemia with: (1) vehicle; (2) iohexol; (3) SBECD; and (4) SBECD-iohexol. Infarct size, hemodynamics, and serum markers were measured.

RESULTS

An eight-fold increase in serum creatine kinase in the iohexol-alone group was observed, compared with no increase in the SBECD-iohexol group. The mean arterial pressure and rate pressure product were depressed in the iohexol-alone group, but not in the SBECD-iohexol group, or controls. No difference in infarct size or serum creatinine among the groups was observed.

CONCLUSION

The results of this study suggest that SBECD-iohexol is superior to iohexol alone, for both the preservation of cardiomyocyte integrity and preservation of myocardial function in myocardial ischemia.

摘要

背景与目的

在心脏和大脑中,评估和治疗急性缺血综合征需要使用碘造影剂进行血管可视化。然而,这些造影剂会导致肾脏和目标器官本身的损伤。目前,在心血管手术中,将磺丁基醚-β-环糊精(SBECD)添加到碘海醇中(SBECD-碘海醇)(LigandPharmaceuticals,Inc.,圣地亚哥,CA 的 Captisol Enabled-iohexol)进行临床试验,以确定其在高危患者中的相对肾脏安全性。临床前研究表明,SBECD-碘海醇通过阻断细胞凋亡减少了啮齿动物模型中的造影剂诱导的急性肾损伤。本研究旨在确定 SBECD-碘海醇是否也具有心脏保护作用,与单独使用碘海醇相比,在雄性大鼠缺血再灌注模型中。

方法

麻醉后,结扎左冠状动脉 30 分钟,然后释放结扎并在牺牲前再灌注 2 小时。在缺血前 10 分钟,1-4 组通过尾静脉注射:(1)载体;(2)碘海醇;(3)SBECD;和(4)SBECD-碘海醇。测量梗死面积、血液动力学和血清标志物。

结果

与 SBECD-碘海醇组相比,碘海醇单独组的血清肌酸激酶增加了 8 倍。仅在碘海醇组中,平均动脉压和心率乘积降低,但在 SBECD-碘海醇组或对照组中没有降低。各组间的梗死面积或血清肌酐无差异。

结论

本研究结果表明,与单独使用碘海醇相比,SBECD-碘海醇在保护心肌细胞完整性和心肌缺血时保护心肌功能方面均具有优势。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c11e/8359965/85b494f1379c/JON-31-706-g003.jpg

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