Faculty Collaboration Database

The proinflammatory environment in potential heart and lung donors: prevalence and impact of donor management and hormonal therapy. Transplantation 2009 Aug 27;88(4):582-8

Date

08/22/2009

Pubmed ID

19696643

DOI

10.1097/TP.0b013e3181b11e5d

Scopus ID

2-s2.0-70349158086 (requires institutional sign-in at Scopus site)   59 Citations

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.

Author List

Venkateswaran RV, Dronavalli V, Lambert PA, Steeds RP, Wilson IC, Thompson RD, Mascaro JG, Bonser RS

Author

Jorge G. Mascaro MD Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Anti-Inflammatory Agents
Biomarkers
Brain Death
Brain Stem
C-Reactive Protein
Calcitonin
Calcitonin Gene-Related Peptide
Double-Blind Method
Female
Heart Transplantation
Humans
Inflammation Mediators
Interleukin-1
Interleukin-6
Lung Transplantation
Male
Methylprednisolone
Middle Aged
Prospective Studies
Protein Precursors
Tissue Donors
Triiodothyronine
Tumor Necrosis Factor-alpha