Background Stress response always occurs in cardiac valve replacement patients undergoing cardiopulmonary bypass (CPB). Methods 60 patients undergoing cardiac valve replacement were recruited and randomized into control and Dex groups. Dex group received 1.0 μg·kg-1 of Dex for 10 min intravenously before anesthesia, followed by 0.5 μg·kg-1·h-1 of Dex, steadily administered throughout the procedure. And controlled group received the identical velocity of saline as Dex group. Plasma level of cortisol (Cor), epinephrine (E), norepinephrine (NE), and serotonin (5-HT) were evaluated at four timepoints: Before administration (T0), sawn sternum (T1), end of extracorporeal circulation (T2), and 24 h post operation (T3). General data of operation and recovery such as heart rate (HR), mean arterial pressure (MAP), intraoperative bispectral index (BIS), and hospitalization time in the intensive care unit (ICU) were also compared. Results Increase of Cor, E, NE, and 5-HT for the Dex group was significant lesser than that in the control group (P < 0.05), and ICU hospitalization time and ventilator support time was significantly shorter in the Dex group. The proportion of patients discharged from the hospital with better prognosis was significantly higher than that in the control group, while there were no significant differences in hospitalization costs and vasoactive drugs use between the two groups. Conclusions Dex reduces plasma Cor, E and NE elevations in patients after CPB, alleviates the stress reaction of the body, shortens the hospitalization time and ventilator support time in ICU, and plays a positive role in the rehabilitation of patients undergoing cardiac valve replacement. Trial registration China Clinical Trial Registry (No. ChiCTR-IPR-17010954) March 22rd, 2017.
Objective To investigate the effect of caspase-3-specific inhibitors of extracorporeal circulation (CPB) on pulmonary ischaemia-reperfusion injury in dogs.Methods Eighteen healthy mongrel dogs were divided into three groups (n = 6) by random number table method, sham-operated group (group C), ischemia-reperfusion group (group I/R) and caspase-3 specific inhibitor (group Z), and the rest of the groups were established as CPB left lung ischemia-reperfusion injury model, and group Z was given caspase-3 specific inhibitor (Z-DEVD) via femoral vein immediately after opening the left pulmonary artery. The caspase-3 specific inhibitor (Z-DEVD-fmk) 0.6mg/Kg was administered to the Z group immediately after opening the left pulmonary artery via the femoral vein. Arterial blood was collected from the femoral artery before chest opening (T1), at the time of shutdown (T2) and at the end of the experiment (T3), and arterial blood gas analysis was performed to calculate respiratory index (RI) and oxygenation index (OI). -N expression, TUNEL assay for apoptosis and HE assay for pathological changes in lung tissue at each time point.Results The expression of RI, Cleaved-caspase3, NLRP3, Clleaved-caspase-1, GSDME-N and apoptotic index in lung tissue increased in the I/R group at T2 and T3 compared with the C group, while the OI decreased (P < 0.05); compared with the I/R group at T3, the expression of RI, Cleaved-caspase3 and apoptotic index in the Z group increased. caspase3, NLRP3, Clleaved-caspase-1, GSDME-N expression and apoptotic index decreased and OI increased in the Z group compared with the I/R group at T3 (P < 0.05); no significant apoptotic cells were seen in the C group at T3; apoptotic cells increased in the I/R group after open left pulmonary arteriovenous reperfusion stimulation, while the Z group had fewer positive cells than the I/R group.Conclusion Caspase-3-specific inhibitors can improve lung function and reduce apoptosis in lung tissue after CPB, it also reduce oxidative stress level and inflammation level. These effects may be achieved by regulating Caspase-3/GSDME signaling pathway and inhibiting pyroptosis.
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