Effects Of Remote Ischemic Perconditioning On Organs Protection In Adult Valve Replacement

ChapterlEffects of Remote Ischemic Perconditioning on Cardiac, Pulmonary,hepatic and Renal Protection in Adult Valve ReplacementObjectivesOur previous study has been proved the remote ischemic perconditioning may reduce the release of cTnI in small number of patients underwent valve replacement. The present study is to evaluate the protective effects of remote ischemic perconditioning on cardiac, pulmonary, renal and liver injury in patients who have prosthetic valve implantation.MethodsThe patients(n=201) admitted for prosthetic valve implantation were divided into two groups randomly. The remote ischemic perconditioning group (RIPerC. n=101) received three cycles of right thigh ischemia(5minutes) and reperfusion(5minutes) caused by the tourniquet inflated to pressure of600mmHg immediately after aortic cross-clamping, while the control group (CON. n=100) merely place the tourniquet without inflation around the right thigh. The clinical data of inotropes requirement, drainage, duration of intubation and intensive care unit, morbidity and mortality were recorded. All patients were followed-up at least for thirty days after operation.The blood samples were obtained before aortic clamping and12h,24h and48h after aortic declamping for testing respectively.①Serum cTnI and CK-MB concentration;②renal function including BUN, creatine concentration, creatinine clearance rate (Ccr), Cystatin C (CysC) and β2-micoglobulin (β2-MG).The diagnosis of acute kidney injury (ARI) was according to the KDIGO clinical practice guideline of Acute Kidney Injury.;③liver functiuon includin TBIL, ALT, AST and ALB;④serum creative response protein(CRP);⑤Blood gas analysis was monitored per hour after operation until extubation. The diagnosis of Acute Lung Injury (ALI) was according to the diagnostic criteria of ALI/ARDS by American-European Consensus Conference1994.Statistical analysis:Statistical analysis was performed with the SPSS17.0. We analyzed categorical data between two group by chi-square test and Measurement data between two group by one-way analysis of variance. The continuous variables were compared with repeated-measures analysis of variance and multiple comparisons at each time point were using post hoc least significant difference test. Pearson correlation was used to the correlation analysis between two independent parameters. The value of p<0.05was significant.ResultsIt was comparable between two groups with regard to the preoperative clinical data, type of procedure, operation time,duration of bypass and aortic cross clamp,the ventilation time, the ICU time and the hospitalization time.The volume of chest drainage in the RIPerC group (24hs after operation) was significantly decreased compared with the CON group (458.2±264.2ml VS545.1±349.0ml, P=0.048).The inotropes score in the RIPerC group was significantly lower than the CON. group (96.4±73.7VS121.5±89.6, P=0.032)。The area under curve(AUC) of cTnI concentration in the RIPerC group was significantly lower than in the CON group (128.6±102.5vs172.3±184.3; P=0.04). The TBIL at48hours after aortic de-clamping in the RIPerC group was significantly lower than in the CON group (18.6±9.7μmol/L vs22.2±12.9μmol/L; P=0.028).The serum creatine concentration48hours after aortic de-clamping in the RIPerC group was significantly lower than the CON group (86.2±18.4μmol/L vs111.3±39.2μmol/L, P=0.000). The serum CysC concentration48hours after aortic de-clamping in the RIPerC group was significantly lower than the CON group (0.91±0.3lmg/L vs1.02±0.48mg/L, P=0.049). The rate of AKI showed no significant differences between two groups.The PaO26hours after aortic de-clamping in the RIPerC group was significantly higher than in the CON group (196.7±53.8mmHg vs178.6±55.5mmHg, P=0.02). The ALI in the RIPerC groups was significantly decreased compared with the CON. group (36.6%VS51%, P=0.040). The lactate levels of different time points after operation showed no differences between two groups. There is no significant difference in the CRP levels between two groups.ConclusionsRemote ischemic perconditioning caused by transient lower limb ischemia reduces the inotropic requirement and relaese of cTnI. The remote ischemic perconditioning also shows the protective effect, to some extend, on the pulmonary, hepatic and renal injuries in patients undergoing valve replacement. Chapter2Effects of Remote Ischemic Perconditioning on Myocardial Expression of MicroRNAs and Apoptosis in Adult Valve ReplacementObjectiveThis study aims to evaluate the effects of remote ischemic perconditioning on the expression of myocardial MicroRNAs and the apoptosis in adult patients undergoing double valve replacement.MethodsThirty patients admitted for selective double prosthetic valve implantation were divided into two groups randomizely. The remote ischemic perconditioning group (RIPerC. n=15) received three cycles of5/5minutes lower limb ischemia and reperfusion immediately after aortic cross-clamping; the limb ischemia was caused by the tourniquet with pressure of600mmHg immediately after aortic cross-clamping. Control group (CON. n=15) merely place the tourniquet without inflation.. The samples of right atrial muscle were harvested from the patients before cave cannulation and5min after aortic de-clamping. The expression of myocardial miRNAs were detected by Microarrays. Real-time Quantitative RT-PCR was used to confirm the findings of myocardial miRNAs profiling and the expression of BCL2, BAX and PDCD4message RNAs. The expression of BCL2, BAX and PDCD4were detected by the Western Blot analysis. Apoptosis was detected by TUNEL array. The clinical data were recorded.Statistical analysis:Statistical analysis was performed with the SPSS17.0. We analyzed categorical data between two group by chi-square test and measurement data between two group by one-way analysis of variance. The continuous variables were compared with repeated-measures analysis of variance. The value of p<0.05was significant.ResultsIt was comparable between two groups with regard to the preoperative clinical data, type of procedure, operation time,duration of bypass and aortic cross clamp,the ventilation time, the ICU time and the hospitalization time.It was found that17human myocardial miRNAs were significantly dysregulated after CPB.Thirteen of these were upregulated (miR-1, miR-17, miR-19b, miR, miR, miR, miR-140-5p, miR-195, miR, miR-324-5p, miR-377, miR-491-5p and miR-657),and four of these were downregulated (miR-21, miR-24, miR-1275and miR-1973). Compared with CON group, the expression of miR-1, miR-17, miR-20a,, miR-130a, miR-140-5p, miR-195were downregulated, and the expression of miR-21, miR-24, miR-1275were upregulated in the RIPerC group. The expression of miR-19b, miR-33a, miR-301a, miR-324-5p, miR-377, miR-491-5p, miR-657and miR-1973showed no differences in RIPerC groupThe Quantitative detection of miR-1, miR-21, miR-24and miR-195showed that compared with the CON group, the myocardial miRNA-1and miR-195was significantly downregulated (P<0.05). There were no significant changes in the expression of miRNA-24and miRNA-21after CPB in RIPerC group.The expression of BCL2mRNA was significanly upregulated in RIPerC group (2.4-fold, P<0.05) compared with CON group. There were no significant changes in the expression of BAX mRNA and PDCD4mRNA in RIPerC group.The expression of BCL2protein was significanly increased (1.3-fold, P<0.05)in the RIPerC group. The expression of BAX protein was significanly decreased (0.5-fold, P<0.05).TUNEL array shows that the myocardial apoptosis index in RIPerC group was much lower than the CON group after CPB.ConclusionsIn the human cardioplegic arrest setting, myocardial miRNAs were significantly differently expressed. The remote ischemic perconditioning downregulated the myocardial expression of miR-1and miR-195. The remote ischemic perconditioning also attenuates the myocardial apopotosis. These anti-apopotosis on myocardium of RIPerC maybe partly related to the regulation of miRNAs expression.