The Significance Of Serum IL-1β On Hormone Replacement Therapy Easing Damage Of Donor Lung With Brain-dead Pigs

Background and objective:Lung transplantation has been regarded as the only effective way to curee nd-stage lung disease. Recently, with the increasing of lung transplantation, th-e shortage of donor lung which restricts the development of lung transplantati-on becomes more and more severe. At present, taking advantage of organ don or from brain-dead donor is one effective way to solve this problem. But brai n death is a process of severe physiopathology. The changes of every system have occurred during brain death, which lead to damage of organ donor. So to study injuring mechanism of organ donor could provide experimental basis for efthefective using lung donor from brain dead donor.At present, the injuring mechanism of lung donor in the process of brain death is unclear. Literature reports have confirmed that inflammatory mediators (IL-1β,IL-6 and TNF-a) which lead to abnormal immunoreactions become increasing during brain death. IL-1(3 plays a major role in the process of damage of donor lung from brain-dead donor. IL-1βis secreted by mononuclear macrophages, and is found in blood circulation. Together with TNF-α, they start-up inflammation response, and promot neutrophil granulocyte to release inflammatory mediators, which destroy structural integrality of Lung tissue. As we all know, hormone has significant function of anti-inflammatory. Researches show that hormone replacement therapy could protect liver and kidney from damaging during brain death. However, the literature research about effect of hormone replacement therapy on lung donor has not been yet reported domestic. This topic investigates injuring mechanism of donor lung from brain-dead pigs by establishing brain-dead model, and monitoring the level of IL-1βand function of donor lung. Otherwise, the protective role of donor lung was observed by using hormone replacement therapy to provide theoretical and experimental basis for the clinical use of the donor lung from brain-dead donor.Materials and methodsTwenty-four pigs from Sweden were seperated into 3 groups,8pigs in each group:control group(group C),brain-dead group(group B) and hormonal group(group H). Brain-dead model were established in group B and H. There was no inflation of foley balloon in group C,and the other operation was the same as the group B. Cortisol at 0.17mg/kg/h, T3 at 0.85ug/kg/h and T4 at 0.85ug/kg/h were injected via the ear margin veins in group H immediately after the brain death. The levels of mean arterial pressure, heart rate and pulmonary artery perfusion were recorded respectively before increasing epidural pressure in the process of the experiment. Before increasing epidural pressure, and 6h,12h and 24h after confirmation brain death, blood samples 2ml were collected for monitoring the changes of arterial blood gas. The level of Interleukiln-1β(IL-1β) in group B and H was measured by enzyme-linked immunosorbent assay (ELISA) at 6h,12h and 24h after confirmation brain death. All data were analyzed by statistic software SPSS 17.1.Results1. Brain-dead model was established successfully in Group B and H. 2 The changes of MAP:The changes of MAP in Group B and H were significantly higher during inflation of Foley balloon. Contrast to group C, there was significantly difference (p<0.05). The level of MAP in group B was gradually lower after brain death.Contrast to group H, the difference was statistically significant (p<0.05).3 The changes of PAF:The levels of PAF in group B was gradually lower after brain death. The difference between 6h after brain death and before brain death was significantly significant (p<0.05). The level of PAF in group H has no significant changes, The difference at the point of 12h after brain death between group B and H was significantly significant(p<0.05).4 The changes of IL-1(3:The level of IL-1βin group B was gradually higher after brain death, and it was significantly difference (p<0.05) contrast to group C and H after brain death 24h.5. The changes of arterial blood gas:During the experiment, pH and pCO2 in group B were gradually decreased and PaCO2 was increased. However, the group C and H does not appear respiratory acidosis.6. The temporary and disorderly general tic were observed in group B and H between after inflation of Foley balloon and before brain death; meanwhile the rise of HR and MAP, and the fluctuation of EEG also were showed.7. The brain-dead signs in group B and group H were consistent with the donor criterion of brain death. The brain-dead state was maintained for 24h by respiratory and circulatory support. The brain-dead pigs showed "the heart and lung death" soon after withdrawing respiratory and circulatory support.Conclusion1. The brain-dead mode was established successfully by an improved method of slow and intermittent encephalic pressure, and could simulate effectively clinical BD state. Porcine BD state could be maintained stably for more than 24 hours through effectively support of respiration and circulation, and this method provides a favorable experimental basis to further study morphological and functional changes of the lung in brain-dead state 2. There was tic reaction on all pigs before brain death, so the disappearance of this phenomenon could be preliminarily considered as one of the BD confirmed indexes.3. PAF showed higher and lower with the hemodynamic changes in the process of brain death, which further verified that hemodynamic changes could affect on pulmonary function during brain death.4. The synthesis and release of inflammatory mediator IL-1βin the serum increased during the experiment, accompanying by abnormal changes of lung function. So we suggested that IL-1(3 was related to pulmonary injury of donor during brain death.5. The changes of MAP, PAF and IL-1βon brain-dead pigs were not significant after hormone replacement therapy, and respiratory acidosis did not appear. It demonstrated that hormone replacement therapy not only could significantly improve the internal environmental disorders after the death of brain, but also could reduce the release of inflammatory cytokines. As a result, it alleviated pulmonary injury of donor in the state of brain death at last.