| ObjectiveMechanical ventilation can induce ventilator-associated lung injury.Small tidal volume can alleviate hng injury compared with large tidal volume.But is 6ml/kg or even less better than 8-10ml/kg? And what about those who are not ARDS patients but require,mechanical ventilation?Most of the ventilated ARDS patients died of MODS.The mechanism of mechanical ventilation inducing MODS was unclear.Cytokines may play an im portant role in the process.It is necessary to think about the protection of the body as a whole,not only the lung,when talking about the protective mechani cal strategy.The study about the wide "protective" mechanical ventilation is rare by now.Shock is a kind of common serious diseases and susceptible to ALI/ARDS or MODS,especially the septic shock.It was unclear about appropriate tidal volume during the resuscitation of shock by now.The aim of the research was to study the characteristics of the injury of lung,kidney and intestine of hemorrhag ic and endotoxic shock and the effects of cytokines on the relationship between mechanical ventilation and MODS,and give an approach to the appropriate tidal volume during the resuscitation of shock.Methods48 rabbits were divided into six groups;group A;hemorrhagic shock and ventilated with the small tidal volume of 4-6ml/kg;group B;hemorrhagic shock and ventilated with the medium tidal volume of 8-10ml/kg;group C; hemorrhagic shock and ventilated with the large tidal volume of 12-15ml/kg; group D;endotoxic shock and ventilated with the small tidal volume of 4-6ml/ kg;group E;endotoxic shock and ventilated with the medium tidal volume of 8 -10ml/kg;group F;endotoxic shock and ventilated with the large tidal volume of 12-15ml/kg.Hemorrhagic shock and resuscitation model;the blood was rapidly drawn out from the carotid to maintain the main artery blood pressure at 38-42mmHg for one hour.Then the blood and isotonic saline was infused to maintain the sys tolic blood pressure at 90-100mmHg for two hours.Endotoxic shock and resuscitation model;endotoxin of 1 mg/kg was infused intravenously by the speed of 0.1 mg/min to maintain the mean artery blood pressure at 38-42mmHg for one hour.Then the isotonic saline and dopamine was infused to maintain the systolic blood pressure at 90-100mmHg for two hours.During the shock period,all the animals were ventilated with the tidal vol ume of 8-10ml/kg,FiO221%,PEEP0cmH2O.During the resuscitation peri od,the animals were ventilated with designed tidal volume,FiO2 40%, PEEP0cmH2O,R40bpm for tow hours.After two hours of designed mechanical ventilation,accompanied by resus citation,heart rate,blood pressure,the amount of resuscitation fluid,peak air way pressure,plateau airway pressure,lung compliance,lower inflection point of pressure-volume curve blood gas,Phi(PH value of the mucosa of stom ach)were detected.The concentrations of cytokine TNF-α,IL-6 and IL-10 in the BALF and blood were measured by ELISA method.The pathologic chan ges were observed by optic and electronic microscopy.Apoptosis was detected by TUNEL method.SPSS11.5 software was used to analyze the data.Results1.There was no statistic difference among the blood pressure,heart rate and the amount of resuscitation fluid of the six groups.And the influence may caused by these factors can be excluded.There were 5,1,2 animals using dopa mine in group A,B,C separately.All the animals of the endotoxic shock group used dopamine,and there was no statistic difference among the amount of dopa mine of the three groups of different tidal volume.2.The peak pressure and plateau pressure significantly increased along with the elevation of tidal volume.The lower inflection point of the groups of large tidal volume was higher,and the compliance was lower than that of the groups of other tidal volume.There was no statistic difference between the groups of small and medium tidal volume.No statistic difference among the re spiratory mechanics indexes was detected between the hemorrhagic and endotoxic shock.The respiratory mechanics indexes were better correlated with the patho logic score of lung of the hemorrhagic shock than that of the endotoxic shock.3.There was no statistic difference among the blood gas indexes of the hemorrhagic and endotoxic shock and no statistic correlation between the blood gas indexes and the pathologic scores of kidney and intestine.4.No statistic difference was detected among the Phi of the six groups.The Phi level was negative correlated with the pathologic score of intestine,and had not statistic relationship with blood gas indexes and the pathologic score of kid ney.5.The characteristics of lung injury of the hemorrhagic shock were more significantly dependent on gravitational force,widen of alveolar septum under optic mioroscopy,and decrease of electronic density of luminal bodies of typeⅡalveolar cells under electronic microscopy.The characteristics of lung injury of the endotoxic shock were widely spread and more serious than that of the hemor rhagic shock,additionally widely intra-alveolar effusion under optic microsco py,and widen of