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

Department of Cardiothoracic Surgery, University Hospital Birmingham NHS Trust, Edgbaston, Birmingham, United Kingdom.
Transplantation (Impact Factor: 3.83). 09/2009; 88(4):582-8. DOI: 10.1097/TP.0b013e3181b11e5d
Source: PubMed


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.
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.
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.
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.

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    • "This inflammatory reaction has been associated with increased early allograft dysfunction [8]. In heart transplantation, high tissue and plasma levels of interleukin-1 (IL-1), IL-6 and tumor necrosis factor alpha (TNF-α) were associated with worse donor heart function [9] and post-transplantation graft outcome [2, 9]. C-reactive protein (CRP) and procalcitonin (PCT) were also markers of inflammation; elevated levels of CRP and PCT were observed after brain death and associated with adverse adverse outcomes in heart transplant recipients [2]. "
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    ABSTRACT: Background: Solid organ transplantation is the only definitive treatment available for patients with end-stage organ failure. Organs procured from brain-death donors are the main source of transplants. Following brain death, a burst of inflammatory reaction develops; it is characterized by increased plasma levels of cytokines. This inflammatory reaction has been associated with increased early allograft dysfunction. Objective: In this study, we test if the increased inflammatory response in brain-death donors is associated with more recipient complications. Methods: We prospectively recruited 38 consecutive brain-death donors admitted to the intensive care units (ICUs) of Shiraz University of Medical Sciences. Following the declaration of brain death, the demographics data on donor and recipient characteristics and cause of brain death were recorded. The post-liver transplant complications in recipients were stratified according to the Clavien classification. Plasma levels of cytokines IL-6, IL-2, and TNF-α were measured using enzyme linked immunosorbent assay (ELISA) kits, in all donors before organ procurement. Results: The mean (range) age of donors was 44 (16–74) years. Trauma due to car accident was the most common cause of brain death (79%). The post-liver transplant complications occurred in 19 (50%) recipients. The mean±SD plasma TNF-α concentration was significantly (p<0.001) higher in recipients with grade 1-3 post-transplant complications (68.33±27.74 pg/mL) than those without complication (22.09±4.14 pg/mL). Recipients with complications had also a significantly (p=0.001) higher mean±SD donor plasma concentration of IL-6 (1009±375.5 pg/mL) compared to those without complications (779±202 pg/mL). No significant differences was observed between the two groups in respect to IL-2 concentration (0.295±0.333 vs 0.285±0.342 U/mL, p=0.207). Six recipients died of complications (grade5), in whom no correlation could be found with donor plasma cytokine concentrations. Conclusion: Higher plasma concentrations of IL-6 and TNF-α in donors before organ procurement, are associated with more post-operative complications in liver transplant recipients.
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