Korean J Anesthesiol.  2016 Jun;69(3):262-269. 10.4097/kjae.2016.69.3.262.

Thiamylal sodium increased inflammation and the proliferation of vascular smooth muscle cells

• Miyazaki R
• Hoka S

• KMID: 2164851
• DOI: http://doi.org/10.4097/kjae.2016.69.3.262

Abstract

BACKGROUND
Thiamylal sodium is a common anesthetic barbiturate prepared in alkaline solution for clinical use. There is no previously reported study on the effects of barbiturates on the inflammation and proliferation of vascular smooth muscle cells (VSMCs). Here, we examined the effects of clinical-grade thiamylal sodium solution (TSS) on the inflammation and proliferation of rat VSMCs.
METHODS
Expression levels of interleukin (IL)-1α, IL-1β, IL-6, and toll-like receptors in rat VSMCs were detected by quantitative reverse transcription-polymerase chain reaction and microarray analyses. The production of IL-6 by cultured VSMCs or ex vivo-cultured rat aortic segments was detected in supernatants by enzyme-linked immunosorbent assay. VSMC proliferation and viability were determined by the water-soluble tetrazolium-1 assay and trypan blue staining, respectively.
RESULTS
TSS increased expression of IL-1α, IL-6, and TLR4 in VSMCs in a dose-dependent manner, and reduced IL-1β expression. Ex vivo TSS stimulation of rat aorta also increased IL-6. Low concentrations of TSS enhanced VSMC proliferation, while high concentrations reduced both cell proliferation and viability. Expression of IL-1 receptor antagonist, which regulates cell proliferation, was not increased by TSS stimulation. Exposure of cells to the TSS additive, sodium carbonate, resulted in significant upregulation of IL-1α and IL-6 mRNA levels, to a greater extent than TSS.
CONCLUSIONS
TSS-induced proinflammatory cytokine production by VSMCs is caused by sodium carbonate. However, pure thiamylal sodium has an anti-inflammatory effect in VSMCs. TSS exposure to VSMCs may promote vascular inflammation, leading to the progression of atherosclerosis or in-stent restenosis, resulting in vessel bypass graft failure.

Keyword

Inflammation; Interleukins; Thiamylal

MeSH Terms

Animals
Aorta
Atherosclerosis
Barbiturates
Carbon
Cell Proliferation
Enzyme-Linked Immunosorbent Assay
Inflammation*
Interleukin-1
Interleukin-6
Interleukins
Muscle, Smooth, Vascular*
Rats
RNA, Messenger
Sodium
Thiamylal*
Toll-Like Receptors
Transplants
Trypan Blue
Up-Regulation
Barbiturates
Carbon
Interleukin-1
Interleukin-6
Interleukins
RNA, Messenger
Sodium
Thiamylal
Toll-Like Receptors
Trypan Blue