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催产素不会直接改变兔或人心肌细胞的心脏复极化。

Oxytocin does not directly alter cardiac repolarization in rabbit or human cardiac myocytes.

机构信息

Safety and Exploratory Pharmacology, Toxicology Sciences, Amgen Inc. Thousand Oaks, CA, 91320.

Neuroscience, Amgen Inc. Thousand Oaks, CA, 91320.

出版信息

Pharmacol Res Perspect. 2015 Feb;3(1):e00102. doi: 10.1002/prp2.102. Epub 2014 Dec 9.

Abstract

Oxytocin, a nine amino acid peptide, is highly conserved in placental mammals, including humans. Oxytocin has a physiological role in parturition and parenteral administration of the synthetic peptide is used to induce labor and control postpartum hemorrhage. Endogenous levels of oxytocin before labor are ∼20 pg/mL, but pharmacological administration of the peptide can achieve levels of 110 pg/mL (0.1 nmol/L) following intravenous administration. Cardiac arrhythmia and premature ventricular contractions have been associated with oxytocin administration in addition to QTc interval prolongation. In the conscious rabbit model, intravenous oxytocin produced QT and QTc prolongation. The mechanism of oxytocin-induced QTc prolongation is uncertain but could be the result of indirect changes in autonomic nervous tone, or a direct effect on the duration of cardiomyocyte repolarization. The purpose of this study was to examine the ability of oxytocin to alter cardiac repolarization directly. Two conventional models were used: QTc interval evaluation in the isolated rabbit heart (IRH) and assessment of action potential duration (APD) in human ventricular myocytes (HVM). Oxytocin did not prolong QTc intervals in IRH or APD in HVM when tested at suprapharmacological concentrations, for example, up to 1 μmol/L. The results indicate that oxytocin has very low risk for eliciting QTc and APD prolongation directly, and infer that the QTc changes observed in vivo may be attributed to an indirect mechanism.

摘要

催产素是一种九肽,在包括人类在内的胎盘哺乳动物中高度保守。催产素在分娩中具有生理作用,而合成肽的外周给药被用于诱导分娩和控制产后出血。分娩前催产素的内源性水平约为 20pg/ml,但静脉内给予该肽可使内源性水平达到 110pg/ml(0.1nmol/L)。除了 QTc 间期延长外,催产素给药还与心律失常和室性早搏有关。在清醒兔模型中,静脉内给予催产素可导致 QT 和 QTc 延长。催产素引起 QTc 延长的机制尚不确定,但可能是自主神经张力间接变化的结果,或者是对心肌细胞复极持续时间的直接影响。本研究旨在直接检查催产素改变心脏复极的能力。使用了两种传统模型:在离体兔心(IRH)中评估 QTc 间期和在人心室肌细胞(HVM)中评估动作电位持续时间(APD)。当以超药理学浓度(例如高达 1μmol/L)测试时,催产素并未延长 IRH 中的 QTc 间期或 HVM 中的 APD。结果表明,催产素直接引起 QTc 和 APD 延长的风险非常低,并推断体内观察到的 QTc 变化可能归因于间接机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c66e/4317233/ca1e5ec7f0bb/prp20003-e00102-f1.jpg

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