Intra-aortic Balloon Pump In Canine Model--Septic Shock

犬主动脉内球囊反搏模型--感染性休克

• 批准号: 7212424
• 负责人: Michael A 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/7212424
• 关键词: Escherichia coli infections; animal mortality; antibiotics; aortic balloon pump; blood chemistry; cardiac output; cardiovascular disorder therapy; combination therapy; disease /disorder model; dogs; drug screening /evaluation; heart contraction; hemodynamics; kidney function; microorganism disease chemotherapy; myocardial ischemia /hypoxia; nonhuman therapy evaluation; septic shock; septicemia; vasoconstrictors

Septic shock is the most common cause of death in medical and surgical intensive care units in the United States. Thirty percent of patients who die from sepsis are noted to have low cardiac output. The purpose of this study is to examine the role of intra-aortic balloon pump counterpulsation (IABC) in the treatment of septic shock. The goal of placing an intra-aortic balloon pump (IABP) is twofold. It reduces the afterload on the heart, thereby allowing it to do less work, "assisted systole", while enhancing its coronary blood flow, thereby providing it with more energy, "diastolic augmentation." We have an ACUC approved protocol to perform a controlled, randomized survival study of IABC in a well characterized low cardiac output animal model of sepsis. We have tested various IABP sizes in the animals to determine the levels of diastolic augmentation and systolic assistance that can be provided. The commercially available sizes did not provide adequate augmentation, therefore a custom sized IABP was developed and tested. The custom IABP provided excellent augmentation during short term testing and subsequently underwent long term testing (48 hours) to establish if the IABP caused any alterations in renal function or direct injury to the kidneys. The custom IABPs did not alter renal function and did not cause injury to the kidneys. The proposed study is the first controlled, randomized survival study of IABC in a well characterized low cardiac output animal model of sepsis. There are three phases in this study: phase 1 (baseline), phase 2 (sepsis), and phase 3 (recovery). During the sepsis phase all animals will receive bacterial clot (5 x 10^9 cfu's of E. coli) intravenous fluids (Ringer's solution with 5% dextrose) and antibiotics (Ceftriaxone). In addition, the animals will be randomized to one of four groups: Group 1 (control group), Group2 (vasopressors), Group 3 (IABP) and Group 4 (vasopressors + IABP). This study design will allow us to determine the benefit of each treatment intervention (vasopressors or IABP) compared to control and to detect any interaction between the interventions. The same animals will be studied in each of the three phases. The measurements to be obtained in each phase of the study include: hemodynamics (blood pressure, pulmonary artery pressure, pulmonary capillary wedge pressure, cardiac output, ejection fraction, and heart rate), venous and arterial blood gases, complete blood counts, serum chemistries, quantitative blood cultures, endotoxin levels, tumor necrosis factor levels, lactate levels, creatinine kinase levels, and creatinine kinase isoenzymes-CK and CK-MM. We have begun the sepsis protocol and have performed three cycles of the experiment to date. The overall effect of the IABC is to increase myocardial oxygen supply by increasing coronary perfusion during diastole, and decrease myocardial oxygen demand by decreasing afterload during systole. We believe that the IABC may reduce the myocardial depression of sepsis by improving coronary blood flow and reducing left ventricular work; therefore result in a decrease in mortality during sepsis.

败血症休克是美国内科和外科重症监护病房最常见的死亡原因。在死于败血症的患者中，有30%的患者的心输出量较低。本研究的目的是探讨主动脉内球囊反搏(IABC)在感染性休克治疗中的作用。放置主动脉内球囊反搏(IABP)的目的有两个。它减少了心脏的后负荷，从而允许它做更少的工作，即“辅助收缩”，同时增强其冠脉血流，从而为其提供更多的能量，即“舒张期增强”。我们有一个ACUC批准的方案，可以在一个特征良好的低心输出量脓毒症动物模型中进行IABC的随机对照生存研究。 我们已经在动物身上测试了不同的IABP大小，以确定可以提供的舒张期增强和收缩辅助的水平。商业上可用的尺寸不能提供足够的增强，因此开发和测试了定制尺寸的IABP。定制的IABP在短期测试中提供了出色的增强效果，随后进行了长期测试(48小时)，以确定IABP是否导致肾功能改变或对肾脏造成直接损害。定制的IABPS不会改变肾功能，也不会对肾脏造成损害。 这项拟议的研究是在一种具有良好特征的低心输出量脓毒症动物模型中进行的首个IABC对照随机生存研究。这项研究分为三个阶段：阶段1(基线)、阶段2(脓毒症)和阶段3(恢复)。在脓毒症阶段，所有动物将接受细菌凝块(5x10^9cfu的大肠杆菌)静脉输液(含5%葡萄糖的林格氏液)和抗生素(头孢曲松)。此外，动物将被随机分成四组之一：组1(对照组)、组2(加压药)、组3(IABP)和组4(加压药+IABP)。这项研究设计将使我们能够确定每种治疗干预措施(血管加压药或IABP)与对照相比的益处，并检测干预措施之间的任何相互作用。在这三个阶段中的每一个阶段都将研究相同的动物。在研究的每个阶段将获得的测量包括：血流动力学(血压、肺动脉压、肺毛细血管楔压、心输出量、射血分数和心率)、静脉和动脉血气、全血计数、血清化学、定量血培养、内毒素水平、肿瘤坏死因子水平、乳酸水平、肌酸激酶水平和肌酸激酶同工酶-CK和CK-MM。我们已经开始了败血症方案，到目前为止已经进行了三个周期的实验。 IABC的总体作用是在舒张期通过增加冠脉灌注量来增加心肌供氧，在收缩期通过减少后负荷来减少心肌耗氧量。我们认为，IABC可能通过改善冠脉血流量和减少左心做功来减轻脓毒症的心肌抑制，从而降低脓毒症的死亡率。