| A protective antiarrhythmic role of ursodeoxycholic acid in an in vitro rat model of the cholestatic fetal heart. | |
| | |
MedLine Citation:
|
PMID: 21809354 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Intrahepatic cholestasis of pregnancy may be complicated by fetal arrhythmia, fetal hypoxia, preterm labor, and, in severe cases, intrauterine death. The precise etiology of fetal death is not known. However, taurocholate has been demonstrated to cause arrhythmia and abnormal calcium dynamics in cardiomyocytes. To identify the underlying reason for increased susceptibility of fetal cardiomyocytes to arrhythmia, we studied myofibroblasts (MFBs), which appear during structural remodeling of the adult diseased heart. In vitro, they depolarize rat cardiomyocytes via heterocellular gap junctional coupling. Recently, it has been hypothesized that ventricular MFBs might appear in the developing human heart, triggered by physiological fetal hypoxia. However, their presence in the fetal heart (FH) and their proarrhythmogenic effects have not been systematically characterized. Immunohistochemistry demonstrated that ventricular MFBs transiently appear in the human FH during gestation. We established two in vitro models of the maternal heart (MH) and FH, both exposed to increasing doses of taurocholate. The MH model consisted of confluent strands of rat cardiomyocytes, whereas for the FH model, we added cardiac MFBs on top of cardiomyocytes. Taurocholate in the FH model, but not in the MH model, slowed conduction velocity from 19 to 9 cm/s, induced early after depolarizations, and resulted in sustained re-entrant arrhythmias. These arrhythmic events were prevented by ursodeoxycholic acid, which hyperpolarized MFB membrane potential by modulating potassium conductance. Conclusion: These results illustrate that the appearance of MFBs in the FH may contribute to arrhythmias. The above-described mechanism represents a new therapeutic approach for cardiac arrhythmias at the level of MFB. (HEPATOLOGY 2011;). |
| | |
Authors:
|
Michele Miragoli; Siti H Sheikh Abdul Kadir; Mary N Sheppard; Nicoló Salvarani; Matilda Virta; Sarah Wells; Max J Lab; Viacheslav O Nikolaev; Alexey Moshkov; William M Hague; Stephan Rohr; Catherine Williamson; Julia Gorelik |
Related Documents
:
|
7064764 - Fetal femur length and gestational age. 3532804 - Ultrasonic measurement of fetal femoral length in singleton and twin pregnancies. 22546424 - Cystically degenerated leiomyoma of the rectosigmoid managed laparoscopically at 13 wee... 18537004 - Comparison between canscore and other anthropometric indicators in fetal malnutrition. 18655864 - The negative impact of maternal bulimic symptoms on parenting behavior. 7113684 - Does cervix conization increase the risk of complications in subsequent pregnancies? |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-8-1 |
Journal Detail:
|
Title: Hepatology (Baltimore, Md.) Volume: - ISSN: 1527-3350 ISO Abbreviation: - Publication Date: 2011 Aug |
Date Detail:
|
Created Date: 2011-8-2 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8302946 Medline TA: Hepatology Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
|
Copyright © 2011 American Association for the Study of Liver Diseases. |
Affiliation:
|
National Heart and Lung Institute, Imperial College London, London, England. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Castration resistant prostate cancer is associated with increased blood vessel stabilization and ele...
Next Document: Occult hepatitis B infection and HBV replicative activity in patients with cryptogenic cause of hepa...