Effect of Diabetes on Outcome after Cardiac Arrest and Cardiopulmonary Resuscitation with Postconditioning Strategies in a Rodent Model

啮齿动物模型中糖尿病对心脏骤停和心肺复苏后处理策略结果的影响

• 批准号: 397561247
• 负责人: Dr. Claudius Balzer
• 金额: --
• 依托单位: Department of Anesthesiology
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/397561247?language=en
• 关键词: Effect; Diabetes; Outcome; after; Cardiac

Even with the best methods of cardiopulmonary resuscitation (CPR), more than 90% of the estimated 100,000 patients with out-of-hospital cardiac arrest (CA) in Germany each year die or have severe neurological deficits. This is due to the fact that successful outcome from CPR is inversely proportional to the duration of untreated CA. Unfortunately, 60-80% of patients do not receive bystander CPR, and first responders arrive on average 8-10 minutes after the emergency call. The molecular and metabolic changes resulting from abrupt reperfusion, i.e. reintroduction of blood flow during the start of chest compressions, after prolonged global ischemia during CA, may be of greater consequence than the injury caused by the initial ischemia itself. A novel strategy applied during CPR is ischemic postconditioning (IPostC), to mitigate the development of IR injury to the heart and brain. In contrast to regular animal models, CA victims are rarely healthy, often suffering from a variety of chronic diseases, such as obesity and type 2 diabetes mellitus (T2DM), that increase their risk for adverse events. Moreover, when optimally treated, T2DM patients are routinely on one or more antidiabetic medications. Both T2DM and its treatments, however, may differentially interfere with important signaling pathways of otherwise highly efficacious conditioning strategies like IPostC, by abrogating or restoring their benefit, respectively. Thus, the overall goal of my postdoctoral research grant is to explore the interaction of T2DM and its treatments with outcome after CA and CPR ± IPostC in an established rat model of resuscitation by using the Zucker diabetic fatty (ZDF) rat. I aim to 1) determine the effect of IPostC on outcome in lean, healthy ZDF rats compared to standard (S)-CPR following CA; 2) determine the effect of T2DM on outcome in diabetic ZDF rats after S-CPR vs IPostC-CPR following CA; 3) determine the effect of insulin treatment on outcome after S-CPR vs IPostC-CPR following CA in diabetic rats; and 4) metformin treatment instead of insulin. Knowledge from this highly innovative, translationally relevant proposal would, for the first time, shed much needed new light on the interaction of diabetes and its standard treatments with the ability to successfully resuscitate after CA and to further improve outcome by postconditioning.

即使使用最好的心肺复苏（CPR）方法，在德国每年估计的10万名院外心脏骤停（CA）患者中，仍有超过90%的患者死亡或患有严重的神经功能缺损。这是因为心肺复苏的成功结果与未经治疗的CA的持续时间成正比。不幸的是，60-80%的患者没有接受旁观者心肺复苏术，急救人员平均在紧急呼叫后8-10分钟到达。在CA期间长时间的全脑缺血之后，突然再灌注（即，在胸外按压开始期间重新引入血流）导致的分子和代谢变化可能比初始缺血本身引起的损伤具有更大的后果。在CPR期间应用的一种新策略是缺血后处理（IPostC），以减轻对心脏和大脑的IR损伤的发展。与常规动物模型相比，CA受害者很少健康，通常患有各种慢性疾病，如肥胖和2型糖尿病（T2 DM），这增加了他们发生不良事件的风险。此外，当最佳治疗时，T2 DM患者常规使用一种或多种降糖药物。然而，T2 DM及其治疗可能分别通过消除或恢复其益处而不同地干扰其他高效调节策略（如IPostC）的重要信号传导途径。因此，我的博士后研究资助的总体目标是通过使用Zucker糖尿病脂肪（ZDF）大鼠在已建立的复苏大鼠模型中探索T2 DM及其治疗与CA和CPR ± IPostC后结局的相互作用。我的目的是1）确定与CA后标准（S）-CPR相比，IPostC对瘦的健康ZDF大鼠结局的影响; 2）确定T2 DM对糖尿病ZDF大鼠CA后S-CPR与IPostC-CPR后结局的影响; 3）确定糖尿病大鼠CA后S-CPR与IPostC-CPR后胰岛素治疗对结局的影响; 4）二甲双胍治疗代替胰岛素。这一高度创新、翻译相关的提案中的知识将首次为糖尿病及其标准治疗方法与CA后成功复苏并通过后处理进一步改善结果的能力之间的相互作用提供急需的新线索。

项目成果

Mechanical adjuncts for cardiocerebral resuscitation

• DOI: 10.1080/17434440.2019.1649135
• 发表时间: 2019-08-03
• 期刊: EXPERT REVIEW OF MEDICAL DEVICES
• 影响因子: 3.1
• 作者: Riess，Matthias L.;Balzer，Claudius
• 通讯作者: Balzer，Claudius

Abstract 119: Influence of Anesthetics on the Hemodynamic Response in a Rat Model of Hemorrhagic Shock

摘要 119：麻醉药对失血性休克大鼠模型血流动力学反应的影响

• DOI: 10.1161/circ.140.suppl_2.119
• 发表时间: 2019
• 期刊: Circulation
• 影响因子: 37.8
• 作者: Balzer C;Baudenbacher Franz J;Eagle Susan S;Salzman Michele M;Cleveland William J;Riess Matthias L
• 通讯作者: Riess Matthias L

Abstract 20: Peripheral Intravenous Analysis Detects Return of Spontaneous Circulation Without Interruption of Chest Compressions in a Rat Model of Cardiopulmonary Resuscitation

摘要 20：外周静脉分析检测大鼠心肺复苏模型中不中断胸外按压的自主循环恢复情况

• DOI: 10.1161/circ.140.suppl_2.20
• 发表时间: 2019
• 期刊: Circulation
• 影响因子: 37.8
• 作者: Balzer C;Baudenbacher Franz J;Hernandez A;Salzman Michele M;Riess Matthias L;Eagle Susan S
• 通讯作者: Eagle Susan S

Abstract 328: Hemodynamic Comparison of Zucker Diabetic Fatty Rats to Their Lean Littermates After Asphyxial Cardiac Arrest

摘要 328：窒息心脏骤停后 Zucker 糖尿病肥胖大鼠与其瘦同窝大鼠的血流动力学比较

• DOI: 10.1161/circ.138.suppl_2.328
• 发表时间: 2018
• 期刊: Circulation
• 影响因子: 37.8
• 作者: Balzer C;Baudenbacher F;Salzman MM;Cleveland WJ;Eagle S;Riess ML
• 通讯作者: Riess ML