Effect Of Lipoxin A₄on Cardiac Dysfunction In Post-cardiac Arrest Syndrome

Objective To investigate whether lipoxin, a lipid mediator with wide anti-inflammatory features, can meliorate myocardial dysfunction after cardiopulomonary resuscitation through promoting inflammatory subsidences, andexplore the mechanism of lipoxin protecting myocardium in the rabbit model of asphyxial cardiac arrest.Methods①18Adult New Zealand rabbits were randomly divided into three groups: Sham group(n=6), CPR group(n=6) and Lipoxin group(n=6). All the rabbits were anaesthetized by marginal vein of the ear, deposited a tracheostomy tube, right common carotid artery, jugular vein and femoral artery catheters. The rabbits in CPR group and LX group were induced asphyxial by7-9minutes by clamping.3minutes after cardiac arrest, chest compression and mechanical ventilation were initiated. After ROSC,1.5ug/kg lipoxinA4and equivalent volume of2%ethanol were given to rabbits in LX group and CPR group respectively. After Hemodynamic and rectal temperature were observed for6hours after resuscitation, Femoral artery blood sample was taken to detect routine blood test, blood gas analysis and TnI, and heart sample was taken to detect myocardial necrosis area, pathological structure with optical and electron microscope, apoptosis, IL-1β, IL-6, IL-10, TNF-a and NF-κB(by the method of ELISA, IHC and Western Blot).②Human umbilical vein endothelial cells were randomly divided into three groups:control group, ischemia reperfusion group and LX group. First,flow cytometry was used to detect apoptosis rates of human umbilical vein endothelial cells of each group.CCK-8was used to detect survival rates of human umbilical vein endothelial cells of each group. Then, ELISA was used to detect the levels of TNF-a, ICAM-1, IL-6and IL-8that expressed by the human umbilical vein endothelial cells of each group. The active level of erk, p38and JNK of human umbilical vein endothelial cells of each group were detected with Western Blot. Results The mean aterial pressure (MAP), the left ventricular systolic pressure (LVSP), the scores of dp/dtmax and-dp/dtmax were significantly reduced after resuscition. Compared with those in CPR group, MAP, LVSP, dp/dtmax and-dp/dtmax was higher in LX group; Six hours after resuscitation, the number of leukocyte and neutrophil was significantly lower in LX group; the infarct area was smaller and the apoptosis index was lower in LX group. The myocardial injury in lipoxin group was lighter than that in CPR group with optical microscope and electron microscope. And the neutrophil infiltration was observed in CPR group, but not in LX group. The expression of IL-1β, IL-6, TNF-a and NF-kB was significantly lower in LX group comparing CPR group, and the expression of IL-10in LX group was higher than that in CPR group.Exogenous Lipoxin A4can reduce human umbilical vein endothelial cell necrosis rate and TNF-a expression levels in ischemia reperfusion model.Conclusion This experiment confirms that myocardial function can be significantly improved by injecting exogenous Lipoxin A4. Specific mechanism contains that Lipoxin A4facilitates inflammatory subsidence in myocardial ischemia reperfusion in PCAS, inhibits activation of NF-κB, reduces neutrophil infiltration, lowers the expression of positive inflammatory cytokines, raises the expression of negative inflammatory cytokines, and reduces myocardial necrosis and apoptosis.This study found that administration of exogenous lipoxin A4to reduce ischemia reperfusion umbilical vein endothelial cell necrosis rates and improves ischemia reperfusion umbilical vein endothelial cell survival trend.