Selective Antegrade Cerebral Perfusion Attenuating the TLR4/NF-κB Pathway during Deep Hypothermia Circulatory Arrest in a Pig Model

Abstract

Objectives: The alteration of the Toll-like receptor/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway during deep hypothermia circulatory arrest (DHCA) has not yet been defined. The aim of this study was to explore the expression of the TLR4/NF-κB pathway cytokine in cerebral injury resulting from DHCA as well as the effect of selective antegrade cerebral perfusion (SACP) on TLR4/NF-κB pathway expression. Methods: Twelve pigs were randomly assigned to DHCA alone (n = 6) or DHCA with SACP (n = 6) at 18°C for 80 min. Serum interleukin (IL)-6 was assayed by ELISA. Apoptosis and NF-κB proteins were detected by fluorescence TUNEL and Western blot, respectively. The level of TLR4 mRNA and protein were determined through qRT-PCR and Western blot. Results: The serum IL-6 level of the SACP group was significantly lower than that of the DHCA group at the end of circulation arrest and experimentation. Apoptotic index and NF-κB protein were apparently lower in SACP animals (p < 0.05). Compared to the DHCA group, the levels of TLR4 protein and mRNA in the SACP group were lower with significance (p < 0.05). Conclusions: The TLR4/NF-κB signaling pathway plays a critical role in the pathogenesis of DHCA cerebral injury. Attenuation of the TLR4/NF-κB inflammatory cytokines probably contributes to the neuroprotective effect of SACP. The TLR4/NF-κB inflammatory signaling pathway may be a novel therapeutic target for developing a new strategy for neuroprotection in DHCA.

Differences in atrial fibrillation-associated proteins between the left and right atrial appendages from patients with rheumatic mitral valve disease: A comparative proteomic analysis

“…Western blot analysis was performed as previously described (28). Briefly, protein lysates were prepared from human tissues, separated on SDS-PAGE, transferred to a polyvinylidene difluoride membrane, and subjected to immunoblotting at 4°C overnight with the following antibodies: Anti-aldo-keto reductase family 1 member B10 (AKR1B10; diluted 1:10,000; polyclonal antibody; cat.…”

Neuroprotective effect of selective antegrade cerebral perfusion during prolonged deep hypothermic circulatory arrest: Cerebral metabolism evidence in a pig model

“…The anesthesia, intubation, and establishment of vascular catheters were performed as described previously ( 17 , 18 ). Then, animals were easily equipped with intracerebral probes.…”

“…DHCA was induced as described previously ( 17 ). Animals were systemically cooled for 45 min, and when the body temperature reached 30°C, the ascending aorta was cross clamped and the cardioplegia solution was administered.…”

Nevroprotektiv effekt av hypotermi

“…Det er derfor vanskelig å trekke konklusjoner fra denne studien. Bare fire av de eksperimentelle dyrestudiene var gjort i hjertestansmodeller, to av disse var rottestudier (112,113) og to grisestudier (114,115). Tre av dem støttet hypotermibehandling av hjertestanspasienter (112 -114).…”