Effect Of The Polyethylene Oxide To Liver And Renal Hemodynamics Of Endotoxin Shock Rabbits Detected By Ultrasonography

Septic shock is a type of shock of clinically prevalent and more difficultly treatment. The essence of septic shock is pathogenic microorganisms invade the body and lead to a large number of inflammatory mediators release caused by systemic inflammatory response syndrome (of SIRS). Sepsis is a results lead by acute organ dysfunction secondary to infection, clinical manifestations are fever, chills, tachycardia, altered mental status, and increased leukocyte. Septic shock is also known as toxic shock, endotoxic shock or septic shock, multiple organ failure caused by cause of death. Severe infection and septic shock often leads to acute kidney injury (acute kidney injury, AKI) the occurrence of AKI occurrence of multiple organ dysfunction (multiple organ dysfunction, MODS), and increase mortality. According to foreign literature, although in recent years, antibiotic use, intensive care and support for treatment has been great progress in endotoxemia and peptic shock mortality is still as high as30-60%. Septic shock lead to multiple organ failure caused the death of the ultimate cause of microcirculation is an important link in the pathophysiology of development.Fluid resuscitation currently recognized early endotoxemia in the maintenance of cardiovascular function, the primary treatment measures to restore hemodynamics, organizations and organ perfusion, but the early goals of treatment to restore blood volume can improve blood pressure and heart rate and circulation indicators of their enhance the effect of the survival rate is still not ideal. The reason may not microcirculation is improved, hypoxic ischemic tissues and organs are still ultimately lead to multiple organ failure related. Studies have found that more the number of organ failure and mortality. The continuing deterioration of the microcirculation in multiple organ failure, and ultimately lead to death. As soon as possible within24hours after the occurrence of endotoxemia microcirculation will significantly improve the mortality rate. However, when serious infections and (or) acute kidney injury, the use of vasopressors, there are a lot of controversy. Its use may lead to renal vasoconstriction, thereby reducing the renal blood flow and renal perfusion and increase the AKI. Thus, the major direction of the study for endotoxemia and Septic shock treatment is improved microcirculation, improved tissue and perfusion prevented multiple organ failure.Patients with serious infections complicated by acute renal failure in case fatality rate of upto70%, significantly higher than other causes of ARF fatality. Recent studies suggest that, even if the serum creatinine values increased slightly, also lead the mortality of critically ill patients significantly increased. It can be said that a serious infection caused by the high morbidity and mortality of acute renal injury and the lack of specific treatment, and also its pathogenesis poorly understood. Severe infections caused by acute renal injury in the pathogenesis is multifactorial, related to the change of renal hemodynamics and renal perfusion, changes in renal cell function and injury, inflammation and immune network response and the complexity of the toxin-like substance induced endotoxin in many ways, at home and abroad with septic shock caused by acute kidney injury kidney hemodynamics, there are inconsistent results.Liver of septic shock caused by organ dysfunction, easily damaged, one of the target organ. One:endotoxin can directly stimulate Kupffer cells to release tumor necrosis factor a (TNF-a), platelet-activating factor (PAF), interleukin I (IL-I) and other inflammatory mediators, further the role of liver sinusoidal endothelial cells and microvascularactivation within the coagulation system, resulting in the intrahepatic microcirculation; Activated Kupffer cells release inflammatory factors may promote the aggregation of neutrophils (PMNS) in the sinusoidal further through the "respiratory burst" as a result of liver cell injury; Increased during the reperfusion of LPS with specific antibodies in the hepatocyte membrane binding, directly damage the liver cells; Second, septic shock, hepatic microcirculation blood flow slowed down, reduced hepatic blood flow, ischemia and hypoxia of liver cells, can cause intracellular calcium overload, excessive oxygen free radicals, neutrophils generate increased, thuscause liver cell damage.Septic shock and recovery period can also be caused by hepatic ischemia-reperfusion injury. Hepatic ischemia-reperfusion injury is Shock recovery of local and systemic injury caused by clamping the hepatic pedicle or liver transplantation from the donor liver ischemia re-perfusion in the surgery of liver surgery. Intracellular calcium overload, oxygen free radicals, excessive apoptosis generate excessive and inflammatory cytokine activation and other major pathophysiological mechanism; drugs for the mechanism of injury in order to prevent hepatic ischemia-reperfusion injury of the main measures; the current study confirmed the protective effect: calcium antagonists, free radical scavenger, inflammatory cytokine inhibitor, improvement of microcirculation drugs, energy substrates, such as Chinese