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- Title
The effects of acute triiodothyronine therapy on myocardial gene expression in brain stem dead cardiac donors.
- Authors
James, Sally R.; Ranasinghe, Aaron M.; Venkateswaran, Rajamiyer; McCabe, Christopher J.; Franklyn, Jayne A.; Bonser, Robert S.
- Abstract
Context: After brain stem death (BSD), a low T3 state is common, and T3 supplementation has been advocated to improve heart function and yield for transplantation.Objectives: The aim of the study was to assess the effects of T3 on expression of mRNAs encoding T3-responsive genes in the post-BSD human heart.Design: Within a prospective double-blind trial, potential BSD cardiac donors undergoing hemodynamic optimization were randomized to T3 (0.8 μg · kg−1 bolus; infusion 0.113 μg · kg−1 · h−1) or placebo (5% dextrose) for up to 6 h. Left ventricular biopsies were obtained at end-assessment from 30 donors (T3; n=16). TaqMan real-time PCR was performed to investigate mRNA expression of the voltage-gated potassium channel Kv1.5, β-1 adrenergic receptor (ADRB1), sarcoplasmic reticulum calcium ATPase type 2a (SERCA2a), and phospholamban (PLB).Results: Time between diagnosis of BSD and donor management was 13.2 h (range, 9.7–16.8 h). T3 donors were managed for 7.6 (6.9–8.3) h. Median serum free T3 (fT3) at baseline was 2.9 (2.3–3.8) pmol · liter−1 (reference range, 3.3–7.5 pmol · liter−1). At baseline, 19 of 30 (56.7%) had low serum fT3, and T3 treatment increased fT3 to supraphysiological levels (P < 0.001). Expression of mRNAs encoding Kv1.5 and SERCA2a was increased 1.99-fold and 1.51-fold (P = 0.015 and 0.043). There was no significant change in the expression of mRNAs encoding ADRB1 and PLB. Treatment with T3 did not improve hemodynamic function compared with placebo.Conclusions: Acute administration of T3 in the BSD cardiac donor reverses the low T3 state and increases expression of the mRNAs encoding Kv1.5 and SERCA2a, but not ADRB1 or PLB and is not associated with any improvement in hemodynamic performance.
- Publication
Journal of Clinical Endocrinology & Metabolism, 2010, Vol 95, Issue 3, p1338
- ISSN
0021-972X
- Publication type
Article
- DOI
10.1210/jc.2009-1659