Effect of Heparin on Increased Pulmonary Microvascular Permeability after Bone Marrow Embolism in Awake Sheep

Abstract

We examined the alterations in pulmonary transvascular fluid and protein exchange after intravenous infusion of fat emboli, i.e., bone marrow suspension (BMS) in awake sheep prepared with chronic lung lymph fistulas and compared these changes with those observed in sheep pretreated with heparin. The BMS injection (0.2 ml/kg) over 15 min caused rapid, but transient, increases (p less than 0.05) in mean pulmonary artery pressure and pulmonary vascular resistance. These increases were accompanied by significant increases in the lymph concentrations of thromboxane B2 and 6-keto-PGF1 alpha. Pulmonary lymph flow increased by 3.9-fold (+/- 0.8) over baseline by 120 min after BMS with no change in the lymph-to-plasma protein concentration ratio (L/P ratio). Heparin pretreatment (700 U/kg) enhanced the BMS-induced increases in pulmonary artery pressure and pulmonary vascular resistance. Thromboxane B2 concentrations in the lymph increased, whereas there was no change in the concentration of 6-keto-PGF1 alpha. Lung lymph flow increased 4-fold (+/- 1.0) over baseline by 120 min after BMS without a change in L/P ratio. Changes in lung vascular permeability were evaluated by elevating pulmonary microvascular pressure (left atrial balloon catheter inflation) at 120 min after BMS. Lung lymph flow increased 7-fold (+/- 1.1) from baseline, whereas the L/P ratio decreased to a mean value of 0.48 +/- 0.03. The protein reflection coefficient (sigma = 1 - L/P ratio) decreased from a control mean of 0.69 +/- 0.02 to 0.52 +/- 0.03 after the BMS challenge.(ABSTRACT TRUNCATED AT 250 WORDS)