Decrease in inflammatory response does not prevent placental dysfunction after fetal cardiac bypass in goats

• Published in: The Journal of thoracic and cardiovascular surgery Vol. 143; no. 2; pp. 445 - 450
• Main Authors: Zhou, Cheng-Bin, MD, Zhuang, Jian, MD, Chen, Ji-Mei, MD, Zhang, Xiao-Hua, MD, Lui, Raphael C., MD
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.02.2012; Elsevier
• Subjects: 6-Ketoprostaglandin F1 alpha - blood; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Anti-Inflammatory Agents - pharmacology; Biological and medical sciences; Cardiac Surgical Procedures - adverse effects; Cardiology. Vascular system; Cardiothoracic Surgery; Electrophoretic Mobility Shift Assay; Endothelin-1 - blood; Female; Fetal Blood - metabolism; Fetal Heart - surgery; Gestational Age; Goats; Inflammation - blood; Inflammation - immunology; Inflammation - physiopathology; Inflammation - prevention & control; Inflammation Mediators - antagonists & inhibitors; Inflammation Mediators - metabolism; Interleukin-6 - blood; Interleukin-6 - genetics; Medical sciences; NF-kappa B - antagonists & inhibitors; NF-kappa B - blood; Nitric Oxide - blood; Placenta - blood supply; Placenta - drug effects; Placenta - immunology; Placenta - metabolism; Placenta Diseases - blood; Placenta Diseases - immunology; Placenta Diseases - physiopathology; Placenta Diseases - prevention & control; Placental Circulation - drug effects; Pneumology; Pregnancy; Pyrrolidines - pharmacology; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - blood; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the heart; Thiocarbamates - pharmacology; Thromboxane B2 - blood; Tumor Necrosis Factor-alpha - blood; Tumor Necrosis Factor-alpha - genetics; Vascular Resistance - drug effects; NO; 25; PDTC; FP; control group; 6-keto-prostaglandin F1α; thromboxane A 2; electrophoretic mobility shift assay; thromboxane B 2; TXB2; EMSA; fetal cardiac bypass group; fetal cardiac bypass with pyrrolidine dithiocarbamate group; nitric oxide synthase; endothelin-1; interleukin; nitric oxide; IL; CG; NF-KB; TXA2; ET-1; NOS; 6-K; TNF-α; tumor necrosis factor-α; nuclear factor kappa-B; FB; 20; pyrrolidine dithiocarbamate; Heart; Prevention; Response; Vertebrata; Mammalia; Placenta; Treatment; Decrease; Bypass; Dysfunction; Surgery; Anesthesia; Fetus; Goat; Artiodactyla; Circulatory system; Cardiology; Ungulata
• ISSN: 0022-5223; 1097-685X
• DOI: 10.1016/j.jtcvs.2011.07.011

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 B2 (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, TXB2 , 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.