PMID- 17234521 OWN - NLM STAT- MEDLINE DCOM- 20070201 LR - 20220331 IS - 1557-3117 (Electronic) IS - 1053-2498 (Linking) VI - 26 IP - 1 DP - 2007 Jan TI - Glucocorticoids alter the balance between pro- and anti-inflammatory mediators in the myocardium in a porcine model of brain death. PG - 78-84 AB - BACKGROUND: Cardiac dysfunction after brain death (BD) limits donors for cardiac transplantation. Glucocorticoids ameliorate brain death-induced donor heart dysfunction. We hypothesized that glucocorticoid therapy alleviates myocardial depression through altering the balance between pro- and anti-inflammatory mediators via the nuclear factor-kappaB (NF-kappaB)/inhibitor of kappaB-alpha (IkappaBalpha) pathway and/or by preserving beta-adrenergic receptor (betaAR) signaling in the heart. METHODS: Crossbred pigs (25 to 35 kg) were randomly assigned to the following groups (n = 5/treatment): sham (Group 1); BD (Group 2); and BD with glucocorticoids (30 mg/kg methylprednisolone), either 2 hours before (Group 3) or 1 hour after BD (Group 4). Tumor necrosis factor-alpha (TNF-alpha) levels were measured in plasma at baseline and 1 hour and 6 hours after BD. Protein levels were measured in left ventricular homogenates procured 6 hours after BD. RESULTS: Pro-inflammatory proteins (TNF-alpha) and interleukin-6 were lower in Group 3 and Group 4 compared with Group 2 at 6 hours after BD (p < 0.01). Intracellular adhesion molecule-1 was also lower in Group 4 compared with Group 2 (p = 0.001). Interleukin-10, an anti-inflammatory mediator, was lower in Group 4 than in Group 2 (p < 0.001), but not different between Groups 2 and 3. At 6 hours after BD, neither NF-kappaB activity nor basal adenylate cyclase activity differed between Groups 3 and 4 compared with Group 2. CONCLUSIONS: Glucocorticoids maintained myocardial function and shifted the balance of pro- and anti-inflammatory mediators after BD. The mechanisms by which glucocorticoids preserve myocardial function, however, do not appear to involve the NF-kappaB pathway or betaAR signaling. FAU - McLean, Kelly M AU - McLean KM AD - Division of Cardiothoracic Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA. FAU - Duffy, Jodie Y AU - Duffy JY FAU - Pandalai, Prakash K AU - Pandalai PK FAU - Lyons, Jefferson M AU - Lyons JM FAU - Bulcao, Christian F AU - Bulcao CF FAU - Wagner, Connie J AU - Wagner CJ FAU - Akhter, Shahab A AU - Akhter SA FAU - Pearl, Jeffrey M AU - Pearl JM LA - eng GR - 5T32-GM-008478-13/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - J Heart Lung Transplant JT - The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation JID - 9102703 RN - 0 (Glucocorticoids) RN - 0 (I-kappa B Proteins) RN - 0 (Interleukin-6) RN - 0 (NF-kappa B) RN - 0 (Tumor Necrosis Factor-alpha) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) RN - 130068-27-8 (Interleukin-10) SB - IM MH - Animals MH - Brain Death/*metabolism/pathology MH - Disease Models, Animal MH - Glucocorticoids/*pharmacology MH - Heart Ventricles/*drug effects/pathology MH - I-kappa B Proteins/metabolism MH - Intercellular Adhesion Molecule-1/*metabolism MH - Interleukin-10/*metabolism MH - Interleukin-6/*metabolism MH - Myocardium/metabolism/pathology MH - NF-kappa B/metabolism MH - Swine MH - Tumor Necrosis Factor-alpha/*metabolism EDAT- 2007/01/20 09:00 MHDA- 2007/02/03 09:00 CRDT- 2007/01/20 09:00 PHST- 2006/05/15 00:00 [received] PHST- 2006/10/05 00:00 [revised] PHST- 2006/10/19 00:00 [accepted] PHST- 2007/01/20 09:00 [pubmed] PHST- 2007/02/03 09:00 [medline] PHST- 2007/01/20 09:00 [entrez] AID - S1053-2498(06)00734-0 [pii] AID - 10.1016/j.healun.2006.10.011 [doi] PST - ppublish SO - J Heart Lung Transplant. 2007 Jan;26(1):78-84. doi: 10.1016/j.healun.2006.10.011.