The Clinical And Basic Research Of Septic Shock Associated Cardiac Dysfunction

Objective To research and analysis the clinical and hemodynamic status of refractory septic shock associated cardiac dysfunction,then to assess the role of different administrative level parameters of cardiac function in evaluating the endotoxic shock induced cardiac dysfunction,especially the role of relationship between the stress and strain;furthermore,to research the role of UCP2 in the mechanism of endotoxic shock induced cardiac dysfunction.Methods(1)70 refractory septic shock patients were studied.In the duration of hemodynamic optimization,the patients were divided into observation group who achieved the goals(CVP≥8mmHg,MAP≥65mmHg and SvO2≥65%)of goal-directed therapy(GDT)and controll group who had not achieved the goals.Every patient was placed a pulmonary artery catheter.Before it and 24hours later, hemodynamic parameters,lactate concentration and APACHEⅡscores were obtained.All the abtained values were analysised by statistics method.(2) 15 pentobarbital anesthetized and mechanically ventilated mongrel dogs were randomize divided into 2 groups:(A group) no injection of LPS(control group,n=6) and(B group) with LPS injection(n=7);Every dog was placed a pulmonary artery catheter and a Picco system. A single bolus injection of LPS(2mg/kg) through pulmonary aterial lumen of PAC was adopted to make endotoxic shock model.Hemodynamic parameters,transesophageal echocardiographic and Tissue Doppler Image(TDI)data are recorded every hour in the 6-hours duration of research.All the abtained values were analysised by statistics mcthod.(3) 26 pentobarbital anesthetized and mechanically ventilated mongrel dogs were randomize divided into 4 groups:(A group) no injection of LPS(control group,n=6); (B2group) 2 hours after LPS injection(n=6);(B4group) 4 hours after LPS injection (n=6);and(B6group) 6 hours after LPS injection(n=7).A single bolus injection of LPS(2mg/kg) through pulmonary aterial lumen of PAC was adopted to make endotoxic shock model.Hemodynamic parameters,transesophageal echocardiographic and Tissue Doppler Image(TDI)data are recorded to evaluate the cardiac function and myocardial function in the duration of research.Myocardial samples of every group are incised and studied by HPLC,western blots and RT-PCR.Results(1) 37%refractory septic shock patients had not acheived the goals of EGT.Age of observation group patients is significantly higher than patients of control group;CVP,PAOP,PAP,SVRI,PVRI,O2ext in observation group were significantly different from those in control group,CO,CI,D02I,SVO2 were significantly lower than patients of control group,SVO2 had a strong correlation with CI.If patients were regrouped by nonsurvivors and survivors,in patients complicated with cardiac dysfunction(observation group),ApacheⅡscores of nonsurvivors were significantly higher than survivors;Clac%(median 22%) of nonsurvivors were significantly lower than survivors(median -25%),P＜0.05.(2)CO,SV in endotoxic shock group were significantly different from those in control group at 6 hour,EF in endotoxic shock group were significantly different from those in control group at 5 hour,mVCF,Sm,SR in endotoxic shock group were significantly different from those in control group at 4 hour,the stress-strain characteristics of left ventricular myocardium in endotoxic shock group were significantly different from those in control group at 3 hour;cTnI have an negative corelation with EF and an strong correlation with mVCF,Sm and SR,NTproBNP have an negative an strong correlation with mVCF,Sm,SR and have an correlation with PAWP.(3) In endotoxic shock dogs,myocardial ATP,PCr are decreased and ADP are increase,ATP/ADP are decreased,PCr/ATP are decreased significantly; UCP2 expression are increased and UCP2 proteins are increased too;both are increased before the onset of myocardial dysfunction.Conclusion(1) In refractory septic shock patients,cardiac dysfunction was the main reason of not achieving the goals of GDT and maybe the reason leading to the bad outcome.Higher CVP and PAOP and lower SVO2 indicate the onset of cardiac dysfunction.The patients with significantly higher initial Lac and lower Clac%had bad outcome.(2) The different administrative level parameters of cardiac function,especially the stress and strain relation play a important role in evaluating and early discovering the endotoxic shock induced cardiac dysfunction,some cardiac biochemical marker:cTnI and BNP have a promising role to discover the endotoxie shock induced cardiac dysfunction(3) UCP2 have important impact in the mechanism of endotoxic shock induced cardiac dysfunction,UCP2 are increased before the onset of myocardial dysfunction.