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

在美国，感染性休克是内科和外科重症监护病房中最常见的死亡原因。30%死于败血症的患者心输出量低。本研究的目的是探讨主动脉内球囊反搏（IABC）在治疗感染性休克中的作用。放置主动脉内球囊反搏（IABP）的目的是双重的。它减少了心脏的后负荷，从而使它做更少的工作，“辅助收缩”，同时增强其冠状动脉血流量，从而为它提供更多的能量，“舒张增强”。“我们有一个ACUC批准的方案，在一个特征良好的低心排动物败血症模型中进行IABC的对照、随机生存研究。 我们已经在动物身上测试了不同尺寸的主动脉内球囊反搏，以确定可以提供的舒张增强和收缩辅助水平。市售尺寸无法提供充分的增强，因此开发并测试了定制尺寸的主动脉内球囊反搏。定制IABP在短期测试期间提供了极好的增强，随后进行了长期测试（48小时），以确定IABP是否引起肾功能的任何改变或对肾脏的直接损伤。定制IABP不会改变肾功能，也不会对肾脏造成损伤。 该研究是首次在特征明确的低心排动物脓毒症模型中进行的IABC对照、随机生存研究。本研究分为三个阶段：1期（基线）、2期（脓毒症）和3期（恢复期）。在脓毒症阶段，所有动物将接受细菌凝块（5 x 10^9 cfu的E.大肠杆菌）静脉输液（含5%葡萄糖的林格氏溶液）和抗生素（头孢曲松）。此外，将动物随机分配至四组之一：第1组（对照组）、第2组（血管加压药）、第3组（IABP）和第4组（血管加压药+ IABP）。本研究设计将使我们能够确定每种治疗干预（血管加压药或IABP）与对照相比的获益，并检测干预之间的任何相互作用。在三个阶段的每一个阶段将研究相同的动物。在研究的每个阶段获得的测量值包括：血流动力（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、全血细胞计数、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、肌酸酐激酶水平、和肌酸酐激酶同工酶-CK和CK-MM。我们已经开始脓毒症方案，并已进行了三个周期的实验。 IABC的总体作用是通过增加冠脉灌注增加心肌氧供应，并通过减少收缩期后负荷减少心肌氧需求。我们认为，IABC可能通过改善冠状动脉血流和减少左心室作功来减轻脓毒症的心肌抑制，从而降低脓毒症的死亡率。

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.