| BackgroundALI(acute lung injury)/ARDS (acute respiratory distress syndrome) is severe disease occurring in the development of certain non-cardiac disease such as infection, shock, trauma and burns.Pulmonary capillary endothelial cells and alveolar epithelial cells are injured,then the interstitia and the alveoli of lung hydropsia extensively.As a result,the acute respiratory insufficiency or failure is formed. Lung volume reduction, lung compliance decling and severe ventilation/perfusion disorder are the most important pathophysiological characteristics of acute respiratory distress syndrom. The clinical mortality rate of ARDS is very high,so it becomes one of the most urgentevents.When talking about the treatment of ARDS, the lung protective ventilation strategy (LPVS) is generally received by doctors and scholars. The application of LPVS has been shown to reduce the mortality rate in patients with ARDS, but it's mortality rate is still as high as 40% to 50%. Hypoxic pulmonary vasoconstriction (HPV) has played an important role in the process of ARDS Hypoxemia is the most important characteristics of ARDS, while the sharp decrease of oxygen pressure will cause the pulmonary vascular to contract,which is an adjustment mechanism to match the lung perfusion and ventilation in regional area at the time of oxygen deficiency.But when the whole body hypoxias, the sustaining pulmonary vasoconstriction will lead to the pulmonary hypertension, pulmonary edema, pulmonary vascular rebuilding and even pulmonary heart failure further, which will seriously impede thepatients with ARDS to recover. In view of this situition, increasing the blood oxygen content and blocking the HPV may reverse the continuous deterioration in lung. In order to maintain the body's oxygen supply,many doctors try hard to find a goodstrategy for the treatment of ARDS. Vasodilator, especially the highly selective pulmonary vasodilator is taken to be one of the options to improve PaO2.Vasodilator is the primary means to rectify the pulmonary vasoconstriction. Most of the vasodilators expand the vein and also expand the artery which easily leads to low blood pressure and has an impact on cardiac function. In addition, these hypoxic vasodilators inhibit the constriction of the artery in the anoxic region which increases the pulmonary arteriovenous shunt,deteriors the ventilation / perfusion ratio further more and does not contribute to the recover of the patients with ARDS.So most of them can not be applied to clinical therapy. Inhaled nitric oxide (NO) has the characteristic of pulmonary vascular selectivity, but the prior of it's improvement insurvival rate of ARDS patients has not been confirmed and it's potential toxicity, high prices, complex storage device further restrict it's study and application. Commonly known as Viagra, Sildenafil is a highly selective inhibitor of the phosphodiesterase-5. Sildenafil inhibits the cGMP which is the diastolic messenger in vascular smooth muscle to convert to the GTP.As the cGMP level increasing, the vascular smooth muscles relax and the vessels expand. Studies have shown that sildenafil has a definite selectivity for the pulmonary vascular and it plays little role in the blood vessels located in non-ventilated areas.It is supposed that sildenafil willmatch the ventilation/flow ratio better.Objectivesâ… .One objective is to make a good and stable rabbit model of ARDS through experiment to .provide model for the study of sildenaf l.â…¡.The other objective is to study the effect of sildenafil for pulmonary function improvement in rabbits with ARDS so as to determine the practical effect of the drug for the improvement of respiratory function and provide the evidence of the drug's possobility for the treatment of ARDS.Methodsâ… .the building of ARDS modelNew Zealand white rabbits are ramdomly grouped into the oleic acid group(10 rabbits) and the control group(10 rabbits). The ones in the oleic acid group are slowly injected with oleic acid(0.16ml/kg) through vein and the ones in the control group areslowly injected with normal saline(0.16ml/kg) through vein. Then the blood gas analysis and blood pressure test are taken at several time.The experiment also requires calculating the lung ratio, measuring the TNF-a level in lung tissue and taking thepathological examination of HE.â…¡. Effect of sildenafil for the treatment of ARDSNew Zealand white rabbits are randomly grouped into the sildenafil treatment group(12 rabbits) and the control group(12 rabbits). After establishing the ARDS rabbit model, this point is defined the time of 0h, the ones in sildenafil group are taken with sildenafil(100mg sildenafil solved in 5ml normal saline) through the gastric tube and the ones in the normal saline group are taken with normal saline(5ml)through the gastric tube. PaO2, PaCO2, A-aDO2, contraction bloode pressure, diastolic blood pressure and central venous pressure at the time of 0.5h, 1h, 2h, 3h, 4h are measured. The lung ratio is caculated, the TNF-a level in lung tissue is tested and thepathological examination of HE also is taken.Results1. 1 hour after intravenous injection of oleic acid, the PaO2 of each rabbit in oleic acid group is <60mmHg,the PaO2/FaO2 is <300mmHg and the ARDS rabbit model is built up successfully.2. There are statistical differences between the Sildenafil group and the control group in PaO2, PaCO2, A-aDO2 at the time of 0.5h, 1h, 2h, 3h, 4h (P in each group<0.05).The PaO2 of the Sildenafil group is higher than that of the control group and the PaCO2, A-aDO2 are lower than these of the control group.3.In the sildenafil treatment group, the systolic pressure and the diastolic blood pressure decrease and are not statistically different (P>0.05)when comparing with the control group.The central venous pressure increases and has no statistical differences with the one of the control group(P >0.05).4. In the sildenafil treatment group, there is less pulmonary infiltration of inflammatory cells than that in the control group.The pulmonary edema in the sildenafil group is more slight than the one in the control group. TNF-a levels in the sildenafil group are lower than the one in the control group (P <0.05).Conclusions1. By slowly injecting the oleic acid through vein, a rabbit model of ARDS can be successfully established2. Sildenafil can improve the respiratory function of the ARDS rabbits, it makes the PaO2 of the ARDS rabbits increase and the PaCO2 A-aDO2 decline.It plays no statistically effect on the arterial blood pressure and the central venous pressure.3. Sildenafil can reduce the level of TNF-a in lung tissue and the infiltration of inflammatory cells.It can allievate the pulmonary edema, decrease the lung ratio and reduce the inflammatory response in the process of ARDS.4. Sildenafil will certainly help to the study of patients with ARDS. |
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