Comparison of the cardiopulmonary responses to single bolus and continuous infusion of endotoxin in an ovine model

We compared the cardiopulmonary responses to a single bolus (1.5 μg/kg) vs. continuous infusion of endotoxin (LPS)(24 ng/kg/hr) in unaesthetized sheep. A single bolus produced an initial marked increase in pulmonary arterial pressure and plasma thromboxane levels and an elevated flow rate of lung lymph low in protein. Concomitantly, the cardiac output dropped and systemic vascular resistance rose. In the animals that received a continuous infusion of LPS, only very small changes in these variables were noted during this early period. Later, lung lymph flow rate and protein flux were elevated in both groups with a greater response in the bolus group. At 6 hr after LPS, the systemic vascular resistance fell in both groups, but to a greater extent in the bolus group, whereas the cardiac output rose to the same extent. Plasma levels of neutrophils, lymphocytes, and plasma prekallikrein levels decreased in both groups; neutropenia was more pronounced in the bolus group. The most important difference between both endotoxemia models during this phase was the reduction of the stroke work index in the bolus model, which was not observed with the continuous infusion. The apparent myocardial depression, the early reduction in cardiac output, and eicosanoid mediated pulmonary hypertension are the major differences between the two responses.