| Multiple organ dysfunction syndrome (MODS), a clinical syndrome, complicated with two or more systems/organs dysfunction or failure caused by severe damage or sepsis. Recent studies have shown that immunodisorder of Systemic Inflammatory Response syndrome (SIRS) and Compensatory anti-inflammatory response syndrome (CARS) is the basic pathophysiology in the pathogenesis of MODS. Many experiments and clinical studies have been put up aiming at the course of SIRS and MODS. These studies demonstrated that early blocking the development of SIRS might be a breakthrough for the therapy of MODS. Studies have demonstrated that the drug therapy against inflammatory mediators could not decrease the morbidity and mortality of MODS, therefore research turned to investigate the extracorporeal therapies because removing inflammatory mediators from blood is surely beneficial for the outcome of septic shock and MODS. It has been demonstrated that continuous hemofiltration can clear all kinds of soluble inflammatory mediators though convection and adsorption, which can adjust immune balance, block inflammatory response and improve prognosis of MODS.Objective: The purpose of this study is to investigate the effect and mechanism of different volume of continuous veno-venous hemofiltration (CVVH) and high volume hemofiltration (HVHF) on endotoxic shock and MODS by inducing animal model in early stage of cardiopulmonary damage with Escherichia coli endotoxin. The effect of different volume hemofiltration on cardiopulmonary damage and the production of inflammatory mediators were investigated in our study. Furthermore, to evaluate the effect of HVHF, we also carried out clinical observation on patients with MODS, which can provide theoretical and experimental foundation for clinic. Methods: 1 Twelve healthy male sheep, 7~8 months old, were used. All sheep were assigned randomly to the control group and the endotoxin group (6 for each group). The sheep skins was put sterile fabric after it poodled and antisepsis, and the right internal jugular vein was punctured and inserted with a 5 Fr Swan-Ganz catheter to monitor hemodynamics. The animals were anaesthetized with intravenous midazolam (400 ug·kg-1) and vecuronium (80 ug·kg-1). After tracheal intubation, the animals were mechanically ventilated. The animals were all stabilized, muscle released with continuously intravenous midazolam (50 ug·kg-1·h-1) and vecuronium (40 ug·kg-1·h-1) through the injectoc pum. The left internal jugular vein and femoral vein was punctured with a 8 Fr catheter and the left femoral arterial was put into a 20 G needle to connect the monitor. All invasive methods were conducted under local anaesthesia with 2% lidocaine.After stabilization for 30 min, endotoxin (L-2880 sigma) 1mg·kg-1 was infused i.v. in endotoxin group and 0.9% physiological saline 60 ml·h-1 in control group for 30 min. Both groups were treated with lactated Ringer's solution at 15 ml·kg-1·h-1 for 6 hours at the beginning of injection. Blood samples were collected from all animals before endotoxin infusion (T0, baseline) and at 60 min (T1), 360 min (T2) after endotoxin infusion was started. The blood uria nitrogen (BUN) and total bilirubin (TBIL) were measured in serum samples and the blood gas was analyzed in arterial blood. Heart rate (HR), mean arterial pressure (MAP), mean pulmonary arterial pressure (MPAP), pulmonary arterial wedge pressure (PAWP), systemic vascular resistance index (SVRI), pulmonary vascular resistance index (PVRI), stroke volume (SV), cardiac index (CI) and left ventricular stroke work index (LVSWI) were measured, calculated and recorded at T0~3. All animals were executed at the end of the experiment, and the cardiac, lung, liver and kidney were taken and fixed with 10% formalin. The same part was taken and embed with olefin, sliced up and dyed in HE method. The cardiac tissue slice was dyed in PATH method and observed with microscope. 2 Eighteen healthy male sheep, 7~8 months old, were used and assigned randomly to endotoxin group, CVVH gr...
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