PULMONARY VASCULAR EFFECTS OF ENDOTOXIN IN CANINE LOBES PRETREATED WITH DAPSONE

Endotoxin results in a granulocyte mediated loss of hypoxic pulmonary vasoconstriction (HPV). Dapsone blocks the granulocyte respiratory bur st and might, therefore, preserve HPV following endotoxin. Isolated-pe rfused canine lobes (n = 6) were pretreated with 18 mg/kg dapsone (dap sone group), and compared to six robes which did not receive dapsone ( control group). Total pulmonary vascular resistance (Rtot) and arteria l, middle (Rm), and venous segmental resistances were calculated by a vascular occlusion technique. We then administered endotoxin (2 mg/kg) and repeated measurements at 5, 30, and 90 min. The increase in Rm du ring 3% O-2 compared to 35% O-2 ventilation was used to define the pre sence of HPV. In the control group, following endotoxin, values of Rm did not change (P>0.05) during 3% O-2 ventilation (0.011+/-0.006 cm H2 O/ml/min) compared with 35% O-2 ventilation (0.014+/-0.005 cm H2O/ml/m in). In the dapsone group, following endotoxin, values of Rm increased (P<0.05) during 3% O-2 ventilation (0.06+/-0.026 cm H2O/ml/min) compa red with 35% O-2 ventilation (0.03+/-0.015 cm H2O/ml/min). Changes in 6-keto PGF(1 alpha) or thromboxane B-2 do not explain these observatio ns. We conclude that in this experimental preparation, pretreatment wi th dapsone prevents the loss of HPV associated with endotoxin. (C) 199 4 Wiley-Liss, Inc.