Role and mechanism of sivelestat sodium in protecting lung function in elderly patients undergoing aortic valve replacement under cardiopulmonary bypass
Objective To observe the role of sivelestat sodium in protecting lung function in elderly patients undergoing aortic valve replacement under cardiopulmonary bypass,and to explore its mechanism.Methods Seventy-six elderly patients underwent aortic valve replacement under cardiopulmonary bypass in Henan Provincial People's Hospital from October 2021 to October 2022,among whom 38 patients received intravenous pumping of 0.2 mg/(kg·h)sivelestat sodium 10 min before anesthesia induction till the end of mechanical ventilation(observation group),while the other 38 patients received intravenous pumping of normal saline(control group).The venous blood samples were collected from both groups at the following time points:before skin incision(T0),immediately after surgery(T1),24 h after surgery(T2),and 48 h after surgery(T3).Peripheral blood mononuclear cells(PBMCs)were isolated from the blood samples using Ficoll density gradient centrifugation.Real-time fluorescence quantitative PCR was used to detect the relative expressions of interleukin(IL)-18 and IL-1β mRNA in PBMCs.Western blot technique was used to detect the relative expressions of NLRP3,caspase-1,and gasdermin D(GSDMD)proteins in PBMCs.The morphological changes of PBMCs at T3 were observed.Arterial blood gas analysis was conducted at T0,T1,T2 and T3 to measure pa(O2),pa(CO2),alveolar-arterial oxygen partical pressure difference(PA-aDO2),oxygenation index(OI),and respiratory index(RI).The durations of cardiopulmonary bypass,aortic cross-clamping,surgery and anesthesia,intraoperative blood loss and fluid intake,intraoperative ventilation duration,length of ICU stay,time to first ambulation after surgery,and length of hospital stay were recorded.The intraoperative sinus bradycardia/tachycardia,hypotension/hypertension,respiratory depression,and postoperative skin itching,nausea/vomiting and infection were compared between two groups.Results At T0,there were no significant differences in the pa(O2),pa(CO2),oxygen saturation,PA-aDO2,RI and OI between two group(P＞0.05).At T1,T2 and T3,the values of PA-aDO2 and RI were lower,while OI values were higher in observation group than those in control group(P＜0.05).The values of PA-aDO2 and RI were higher and the OI values were lower at T1,T2 and T3 than those at T0 in both groups(P＜0.05).At T3,the morphological changes of PBMCs in control group included swelling,roundness,bubble-like protrusions,variable sizes,cell membrane lysis,fragmentation,widened intercellular gaps,and disorganized arrangement,which were milder in observation group.At T0,there were no significant differences in the relative expressions of IL-18 mRNA,IL-1β mRNA,NLRP3 protein,caspase-1 protein and GSDMD protein between two groups(P＞0.05).However,at T1,T2 and T3,the relative expressions of IL-18 mRNA,IL-1β mRNA,NLRP3 protein,caspase-1 protein and GSDMD protein were lower in observation group than those in control group(P＜0.05),which were higher than those at T0 in both groups(P＜0.05).The duration of postoperative mechanical ventilation and length of ICU stay were shorter in observation group[(33.3± 8.0),(51.9±7.8)h]than those in control group[(39.9±9.6),(61.7±8.4)h](t=3.256,P=0.002;t=5.270,P＜0.001).There were no significant differences in the durations of cardiopulmonary bypass,aortic cross-clamping,surgery and anesthesia,intraoperative blood loss and fluid intake,perioperative transfusion of packed red blood cells and fresh frozen plasma,time to first ambulation after surgery,and length of hospital stay between two groups(P＞0.05).Both groups had no respiratory depression or deep vein thrombosis during surgery.The incidences of sinus bradycardia,sinus tachycardia,hypotension,hypertension,postoperative nausea/vomiting,skin itching and infection were similar between two groups(P＞0.05).Conclusion Sivelestat sodium exerts a protective effect on postoperative lung function in patients undergoing aortic valve replacement under cardiopulmonary bypass by modulating the NLRP3 inflammatory signaling pathway and inhibiting pyroptosis of PBMCs,and it does not increase the perioperative adverse events.
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