EFFECTS OF A NOVEL PANCREATITIS-ASSOCIATED PROTEIN ON PULMONARY VASCULAR-RESISTANCE AND PERMEABILITY

Severe pancreatitis is often complicated by acute lung injury. Recentl y it has been demonstrated that a specific pancreatic secretory protei n is synthesized during pancreatitis in humans and in rats. The secret ion of this pancreatitis-associated protein (PaP) increases as a funct ion of the severity of pancreatitis. The aim of this study was to inve stigate the effect of PaP on pulmonary vascular resistance and permeab ility and to analyse potential mechanisms of action in the isolated pe rfused rabbit lung model. Methods: 19 isolated lungs from anesthesized rabbits were ventilated and recirculatingly perfused (200 ml/min) wit h 200 ml cell-free buffer solution to which PaP in a concentration of 260 ng/ml was added (n = 3). It was tested whether the cyclooxygenase inhibitor diclofenac (10 mu g/ml, n = 3), the bradykinin B-2-receptor antagonist CP 0127 (1 mu M, n = 3), the H-1- and H-2-receptor antagoni sts (dimetindenmaleat and cimetidin; 10 mu M, n = 3), and the platelet -activating factor (PAF) antagonist WEB 2086 (100 mu M, n = 3) exert a protective effect on the PaP-induced pulmonary vascular reaction and mediator release. Four sham operated lungs served as control. Arterial pressure and weight changes indicating volume shifts between intra- a nd extravascular space were continuously monitored. Results: Edema for mation was induced by PaP resulting in a weight gain of approx. 30 g 1 50 min after PaP challenge, paralleled by an increase in pulmonary art erial pressure of approx. 16 mmHg from baseline values. Diclofenac, CP 0127, H-receptor antagonists, and WEB 2086 failed to inhibit the pulm onary vascular reactions due to PaP. Conclusion: The data demonstrated , that PaP causes edema formation and alterations of pulmonary vascula r tone, which might be relevant for pulmonary injury during severe pan creatitis. Pathomechanisms mediated via bradykinin B-2-receptors, H-re ceptors and PAF do not seem to be essentially involved in the acute pu lmonary responses induced by PaP.