title: The proinflammatory environment in potential heart and lung donors: prevalence and impact of donor management and hormonal therapy.
abstract: BACKGROUND
  Brain stem death can elicit a potentially manipulable cardiotoxic proinflammatory cytokine response. We investigated the prevalence of this response, the impact of donor management with tri-iodothyronine (T3) and methylprednisolone (MP) administration, and the relationship of biomarkers to organ function and transplant suitability.
  
  
  METHODS
  In a prospective randomized double-blinded factorially designed study of T3 and MP therapy, we measured serum levels of interleukin-1 and -6 (IL-1 and IL-6), tumor necrosis factor-alpha (TNF-alpha), C-reactive protein, and procalcitonin (PCT) levels in 79 potential heart or lung donors. Measurements were performed before and after 4 hr of algorithm-based donor management to optimize cardiorespiratory function and +/-hormone treatment. Donors were assigned to receive T3, MP, both drugs, or placebo.
  
  
  RESULTS
  Initial IL-1 was elevated in 16% donors, IL-6 in 100%, TNF-alpha in 28%, CRP in 98%, and PCT in 87%. Overall biomarker concentrations did not change between initial and later measurements and neither T3 nor MP effected any change. Both PCT (P =0.02) and TNF-alpha (P =0.044) levels were higher in donor hearts with marginal hemodynamics at initial assessment. Higher PCT levels were related to worse cardiac index and right and left ventricular ejection fractions and a PCT level more than 2 ng x mL(-1) may attenuate any improvement in cardiac index gained by donor management. No differences were observed between initially marginal and nonmarginal donor lungs. A PCT level less than or equal to 2 ng x mL(-1) but not other biomarkers predicted transplant suitability following management.
  
  
  CONCLUSIONS
  There is high prevalence of a proinflammatory environment in the organ donor that is not affected by tri-iodothyronine or MP therapy. High PCT and TNF-alpha levels are associated with donor heart dysfunction.
authors.affiliation: Department of Cardiothoracic Surgery, University Hospital Birmingham NHS Trust, Edgbaston, Birmingham, United Kingdom.
authors.forename: Rajamiyer V
authors.initials: RV
authors.lastname: Venkateswaran
authors.forename: Vamsidhar
authors.initials: V
authors.lastname: Dronavalli
authors.forename: Peter A
authors.initials: PA
authors.lastname: Lambert
authors.forename: Richard P
authors.initials: RP
authors.lastname: Steeds
authors.forename: Ian C
authors.initials: IC
authors.lastname: Wilson
authors.forename: Richard D
authors.initials: RD
authors.lastname: Thompson
authors.forename: Jorge G
authors.initials: JG
authors.lastname: Mascaro
authors.forename: Robert S
authors.initials: RS
authors.lastname: Bonser
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood; D001926:Brain Death; D001933:Brain Stem / Q000503:physiopathology; D002097:C-Reactive Protein / Q000378:metabolism; D002116:Calcitonin / Q000097:blood; D015740:Calcitonin Gene-Related Peptide; D004311:Double-Blind Method; D005260:Female; D016027:Heart Transplantation / Q000502:physiology; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016040:Lung Transplantation / Q000502:physiology; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage; D008875:Middle Aged; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood; D014019:Tissue Donors; D014284:Triiodothyronine / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; C000606589:CALCA protein, human; C508600:IL6 protein, human; D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D011498:Protein Precursors; D014409:Tumor Necrosis Factor-alpha; D014284:Triiodothyronine; D002116:Calcitonin; D002097:C-Reactive Protein; D015740:Calcitonin Gene-Related Peptide; D008775:Methylprednisolone