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Study on the Significance and Correlative Therapy of Endothelin during Traumatic Shock

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Tutor: HuangZongHai
School: First Military Medical University
Course: General Surgery
Keywords: shock,traumatic,endothelin,nitric oxide,oxygen partial pressure,Caffeic acid,L-a
CLC: R605.971
Type: Master's thesis
Year:  2003
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BackgroundThe morbidity of trauma is increasing year by year, and traumatic shock is still one of the main diseases which pose a threat to human life in the world. There is almost no perfect methods has been proved highly effective for shock, especially for severe shock by now. It is encouraging, however, that more and more new concepts and new measures for shock therapy appear constantly as well as anti-cytokines. Some inhibitors for cytokine and receptor antagonists have been implied in clinic for their impactful effects in animal models. Although there is still much controversy on their effect, cytokine inhibitors and receptor antaganists for traumatic shock treatment have been concerned by more and more researchers.As an extremely potent, vasoactive 21-amino-acid peptide, endothelin has been shown to have profound effects on blood pressure and vascular resistance in a variety of physiological responses. It plays important roles in the processes of shock pathophysiology, which has been attracted attention to by more and more scientific and medical workers. Researches of endothelin in septic shock, hemorrhagic shock and burns are more systemic than in traumatic shock. Contrast to the other types of shock, researches in the processes of traumatic shock are much more complex because it is very hard to hold the identity of factors and extent of injuries. Therefore, there are much more controversies over researches in traumatic shock than in other types of shock.ObjectiveTo establish a standard experiment model of traumatic shock in rats that would not only imitate clinical features, but also be performed easily, and to study the role of endothelin in the pathogenesis of traumatic shock. Caffeic acid, a new kind of endothelin antagonist was infused during traumatic shock to study the therapeutic effect of it and the significance of endothelin in the pathogenesis of traumatic shock. And then, L-arginine,BQ-123 (selective endothelin-A receptor antagonist) and PD142893( non-selective endothelin-A/endothelin-B) receptor antagonist ) were infused in turn when rescisutation to evaluate the therapeutic role on traumatic shock in rats and explore the possible machanisms.Methods and Results1. Development of the experiment model the dynamic changes of plasma endothelin and tissues oxygen partial pressure on traumatic shock in ratsMultiple injuries involving the leg bones , the soft tissue and hemorrhage in Sprague-Daulay rat were made by hitting its legs on both sides with a 2500g pontil from 30cm high to induce traumatic shock. Dynamic changes of plasma endothelin, Arterial Blood Gas Analysis and oxygen partial pressure in the tissues from the skeletal muscles, liver and small intestine were measured at pre-trauma and post-shock. Meanwhile, hemodynamic data of the rats and their survival time were monitored and recorded. The results showed that the model proved to be relatively simple, stable and basically closed to clinical features of traumatic shock. It was a reliable, acute animal model for experimental study of traumatic shock.The plasma endothelin levels increased significantly after traumatic shock, reaching a peak of about 2.5 times of normal levels. There was statistically significance of Arterial Blood Gas Analysis and tissues oxygen partial pressure between pretrauma and postshock(P<0.05). Metabolic acidosis appeared during traumatic shock. The changes of liver and small intestine oxygen partial pressure were more significant than that of skeletal muscles(P<0.01).2. Effect of endothelin antagonist on traumatic shock in ratsTraumatic shock models in Sprague-Daulay rats were made and randomly devided into 4 groups based on occasion of Caffeic acid treatment: group A(no remedy), B(before injury), C(the moment of resuscitation) and D(3h after resuscitation). Plasma endothelin levels and oxygen partial pressure in the tissues were detected at 5h after resuscitation. Hemodynamic data and survival time of the rats were monitored and recorded. The datashowed that pla
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