intercellular junctions under electronic microscopy.The degree of lung injury was most mild in the groups of small tidal volume compared with the other groups.The apoptotic index of lung was not paralleled with the patho logic score of lung.6.The injury of kidney of the hemorrhagic shock was more serious than that of the endotoxic shock,and characterized by relatively significantly interstitial e- dema under optic microscopy,and mitochondrial injury of epithelial cells of re nal tubuli under electronic microscopy.The injury of kidney of the groups of large tidal volume was more serious than that of the other groups,and character ized by thicken of the base membrane of renal glomeruli.There was no statistic difference between the pathologic scores of kidney of the groups of small and me dium tidal volume,but the apoptotic index of kidney of the group of medium tid al volume of the hemorrhagic shock was lower than that of the small one,and no statistic difference was detected between the apoptotic indexs of kidney of small and medium tidal volume of the endotoxic shock.7.The injury of intestine of the endotoxic shock was more serious than that of the hemorrhagic shock,and the injury of the intercellular junctions was more obvious under the electronic microscopy.The injury of intestine of the groups of large tidal volume was heavier than that of the other groups,and with heavier cilia injury under electronic microscopy.The pathologic scores of intestine had no statistics difference between the groups of small and medium tidal volume of the two type of shock.The apoptotic index of intestine of the medium tidal vol ume group had the reducing trend compared with that of small tidal volume group in the hemorrhagic shock,but had no statistic difference in the endotoxic shock.8.The concentration of TNF-αin the BALF had no difference among the three groups of the hemorrhagic shock,but increased significantly with the ele vation of tidal volume in the endotoxic shock.The concentration of TNF-αin the blood increased significantly with the elevation of tidal volume in the two types of shock,and was positively correlated with the pathologic scoreof intes tine.The concentrations of TNF-αin both the BALF and the blood of the en dotoxic shock were higher than those of the hemorrhagic shock.9.The concentrations of IL-6 in BALF and blood in the two types of shock were all increased with the elevation of tidal volume.And the concentra tions of them in the endotoxic shock were higher than those of the hemorrhagic shock.The IL-6 level in the BALF was positively correlated with the injury of the lung,and the IL-6 level in blood was positively correlated with the injury of the kidney and intestine.No statistic difference was detected among the con centrations of IL-10 in BALF and blood of the six groups,and the IL-10 level was not correlated with the injury of lung,kidney and intestine.10.The ratio of IL-6/IL10 was increased with the elevation of tidal vol ume not only in BALF but also in blood,and was higher in the endotoxic shock than in the hemorrhagic shock.The ratio in the BALF was positively correlated with the injury of lung,and the ratio in blood was positively correlated with the injury of kidney and intestine.Conclusions1.There was no statistic difference in the respiratory index and blood gas between the two types of shock.The injury of lung,kidney,and intestine of the hemorrhagic shock was lighter,heavier,and lighter separately than that of the endotoxic shock.2.The injury of lung,kidney,and intestine in the groups of large tidal vol ume was most serious.In the hemorrhagic shock,the injury of lung of the group of small tidal volume had lighter trend compared with the group of medium tidal volume.No statistic difference was found between the injuries of the groups of small and medium tidal volume.But the apoptotic index of kidney of the group of medium tidal volume was lower than that of the group of small tidal volume, and the apoptotic index of intestine had lower trend.In the endotoxic shock,the injury of lung was lighter in the group of small tidal volume than in the group of medium tidal volume,and there was no difference between the injury of kidney and intestine between the groups of small and medium tidal volume.3.In general,the appropriate ventilation tidal volume should be 8-10ml/ kg in the hemorrhagic shock and 4-6ml/kg in the endotoxic shock.4.Mechanical ventilation by the stimulation of endotoxin could increase the expression of TNF-α.The intestine might be a sensitive target of TNF-α. And the TNF-αlevel in blood could not totally evaluate the injury of multiple organ of the whole body.Either Mechanical or endotoxin could increase the ex pression of IL-6,the IL-6 level was a important marker of organ injury.It was support the theory of balance of inflammatory and anti-inflammatory cyto kines that the ratio of IL-6/IL-10 in BALF was positively correlated with the injury of lung,and the ratio in blood was positively correlated with the injury of kidney and intestine.
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