medicine.Drag-reducing polymers (DRPs) are polymers which can reduce the flow resistance. Toms (1948) was first reported drag reduction phenomenon (Toms effect): a small amount of DRPs in the liquid can reduce the transport of liquid in the pipe turbulence resistance, and thus increase traffic in the case of constant delivery pressure, or the same situation in the flowto lower the delivery pressure. The DRPs are used in medicine included synthetic polymers and polysaccharide polymers natural materials from natural materials (e.g., plants, bacteria and animal blood). The synthetic DRPs included:polyethylene oxide (PEO), polyethylene glycol (PEG), the anionic polysaccharide (Separan), et al. Has been demonstrated in DRPs can increase coronary blood flow, improve the prognosis of acute ischemic animals, inhibition of in vivo atherosclerosis plaque formation; can improve the survival rate of hemorrhagic shock animals, improve perfusion and tissue oxygen supply; acts as a diuretic, paul sodium potassium row.A lot of studies have confirmed that the DRA can significantly improve the survival time of fatal hemorrhagic shock animals, improve the shock microcirculation perfusion play an anti-shock effect, reducing the damage of the mechanical action on erythrocyte. Otherwise, Donald et al found the DRA can be diuretic and potassium row the function of the sodium. Existing research suggests that play more than the possible mechanism as follows:(1) increase the red blood cell deformability, making it easier through the microcirculation;(2) reduce plasma distance themselves from the effects (plasma skimming effect), the red blood cell suspensionmicrovascular flow, near the tube wall will produce a relatively small area cells, a phenomenon for the plasma to distance themselves from the DRA can be significantly reduced near the pipe wall thickness of less red blood cell plasma, the red blood cellsredistribution near the tube wall, making the arterial and capillary blood gas exchange more convenient;(3) decreased plasma flow reynolds to reduce the plasma flow turbulence, reducing vascular resistance;(4) reduce the "method-Lin efficiency (Farhaeus-Lindqvist effect)"reversal of the critical radius can make the red blood cells smaller microcirculation resistance decreased, thereby increasing the red blood cell oxygen supply to the local tissue. All of these studies prompted the DRA for blood flow acceleration.However, Dppis used for severe infections or septic shock research rarely reported. Therefore, to the DRA on the treatment of severe infections or septic shock, looking for new and effective drugs for clinical treatment, have important clinical significance. The study intends to establish a model of endotoxin septic shock in rabbits, the use of ultrasound monitoring observation of endotoxin shock in rabbits by DRA treatment of renal hemodynamics and tissue/organ perfusion changes and the impact on renal function, liver blood flowmechanical changes, and liver function, AKI due to septic shock or acute renal failure (acute renal failure, ARF), and liver dysfunction to explore new avenues of treatment.Ultrasound as a noninvasive monitoring tool to study accurately reflected the rabbit shock renal hemodynamic and liver Hemodynamic changes. Adjust each ultrasonic measurement parameters under the premise of accurate real-time measurement of kidney three intravascular blood flows and the hepatic artery and portal vein blood flow, measured by the flow rate of resistance index and power index, but also clearly the nature of blood flow through the blood flow waveform. Furthermore, two-dimensional ultrasound can real-time monitoring of liver and kidney essence of change and nature the blood character by the flow waveform.1Materials and methods1.1Drugs and reagentsEscherichia coli endotoxin (LPS, Escherichia coli, serotype L2630, Sigma Company), PEO5000(Sigma), normal saline,20%urethane.1.2Instruments Monitor (Philips Intellivue MP20), micro-infusion pump (Germany Fresenlus the Kabi injectomat Agilia the RC), cellulose membrane dialysis bag (Spectrum), color Doppler ultrasound instrument (GE LOGIQ-e).1.3AnimalsOrdinary level20New Zealand white rabbits (Southern Medical Experimental Animal Center),2-2.5kg.1.4Method1.4.1Preparation of DRAWeigh of PEO20mg, dissolved in1000ml normal saline was prepared by the solution concentration of20ppm, and the molecular interception of40,000dialysis bags in saline dialysis24hours to remove impurities, and stored at4℃refrigerator.1.4.2Preparation of animal models20New Zealand white rabbits, weighing2-2.5kg,20%urethane3.5ml/kg, ear vein anesthesia. Ear vein24G intravenous catheter is indwelling for infusion and drug delivery. Right groin and skin preparation, sterilization, free shares, arterial puncture catheter, connect the monitor to monitor arterial pressure. When the blood pressure is stable, the marginal ear vein injection of endotoxin (the lipopolysaccharide, LPS),0.6mg/kg, the preparation of sepsis shock in rabbit model of infection. Such as decreased blood pressure≥30%, and is considered shock.1.4.3Model grouping and data acquisitionWere randomly divided into two groups of PEO group containing20ppm DRA saline resuscitation to reach the standards of the shock model, the NS group with the same dose of saline resuscitation, infusion rate was5ml/kg/h. When