title: Organ-protective effects on the liver and kidney by minocycline in small piglets undergoing cardiopulonary bypass.
abstract: Cardiopulmonary bypass (CPB) often is required for the operative correction of congenital heart defects in small infants. Unfortunately, CPB is associated with injury of inner organs such as the brain, kidney, lung, and liver. Renal failure and increase in liver enzymes are typical side effects observed after CPB. Here, we investigate whether organ protection of the kidney and liver can be achieved with the application of minocycline, which is known-besides its anti-infective effects-to act as a poly-ADP-ribose-polymerase inhibitor. Twenty-nine 4-week-old Angler Sattelschwein-piglets (8-15 kg) were divided into four groups: control group (n = 8), CPB group (n = 9), minocycline-control group (n = 6), and the minocycline-CPB group (n = 6). CPB groups were thoracotomized and underwent CPB for 120 min (cross-clamp, 90 min; reperfusion, 30 min) followed by a 90-min recovery time. The control groups also were thoracotomized but not connected to CPB. The minocycline group received 4 mg/kg minocycline before and 2 mg/kg after CPB. In the kidneys, CPB histologically resulted in widening of Bowman's capsule, and-mainly in tubules-formation of poly-ADP-ribose, nitrosylation of tyrosine-residues, nuclear translocation of hypoxia-induced factor HIF-1α, and of apoptosis-inducing factor (AIF). In addition, we found significantly less ATP in the kidney and significantly increased plasma urea and creatinine. Similar but gradually attenuated changes were found in the liver together with significantly elevated de-Ritis coefficient. These changes in the kidney and liver were significantly diminished by minocycline (except AIF in the liver which was similar in all groups). In conclusion, CPB causes damage in the kidney and-to a lower degree-in the liver, which can be attenuated by minocycline.
authors.affiliation: Clinic for Cardiac Surgery, University of Leipzig, Heart Centre, Leipzig, Germany, Stefan.Dhein@medizin.uni-leipzig.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Dhein
authors.forename: Maria
authors.initials: M
authors.lastname: Grassl
authors.forename: Maria
authors.initials: M
authors.lastname: Gerdom
authors.forename: Marcel
authors.initials: M
authors.lastname: Vollroth
authors.forename: Farhad
authors.initials: F
authors.lastname: Bakhtiary
authors.forename: Sandy
authors.initials: S
authors.lastname: von Salisch
authors.forename: Klaus
authors.initials: K
authors.lastname: Krämer
authors.forename: Axel
authors.initials: A
authors.lastname: Sobiraj
authors.forename: Martin
authors.initials: M
authors.lastname: Kostelka
authors.forename: Friedrich-Wilhelm
authors.initials: FW
authors.lastname: Mohr
authors.forename: Aida
authors.initials: A
authors.lastname: Salameh
mesh_terms: D000818:Animals; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D002315:Cardiopulmonary Bypass; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008911:Minocycline / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D013552:Swine; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D051033:Apoptosis Inducing Factor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D020011:Protective Agents; C002744:3-nitrotyrosine; D014443:Tyrosine; D011065:Poly(ADP-ribose) Polymerases; D008911:Minocycline