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

基本信息

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

项目摘要

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.

即使采用最好的心肺复苏 (CPR) 方法，德国每年估计有 100,000 名院外心脏骤停 (CA) 患者，仍有超过 90% 死亡或患有严重的神经功能缺损。 CPR 的成功结果与未经治疗的 CA 的持续时间成反比，不幸的是，60-80% 的患者没有接受旁观者 CPR，并且急救人员平均到达。紧急呼叫后 8-10 分钟，由于突然再灌注（即在 CA 期间长时间整体缺血后重新引入血流）导致的分子和代谢变化可能比最初造成的损伤更严重。心肺复苏期间应用的一种新策略是缺血后处理 (IPostC)，以减轻心脏和大脑的 IR 损伤。与常规动物模型相比，CA 受害者很少是健康的，通常患有缺血性心脏病。各种慢性疾病，如肥胖和 2 型糖尿病 (T2DM)，会增加不良事件的风险。此外，如果得到最佳治疗，T2DM 患者通常会服用一种或多种抗糖尿病药物，但是，可能会分别通过废除或恢复其益处来差异性地干扰 IPostC 等其他高效调节策略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探索它们之间的相互作用。 T2DM 及其在使用 Zucker 糖尿病肥胖 (ZDF) 大鼠建立的复苏大鼠模型中进行 CA 和 CPR ± IPostC 后的治疗结果，我的目的是 1) 确定与瘦健康 ZDF 大鼠相比 IPostC 对结果的影响。 CA 后的标准 (S)-CPR；2) 确定 S-CPR 与 CA 后的 IPostC-CPR 后 T2DM 对糖尿病 ZDF 大鼠结局的影响 3) 确定胰岛素治疗的效果；糖尿病大鼠 CA 后 S-CPR 与 IPostC-CPR 的结果；4）二甲双胍治疗代替胰岛素。糖尿病及其标准治疗能够在 CA 后成功复苏，并通过后处理进一步改善结果。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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; Hern;ez A; Salzman Michele M; Riess Matthias L; Eagle Susan S
通讯作者：
Eagle Susan S

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; Clevel;William J; Riess Matthias L
通讯作者：
Riess Matthias L

Mechanical adjuncts for cardiocerebral resuscitation

心脑复苏机械辅助设备