EFFECTS OF CYCLOOXYGENASE INHIBITORS ON LUNG MICROVASCULAR INJURY FOLLOWING PULMONARY INTRAVASCULAR COAGULATION (PIC)

Abstract

We compared the effects of cyclooxygenase inhibitors, meclofenamate (MEC) and ibuprofen (IBU) on the development of lung mcirovascular injury after PIC induced by i.v. thrombin (T) infusion (80 U/kg). Studies were made in awake (n=10) sheep with lung lymph fistulas. The animals were pretreated with either MEC or IBU. Lung lymph flow (Qlym) lymph-to-plasma protein concentration ratio (L/P), and transvascular protein clearance (L/P × Qlym) were determined. MEC and IBU prevented the increases in the cyclooxygeanse end-products, thromboxane B2 and 6-keto-PGF1α after T. T resulted in 6-fold increases in Qlym and protein clearance, indicating lung microvascular injury. MEC attenuated the initial rises in Qlym and protein clearance after T, while IBU prevented both initial and steady-state responses. IBU but not MEC reduced the increases in pulmonary arterial pressure and PVR after T. In another group (n=11), lung PMN uptake after T was determined by infusing homologous 111-Indium oxine labeled PMN and measuring lung activity with a gamma camera. PMN uptake increased by 11% over baseline after T in controlas, compared to 4.1% in MEC group and none in IBU group. Conclusion: IBU has a greater protective effect in preventing thrombin-induced lung vascular injury than MEC. The protective effect is independent of inhibition of cyclooxygenase but may be related to inhibition of neutrophil margination. (HL-17355 and HL-26551)