PHARMACOLOGICAL MODULATION OF PULMONARY VASCULAR-PERMEABILITY DURING AIR-EMBOLISM

Pulmonary air embolism induces the generation of vasoactive and cytoto xic substances leading to lung injury. In the present study we investi gated, in isolated and perfused rat lungs, the involvement of arachido nic acid metabolites in the alterations of vascular pressure, lung wat er content, and the filtration coefficient (K-f). We also tested the e ffects of a beta-agonist, a calcium channel blocker, and a cyclooxygen ase inhibitor on the hemodynamic and the permeability changes followin g pulmonary air embolism. The artificially ventilated rat lungs were r emoved en bloc and suspended in a humidified chamber at 37 degrees C. The salt and buffered perfusate contained 4% Ficoll as albumin substit ute for osmotic balance. We introduced air bubbles through the pulmona ry artery. Air embolism increased pulmonary arterial resistance and ca used pulmonary hypertension. Lungs receiving air infusion contained 88 .6 +/- 0.6% water, which was significantly greater than the lung water content in the control groups (81.9 +/- 0.4%). Air embolism increased K-f by 145 +/- 19% from the baseline value. Pretreatment with indomet hacin, isoproterenol, or nifedipine significantly reduced post-air-emb olism lung water content to 85.8 +/- 0.5%, 84.1 +/- 0.4%, and 86.5 +/- 0.4%, respectively, and reduced the K-f increase to 17 +/- 8%, 1 +/- 9%, and 72 +/- 8%, respectively. These interventions did not alter the hemodynamic responses, except for the isoproterenol infusion, which s hortened the half-time (T-1/2) for pressure recovery after ending air infusion compared to the group with air embolism alone. Our results sh owed that indomethacin prevented vascular permeability increase and re duced pulmonary edema, suggesting that the cyclo-oxygenase products pa rtially mediate the lung injury following air embolism. Furthermore, i soproterenol and nifedipine prevented or reduced the permeability incr ease, suggesting that alterations of the intracellular cAMP and cytoso lic Ca2+ level play an important role in the pathophysiology of pulmon ary air embolism.