Iloprost ameliorates post-ischemic lung reperfusion injury and maintains an appropriate pulmonary ET-1 balance.
BACKGROUND
Ischemia-reperfusion (I/R) injury of the lung involves increased pulmonary vascular resistance. Prostaglandins are thought to have a beneficial effect in lung transplantation, but their mechanism in I/R injury is unknown. We investigated whether iloprost, a stable prostacyclin analogue, prevents I/R-associated pulmonary vascular dysfunction and whether it affects endothelin-1 (ET-1) balance.


METHODS
In an isolated blood-perfusion model, we subjected lungs of Lewis rats to 45 minutes of ischemia at 37 degrees C and randomly allocated the lungs to 3 groups (n = 6 each): iloprost (33.3 nmol/liter) added to the perfusate before ischemia and reperfusion (ILO+IR), iloprost (33.3 nmol/liter) given only before reperfusion (ILO+R), and controls without iloprost treatment (ILO-).


RESULTS
Reperfusion induced marked pulmonary edema in non-treated controls (ILO-), which was attenuated in ILO+R lungs and completely prevented in ILO+IR lungs. At 60 minutes reperfusion, arterial oxygen tension was significantly greater in both ILO+R and ILO+IR lungs compared with ILO- controls. Mean pulmonary artery pressure and pulmonary vascular resistance were slightly decreased in the ILO+R and significantly decreased in the ILO+IR group compared with the ILO- controls. Plasma levels of big ET-1, measured in both afferent and efferent blood, showed that I/R results in increased pulmonary venous levels of big ET-1. Interestingly, the increased venoarterial ET-1 gradient in ILO- lungs decreased significantly in the ILO+IR group.


CONCLUSIONS
We demonstrated in an isolated lung perfusion model that iloprost ameliorates post-ischemic lung reperfusion injury and maintains an appropriate pulmonary ET-1 balance.
Kawashima
Masahiro
M
Department of Thoracic and Cardiovascular Surgery, University of Saarland, Homburg/Saar, Germany.
Nakamura
Takayuki
T
Schneider
Sven
S
Vollmar
Brigitte
B
Lausberg
Henning F
HF
Bauer
Michael
M
Menger
Michael D
MD
Schäfers
Hans-Joachim
HJ
D000818:Animals; D001835:Body Weight; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000187:drug effects* / Q000378:metabolism*; D016285:Iloprost / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008955:Models, Cardiovascular; D010100:Oxygen / Q000097:blood; D011652:Pulmonary Circulation / Q000187:drug effects; D011654:Pulmonary Edema / Q000378:metabolism / Q000503:physiopathology; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D012128:Respiratory Distress Syndrome / Q000378:metabolism* / Q000503:physiopathology; D012720:Severity of Illness Index; D013223:Statistics as Topic; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D019332:Endothelin-1; D014665:Vasodilator Agents; D016285:Iloprost; D010100:Oxygen