GLYCERYL TRINITRATE PREVENTS NEUTROPHIL ACTIVATION BUT NOT THROMBOXANE RELEASE FOLLOWING ISCHEMIA-REPERFUSION INJURY

The aim of this study was to determine whether glyceryl trinitrate (GT N) has a protective effect on neutrophil-mediated lung injury in a mod el of aortic occlusion (30 min) and reperfusion (120 min). Sprague-Daw ley rats were randomized into control (n = 11), ischaemia-reperfusion (TR) (n = 12), and IR treated with GTN (2 mu g kg(-1) min(-1)) during reperfusion (n = 10). Myeloperoxidase (MPO) activity measured pulmonar y neutrophil influx. Pulmonary endothelial permeability was measured b y wet:dry weight ratio, bronchoalveolar lavage (BAL) protein and neutr ophil counts. Neutrophil superoxide release was measured by flow cytom etry in a further IR versus GTN experiment (n = 6 in each group). The significant increase in MPO activity produced by IR to a level of 7.99 units g(-1) was prevented by GTN which reduced the level to 4.73 unit s g(-1). The increase in pulmonary microvascular leakage after reperfu sion was also prevented by GTN: BAL protein without GTN was 992 mu g m l(-1) and with GTN 579 mu g ml(-1); BAL neutrophil count without GTN w as 3219 cells mm(-3) and with GTN 820 cells mm(-3); the wet:dry lung w eight ratio without GTN was 3.8 and with GTN 3.3. Neutrophil superoxid e release increased significantly after 40 min of reperfusion in the u ntreated IR group (P<0.05). This increase was prevented in the GTN-tre ated group. GTN administration had no effect on plasma thromboxane pro duction during revascularization. These data suggest that GTN administ ration during the reperfusion phase has the potential to decrease pulm onary microvascular injury.