The endothelin receptor antagonist TAK-044 in the treatment of reperfusion injury in organ transplantation.
Ischaemia and reperfusion are complex interrelated events that involve the vascular endothelium. The endothelium produces endothelin (ET), the most potent vasoconstrictor identified to date. During ischaemia, endothelial transcription of ET is increased, leading to strong and sustained vasoconstriction. Ischaemia and reperfusion are indispensable parts of solid organ transplantation. Various experimental data discussed in this review show an efficacy of the mixed ET(A/B) antagonist TAK-044 in the treatment of reperfusion injury. The overall safety and tolerability of TAK-044 in humans seems to be excellent. Large clinical randomised trials on the use of TAK-044 in the treatment of reperfusion injury in different clinical situations are missing, nevertheless, the future for ET antagonists is promising.
Behrend
M
M
Abteilung für Viszeral- und Transplantationschirurgie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30623 Hannover, Germany. Behrend.Matthias@mh-hannover.de