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，脓毒症的潜在可逆心肌抑制在人类和动物中得到了充分的证明。脓毒症引起心肌抑制的机制尚不完全清楚。脓毒症引起的心肌功能障碍不能用心肌供氧不足或心肌能量合成能力不足来解释。研究人员已经假设了脓毒症的心肌抑制因子，但细菌、它们的毒素和宿主细胞因子干扰正常心功能的机制尚不清楚。促炎介质在充血性心力衰竭和败血症的心肌抑制的发病机制中有牵连。电镜显示，感染性动物心脏微血管弥漫性异常，以内皮细胞肿胀和血管内非闭塞性纤维蛋白沉积为特征。我们可以假设，细菌毒素和诱导宿主的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，心脏通过重塑机制适应和维持卒中容量，从而导致可逆的心室扩张。脓毒症中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，在人类和动物中，左室射血分数下降，但左室扩张没有下降。本研究的目的是更好地定义败血症期间心脏的收缩和舒张异常，并确定败血症诱导的促炎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）来量化心功能的变化。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，本研究旨在明确脓毒症引起的心肌抑制是否与微血管流动异常和左室扩张有关。

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.