Many animal studies have attempted to simulate the circulatory responses to Gram-negative septicemia (iv infusion of live bacteria, fecal inoculation into body cavities, and administration of purified endotoxins by various routes), but the contribution of the heart to the adverse hemodynamic derangements and thus to the pathogenesis of shock is difficult to determine because of peripheral vascular events that influence cardiac performance. When blood pools in the periphery, venous return decreases and cardiac output can decrease without a primary myocardial defect being present. However, early heart dysfunction has been recognized in sepsis. Hemodynamic monitoring has not reduced overall mortality, but it has been helpful in guiding fluid administration and evaluating response to vasopressor therapy.