Clinical And Experimental Research On Myocardial Depression Induced By Severe Sepsis

Objective The objectives of this study was to investigate the influence of myocardial depression on patients with septic shock. Then to evaluate the effect of mitochondrial resuscitation on myocardial depression induced by severe sepsis, assess the role of melatonin on heart function, prognosis and myocardial energetics in a rat model.Methods Seventy seven septic shock patients were retrospectively studied, they were divided into two groups based on cardiac index (CI) after early resuscitation, high CI group:CI>3 L/min-m2, low CI group:CI<3 L/min-m2. Rate of goal achievement, prognosis and whether the global end diastolic volume index (GEDI) increases with central venous pressure (CVP) growth of the two groups were compared. Rats were divided into four groups, B group(Baseline, n=10)- no operation, S group(Sham operation, n=10)-only laparotomy without cecal ligation and puncture, C group(CLP, n=40)- cecal ligation and double puncture, M group(Melatonin, n=40)- underwent cecal ligation and double puncture, then melatonin injection 30mg/kg, at 3h,6h,12h,18h,24h. The mortaltiy rate of C and M group being compared. The myocardial mitochondial cytochrome oxidase(CcOX) activities at 48h were detected, and so were blood gas, serum cardiac troponin I, serum B-type natriuretic peptide, myocardial adenosine triphosphate(ATP), adenosine diphosphate(ADP), phosphocreatine(Pcr), and myocardial glucose transporter 4(GLUT4). Heart function were being evaluated by echocardiography at baseline,24h and 48h. Myocardial 18-Fluorodeoxyglucose (18F-FDG) uptake of B goup, C group and M group were evaluated using positron emission tomography(PET) at 24h and 48h.Results (1)There were 38 patients in the low CI group, and 39 patients in the high CI group; Compared with patients in the high CI group, patients in the low CI group had older age and higher APACHE II score, P<0.05; Compared with patients in the high CI group, patients in the low CI group had higher mortality rate and lower rate of goal achievement, P<0.05; In low CI group,16 patients'GEDI didn't increase with CVP growth, and in high CI group only 6 patients'GEDI didn't increase with CVP growth, P<0.05; In low CI group, Patients whose GEDI didn't increase with CVP growth had higher arterial lactate, lower CI, lower ScvO2, lower rate of goal achievement and worse prognosis than patients whose GEDI increased with CVP growth. P<0.05. (2) Myocardial mtionchondrial CcOX activities of C group were much lower than those of B group, S group and M group, P<0.01. (3) The mortality rate of C group was much lower than that of M group,χ2=4.607, P<0.05. (4) Serum lactate level in C group were much higher than those in B group, S group and M group, P<0.05. (5) Serum cTnI and BNP level in C group and M group were much higher than those in B group and S group, P<0.05. (6) Ejection fraction(EF) of C group were lower than M group at 48h, P< 0.05.EF in C group and M group correlated with CcOX activity, r=0.547, P=0.028. (7) The myocardial ATP level of C group was lower than B group and S group, P<0.05; The ATP level of M group was lower than B group, P<0.05. The Pcr level of C group was much lower than B group, S group and M group, P<0.01; The Pcr level in M group was lower than B group and S group, P<0.01. (8) The uptake of 18F-FDG in C group and M group was higher at 48h than B group, P<0.05. (9) The optical density(OD) of GLUT4 in C group was higher than B group and S group, P<0.01; The OD of GLUT4 in C group was also higher than M group, P<0.05.Conclusions:(1) Septic shock patients with CI<3 L/min-m2 after early resuscitation tend to have worse prognosis. Correlation between CVP and GEDI can reflect cardiac function for septic shock patients. Patients whose GEDI doesn't increase with CVP growth often have myocardial depression and worse prognosis.Older septic shock patients and those with higher APACHEⅡscore tend to have the complication of myocardial depression. (2) Mitochondrial dysfunction ermerged in severe sepsis characerized by decline of cytochorome oxidase activity, which correlated with EF; Myocardial ATP and Pcr were below the normal level in severe sepsis, while myocardial GLUT4 expression and uptake of 18F-FDG were above the normal level. Melatonin increased mitochondrial oxidase activity in septic heart through decreasing reactive oxygen species and reactive nitrogen species, thus ameliorated the myocardial energetics, EF and SV. Mitochondrial resuscitation can be beneficial to heart function, tissue perfusion and prognosis.