| At present,the incidence rate of acute myocardial infarction(AMI)showed an upward trend,age of onset was younger trend.Percutaneous coronary intervention(PCI)reopens the infarct-related coronary artery to reduce the infarct size and the death rate as well as improve the prognosis in patients with AMI,which has become the pivotal treatment for AMI.Although studies have shown that patients with AMI have reopened epicardial coronary artery by thrombolysis or PCI treatment,but the survival rate has not been improved significantly.The reason may lie in that the patients unable to restore effective myocardial perfusion after the ischemia related coronary artery revascularization,which was named coronary microvascular dysfunction(CMVD).However,the process of myocardial reperfusion can itself induces further cardiomyocyte injury,known as ischemia and reperfusion(I/R)injury,which can attenuate the full benefits of myocardial reperfusion.Prolonged myocardial ischemia gives rise to endothelial cells swelling,myocardial cell swelling and interstitial edema,which might cause microvascular compression.A massive infiltration of coronary microcirculation by neutrophils and platelets occurs at the time of reperfusion to result in activating endothelial cell,neutrophils,and platelets,subsequently releasing oxygen free radicals,proteolytic enzymes,and pro-inflammatory mediators that make the synthetize of nitric oxide decrease and the production of superoxide increase within reperfusion of ischemic tissues in minutes.This state leads to an exacerbation of the inflammatory state,a injury to myocytes,and a disturbance of coronary microcirculation.Myocardial microcirculation perfusion is one of the important factors for the success for reperfusion therapy.The mechanism of CMVD has not been clearly elucidated so far.A lot of researchers make efforts on that,however,they haven’t come with a systemic scheme.Prostaglandin E1(PGE1)is an important endogenous substance with many physiological and pharmacological actions and has widely applied in clinical practice.As a vasodilator,PGE1 has gained a good effective on pulmonary hypertension.In recent years,experiments have proved PGE1 can reduce myocardial infaction area,reducing the level of myocardial infaction and inhibit platelet adhesion and aggregation from myocardial I/R injury.Liposomal prostaglandin E1(Lipo-PGE1)has features of good targeting,continuity and high efficiency.Which can reduce platelet aggregation through increased platelet in c-AMP content.Studies have shown that Lipo-PGE1 has an early protective effect on the myocardial I/R injury and could decrease the myocardial infarct size.However,there has been no report on the effect of Lipo-PGE1 on CMVD in patients with I/R injury in acute myocardial infarction.This study consists of the following three parts.Part one Effect of intravenous administration of Lipo-PGE1 on microcir-culation in patients with STEMI undergoing primary PCIObjectives: The aim of this study was to discuss that Effect of intravenous administration of Lipo-PGE1 on microcirculation in patients with STEMI undergoing primary PCI.Methods: 68 patients with STEMI undergoing primary PCI were randomly assigned to two groups: intravenous administration of Lipo-PGE1(group PGE1),and no Lipo-PGE1 administration(group CON).The ST-segment resolution(STR),corrected TIMI frame count(CTFC)and myocardial blush grade(MBG)were calculated.Patients were followed up for 6 months.Major adverse cardiac events(MACE)were also measured.Results: There was no significant difference in the baseline characteristics between the two groups.The CTFC parameter in group PGE1 was significantly lower than group CON(18.06± 2.06 vs.25.31 ± 2.59,P<0.01).The ratio of final MBG grade-3 was significantly higher(P<0.05)in group PGE1(87.9%)relative to group CON(65.7%).The STR in 90 min after PCI of group PGE1(71.5 ± 7.31)% was significantly higher than group CON(59.4 ±9.63)%(P<0.01).Patients were followed up for 6 months and the occurrence of MACEs in group PGE1 was significantly lower than that in group CON(6.1% vs.25.7% respectively,P<0.05).Conclusions: Lipo-PGE1 pretreatment can obviously increase myocardial perfusion and improve myocardial microcirculation in patients with STEMI undergoing primary PCI.Part two The effect of Lipo-PGE1 on myocardial reperfusion in patients with NSTEMI after elective PCIObjectives: The purpose of this study was to to assess the effect of Lipo-PGE1 on myocardial microcirculation reperfusion in patients with NSTEMI after elective PCI by myocardial contrast echocardiography(MCE).Methods: 85 cases with confirmed diagnosis of NSTEMI were randomly assigned to two groups: routine medical therapy group(group CON),and Lipo-PGE1 plus routine medical therapy group(group PGE1).Group CON was given anticoagulation,antiplatelet aggregation,against myocardial ischemia and other treatment.Group PGE1 was given Lipo-PGE1(20μg per day,intravenous)besides basic treatment.The coronary angiography and PCI were performed after 10 days in 57 cases.MCE was taken since 48 hours after PCI.Observation parameters include: myocardial perfusion time(MPT),contrast