Modulation of reperfusion injury after single lung transplantation by pentoxifylline, inositol polyanions, and sin-1.
OBJECTIVE
Previous studies have suggested reductions in lung reperfusion injury with pentoxifylline, inositol polyanions, and the nitric oxide donor, SIN-1, but these agents have never been directly compared to ascertain which is superior. We investigated these agents in a porcine model of left single lung transplantation.


METHODS
Donor lungs were preserved with modified Euro-Collins solution for a mean ischemic time of 18.4 hours. Neutrophil trapping in the graft, pulmonary vascular resistance, free radical release (measured by malonaldehyde levels) and gas exchange were assessed over a 12-hour period. All groups were reperfused at an initial pulmonary artery pressure of 20 mm Hg. Group A (n = 5) was a control group with no interventions added; group B was reperfused with the addition of intravenous inositol polyanions (0.02 mg/kg/h), and group C was reperfused with intravenous SIN-1 (0.02 mg/kg/h). Group D was reperfused with the addition of intravenous pentoxifylline (2 mg/kg/h).


RESULTS
Neutrophil sequestration was observed within 10 minutes of reperfusion in group A. This was attenuated significantly by interventions in groups B, C, and D. In group D, malonaldehyde levels were significantly lower than in other groups and was associated with superior oxygenation. Pulmonary vascular resistance was reduced in groups B, C, and D compared with group A.


CONCLUSIONS
Pentoxifylline, when administered only to recipient animals was superior to the other interventions studied. Inositol polyanions are promising as a possible therapeutic intervention but were not as effective as the other agents studied.
Clark
S C
SC
Cardiothoracic Centre, Freeman Hospital, and Comparative Biology Centre, The University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom.
Sudarshan
C
C
Roughan
J
J
Flecknell
P A
PA
Dark
J H
JH
D000818:Animals; D001792:Blood Platelets / Q000473:pathology; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000494:pharmacology; D008168:Lung / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D016040:Lung Transplantation; D008315:Malondialdehyde / Q000032:analysis; D008981:Molsidomine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D009504:Neutrophils / Q000473:pathology; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000494:pharmacology; D010431:Pentoxifylline / Q000008:administration & dosage* / Q000494:pharmacology; D010833:Phytic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D011652:Pulmonary Circulation; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D013552:Swine; D014655:Vascular Resistance
D016166:Free Radical Scavengers; D020030:Nitric Oxide Donors; D008315:Malondialdehyde; C002385:linsidomine; D010833:Phytic Acid; D008981:Molsidomine; D010431:Pentoxifylline