Pulmonary microvascular changes during hyperdynamic sepsis in an ovine model.
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.
D000818:Animals; D002302:Cardiac Output; D005609:Free Radicals; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000494:pharmacology; D008163:Luminescent Measurements; D008208:Lymphatic System / Q000503:physiopathology; D008833:Microcirculation; D011652:Pulmonary Circulation; D018805:Sepsis / Q000503:physiopathology*; D012756:Sheep; D014655:Vascular Resistance
D005609:Free Radicals; D008070:Lipopolysaccharides