title: Amiodarone pretreatment of organ donors exerts anti-oxidative protection but induces excretory dysfunction in liver preservation and reperfusion.
abstract: The continuous shortage of organs necessitates the use of marginal organs from donors with various diseases, including arrhythmia-associated cardiac failure. One of the most frequently used anti-arrhythmic drugs is amiodarone (AM), which is given in particular in emergency situations. Apart from its anti-arrhythmic actions, AM provides anti-oxidative properties in cardiomyocytes. Thus, we were interested in whether AM donor pretreatment affects the organ quality and function of livers procured for preservation and transplantation. Donor rats were pretreated with AM (5 mg/kg of body weight) 10 minutes before flush-out of the liver with a cold (4 degrees C) histidine-tryptophan-ketoglutarate solution (n = 8). Livers were then stored for 24 hours at 4 degrees C before ex situ reperfusion with a 37 degrees C Krebs-Henseleit solution for 60 minutes in a nonrecirculating system. At the end of reperfusion, tissue samples were taken for histology and Western blot analysis. Animals with vehicle only (0.9% NaCl) served as ischemia/reperfusion controls (n = 8). Additionally, livers of untreated animals (n = 8) not subjected to 24 hours of cold ischemia served as sham controls. AM pretreatment effectively attenuated lipid peroxidation, stress protein expression, and apoptotic cell death. This was indicated by an AM-mediated reduction of malondialdehyde, heme oxygenase-1, and caspase-3 activation. However, AM treatment also induced mitochondrial damage and hepatocellular excretory dysfunction, as indicated by a significantly increased glutamate dehydrogenase concentration in the effluate and decreased bile production. In conclusion, AM donor pretreatment exerts anti-oxidative actions in liver preservation and reperfusion. However, these protective AM actions are counteracted by an induction of mitochondrial damage and hepatocellular dysfunction. Accordingly, AM pretreatment of donors for anti-arrhythmic therapy should be performed with caution.
authors: Department of General, Vascular, and Pediatric Surgery, Homburg/Saar, Germany.
authors: Mohammed Reza
authors: MR
authors: Moussavian
authors: Otto
authors: O
authors: Kollmar
authors: Michael
authors: M
authors: Schmidt
authors: Claudia
authors: C
authors: Scheuer
authors: Matthias
authors: M
authors: Wagner
authors: Jan Erik
authors: JE
authors: Slotta
authors: Gernot
authors: G
authors: Gronow
authors: Christoph
authors: C
authors: Justinger
authors: Michael Dieter
authors: MD
authors: Menger
authors: Martin Karl
authors: MK
authors: Schilling
mesh_terms: D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D051547:Heme Oxygenase-1 / Q000096:biosynthesis; D015227:Lipid Peroxidation; D008099:Liver / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions / Q000378:metabolism / Q000494:pharmacology; D016377:Organ Transplantation / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D019188:Organ Preservation Solutions; D008315:Malondialdehyde; D051547:Heme Oxygenase-1; D020169:Caspases; D000638:Amiodarone