Pharmacological strategies against cold ischemia reperfusion injury.
BACKGROUND
Good organ preservation is a determinant of graft outcome after revascularization. The necessity of increasing the quality of organ preservation, as well as of extending cold storage time, has made it necessary to consider the use of pharmacological additives.


METHODS
The complex physiopathology of cold-ischemia-reperfusion (I/R) injury--and in particular cell death, mitochondrial injury and endoplasmic reticulum stress--are reviewed. Basic principles of the formulation of the different preservation solutions are discussed.


RESULTS
Current strategies and new trends in static organ preservation using additives such as trimetazidine, polyethylene glycols, melatonin, trophic factors and endothelin antagonists in solution are presented and discussed. The benefits and mechanisms responsible for enhancing organ protection against I/R injury are also discussed. Graft preservation was substantially improved when additives were added to the preservation solutions.


CONCLUSIONS
Enrichment of preservation solutions by additives is clinically useful only for short periods. For longer periods of cold ischemia, the use of such additives becomes insufficient because graft function deteriorates as a result of ischemia. In such conditions, the preservation strategy should be changed by the use of machine perfusion in normothermic conditions.
Zaouali
Mohamed Amine
MA
Experimental Hepatic Ischemia-Reperfusion Unit, Institut d'Investigacions Biomèdiques de Barcelona, CSIC-IDIBAPS, C/Rosselló 161, 7th floor, E-08036-Barcelona, Spain. jrcbam@iibb.csic.es
Ben Abdennebi
Hassen
H
Padrissa-Altés
Susagna
S
Mahfoudh-Boussaid
Asma
A
Roselló-Catafau
Joan
J
D050377:Cold Ischemia; D003080:Cold Temperature; D065128:Endothelin Receptor Antagonists; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008550:Melatonin / Q000494:pharmacology; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions / Q000494:pharmacology*; D010477:Perfusion; D011092:Polyethylene Glycols / Q000494:pharmacology; D015427:Reperfusion Injury / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control*; D009927:Tissue and Organ Procurement / Q000379:methods*; D014292:Trimetazidine / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D036341:Intercellular Signaling Peptides and Proteins; D019188:Organ Preservation Solutions; D011092:Polyethylene Glycols; D008550:Melatonin; D014292:Trimetazidine