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.
