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J Thorac Cardiovasc Surg 1999;117:556-564
© 1999 Mosby, Inc.


CARDIOTHORACIC TRANSPLANTATION

MODULATION OF REPERFUSION INJURY AFTER SINGLE LUNG TRANSPLANTATION BY PENTOXIFYLLINE, INOSITOL POLYANIONS, AND SIN-1

Stephen C. Clark, FRCSa, Catherine Sudarshan, FRCSa, Jonathan Roughan, PhDb, Paul A. Flecknell, MRCVSb, John H. Dark, FRCSa

From The Cardiothoracic Centre, Freeman Hospital,a and Comparative Biology Centre,b The University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom.

This study was funded by a Research Fellowship from the Royal College of Surgeons of England and a Project Grant from the Northern and Yorkshire Health Authority.

Received for publication Feb 11, 1998. Revisions requested April 21, 1998. Revisions received Oct 6, 1998. Accepted for publication Oct 8, 1998. Address for reprints: S. Clark, FRCS, The Cardiothoracic Centre, Freeman Hospital, Newcastle upon Tyne, NE7 7DN, United Kingdom.

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.




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