ABSTRACT
Objective:To investigate the effects of dexmedetomidine on monocyte pyroptosis in peripheral blood of patients with cardiac valve replacement.Methods:Forty-four American Society of Anesthesiologists physical status Ⅱ or Ⅲ patients of both sexes, aged 45-64 yr, with body mass index of 18-25 kg/m 2, of New York Heart Association Ⅱ or Ⅲ, scheduled for elective cardiac valve replacement, were divided into 2 groups ( n=22 each) using a random number table method: dexmedetomidine group (group Dex) and normal saline group (group NS). In group Dex, dexmedetomidine was intravenously infused in a dose of 0.5 μg/kg over 10 min starting from the end of anesthesia induction, followed by a continuous infusion at 0.5 μg·kg -1·h -1 until the end of operation, while the equal volume of normal saline was given instead of dexmedetomidine in group NS.Before skin incision (T 1), at 30 min after the beginning of cardiopulmonary bypass (CPB) (T 2), immediately after the end of CPB (T 3) and at 24 h after CPB (T 4), the blood samples of internal jugular vein were collected for determination of the concentrations of plasma interleukin-18 (IL-18) and IL-1β (by enzyme-linked immunosorbent assay), and the expression of NOD-like receptor family, pyrin domain containing 3 (NLRP3), caspase-1 and gasdermin-D (GSDMD) in monocytes (by Western blot). The intraoperative consumption of propofol, sufentanil and norepinephrine, time of postoperative mechanical ventilation and time of intensive care unit stay were recorded. Results:The levels of plasma IL-18 and IL-1β and expression of NLRP3, caspase-1 and GSDMD in monocytes were significantly higher at T 2-4 than at T 1 in two groups ( P<0.05). Compared with group NS, the levels of plasma IL-18 and IL-1β were significantly decreased and the expression of NLRP3, caspase-1 and GSDMD was down-regulated at T 2-4, postoperative mechanical ventilation time was shortened ( P<0.05), and no significant change was found in the consumption of propofol, sufentanil and norepinephrine and time of intensive care unit stay in group Dex ( P>0.05). Conclusion:The mechanism by which dexmedetomidine reduces inflammatory responses may be related to inhibiting the NLRP3/caspase-1 pathway and reducing monocyte pyroptosis in the patients undergoing cardiac valve replacement.
ABSTRACT
Objective To evaluate the effect of dexmedetomidine on Toll-like receptor 4 ( TLR4)/myeloid differentiation factor 88 ( MyD88)/nuclear factor Kappa B ( NF-κB) signaling pathway in the pe-ripheral blood mononuclear cells of elderly patients with diabetes mellitus undergoing lower extremity surger-y. Methods Forty elderly patients of both sexes with type 2 diabetes mellitus, aged 65-80 yr, with body mass index of 18. 5-27. 9 kg/m2 , of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, with New York Heart Association Ⅰ or Ⅱ, undergoing lower extremity surgery with tourniquets under general anesthesia, were divided into 2 groups ( n=20 each) by using a random number table method: control group ( group C) and dexmedetomidine group ( group D) . Combined intravenous-inhalational anesthesia was applied. Dexmedetomidine was infused over 15 min in a dose of 1μg/kg after induction of anesthesia, fol-lowed by a continuous infusion of 0. 5 μg·kg-1 ·h-1 until the end of surgery in group D, while the equal volume of normal saline was given instead of dexmedetomidine in group C. Before using the the tourniquet and at 15 min, 1 h and 24 h after loosing the tourniquet, arterial blood samples were collected for determi-nation of the expression of TLR4, NF-κB and MyD88 in peripheral blood mononuclear cells and concentra-tions of tumor necrosis factor-alpha ( TNF-α) , interleukin-1β ( IL-1β) , cardiac troponin I ( cTnI ) and creatine kinase-MB ( CK-MB) in plasma. Results Compared with group C, the expression of TLR4, NF-κB and MyD88 in peripheral blood mononuclear cells was significantly down-regulated, and the concentra-tions of TNF-α, IL-1β, cTnI and CK-MB in plasma were decreased at each time point after loosing the tourniquet in group D ( P＜0. 05) . Conclusion The mechanism by which dexmedetomidine reduces myo-cardial damage may be related to inhibiting TLR4/MyD88/NF-κB signaling pathway and reducing systemic inflammatory responses in elderly patients with diabetes mellitus undergoing lower extremity surgery.