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SURGICAL ASPECT OF SHOCK AND HYPOXIA

休克和缺氧的手术方面

基本信息

批准号：
3335888
负责人：
IRSHAD H CHAUDRY
金额：
$ 39.3万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1977
资助国家：
美国
起止时间：
1977-02-01 至 1986-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3335888
关键词：
adenosine triphosphate bactericidal immunity burns calcium metabolism cardiovascular disorder chemotherapy cardiovascular surgery cell components cell membrane cellular immunity cerebral ischemia /hypoxia cyclophosphamide electron microscopy epinephrine freeze etching gamma globulin heart function heart revascularization hemorrhagic shock high energy compound humoral immunity hypoxia immunoregulation ion transport liver liver metabolism magnesium membrane permeability membrane potentials membrane structure muscle metabolism myocardial ischemia /hypoxia nicotinamide nutrition related tag peptides peritonitis phosphates potassium prostaglandins pulmonary edema radioimmunoassay renal ischemia /hypoxia shock smooth muscle sodium splenectomy suppressor T lymphocyte thyroid function tissue /cell culture

项目摘要

The major thrust of this proposal is to continue our work on various aspects of shock and hypoxia, which are of particular importance for the surfical patient. Our prevoius observations of changes in cellular and sub-cellular functions following shock and correction of some of those functions will serve as the basis on which we now plan to determine: a) the role humoral factors play in producing such changes; b) the interrelationships and perhaps interdependence of such changes, parricularly of cellular energetics and membrane function; c) the reason for organ failure, partucularly muscle and liver cellular metabolic and mitochondrial failure in late sepsis and with multiple systems failure; d) the sequences of and reasons for remote organ failure with sepsis; e) the reason for depressed immunocompetence following burn trauma; and f) further therapeutic considerations aimed at improving cell function and the mechanisms for this. Specific areas of activity include: 1) the role epinephrine plays in producing hepatic depolarization, metabolic depression, insluin resistance and alterations in membrane permeabilityu with shock; 2) evaluation of the role of the thyroid in late sepsis and organ failure and the possibility of "myxedematous mitochondria" causing the terminal metabolic failure of muscle and liver; 3) further study of the precise mechanism by which high energy phosphate compounds produce salutary effects; 4) characterization, kinetics and localization of adenine nucleotide uptake in the cell and determination of a potential transport carrier system; 5) further studies to determine critical energy levels for various aspects of cell function; 6) necessary background information for clinical trials of ATP-MgC12; 7) the status of calcium regulation in low flow conditions; 8) the nature of alterations in hepatic metabolic capabilities in sepsis; 9) study of kidney preservation following normothermic ischemia; 10) whether creatine phosphate or other substrates will help prevent ischemic damage to the heart during coronary insufficiency and to the central nervous system during and after an acute ischemic insult; 11) study of tuftsin on increased pulmonary retention of particulate matter following splenectomy and sepsis; and 12) whether therapy involving ablations of precursors of suppressor-T cells would improve the resistance to infection following burn injury.

该提案的主旨是继续我们在各种方面的工作休克和缺氧方面，这对于表面病人。我们之前对细胞和细胞变化的观察冲击后的亚细胞功能和其中一些的纠正函数将作为我们现在计划确定的基础：a) 体液因素在产生这种变化中所起的作用； b) 的这些变化之间的相互关系，或许还有相互依赖，特别是细胞能量学和膜功能； c) 原因用于器官衰竭，特别是肌肉和肝细胞代谢和脓毒症晚期线粒体衰竭和多系统衰竭； d) 脓毒症远端器官衰竭的顺序和原因； e) 的烧伤后免疫功能低下的原因； f) 进一步旨在改善细胞功能和机制。具体活动领域包括： 1) 角色肾上腺素在产生肝脏去极化、代谢抑郁、胰岛素抵抗和膜通透性改变震惊； 2）评估甲状腺在晚期脓毒症中的作用和器官衰竭和“线粒体粘液性水肿”引起的可能性肌肉和肝脏的终末代谢衰竭； 3）进一步研究高能磷酸盐化合物产生有益物质的精确机制影响； 4) 腺嘌呤的表征、动力学和定位细胞中的核苷酸摄取和潜在转运的确定载体系统； 5）进一步研究以确定临界能量水平细胞功能的各个方面； 6）必要的背景资料 ATP-MgC12的临床试验； 7）低钙调节状态流动条件； 8）肝脏代谢改变的本质败血症的能力； 9) 肾脏保存研究如下常温缺血； 10) 是否是磷酸肌酸或其他底物有助于预防冠状动脉粥样硬化期间心脏缺血性损伤急性发作期间和之后的功能不全和对中枢神经系统的影响缺血性损伤； 11) Tuftsin 增加肺潴留的研究脾切除术和败血症后的颗粒物； 12) 是否涉及消除抑制性 T 细胞前体的疗法将提高烧伤后的抗感染能力。