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The Effect And Mechanism Of Remote Ischemic Posteconditioning On Ischemia-reperfusion Injury

Posted on:2017-09-11Degree:DoctorType:Dissertation
Country:ChinaCandidate:H P WangFull Text:PDF
GTID:1364330488455204Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Part ? The effect of remote ischemic postconditioning induced by upper limb in patients with ST-Segment Elevation Myocardial InfarctionObjective:To explore the effect of remote ischemic postconditioning(RIPostC)on ischaemia-reperfusion injury(IRI)in patients with ST-segment elevation myocardial infarction(STEMI).To explore the effect of RIPostC on renal protectional in patients with STEMI.Methods:From October,2014 to June,2015,80 consecutive patients with STEMI were randomly to receive primary percutaneous coronary intervention(PPCI)without RIPostC(PPCI group,n=36)or PPCI plus RIPostC(PPCI+RIPostC group,n=44).RIPostC consisted of 4 cycles of 5 min/5 min ischemia/reperfusion by cuff inflation/deflation of the upper limb.Protocol was started in 3 minutes after the first balloon inflation during PPCI operation.Peripheral venous blood sample in allpatients were collected before PPCI operation and 0.5?8?24?48?72 hours after PPCI peration to detect creatine kinase-MB(CK-MB),nitric oxide(NO)and stromal cell-derived factor-1alpha(SDF-1?)concentration in serum.Peripheral venous blood sample in all patients were collected before operation and 24?72 hours after operation,to detect the blood urea nitrogen(BUN)and serum creatinine(SCr)concentration in serum,and calculated the cute kidney injury(AKI)rate and estimated glomerular filtration rate(eGFR).The transthoracic echocardiography was performed on all patients 7 days after operation to assess left ventricular ejection fraction(LVEF)and wall motion score index(WMSI).Results:1.There were no significant differences in baseline characteristics:age,male sex,current smoking,hypertension,Hypercholesterolemia,diabetes mellitus,prior myocardial infarction,contrast agent,stent implantation between the two groups.2.The peak CK-MB serum concentration in PPCI+RIPostC was significantly lower compare to PPCI group(280.60±45.83 ng/ml VS 352.21±65.42 ng/ml,P<0.01).The median CK-MB area under the curve(AUC)over 72 h of PPCI+RIPostC group was significantly less then PPCI group(717.25[364.63-921.98]VS 807.00[693.30-1136.00],P=0.02).3.There were 22 patients had AKI,the overall incidence of AKI rate was 27.5%.AKI rate was significantly lower in the PPCI+RIPostC group compared to PPCI group(11.1%VS 40.9%,P<0.01).There was no significant difference of eGFR before PPCI operation between the tow groups(102.26±18.33 ml/min/1.73m~2 VS 100.34±12.86ml/min/1.73m~2,P=0.60),the lowest eGFR in PPCI+RIPostC group was significantly higher compared to PPCI group after PPCI operation(98.72±13.34ml/min/1.73m~2 VS78.13±12.40ml/min/1.73m~2,P<0.01).However,eGFR decline was significantly more marked in PPCI compared to PPCI+RIPostC group(-22.21±12.46ml/min/1.73m~2 VS-3.54±14.45 ml/min/1.73m~2,P<0.01).4.The median serum concentration of NO AUC was more markble increased in PPCI+RIPostC group compare to PPCI group(5.826[3.923-13.172]VS 4.936[3.296-6.141],P=0.048).5.The median serum concentration of SDF-1?AUC was more markble increased in PPCI+RIPostC group compare to PPCI group(410.800[314.200-629.000]VS 351.000[257.600-478.900],P=0.044).6.LVEF assessed by transthoracic echocardiography in PPCI+RIPostC group was significantly higher compare to PPCI group(54.50±9.73%VS 48.14±7.04%,P=0.01).The median WMSI score ofPPCI+RIPostC group was 2,markble less than PPCI group which had median WMSI score of 3(P=0.02).Conclusion::1.The use of RIPostC on upper limb could attenuates CK-MB release,improve the LVEF,may protect patiens with STEMI from IRI.2.The use of RIPostC on upper limb could decrease the AKI rate and attenuates eGFR decline in patiens with STEMI,may have protective effect on renal function.3..The use of RIPostC on upper limb could increase serum concentration of NO and SDF-1?in patiens with STEMI.Part ? The effect of remote ischemic postconditioning on ischaemia-reperfusion injury in rat heartObjective:To explore the effect of RIPostC on ischaemia-reperfusion injury in rat heart,and to explore the effect of highly specific inhibitor of SDF-1?receptor CXCR4(AMD3100)on RIPostC.Methods:In first section,thirty rats were randomly allocated to three groups:(1).I/R group:Left anterior descending coronary artery(LAD)was ligated for 30 minutes and then reopened for 120 minutes before chest closure.5 intracardiac injections were administered into myocardium adjacent to the ischemic zone using PBS at the time of reperfusion(5?L for one injection).(2)SDF-1?group:LAD was ligated for 30 minutes and then reopened for120 minutes before chest closure.5 intracardiac injections were administered into myocardium adjacent to the ischemic zone using recombinant mature rat SDF-1?protein at the time of reperfusion(5?L for one injection).(3)Sham groups:only thoracotomy without ligation on LAD.In second section,forty rats were randomly allocated to four groups:(1).I/R group:LAD was ligated for 30 minutes and then reopened for 120 minutes before chest closure,without RIPostC.(2)RIPostC group:LAD was ligated for 30 minutes and then reopened for 120 minutes before chest closure,RIPostC was performed at the time of reperfusion.PBS was delivered by intraperitoneal injection 10 min before RIPostC.(3)RIPostC+AMD3100 group:LAD was ligated for 30 minutes and then reopened for 120minutes before chest closure,RIPostC was performed at the time of reperfusion.AMD3100(10?g/kg)was delivered by intraperitoneal injection 10 min before RIPostC.(4)Sham groups:only thoracotomy without RIPostC and ligation on LAD.RIPostC was administered by tightening of a ligature around lower limb for 3 cycles of 5 minutes followed by release for 5 minutes.Myocardial infarct size were assessed with2,3,5-triphenyltetrazolium chloride(TTC)and evans blue staining after 120 min reperfusion.Results:In first section,myocardial infarct size in SDF-1?group was significantly lower compare to I/R group(40.61±7.23%VS 56.33±5.11%,P<0.01).In the second section,myocardial infarct size in RIPostC group was significantly lower compare to I/R group(38.41±4.52%VS 55.65±8.49%,P<0.01).Myocardial infarct size in RIPostC group was significantly lower compare to RIPostC+AMD3100 group(38.41±4.52%VS57.32±7.23%,P<0.01).There was no significant difference of infarct size between RIPostC+AMD3100 group and I/R group(P=0.60).Conclusion:1.The use of RIPostC on lower limb could attenuates myocardial infarct size in rat heart.SDF-1?also show protective effect on nfarct size in rat heart.2.The protective effect of RIPostC was blocked by AMD3100,which is the highly specific inhibitor of SDF-1?receptor CXCR4.
Keywords/Search Tags:Remote ischemic postconditioning(RIPostC), ST-segment elevation myocardial infarction(STEMI), stromal cell-derived factor-1alpha(SDF-1?), AMD3100, ischaemia-reperfusion injury
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