Impact of arachidonic acid on microhemodynamics and leukocyte adhesion in alveolar capillaries during endotoxemia

Background: Development of acute lung injury is characterized by accumulati on of leukocytes in pulmonary microvessels, followed by endothelial cell da mage and interstitial edema formation. In vitro results indicate enhancemen t of leukocyte adherence and endothelial cell damage by arachidonic acid (A A). Therefore, the aim of our study was to investigate whether enhanced ava ilability of AA promotes development of acute lung injury in vivo. Methods: Eighteen New Zealand White rabbits were anesthetized, ventilated a nd randomly assigned to 2 groups. AA-group received parenteral infusion of AA (5 mg/ h) dissolved in medium chain triglycerides (MCT, 100 mg/h), contr ol-group was infused with MCT (100 mg/h) alone. Arterial pressure (AP,) was measured and pulmonary arterial pressure divided by cardiac output (PAP/CO ) was calculated as index of pulmonary vascular resistance. Implantation of a transparent window into the right thoracic wall combined with intravital microscopy enabled quantification of erythrocyte velocity (V-rbc), functio nal capillary perfusion index (CPI), width of alveolar septa and number of adherent leukocytes in alveolar capillaries. After 4 h of continuous infusi on of AA or MCT respectively, investigations were performed before (pre) an d 60 min after intravenous injection of endotoxin (20 mu g/kg b.w.). Results: In the AA-group APm was reduced (76 +/- 5; 51 +/- 4(a) [mmHg]) and PAP/CO was ina eased (39 +/- 5; 75 +/- 21(b) [mmHg . l(-1) . min]) 60 min, after i.v. injection of endotoxin. In the control-group AP(m) and PAP/CO r emained constant. Reduction of V-rbc (345 +/- 43; 133 +/- 61(b) [mu m/s]) a nd CPI (18 +/- 8(a,b) [% pre]) was more pronounced in AA-group ill comparis on to control-group (V-rbc: 424 +/- 80; 226 +/- 59 [mu m/s], CPI: 62+/-18(b ) [% pre]). Width of alveolar septa was increased in AA-group 60 min after injection of endotoxin (AA: 34 +/- 3(a), control: 23 +/- 2 [mu m]). L-ad we re slightely elevated in both groups (AA: 516 +/- 88; 877 +/- 139, control: 410 +/- 115; 578 +/- 79 [mm(-2)]). Conclusion: Increased availability of AA promotes development of endotoxin induced acute lung injury in vivo.