Expression of endothelin-1 and effects of an endothelin receptor antagonist, TAK-044, at reperfusion after cold preservation in a canine lung transplantation model.

Abstract

BACKGROUND:

Rapid increase of pulmonary vascular resistance (PVR) early after reperfusion remains a major issue in clinical lung transplantation. A potent vasoconstrictor peptide, endothelin- plays an important role in various pulmonary pathophysiologic conditions and might induce increased PVR. We investigated the expression and influence of endothelin-1, and the effects of an ETA and ETB nonselective endothelin receptor antagonist, TAK-044, at reperfusion after cold preservation in a canine lung transplantation model.

METHODS:

Left single lung allotransplantation procedures were performed in three groups of animals. In group I (n=5) lungs were preserved for 12 hours; in group II (n=5) lungs were preserved for 18 hours; and in group III (n=6) lungs were also preserved for 18 hours, and TAK-044 (5 mg/kg) was administered just before reperfusion. All donor lungs were flushed and preserved with low-potassium dextran glucose solution at 4 degrees C.

RESULTS:

Six hours after reperfusion, arterial oxygen tension (mm Hg, inspired oxygen fraction=1.0) was 512.9+/-34.7 in group I, 152.4+/-46.7 in group II, and 509.6+/-29.0 in group III; PVR index (dyne x sec x cm(-5) x m2) was 1130+/-142 in group I, 1820+/-142 in group II, and 1287+/-191 in group III. Plasma endothelin-1 level was elevated significantly, and endothelin-1-like immunoreactivity was found in a variety of pulmonary vascular tissue and was seen less with immunohistochemical evaluation in group II in bronchial tissue.

CONCLUSIONS:

These results suggest that endothelin-1 is expressed as a result of ischemia-reperfusion injury and may worsen early graft function. TAK-044 is beneficial in protecting the graft from high pulmonary vascular resistance and pulmonary edema during the early posttransplantation stage.

• Authors: H Mizutani, K Minamoto, M Aoe, M Yamashita, H Date, A Andou, N Shimizu
• Journal: The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation (J Heart Lung Transplant) Vol. 17 Issue 8 Pg. 835-45 (Aug 1998) ISSN: 1053-2498 [Print] United States
• PMID: 9730434 (Publication Type: Journal Article)

Chemical References

• Endothelin Receptor Antagonists
• Endothelin-1
• Peptides, Cyclic
• TAK 044

Topics

• Animals
• Cryopreservation
• Dogs
• Endothelin Receptor Antagonists
• Endothelin-1 (biosynthesis)
• Lung (blood supply, drug effects, metabolism)
• Lung Transplantation
• Peptides, Cyclic (pharmacology)
• Pulmonary Circulation
• Pulmonary Gas Exchange
• Reperfusion Injury (metabolism)
• Vascular Resistance