Amelioration of reperfusion injury by pentoxifylline after lung transplantation. The Université Paris-Sud Lung Transplant Group.
BACKGROUND
Pentoxifylline attenuates neutrophil-mediated lung injury in several models of acute lung inflammation.


METHODS
Because pulmonary neutrophil sequestration is the main determinant of lung reperfusion injury, we sought to determine whether pentoxifylline prevented reperfusion injury in isolated perfused rat lung (4-hour cold ischemia, 1-hour reperfusion; pentoxifylline intravenously 40 mg) and in pigs after left lung allotransplantation (24-hour cold ischemia, 4-hour reperfusion; pentoxifylline 1.5 mg/kg/hr intravenously). In the pigs, inflatable cuffs placed around each pulmonary artery enabled us to evaluate each lung separately.


RESULTS
In rat lungs, the coefficient of lung permeability increased by 75% +/- 10% in controls and by 3% +/- 2% (p < 0.01) in pentoxifylline-treated lungs. In the pigs, with blood flow to the transplanted lung alone and ventilation with an inspired oxygen fraction of 1, the arterial oxygen tension was greater in the pentoxifylline group than in the control group (423 +/- 49 versus 265 +/- 43 mm Hg, p < 0.05), whereas the total pulmonary vascular resistance was lower (15 +/- 1 versus 30 +/- 9 mm Hg/L/min, p < 0.02). After reperfusion, the decrease in circulating leukocyte count fell by 35% +/- 3% in the control group and remained unchanged in the pentoxifylline group, and the leukocytes count per microscopic field in the transplanted lung was lower in the pentoxifylline group than in the control group (15 +/- 2 versus 140 +/- 50, p < 0.02).


CONCLUSIONS
These data suggest that pentoxifylline prevented reperfusion injury by decreasing neutrophil lung sequestration.
Chapelier
A
A
Laboratoire de Chirurgie Expérimentale, Hôpital Marie Lannelongue, Université Paris Sud, Le Plessis Robinson, France.
Reignier
J
J
Mazmanian
M
M
Dulmet
E
E
Libert
J M
JM
Dartevelle
P
P
Barbotin
F
F
Hervé
P
P
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects; D007958:Leukocyte Count / Q000187:drug effects; D016040:Lung Transplantation / Q000473:pathology*; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D010100:Oxygen / Q000097:blood; D010431:Pentoxifylline / Q000494:pharmacology*; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D002245:Carbon Dioxide; D010100:Oxygen; D010431:Pentoxifylline