Improvements in lung compliance after pulmonary transplantation: correlation with interleukin 8 expression.
OBJECTIVE
Previous studies have suggested reductions in lung reperfusion injury when initial reperfusion is undertaken with the addition of pharmacological modulators. We investigated three pharmacological agents in a porcine model of left single lung transplantation to determine the effect on lung compliance and its relationship with the expression of the cytokine, interleukin-8 (IL-8).


METHODS
Donor lungs were preserved with modified Euro-Collins for a mean ischaemic time of 18.6 h. Pulmonary venous oxygenation, lung compliance and IL-8 expression were assessed over a 12-h period. Group A (n=5) was a control group with no interventions added, Group B was reperfused with the addition of intravenous inositol hexakisphosphate (InSP6) (0.02 mg/kg per min), Group C received the nitric oxide donor, 3-morpholinosydnonimine (SIN-1) (0.02 mg/kg per min) and Group D received intravenous Pentoxifylline (2 mg/kg per h). All interventions were administered at a pulmonary artery pressure of 20 mmHg.


RESULTS
Group D yielded the best oxygenation (P=0.0041) while Groups B and C were similar. All were superior to Group A (P<0.001). Lung compliance was significantly improved in Groups B, C and D compared to group A. In Group D, the greatest improvements in lung compliance were observed (P<0.0001). Similar observations were seen with regard to pulmonary vascular resistance. IL-8 expression was delayed until after 30 min of reperfusion in Group D, but was evident after 10 min in all the other groups. This correlates with the compliance and oxygenation data.


CONCLUSIONS
The addition of InSP6 or SIN-1 at reperfusion significantly attenuates reperfusion injury compared with controls and improves lung compliance. The unique comparison with Pentoxifylline afforded by this study indicates that at the doses studied Pentoxifylline appears to be superior, correlating with a greater inhibition of IL-8 expression.
Rao
Jagan N
JN
Cardiothoracic Centre, Freeman Hospital, Newcastle upon Tyne NE7 7DN, UK.
Clark
Stephen C
SC
Ali
Simi
S
Kirby
John
J
Flecknell
Paul A
PA
Dark
John H
JH
D000818:Animals; D019540:Area Under Curve; D002868:Chromosomal Proteins, Non-Histone / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000494:pharmacology; D005260:Female; D016209:Interleukin-8 / Q000235:genetics*; D008168:Lung / Q000098:blood supply* / Q000503:physiopathology; D008170:Lung Compliance; D016040:Lung Transplantation; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010431:Pentoxifylline; D010833:Phytic Acid / Q000494:pharmacology; D016133:Polymerase Chain Reaction / Q000379:methods; D011651:Pulmonary Artery; D012333:RNA, Messenger / Q000032:analysis*; D012039:Regional Blood Flow; D015427:Reperfusion Injury / Q000276:immunology / Q000517:prevention & control*; D029701:Saccharomyces cerevisiae Proteins; D013552:Swine; D014655:Vascular Resistance; D014665:Vasodilator Agents / Q000494:pharmacology
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D016209:Interleukin-8; D020030:Nitric Oxide Donors; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D014665:Vasodilator Agents; D010833:Phytic Acid; C069938:SPT2 protein, S cerevisiae; D010431:Pentoxifylline