Clinical and genomic responses to remote ischemic preconditioning

对远程缺血预处理的临床和基因组反应

• 批准号: 7687483
• 负责人: BRIAN W MCCRINDLE
• 金额: $ 20.97万
• 依托单位: HOSPITAL FOR SICK CHLDRN (TORONTO)
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7687483
• 关键词: Acids; Address; Adverse effects; Airway Resistance; Anesthesia procedures; Anti-Inflammatory Agents; Anti-inflammatory; Arrhythmia; Blood; Blood Pressure; Brain Hypoxia-Ischemia; Bypass; Cardiac; Cardiac Surgery procedures; Cardiopulmonary Bypass; Characteristics; Child; Childhood; Childhood Injury; Clinical; Clinical Trials; Complete Blood Count; Controlled Clinical Trials; Creatinine; Data; Double-Blind Method; Economic Inflation; Effectiveness; Environmental air flow; Fluid Balance; Functional disorder; Gene Cluster; Gene Expression; Gene Expression Profile; Gene Expression Profiling; Genomics; Hemodilution; Hemolysis; Hepatic; Hour; Human; Inflammation; Inflammatory; Inflammatory Response; Injury; Intensive Care Units; Intervention; Ischemia; Ischemic Preconditioning; Kidney; Length of Stay; Lesion; Low Cardiac Output Syndrome; Lower Extremity; Lung; Measures; Mechanical ventilation; Mechanics; Mediator of activation protein; Metabolic; Molecular Profiling; Morbidity - disease rate; Operative Surgical Procedures; Organ; Outcome; Outcome Measure; Output; Oxidative Stress; Oxygen; Patients; Pattern; Physiological; Physiology; Population Control; Postoperative Period; Preparation; Process; Randomized; Randomized Controlled Clinical Trials; Recovery; Recovery of Function; Relative (related person); Reperfusion Injury; Reperfusion Therapy; Research Personnel; Risk; Safety; Sternum; Stimulus; Stratification; Stress; Subgroup; Time; Transaminases; Troponin I; Urea; Urine; Variant; Venous; abstracting; base; clinical effect; clinically relevant; cytokine; improved; indexing; induced hypothermia; inflammatory marker; innovation; mortality; neurotrophic protein S100beta; neutrophil; prevent; primary outcome; programs; repaired; response; secondary outcome; treatment effect

DESCRIPTION (provided by applicant): The use of cardiopulmonary bypass for cardiac surgery in children results in important morbidity and sometimes mortality related to the adverse effects of bypass induced by hypothermia, hemolysis, acid-base management, hemodilution and hypoxia-ischemia. After bypass, reperfusion occurs and induces ischemia reperfusion injury. Inflammation and oxidative stress are key mediators in this process. The objective of this study is to determine if application of a stimulus of remote ischemic preconditioning (RIPC) prevents or lessens the multi-organ dysfunction related to ischemia-reperfusion injury in children undergoing open heart surgery with cardiopulmonary bypass. We will also seek to determine mechanistic gene expression profiles associated with this treatment effect, and baseline profiles that are predictive of clinical outcomes after surgery. We propose a randomized, double-blind sham-controlled clinical trial. At the time preparation for surgery, 4 cycles of 5 minutes each of lower limb ischemia will be induced by inflation of a blood pressure cuff. Gene expression profiling will be noted at induction of anesthesia before application of the RIPC stimulus, 15 minutes after RIPC and at 24 after cessation of cardiopulmonary bypass. The primary outcome will be total duration of post-operative hospital stay, and 1200 patients will be studied, with a hypothesized decrease of 1 day associated with RIPC. Additional outcomes will reflect multi-organ dysfunction and inflammation and their impact, and include duration of mechanical ventilation, duration of stay in the intensive care unit, and physiologic measures over the first 48 hours after surgery. These measures will include indices of renal (urine output, urea, creatinine), cardiac (troponin I, inotrope score), pulmonary (pulmonary and airway mechanics, ventilation parameters), hematologic (blood counts), hepatic (transaminases, INR), metabolic (lactate, arterial and mixed venous oxygen saturations) dysfunction and inflammatory markers (cytokines, CRP). The impact of RIPC on these outcomes will be compared, and related to gene expression patterns, particularly those involved in the inflammatory cascade. Our study will have an important impact on improving the recovery and reducing complications for children undergoing open heart surgery. It will also define important ways in which the body can be further protected from the stresses of undergoing surgery using heart-lung bypass. (End of Abstract)

描述（由申请人提供）： 在儿童心脏手术中使用心肺转流导致重要的发病率，有时甚至死亡率，这与低温、溶血、酸碱管理、血液稀释和缺氧缺血引起的转流不良反应有关。转流后，再灌注发生并诱导缺血再灌注损伤。炎症和氧化应激是这一过程中的关键介质。本研究的目的是确定远程缺血预处理（RIPC）的刺激的应用程序是否预防或减轻与缺血再灌注损伤的儿童接受体外循环心内直视手术的多器官功能障碍。我们还将寻求确定与这种治疗效果相关的机制基因表达谱，以及预测手术后临床结果的基线谱。我们提出了一个随机、双盲、假对照的临床试验。在准备手术时，将通过血压袖带充气诱导4个周期的下肢缺血，每个周期5分钟。在应用RIPC刺激前的麻醉诱导时、RIPC后15分钟和心肺转流停止后24分钟记录基因表达谱。主要结局将是术后住院总时间，将研究1200例患者，假设与RIPC相关的时间缩短1天。其他结局将反映多器官功能障碍和炎症及其影响，包括机械通气持续时间、重症监护室停留时间和术后前48小时内的生理指标。这些指标将包括肾脏（尿量、尿素、肌酐）、心脏（肌钙蛋白I、正性肌力评分）、肺（肺和气道力学、通气参数）、血液学（血细胞计数）、肝脏（转氨酶、INR）、代谢（乳酸盐、动脉和混合静脉氧饱和度）功能障碍和炎症标志物（细胞因子、CRP）的指标。将比较RIPC对这些结果的影响，并与基因表达模式相关，特别是那些参与炎症级联反应的基因。我们的研究将对改善儿童心脏直视手术的恢复和减少并发症产生重要影响。它还将确定重要的方式，其中身体可以进一步保护从压力接受手术使用心肺旁路。(End摘要）