The Proinflammatory Environment in Potential Heart and Lung Donors: Prevalence and Impact of Donor Management and Hormonal Therapy

Rajamiyer V. Venkateswaran, Vamsidhar Dronavalli, Peter A. Lambert, Richard P. Steeds, Ian C. Wilson, Richard D. Thompson, Jorge G. Mascaro, Robert S. Bonser

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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. (C) 2009 Lippincott Williams & Wilkins, Inc.
Original languageEnglish
Pages (from-to)582-588
Number of pages7
JournalTransplantation
Volume88
Issue number4
DOIs
Publication statusPublished - Aug 2009

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Keywords

  • interleukins-1
  • interleukins 6
  • tumor necrosis factor-alpha
  • procalcitonin
  • donor heart
  • donor management
  • heart transplantation
  • lung transplantation

Cite this

Venkateswaran, R. V., Dronavalli, V., Lambert, P. A., Steeds, R. P., Wilson, I. C., Thompson, R. D., Mascaro, J. G., & Bonser, R. S. (2009). The Proinflammatory Environment in Potential Heart and Lung Donors: Prevalence and Impact of Donor Management and Hormonal Therapy. Transplantation, 88(4), 582-588. https://doi.org/10.1097/TP.0b013e3181b11e5d