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Thyroid hormone signalling is altered in response to physical training in patients with end-stage heart failure and mechanical assist devices: potential physiological consequences?
Adamopoulos S, Gouziouta A, Mantzouratou P, Laoutaris ID, Dritsas A, Cokkinos DV, Mourouzis I, Sfyrakis P, Iervasi G, Pantos C
Interactive Cardiovascular and Thoracic Surgery 2013 Oct;17(4):664-668
clinical trial
3/10 [Eligibility criteria: Yes; Random allocation: Yes; Concealed allocation: No; Baseline comparability: No; Blind subjects: No; Blind therapists: No; Blind assessors: No; Adequate follow-up: No; Intention-to-treat analysis: No; Between-group comparisons: Yes; Point estimates and variability: Yes. Note: Eligibility criteria item does not contribute to total score] *This score has been confirmed*

OBJECTIVESThe present study investigated the potential of the failing myocardium of patients with ventricular assist devices (VAD) to respond to physiological growth stimuli, such as exercise, by activating growth signalling pathways. This may be of therapeutic relevance in identifying novel pharmacological targets for therapies that could facilitate recovery after VAD implantation. METHODS: Twenty-two patients bridged to heart transplantation (HTx) with VAD were included in the study. A group of patients underwent moderate intensity aerobic exercise (GT), while another group of patients did not receive exercise training (CG). Thyroid hormone receptor alpha1 (TRalpha1) protein and total (t) and phosphorylated (p) protein kinase B (Akt) and c-Jun N-terminal kinase (JNK) kinase signalling were measured in myocardial tissue by western blotting at pre-VAD and pre-HTx period. In addition, thyroid hormone (TH) levels were measured in plasma. RESULTS: Peak oxygen consumption (VO2) at pre-HTx period was higher in patients subjected to training protocol (18.0 (0.8) for GT when compared with 13.7 (0.7) for CG group, p = 0.002). N-terminal-prohormone of brain natriuretic peptide (NT-proBNP) levels were 1,068 (148) for CG versus 626 (115) for GT group, p = 0.035. A switch towards up-regulation of physiological growth signalling was observed: the ratio of p-Akt/t-Akt was 2-fold higher in GT versus CG, p < 0.05 while p-JNK/t-JNK was 2.5-fold lower (p < 0.05) in GT versus CG, in pre-HTx samples. This response was accompanied by a 2.0-fold increase in TRalpha1 expression in pre-HTx samples with concomitant increase in circulating T3 in GT versus CG, p < 0.05. No differences in peak VO2, NT-proBNP, T3, TRalpha1, p/t-AKT and p/t-JNK were found between groups in the pre-VAD period. CONCLUSIONS: The unloaded failing myocardium responded to physical training by enhancing thyroid hormone signalling. This response was associated with an up-regulation of Akt and suppression of JNK activation.

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