Changes in platelet Bax levels contribute to impaired platelet response to thrombin after cardiopulmonary bypass: prospective observational clinical and laboratory investigations.
Br J Anaesth
; 119(6): 1118-1126, 2017 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-29040496
ABSTRACT
Background:
Anucleate platelets can undergo apoptosis in response to various stimuli, as do nucleated cells. Cardiopulmonary bypass (CPB) causes platelet dysfunction and can also activate platelet apoptotic pathways. We therefore evaluated time-dependent changes in blood platelet Bax (a pro-apoptotic molecule) levels and platelet dysfunction after cardiac surgery.Methods:
We assessed blood samples obtained from subjects having on-pump or off-pump coronary artery bypass graft surgery ( n =20 each). We also evaluated the in vitro effects of platelet Bax increase in eight healthy volunteers.Results:
Thrombin-induced platelet calcium mobilisation and platelet-surface glycoprotein Ib (GPIb) expression were lowest at weaning from CPB and did not recover on postoperative day one. On-pump surgery increased platelet expression of Bax, especially the oligomerised form, along with translocation of Bax from the cytosol to mitochondria and platelet-surface tumour necrosis factor-alpha (TNF-α)-converting enzyme (TACE) expression. In contrast, mitochondrial cytochrome c expression was reduced. While similar in direction, the magnitude of the observed changes was smaller in patients having off-pump surgery. In vitro , a cell-permeable Bax peptide increased platelet Bax expression to the same extent seen during bypass and produced similar platelet changes. These apoptotic-like changes were largely reversed by Bcl-xL pre-administration, and were completely reversed by combined application of inhibitors that stabilise outer mitochondrial membrane permeability and TACE.Conclusions:
CPB increases platelet Bax expression, which contributes to reduced platelet-surface GPIb expression and thrombin-induced platelet calcium changes. These changes in platelet apoptotic signalling might contribute to platelet dysfunction after CPB. Clinical trial registration UMIN Clinical Trials Registry (number UMIN000006033).Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Complicações Pós-Operatórias
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Plaquetas
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Trombina
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Ponte Cardiopulmonar
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Proteína X Associada a bcl-2
Tipo de estudo:
Observational_studies
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Risk_factors_studies
Limite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Br J Anaesth
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Japão