title: Remote ischemic preconditioning regulates HIF-1α levels, apoptosis and inflammation in heart tissue of cardiosurgical patients: a pilot experimental study.
abstract: Transient episodes of ischemia in a remote organ (remote ischemic preconditioning, RIPC) bears the potential to attenuate myocardial injury, but the underlying mechanisms are only poorly understood. In the pilot experimental study presented we investigated cellular and molecular effects of RIPC in heart tissue of cardiosurgical patients with cardiopulmonary bypass (CPB) and focussed on apoptotic events, local and systemic inflammation as well as the regulation of the hypoxia induced factor-1α (HIF-1α). RIPC was induced by four 5-min cycles of transient upper limb ischemia/reperfusion using a blood-pressure cuff. Right atrial tissue and serum were obtained from patients receiving RIPC (N = 32) and control patients (N = 29) before and after CPB. RIPC patients showed reduced troponin T serum concentrations in the first 48 h after surgery (P < 0.05 vs. control) indicating cardioprotective effects of RIPC. Samples from RIPC patients that were collected before CPB contained significantly increased amounts of HIF-1α and procaspase-3 (HIF-1α: P < 0.05 vs. control, procaspase-3: P < 0.05 vs. control), whereas activities of caspases 3 and 7 were by trend reduced. Samples from RIPC patients that were taken after CPB showed an increased activity of myeloperoxidase (P < 0.05 vs. control; P < 0.05 vs. RIPC before CPB) as well as elevated tissue concentrations of the interleukin (IL)-1β (P < 0.05 vs. RIPC before CPB). Serum levels of IL-8, IL-1β and TNFα were significantly increased in RIPC patients before CPB (P < 0.05 vs. control before CPB). In summary, RIPC regulates HIF-1α levels, apoptosis and inflammation in the myocardium of cardiosurgical patients and leads to increased concentrations of circulating cytokines.
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Schwanenweg 21, 24105 Kiel, Germany. martin.albrecht@uksh.de
authors.forename: Martin
authors.initials: M
authors.lastname: Albrecht
authors.forename: Karina
authors.initials: K
authors.lastname: Zitta
authors.forename: Berthold
authors.initials: B
authors.lastname: Bein
authors.forename: Gunther
authors.initials: G
authors.lastname: Wennemuth
authors.forename: Ole
authors.initials: O
authors.lastname: Broch
authors.forename: Jochen
authors.initials: J
authors.lastname: Renner
authors.forename: Torben
authors.initials: T
authors.lastname: Schuett
authors.forename: Fabian
authors.initials: F
authors.lastname: Lauer
authors.forename: Daniela
authors.initials: D
authors.lastname: Maahs
authors.forename: Lars
authors.initials: L
authors.lastname: Hummitzsch
authors.forename: Jochen
authors.initials: J
authors.lastname: Cremer
authors.forename: Kai
authors.initials: K
authors.lastname: Zacharowski
authors.forename: Patrick
authors.initials: P
authors.lastname: Meybohm
mesh_terms: D000368:Aged; D017209:Apoptosis; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass; D020169:Caspases / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis*; D007249:Inflammation / Q000517:prevention & control*; D019194:Ischemic Preconditioning; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D009195:Peroxidase / Q000378:metabolism; D010865:Pilot Projects; D020107:Troponin T / Q000097:blood
chemical_list: D016207:Cytokines; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D020107:Troponin T; D009195:Peroxidase; D020169:Caspases