SURGICAL ASPECT OF SHOCK AND HYPOXIA

这一建议的主旨是继续开展我们的各项工作， 休克和缺氧的方面，这是特别重要的 表面病人 我们先前观察到的细胞和 休克后的亚细胞功能以及其中一些功能的纠正 这些职能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） 这些变化的相互关系和相互依赖性， 特别是细胞能量学和膜功能; c）原因 器官衰竭，特别是肌肉和肝脏细胞代谢， 晚期脓毒症和多系统衰竭中的线粒体衰竭; d） 脓毒症导致远端器官衰竭的顺序和原因; e） 烧伤创伤后免疫活性降低的原因;和f）进一步 目的在于改善细胞功能的治疗考虑， 机制对此。 具体活动领域包括：1） 肾上腺素在产生肝去极化、代谢 抑制、胰岛素抵抗和膜通透性的改变 2）评估甲状腺在晚期脓毒症中的作用， 器官衰竭和"粘液水肿性线粒体"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 腺嘌呤的特性、动力学和定位 细胞中的核苷酸摄取和潜在转运的测定 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）必要的背景信息 ATP-MgC12的临床试验; 7）低钙血症的钙调节状况 流动条件; 8）肝代谢改变的性质 脓毒症中的能力; 9）在脓毒症之后的肾脏保存研究 常温缺血; 10）磷酸肌酸或其他底物 将有助于防止冠状动脉粥样硬化期间对心脏的缺血性损伤 在急性脑缺血期间和之后， 缺血性损伤; 11）tuftsin对增加的肺滞留的研究 脾切除术和脓毒症后的颗粒物;以及12）是否 涉及消除抑制性T细胞前体的治疗将 提高对烧伤后感染的抵抗力。

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.