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Endothelial adhesivity, pulmonary hemodynamics and nitric oxide synthesis in ischemia-reperfusion
1Cardiothoracic Surgery Department, College of Physicians and Surgeons, Columbia University, NY, New York 10032, USA. kvural@tr-net.tr
Objective:
Alterations in nitric oxide synthesis, endothelial adhesivity and pulmonary hemodynamics are investigated in an animal model of lung ischemia-reperfusion.
Methods:
Two sets of rats, each containing seven animals, were either subjected to unilateral pulmonary ischemia and reperfusion (Study Group) or underwent the same surgical procedure without ischemia (Control Group). Pulmonary artery pressure (PAP), pulmonary blood flow (PBF) trend, NOS-2, intercellular adhesion molecule-1 (ICAM-1), myeloperoxidase (MPO) and cGMP expression of the reperfused lung tissue and, final paO(2) were compared between the two groups.
Results:
ICAM-1 expression was increased (369+/-114 vs. 115+/-65; P=0.02), NOS-2 expression and tissue cGMP levels were decreased (377+/-44 vs. 452+/-54; P=0.03 and 7.8+/-3.5 vs. 9.4+/-2.3 pmol/ml; P=0.03, respectively) and MPO activity was increased (2.7+/-0.9-3.5+/-0.8; P=0.03) in the reperfused lungs. Pulmonary artery pressure was 15+/-7 mmHg in the Control Group vs. 22+/-16 mmHg in the Study Group (P=0.04) at the 30th min of reperfusion. Pulmonary blood flow was greater in the Study Group at the beginning of reperfusion (9.5+/-4.1 vs. 7.1+/-3.1 ml/min at the 30th min) but considerably reduced thereafter (3.2+/-1. 4 vs. 6.2+/-2.1 at the 60th minute and 2.9+/-1.6 vs. 5.8+/-1.9 at the 120th min). At the end of the experiment, paO(2) was 95+/-30 in the Control Group vs. 71+/-32 in the Study Group (P=0.03).
Conclusions:
These data establish that nitric oxide synthesis was suppressed after reperfusion. Pulmonary blood flow was first increased and then reduced. A parallel increase in MPO and ICAM-1 indicated proinflammatory reaction. Decreased tissue cGMP level was consistent with the suppressed NOS-2 production. Organ function was negatively influenced as represented by the decreased oxygenation, probably due to no-reflow phenomenon.