Cardiac Function In A Canine Model Of Septic Shock

感染性休克犬模型的心脏功能

• 批准号: 6993933
• 负责人: Steven Solomon
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6993933
• 关键词: blood flow measurement; cardiovascular disorder; cardiovascular imaging /visualization; cardiovascular injury; disease /disorder model; dogs; heart contraction; heart function; hemodynamics; inflammation; magnetic resonance imaging; pathologic process; septic shock

The potentially reversible myocardial depression of sepsis is well documented in humans and animals by radionuclide scans and intravascular catheter techniques. The mechanism of sepsis-induced myocardial depression remains incompletely understood. Sepsis induced myocardial dysfunction cannot be explained by inadequate myocardial oxygen supply or insufficient myocardial high-energy synthetic capabilities. Investigators have postulated a myocardial depressant factor of sepsis, but the mechanisms by which bacteria, their toxins, and host cytokines disturb normal cardiac function remains unknown. Proinflammatory mediators have been implicated in the pathogenesis of congestive heart failure and the myocardial depression of sepsis. There is also electron microscopic evidence of diffuse abnormalities of the cardiac microvasculature characterized by endothelial cell swelling and nonocclusive intravascular fibrin deposition in septic animals. One can postulate that bacterial toxins and the induced host proinflammatory response disrupt the integrity of the myocardial microvasculature and subsequently injure the myocytes resulting in myocardial functional depression. Similar to congestive heart failure, the heart adapts and maintains stroke volume through a remodeling mechanism resulting in a reversible ventricular dilatation. The concept of ventricular dilatation in sepsis remains controversial. Sepsis studies using echocardiography to assess ventricular volumes have confirmed in humans and animals the depression of LV ejection fraction but not the LV dilatation. The purpose of this study is to better define systolic and diastolic abnormalities of the heart during sepsis and to determine if the sepsis-induced proinflammatory response results in a cardiac microvascular injury that can lead to myocardial functional depression. We will quantify the changes in cardiac function using both invasive hemodynamic measurements and noninvasive cardiac magnetic resonance imaging (MRI). The data from the invasive measurements will be correlated with the non-invasive MRI data in order to develop an approach suitable for future human studies. Furthermore, this study is designed to definitively determine if sepsis-induced myocardial depression is associated with microvascular flow abnormalities and LV dilatation. Control studies were performed with good MRI imaging and invasive measures correlated. Several sepsis studies were performed but the mortality was greater then expected and MRI/hemodynamic procedures were not able to be performed. The study will be continued after the sepsis model is modified.

通过放射性核素扫描和血管内导管技术，在人类和动物中充分记录了脓毒症潜在的可逆性心肌抑制。脓毒症引起的心肌抑制的机制仍不完全清楚。脓毒症引起的心肌功能障碍不能用心肌供氧不足或心肌高能合成能力不足来解释。研究人员推测败血症是一种心肌抑制因素，但细菌、其毒素和宿主细胞因子扰乱正常心脏功能的机制仍不清楚。促炎介质与充血性心力衰竭和败血症的心肌抑制的发病机制有关。还有电子显微镜证据表明，脓毒症动物的心脏微血管系统弥漫性异常，其特征是内皮细胞肿胀和非闭塞性血管内纤维蛋白沉积。人们可以推测，细菌毒素和诱导的宿主促炎反应破坏了心肌微血管的完整性，随后损伤了肌细胞，导致心肌功能抑制。与充血性心力衰竭类似，心脏通过重塑机制来适应和维持每搏输出量，从而导致可逆的心室扩张。脓毒症中心室扩张的概念仍然存在争议。使用超声心动图评估心室容积的脓毒症研究已证实人类和动物的左心室射血分数降低，但未证实左心室扩张。本研究的目的是更好地定义脓毒症期间心脏的收缩和舒张异常，并确定脓毒症引起的促炎症反应是否会导致心脏微血管损伤，从而导致心肌功能抑制。我们将使用有创血流动力学测量和无创心脏磁共振成像（MRI）来量化心脏功能的变化。来自侵入性测量的数据将与非侵入性 MRI 数据相关联，以便开发适合未来人类研究的方法。此外，本研究旨在明确确定脓毒症引起的心肌抑制是否与微血管血流异常和左心室扩张相关。 对照研究是在良好的 MRI 成像和侵入性措施相关的情况下进行的。进行了几项脓毒症研究，但死亡率高于预期，并且无法进行 MRI/血流动力学检查。该研究将在脓毒症模型修改后继续进行。