Abstract

OBJECTIVE
One of the most significant responses to fetal cardiac bypass is severe placental dysfunction characterized by increased vascular resistance. We tested the hypothesis that fetal cardiac bypass triggers the activation of nuclear factor kappa-B (NF-KB), a major regulator of inflammatory response, and that pharmacologic inhibition of NF-KB activation by pyrrolidine dithiocarbamate alleviates fetal cardiac bypass-induced placental dysfunction.
METHODS
Fifteen pregnant goats at 120 to 140 days' gestation were equally divided into the control group with a sham procedure of fetal sternotomy and cannulation (CG), the fetal bypass group (FB), and the fetal bypass group with 300 mg pyrrolidine dithiocarbamate before sternotomy (FP). Fetal cardiac bypass was performed for 30 minutes. Umbilical arterial flow rate was measured by ultrasonic flowmeter and placental vascular resistance was calculated. Fetal plasma levels of nitric oxide (NO), endothlin-1 (ET-1), 6-keto-prostaglandin F1α (6-K), thromboxane B(2) (TXB2), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) were assayed. IL-6 and TNF-α mRNA were analyzed by real-time polymerase chain reaction. NF-KB activation was evaluated by electrophoretic mobility shift assay.
RESULTS
Placental vascular resistance significantly increased in the FB and FP groups compared with the CG group. Increases in plasma levels of NO were observed in all 3 groups. Plasma levels of ET-1 rose significantly in the FB and FP groups without noticeable difference between them. Plasma levels of 6-K, TXB(2), IL-6, and TNF-α increased significantly in the FB group compared with the CG and FP groups. The transcription levels of IL-6 and TNF-α mRNA in the placental tissues of the FB group were significantly higher than in the FP and CG groups. The amount of activated NF-KB in the placental tissues of the FB group was also significantly higher than that in the FP and CG groups.
CONCLUSIONS
Fetal cardiac bypass-induced inflammatory response possibly mediated by NF-KB caused placental dysfunction. Pharmacologic inhibition of NF-KB activation and decrease in the inflammatory response did not alleviate the placental dysfunction.

Links

Publisher Full Text

Publisher Full Text

Authors

Zhou CB, Zhuang J, Chen JM, Zhang XH, Lui RC

Institution

Department of Cardiovascular Surgery, Guangdong Provincial Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Source

The Journal of thoracic and cardiovascular surgery 143:2 2012 Feb pg 445-50

MeSH

6-Ketoprostaglandin F1 alpha
Animals
Anti-Inflammatory Agents
Cardiac Surgical Procedures
Electrophoretic Mobility Shift Assay
Endothelin-1
Female
Fetal Blood
Fetal Heart
Gestational Age
Goats
Inflammation
Inflammation Mediators
Interleukin-6
NF-kappa B
Nitric Oxide
Placenta
Placenta Diseases
Placental Circulation
Pregnancy
Pyrrolidines
RNA, Messenger
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Thiocarbamates
Thromboxane B2
Tumor Necrosis Factor-alpha
Vascular Resistance

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21821267