Cardiac Function In A Canine Model Of Septic Shock

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的潜在可逆性心肌抑制。脓毒症引起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氧供应不足或心肌高能合成能力不足来解释。研究者已经假定败血症的心肌损害因素，但是细菌、其毒素和宿主细胞因子干扰正常心脏功能的机制仍然未知。促炎介质参与了充血性心力衰竭和脓毒症心肌抑制的发病机制。在败血症动物中，也有心脏微血管弥漫性异常的电子显微镜证据，其特征为内皮细胞肿胀和非闭塞性血管内纤维蛋白沉积。可以假设细菌毒素和诱导的宿主促炎反应破坏心肌微血管的完整性，随后损伤心肌细胞，导致心肌功能抑制。与充血性心力衰竭相似，心脏通过重塑机制适应并维持每搏输出量，从而导致可逆的心室扩张。脓毒症心室扩张的概念仍有争议。使用超声心动图评估心室容积的脓毒症研究证实了人类和动物的LV射血分数降低，但没有LV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，并确定脓毒症诱导的促炎反应是否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，以便开发适合于未来人类研究的方法。此外，本研究旨在明确确定脓毒症诱导的心肌抑制是否与微血管血流异常和LV扩张相关。 对照研究采用良好的MRI成像和相关的侵入性措施进行。进行了几项脓毒症研究，但死亡率高于预期，无法进行MRI/血流动力学程序。本研究将在脓毒症模型改良后继续进行。

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.