score index(CSI)and time intensity curve(TIC)with MCE.Follow-up was conducted for 12 months to assess the occurrence of MACEs.Results: There were no significant differences in baseline characteristics between the two groups.The MPT of group CON significantly higher than that of group PGE1(3.85±1.04 vs.2.92±1.31 P=0.004).The CSI of all objects are not less than 0.5.The CSI of group PGE1(0.96±0.11)was significantly higher than group CON(0.87±0.18)(P=0.027).The A,β and A·β of group CON(4.95±0.73,0.71±0.31,3.81±0.29)was significantly lower than group PGE1(5.32±0.44,0.87±0.26,4.71±0.35),(P=0.025,P=0.039,P=0.000).However,the incidence of MACEs had no difference between two groups(group CON vs.Group PGE1;20.7% vs.14.3%,P=0.781).Conclusions:1 MCE can objectively evaluate myocardial microcirculation perfusion in patients with NSTEMI undergoing elective PCI.2 Lipo-PGE1 can obviously improve myocardial reperfusion in patients with NSTEMI undergoing elective PCI.Further studies should be carried out to determine whether Lipo-PGE1 can improve long-term prognosis of NSTEMI patients.Part three The effect of Lipo-PGE1 on microcirculation disorders induced by myocardial ischemia reperfusion in ratsObjectives: The aim of our study was to establish a ischemia reperfusion injury rat model of myocardial infaction and investigate the effect of Lipo-PGE1 on microcirculation disorders.Methods: 60 adult SD rats were randomly assigned into 3 groups: sham-operation group(SO group),ischemia reperfusion group(I/R group)and Lipo-PGE1 treatment group(PGE1 group),20 in each group.After reperfusion for 120 minuters,the plasma nitric oxide(NO),endothelin-1(ET-1),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)levels were detected.15 SD rats from each group were observed the myocardial capillary perfusion density by ink perfusion method and ultrastructure in myocardial microvascular were also observed under transmission electron microscope in 5 from each group.Results: After reperfusion for 120 minuters,the NO content in I/R group obviously lower to SO group(0.19±0.05 vs.0.24±0.03,P<0.01).The NO content in PGE1 group was nearly unchanged,compared to SO group(0.23±0.03 vs.0.24±0.03,P=0.298).The NO content was higher in PGE1 group than that in I/R group(0.23±0.03 vs.0.19±0.05,P<0.01).The ET-1 content increased obviously in both I/R group and PGE1 group comparing with that in SO group(46.2±2.23 vs.41.8±2.01,P<0.01;43.5±3.15 vs.41.8±2.01,P=0.048).In PGE1 group,the level of ET-1 was significantly lower than that in I/R group(43.5±3.15 vs.46.2±2.23,P<0.01).After reperfusion for 120 minuters,The IL-6 content increased obviously in both I/R group and PGE1 group comparing with that in SO group (146.1±2.74 and 142.6±4.31 vs.137.3±3.61,P<0.01).In PGE1 group,the level of IL-6 was significantly lower than that in I/R group(142.6±4.31 vs.146.1±2.74,P<0.01).The TNF-α content was higher in I/R group than that in SO group(3.29±0.22 vs.2.63±0.12,P<0.01).The TNF-α content in PGE1 group was nearly unchanged,compared to SO group(2.71±0.19 vs.2.63±0.12,P=0.119).In PGE1 group,the level of TNF-α was significantly lower than that in I/R group(2.71±0.19 vs.3.29±0.22,P<0.01).The capillary density decreased obviously in both I/R group and PGE1 group comparing with that in SO group(58.8±7.26 and 82.6±8.33 vs.94.3±9.03,P<0.01).The capillary density was higher in PGE1 group than that in I/R group(82.6±8.33 vs.58.8±7.26,P<0.01).Under light microscope,myocardial perfusion is better and only a few part of infiltration of neutrophilic granulocytes were observed in SO group.Of I/R group,the myocardial capillary perfusion number were decreased significantly,lots of neutrophilic granulocyte were observed.The myocardial capillary perfusion number of PGE1 group were better than that of I/R group and the infiltration of neutrophilic granulocytes were also decreased significantly.The ultrastructure alteration of endothelium in microvessel.In SO group: Normal myocardial capillary consists of single or multiple endothelial cells.The tight junctions between the endothelial cells were normal.The endothelial nuclei swelling and deformation phenomenon were not seen.Lumen was unobstructed,single red blood cell can through the lumen.Which didn’t show any myocardial cell degeneration necrosis,and interstitial hyperemia and edema.In I/R group: The form of the vascular endothelial cell was damaged.The endothelial cell nucleus gap widened and the amount of extend endothelial projections into the lumen of the capillaries increased.The vacuolar change and the tight junctions were loosed.The lumen is narrowed and single red blood cell can’t through the lumen.Myocardial cell degeneration necrosis,and interstitial hyperemia and edema.In PGE1 group: The injury of the vascular endothelial cell was mild.The endothelial cell nuclei had light swelling.The stenosis of capillary lumen was lightly and single red blood cell can through the lumen by deformation.Conclusions:Lipo-PGE1 can improve myocardial microcirculation disorder induced by I/R injury through suppression of inflammation and protection of the capillary endothelial cells. |
PDF Full Text Request