Pulmonary microvascular changes during hyperdynamic sepsis in an ovine model.

Abstract

Hyperdynamic sepsis (increased cardiac output and reduced peripheral vascular resistance) was created in sheep with chronic lung lymph fistulae (n = 8) by giving them a 30-min infusion of 1.5 micrograms/kg of endotoxin (LPS) iv. Four hours after LPS the cardiac output (CO) was reduced (6.56 +/- 0.43 to 4.96 +/- 0.33 liters/min) and lymph flow was increased (5.4 +/- 1.0 to 18.6 +/- 3.1 ml/h). Nine hours after LPS the CO output was increased (8.42 +/- 0.60 liters/min). Early cardiopulmonary changes were associated with a fall in neutrophils (PMNs) (2,667 +/- 748 to 450 +/- 90 cells/microliter) and an elevation of their chemiluminescence (CL), an indication of increased O2 free-radical formation in the blood (1,250 +/- 160 to 3,340 +/- 744 units/1,000 leukocytes). The granulocytic enzyme, aryl sulfatase, was increased in the lymph (0.19 +/- 0.03 to 0.37 +/- 0.05 microgram/h/mg protein) indicating degranulation (activation) of PMNs. When CO was increased (9 h after LPS), blood CL rose even higher (5,330 +/- 173 units/1,000 leukocytes) and CL in the lung lymph decreased (1,160 +/- 220 units/1,000 leukocytes). At this time, lymphatic aryl sulfatase had returned to baseline levels (0.25 +/- 0.02 microgram/h/mg protein). These data suggest that pulmonary microcirculatory injury produced by LPS may be the result of margination of PMNs in the lung and their release of permeability-inducing mediators. Later, as the CO increases, the PMNs or their lesion-producing mediators may be washed from the lung and the lung injury thus may be made less severe.