Iloprost ameliorates post-ischemic lung reperfusion injury and maintains an appropriate pulmonary ET-1 balance.

Abstract

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.

• Authors: Masahiro Kawashima, Takayuki Nakamura, Sven Schneider, Brigitte Vollmar, Henning F Lausberg, Michael Bauer, Michael D Menger, Hans-Joachim Schäfers
• Journal: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation (J Heart Lung Transplant) Vol. 22 Issue 7 Pg. 794-801 (Jul 2003) ISSN: 1053-2498 [Print] United States
• PMID: 12873548 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Endothelin-1
• Vasodilator Agents
• Iloprost
• Oxygen

Topics

• Animals
• Body Weight
• Disease Models, Animal
• Endothelin-1 (drug effects, metabolism)
• Iloprost (pharmacology)
• Lung (drug effects, metabolism, physiopathology)
• Male
• Models, Cardiovascular
• Oxygen (blood)
• Pulmonary Circulation (drug effects)
• Pulmonary Edema (metabolism, physiopathology)
• Pulmonary Gas Exchange (drug effects)
• Pulmonary Wedge Pressure (drug effects)
• Rats
• Rats, Inbred Lew
• Reperfusion Injury (metabolism, physiopathology)
• Respiratory Distress Syndrome (metabolism, physiopathology)
• Severity of Illness Index
• Statistics as Topic
• Vascular Resistance (drug effects)
• Vasodilator Agents (pharmacology)