Glyceryl trinitrate prevents neutrophil activation but not thromboxane release following ischaemia-reperfusion injury.
The aim of this study was to determine whether glyceryl trinitrate (GTN) has a protective effect on neutrophil-mediated lung injury in a model of aortic occlusion (30 min) and reperfusion (120 min). Sprague-Dawley rats were randomized into control (n = 11), ischaemia-reperfusion (IR) (n = 12), and IR treated with GTN (2 micrograms kg-1 min-1) during reperfusion (n = 10). Myeloperoxidase (MPO) activity measured pulmonary neutrophil influx. Pulmonary endothelial permeability was measured by wet:dry weight ratio, bronchoalveolar lavage (BAL) protein and neutrophil counts. Neutrophil superoxide release was measured by flow cytometry 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 units g-1. The increase in pulmonary microvascular leakage after reperfusion was also prevented by GTN: BAL protein without GTN was 992 micrograms ml-1 and with GTN 579 micrograms ml-1; BAL neutrophil count without GTN was 3219 cells mm-3 and with GTN 820 cells mm-3; the wet:dry lung weight ratio without GTN was 3.8 and with GTN 3.3. Neutrophil superoxide release increased significantly after 40 min of reperfusion in the untreated IR group (P < 0.05). This increase was prevented in the GTN-treated group. GTN administration had no effect on plasma thromboxane production during revascularization. These data suggest that GTN administration during the reperfusion phase has the potential to decrease pulmonary microvascular injury.
Barry
M C
MC
Department of Surgery, Beaumont Hospital, Dublin.
Kelly
C J
CJ
Stokes
K
K
Abdih
H
H
Sheehan
S
S
Burke
P
P
Bouchier Hayes
D
D
D000818:Animals; D001018:Aortic Diseases / Q000378:metabolism; D001157:Arterial Occlusive Diseases / Q000378:metabolism; D001794:Blood Pressure; D007958:Leukocyte Count; D008168:Lung / Q000098:blood supply*; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils; D009573:Nitrites / Q000378:metabolism; D005996:Nitroglycerin / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism*; D016897:Respiratory Burst; D013931:Thromboxanes / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology*
D009573:Nitrites; D013931:Thromboxanes; D014665:Vasodilator Agents; D005996:Nitroglycerin