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

Research output: Contribution to journalArticle

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

Fingerprint

Calcitonin
Tissue Donors
Lung
Methylprednisolone
Tumor Necrosis Factor-alpha
Interleukin-1
Interleukin-6
Therapeutics
Biomarkers
Lymphotoxin-beta
Transplants
Brain Death
Stroke Volume
C-Reactive Protein
Brain Stem
Hemodynamics
Placebos
Hormones
Cytokines
Serum

Keywords

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

Cite this

Venkateswaran, Rajamiyer V. ; Dronavalli, Vamsidhar ; Lambert, Peter A. ; Steeds, Richard P. ; Wilson, Ian C. ; Thompson, Richard D. ; Mascaro, Jorge G. ; Bonser, Robert S. / The Proinflammatory Environment in Potential Heart and Lung Donors: Prevalence and Impact of Donor Management and Hormonal Therapy. In: Transplantation. 2009 ; Vol. 88, No. 4. pp. 582-588.
@article{5b1f90cbf9d947c7b1986aa0182bd59b,
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. (C) 2009 Lippincott Williams & Wilkins, Inc.",
keywords = "interleukins-1, interleukins 6, tumor necrosis factor-alpha, procalcitonin, donor heart, donor management, heart transplantation, lung transplantation",
author = "Venkateswaran, {Rajamiyer V.} and Vamsidhar Dronavalli and Lambert, {Peter A.} and Steeds, {Richard P.} and Wilson, {Ian C.} and Thompson, {Richard D.} and Mascaro, {Jorge G.} and Bonser, {Robert S.}",
year = "2009",
month = "8",
doi = "10.1097/TP.0b013e3181b11e5d",
language = "English",
volume = "88",
pages = "582--588",
journal = "Transplantation",
issn = "0041-1337",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

Venkateswaran, RV, Dronavalli, V, Lambert, PA, Steeds, RP, Wilson, IC, Thompson, RD, Mascaro, JG & Bonser, RS 2009, 'The Proinflammatory Environment in Potential Heart and Lung Donors: Prevalence and Impact of Donor Management and Hormonal Therapy', Transplantation, vol. 88, no. 4, pp. 582-588. https://doi.org/10.1097/TP.0b013e3181b11e5d

The Proinflammatory Environment in Potential Heart and Lung Donors: Prevalence and Impact of Donor Management and Hormonal Therapy. / Venkateswaran, Rajamiyer V.; Dronavalli, Vamsidhar; Lambert, Peter A.; Steeds, Richard P.; Wilson, Ian C.; Thompson, Richard D.; Mascaro, Jorge G.; Bonser, Robert S.

In: Transplantation, Vol. 88, No. 4, 08.2009, p. 582-588.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The Proinflammatory Environment in Potential Heart and Lung Donors: Prevalence and Impact of Donor Management and Hormonal Therapy

AU - Venkateswaran, Rajamiyer V.

AU - Dronavalli, Vamsidhar

AU - Lambert, Peter A.

AU - Steeds, Richard P.

AU - Wilson, Ian C.

AU - Thompson, Richard D.

AU - Mascaro, Jorge G.

AU - Bonser, Robert S.

PY - 2009/8

Y1 - 2009/8

N2 - 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.

AB - 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.

KW - interleukins-1

KW - interleukins 6

KW - tumor necrosis factor-alpha

KW - procalcitonin

KW - donor heart

KW - donor management

KW - heart transplantation

KW - lung transplantation

UR - http://www.scopus.com/inward/record.url?scp=70349158086&partnerID=8YFLogxK

UR - http://journals.lww.com/transplantjournal/toc/2009/08270

U2 - 10.1097/TP.0b013e3181b11e5d

DO - 10.1097/TP.0b013e3181b11e5d

M3 - Article

VL - 88

SP - 582

EP - 588

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 4

ER -