blood pressure reduced by≥30%, started to recover, recovery time of1hour. And before the injection of LPS (TO),1.5hour (T1) and the recovery of the ultrasound data were collected after1hour (T2), and blood test kidney function. Blood anticoagulant after 3000r/min centrifugation for10minutes the supernatant was stored at4℃to do a kidney function test.1.4.4Ultrasonic testing methodsSupine fixed the rabbits after anesthesia, and removed the detection zone hair, observed changes in the renal parenchyma and measurement of the right kidney size and the real thickness by the two-dimensional ultrasound (2DUS)(U.S. GE-logiQ,-e color Doppler instrument with12-MHz linear array probe). Usede the Velocity flow imaging (CVI) to observe the renal blood flow distribution through. Monitoring of renal main renal segment, renal interlobar artery peak systolic blood flow velocity (PSV), end diastolic velocity (EDV), resistive index (RI), stroke power index (PI) and the accompanying vein of the average velocity (Vmean) by pulse wave Doppler (PW). Detection of portal vein (PV) maximum velocity (PSV) and minimum velocity (EDV), the detection of hepatic artery (HA), systolic peak velocity (PSV), end diastolic degrees (EDV), resistive index (RI).PW sample volume of1-2mm, the flow direction of the sound beam angle of20-60degrees. Each parameter measured three consecutive waveforms, find the mean number entered into the database statistics. Blooding femoral vein for each stage, and monitoring two group rabbit kidney biochemical indicators.1.4.5The statistical treatmentSPSS13.0statistical analysis on data collected for statistical analysis. All measurement data are mean±standard deviation (x±s), and homogeneity of variance test. The two groups of White Rabbit monitoring indicators at different time points were compared using repeated measure analysis of variance of the data. Each index in each group at each time point was used to compare oneway-ANOVE, said the difference was statistically significant (P<0.05). Separate the two groups of rabbits at each time point were compared using independent sample t test, P<0.05indicated statistically significant difference.2Results1. After recovery in the experimental group of the polyethylene oxide recovery after septic shock in rabbits mean arterial pressure was significantly higher than that in the control group (P=0.001), and more stable than the control group.2. Two groups of rabbits at all levels of the renal artery shock of blood flow velocity was significantly lower than the shock (P<0.05), the artery the PI, RI, compared with before shock was significantly higher recovery of one hour of PEO renal segmental artery and interlobar artery flow rate higher than before the shocksignificantly increased (P<0.05), PI, RI, decline, vein, Interlobar vein flow velocity than the shock of the flow rate was significantly faster (P<0.05), renal artery, the main vein blood flow growth is not obvious; NS group, the levels of renal artery flow velocity on a downward trend, the PI, and RI did not significantly reduce, three renal vein flow velocity slowed down. In addition, the recovery of one hour, compared with the NS group, PEO group at all levels of renal dynamic venous flow. velocity is higher, renal interlobar arteries and interlobar vein flow velocity was significantly increased (P<0.05); of PEO group of threeartery in the recovery after one hour PI, RI, continues to rise compared with the NS group was significantly decreased (P<0.05).3. Renal function:the shock of BUN and, two groups of rabbits and Cr were increased recovery after one hour DRA groups, all significantly lower than in the saline group (P<0.05).4. Two sets of rabbit hepatic artery (HA) in the shock of blood flow velocity was significantly lower than the shock (P<0.05), the artery the PI, and RI than before shock was significantly higher recovery of one hour, of PEO hepatic artery flow rate faster than the shock before significantly increased (P<0.05), PI, RI, decreased portal vein flow velocity than the shock of blood flow velocity was significantly faster (P <0.05), the NS group, the hepatic artery and portal vein blood flow rate on a downward trend, the PI, and RI is not significantly reduced. The two groups of rabbits the main effect of ultrasound hemodynamic parameters between groups, no significant difference (P>0.05).5. Indicators of liver function:two groups of rabbits shock of ALT and AST in increased recovery after one hour of ALT, AST, and the shock of no significant difference between the two groups no significant difference (P>0.05).Conclusion1. A small dose of polyethylene oxide can be significantly improved the blood perfusion of endotoxin shock in rabbit kidney, improve circulation, and renal cortex early ischemia has been effectively improved.2. In the case given the same amount of fluid resuscitation, application of poly ethylene oxide endotoxemia New Zealand rabbit blood pressure is more stable.3. To give the rabbit arterial polyethylene oxide recovery in the recovery of urea and creatinine values decreased, indicating that the polyethylene oxide has a protective effect on the kidneys.4. Polyethylene oxide can significantly improve the endotoxin shock in rabbits liver perfusion, the portal vein and hepatic arterial blood flow to accelerate, improve liver early ischemia.