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RESOLUTION OF NEUROGENIC PULMONARY EDEMA

神经源性肺水肿的解决

基本信息

批准号：
2234922
负责人：
MICHAEL B MARON
金额：
$ 9.65万
依托单位：
NORTHEAST OHIO MEDICAL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-06-14 至 1999-03-31
项目状态：
已结题

项目摘要

DESCRIPTION (Applicant's abstract): Neurogenic pulmonary edema (NPE) is a form of edema that may develop after CNS trauma that massively activates the sympathetic nervous system (SNS). The long term objectives of this program are to determine (1) the basic mechanisms by which such excessive SNS activity affects lung blood flow and fluid balance and how these mechanisms act in concert to produce NPE, and (2) the mechanisms involved in the resolution of this form of edema. An understanding of both the mechanisms of development and recovery is important for the design of effective preventive and treatment measures. We have recently found that the rate of alveolar fluid reabsorption (AFR) is increased during recovery from NPE in a canine model of NPE in which the SNS is massively activated by the administration of veratrine. This project is designed to determine the mechanisms of the increased AFR and has 3 specific aims. The 1st aim is to determine if the increased AFR is mediated by beta-adrenergic stimulated alveolar epithelial sodium reabsorption, and if so, the role played by endogenous epinephrine in this process. Alveolar liquid clearance will be determined from the increase in protein concentration that occurs as fluid is reabsorbed from autologous plasma that has been instilled into the airways. Experiments will be done in adrenalectomized animals and using appropriate blockers to determine the role of adrenal catecholamines, beta2-adrenergic receptors (ICI 118,551), and active Na+ transport (amiloride) in this process. The second aim is designed to determine the dose-response relationship between plasma epinephrine concentration and AFR. This will be accomplished by determining AFR after infusing epinephrine concentrations ranging from those observed during mild to massive SNS activation. The 3rd aim is to determine if the increased AFR observed after massive SNS activation is the maximal attainable in the lung. This will be accomplished by determining if the SNS-induced increased in AFR can be further increased by the administration of drugs that increase intracellular cyclic AMP concentration independently (forskolin, theophylline) of beta2-adrenergic receptor activation.

描述（申请人摘要）：神经源性肺水肿（NPE）是一种 CNS创伤后可能发生的水肿形式，交感神经系统（SNS）。该计划的长期目标是为了确定（1）这种过度SNS的基本机制，活动影响肺血流和液体平衡，以及这些机制如何共同作用产生NPE，以及（2）参与NPE的机制。解决这种形式的水肿。对这两种机制的理解开发和恢复的有效性对于设计有效的预防和治疗措施。我们最近发现，肺泡液体重吸收（AFR）在NPE恢复期间增加， NPE的犬模型，其中SNS被藜芦碱的管理该项目旨在确定增加AFR的机制，并有3个具体目标。第一个目标是确定增加的AFR是否由β-肾上腺素能刺激介导肺泡上皮钠重吸收，如果是这样，所起的作用，内源性肾上腺素的作用肺泡液体清除率将由作为流体出现的蛋白质浓度的增加确定是从自体血浆中重吸收的，航空公司. 实验将在肾上腺切除的动物中进行，并使用适当的阻断剂，以确定肾上腺儿茶酚胺的作用， β 2-肾上腺素能受体（ICI 118，551）和主动Na+转运（阿米洛利）在这个过程中。第二个目标是确定血浆肾上腺素浓度与AFR之间的剂量-反应关系。这将通过输注肾上腺素后测定AFR来实现浓度范围从轻度到大量SNS期间观察到的浓度 activation. 第三个目的是确定在注射后观察到的增加的AFR是否大量SNS激活是肺中可达到的最大值。这将是通过确定SNS诱导的AFR增加是否可以通过给予增加细胞内的药物进一步增加环AMP浓度独立（毛喉素，茶碱）的 β 2肾上腺素能受体激活。