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Background Acute exposure to mercury chloride (HgCl2) can cause liver damage. Whether oleanolic acid (OA) as a hepatoprotective drug can protect against liver injury induced by acute exposure to HgCl2 and related mechanism of action remain unclear. Objective To investigate the protective effect and possible mechanism of OA on liver injury in mice caused by acute exposure to HgCl2. Methods Forty SPF C57BL/6 male mice were randomly divided into four groups with 10 mice in each group according to body weight. The four groups were named control group, OA group (300 mg·kg−1), HgCl2 group (5 mg·kg−1), and OA + HgCl2 group (300 mg·kg−1 OA + 5mg·kg−1 Hgcl2). Soybean oil and OA solution were administered intragastric once a day for two consecutive days. HgCl2 solution was injected intraperitoneally 2 h after the second intragastric administration. Mice were sacrificed after 48 h, and their serum and liver were collected. Liver coefficient was calculated. The changes of liver structure and iron deposition were observed by hematoxylin-eosin (HE) staining and Prussian blue staining. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total superoxide dismutase (T-SOD), reduced glutathione (GSH), malondialdehyde (MDA), and tissue iron content were measured with commercial kits. Western blotting was used to detect nuclear factor erythroid-2 related factor 2 (Nrf2), heme oxygenase 1 (HO-1), glutathione peroxidase 4 (Gpx4), transferrin receptor 1 (TFR1,) and solute carrier family 7 member 11 (SLC7A11). Results The AST and ALT levels of the HgCl2 group were (76.447±9.695) U·g−1 and (98.563±24.673)U·g−1, respectively, which were higher than those of the control group (P<0.05). After the OA pretreatment, the liver coefficient and the above indexes were decreased to (4.769±0.237)%, (57.086±10.087) U·g−1, and (87.294±27.181)U·g−1, respectively. The liver coefficient and AST level of the OA + HgCl2 group were significantly different from those of the HgCl2 group (P<0.05). After acute exposure to HgCl2, the hepatocytes of mice were disordered, accompanied by inflammatory infiltration, positive blue particles appeared in Prussian blue staining of liver tissue, and the above changes in liver tissue were alleviated after the OA pretreatment. The iron content in the HgCl2 group was (3.646±0.238) μmol·g−1, which was higher than that in the control group, (2.948±0.308) μmol·g−1. After the OA pretreatment, the iron content decreased to (3.429±0.415) μmol·g−1. Compared with the control group, acute exposure to HgCl2 resulted in decreased levels of GSH and T-SOD, decreased protein expression levels of Nrf2, HO-1, SLC7A11, and Gpx4, increased level of MDA, and increased protein expression level of TFR1 (P<0.05). After the OA pretreatment, all indicators were improved including increased GSH level, decreased MDA level, increased Nrf2, HO-1, and SLC7A11 protein expression levels, and decreased TFR1 protein expression level; compared with the HgCl2 group, the differences were statistically significant (P<0.05). Conclusion Acute HgCl2 exposure could induce liver injury in mice, and its mechanism may involve iron overload and ferroptosis. OA may alleviate the liver injury caused by acute HgCl2 exposure by affecting iron overload and the ferroptosis-related protein expression.
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Objectives: To compare regional cerebral tissue oxygen saturation (rScO2) changes during cardiac surgery in children with ventricular septal defect (VSD) and tetralogy of Fallot (TOF). Methods: A total of 60 children aged 3~36 months were enrolled (28 in VSD group 32 in TOF group). rScO2was monitored by Fore-Sight near-infrared spectroscopy device. rScO2, pulse oxygen saturation (SpO2), systolic pressure, diastolic pressure, heart rate, stroke volume index, cardiac index, systemic vascular reststance index the maximal slope of systolic upstroke (dp/dt max) were obtained at following time points: after anesthesia induction (t0), pericardium opening (t1), 5 min after cardiopulmonary bypass (CPB) initiation (t2), 5 min before separation from CPB (t3), separation from CPB (t4), post-modified ultrafiltration (t5), end of surgery (t6). Results: (1) The lowest rScO2value was observed at separation from CPB (t4), and which was significantly lower than that at t0(P<0.05) for both groups; rScO2, stoke volume index, cardiac index, and dp/dt max at t5were significantly higher than at t4(all P<0.001) for both groups. (2) rScO2and SpO2were significantly higher at t5and t6than at t0(both P<0.05) in TOF group. rScO2at t0-t2was significantly lower in TOF group than in VSD group (both P<0.05). rScO2increased more significantly after modified ultrafiltration and rScO2was positively correlated with SpO2at t0and t1(r=0.35, P<0.05 and r=0.64,P<0.01) in TOF group. (3) In the total cohort, rScO2was positively correlated with age, weight at t0, t1, t3, t4, t5, t6(all P<0.01). After modified ultrafiltration, the increase in cardiac index was positively correlated with increase in rScO2(r=0.41, P<0.05), and the amount of cardiac index and rScO2increases were negatively correlated with age (r=-0.30;r=-0.34, both P<0.05). Conclusions: rScO2is closely related with age and weight. Cerebral oxygen delivery before biventricular surgical correction is lower in TOF group than in VSD group, and the cerebral oxygenation improves significantly after surgical repair. Modified ultrafiltration could significantly improve systemic hemodynamics and rScO2, and TOF children and younger children benefit more from modified ultrafiltration. Pre- and post-separation from CPB period is vulnerable to cerebral desaturation, it is therefore of importance to maintain the cerebral oxygen delivery-consumption balance at these periods for children with TOF and VSD undergoing surgical repair.
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Objective To study the relationship between regional cerebral tissue oxygen saturation (rScO2) and hemodynamic parameters under different end-tidal carbon dioxide partial pressure (PetCO2) levels during anesthesia induction period in children undergoing ventricular septal defect(VSD) repair.Methods A total of 25 patients aged from 2 to 37 months (median 6 months) were enrolled,who received selective VSD repair at Beijing Anzhen Hospital from April to May 2017.After admission,anesthesia induction and intubation,invasive radial artery pressure were established routinely and hemodynamic device-MostCare was used,Fore-Sight was used to monitor rScO2 of the right frontal brain.By means of adjusting mechanical ventilation parameter,PetCO2 was maintained at 30 (T1),35 (T2),40 (T2),45 (T3) mmHg(1 mmHg =0.133 kPa) in sequence.Pulse oxygen saturation (SpO2),heart rate (HR),systolic pressure (SysP),difference between dicrotic pressure (DicP) and diastolic pressure (DiaP) (Pdic-a),stroke volume index (SVI),cardiac index (CI),systemic vascular resistance index (SVRI),and pulse pressure variation (PPV) were recorded at T1,T2,T3 and T4.Results (1) Comparison among groups:rScO2 at T4,T3,T2 and T1 were (80.5 ± 4.0) ％,(78.2 ± 4.6) ％,(74.4 ± 5.7) ％,(70.8 ± 6.5) ％,respectively,rScO2 at T2,T3 and T4 were higher than that at T1,and the differences were statistically significant (all P ＜ 0.05).SysP at T3 [(85 ± 9) mmHg] and T4 [(84 ± 10) mmHg] were lower than that at T1 [(92 ± 15) mmHg],and the differences were statistically significant (all P＜0.05).DicP at T2[(64 ± 12) mmHg],T3[(60 ± 10) mmHg],and T4 [(59 ±9) mmHg] were significantly lower than that at T1 [(68 ± 15) mmHg],and the differences were statistically significant (all P ＜ 0.05).DiaP at T2 [(44 ± 6) mmHg],T3[(41 ±6) mmHg],and T4 [(41 ±6) mmHg]were lower than that at T1 [(47 ±7) mmHg],and the differences were statistically significant(all P ＜ 0.01).SVRI at T4 [(1 382 ± 262) dyne · s cm-5 · m2] was significantly lower than those at T1 [(1 486 ± 241) dyne · s cm-5 · m2],T2 [(1 440 ± 279) dyne · s cm-5 · m2] and T3 [(1 418 ±266) dyne · s cm-5 · m2],and the differences were statistically significant (all P ＜ 0.05).PPV at T3 [(11 ± 4) ％] and T4 [(13 ± 5) ％] was significantly lower than that at T1 [(18 ± 12) ％],and the differences were statistically significant (all P ＜ 0.05).(2) Correlation analysis:in total population,PetCO2 was positively correlated with rScO2 (r =0.582,P ＜ 0.01).At T1,rScO2 was positively correlated with DiaP and DicP (r =0.600,0.658,all P ＜ 0.01),as well as SysP,CI,SVI,Pdic-a (r =0.460,0.424,0.522,0.534,all P ＜ 0.05),rScO2 was negatively correlated with HR and PPV (r =-0.450,-0.490,all P ＜ 0.05).At T2,rScO2 was positively correlated with DiaP and DicP (r =0.689,0.692,all P ＜ 0.01),as well as SysP,SVI (r =0.534,0.445,all P ＜ 0.05).At T3,rScO2 was positively correlated with SysP (r =0.495,P ＜ 0.05),and negatively correlated with PPV (r =-0.562,P ＜ 0.01).At T4,the rScO2 was not correlated with any hemodynamic parameters (P ＞ 0.05).Conclusions During anesthesia induction in ventricular septal defect children,rScO2 increases significantly with the increase in PetCO2.When PetCO2 is at 30 and 35 mmHg,rScO2 is mainly affected by hemodynamics.When PetCO2 is at 40 and 45 mmHg,rScO2 is mainly affected by PetCO2,but less affected by hemodynamics.
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Objective To compare the difference in pulse pressure variation(PPV)to predict volumetric response in children with ventricular septal defect(VSD)and tetralogy of Fallot(TOF). Methods VSD group consisted of 38 patients,aged 1.05 ± 0.75 years,while TOF group consisted of 36 patients,aged 1.15 ± 0.68 years. After separation from cardiopulmonary bypass,fluid infusion therapy was administered. PPV was recorded using pressure recording analytical method along with cardiac index(CI)before and after fluid infusion. Patients were considered as responders to fluid loading when CI increased ≥15%.Receiver operating characteristic(ROC) analysis was used to assess the accuracy and cutoffs of PPV to predict volumetric response.Results The PPV val-ues before and after fluid infusion were significantly lower in TOF group than that in VSD group(P < 0.01 for both).In VSD group,27 were responders and 11 nonresponders.ROC curve area was 0.89 and cutoff value 17.4%. In TOF group,26 were responders and 10 nonresponders.ROC curve area was 0.79 and cutoff value 13.4%.Con-clusion PPV is predictive of volumetric response in VSD and TOF patients following cardiac surgery.PPV's pre-dictivity and cutoff value are higher than the former. PPV is affected by right ventricle-pulmonary artery circula-tion,under-fluid infusion should be avoided in TOF due to lower PPV,over-fluid infusion should be avoided in VSD due to higher PPV.
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Hemodynamic monitoring is an essential part in the care of children with congenital heart disease during perioperative period to guide clinical management.Currently,there are several methods available for hemodynamic monitoring.The invasive methods include the Fick method,thermodilution method,using the Swan-Ganz catheter and the pulse contour method.The noninvasive methods include partial carbon dioxide resorption,impedance method.In this paper,the principle,advantages and disadvantages of these monitoring methods in children undergoing cardiopulmonary bypass surgery were reviewed.
