Compromised right ventricular contractility in an ovine model of heart transplantation following 24 h donor brain stem death

Wells, M.; Hoe, Louise E. See; Molenaar, Peter; Pedersen, Sanne; Obonyo, Nchafatso G.; McDonald, Charles; Mo, Wei; Bouquet, Mahé; Hyslop, Kieran; Passmore, Margaret; Bartnikowski, Nicole; Suen, Jacky Y.; Peart, Jason Nigel John; McGiffin, David C.; Heart, Dead

doi:10.1016/j.phrs.2021.105631

Cited by 2 publications

(1 citation statement)

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“…Significant brain injury of any etiology will cause a systemic response [ 7 ], creating a pro-inflammatory environment prior to the occurrence of brain death. Brain death itself is responsible for a variety of upregulated in situ inflammatory processes and cell-damage-associated signaling pathways [ 6 , 8 , 9 ], neuro-endocrine modulations [ 10 ], hemodynamic changes [ 6 , 11 , 12 , 13 ], apoptosis induction [ 6 , 14 ], and increased release of inflammatory cytokines and stress hormones [ 6 , 11 , 15 ], which can induce direct and indirect adverse functional sequelae in right ventricle. Similarly, this has been described in heart failure [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Beneficial Effects of Tacrolimus on Brain-Death-Associated Right Ventricular Dysfunction in Pigs

Belhaj

Dewachter

Monier

et al. 2023

IJMS

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Background: Right ventricular (RV) dysfunction remains a major problem after heart transplantation and may be associated with brain death (BD) in a donor. A calcineurin inhibitor tacrolimus was recently found to have beneficial effects on heart function. Here, we examined whether tacrolimus might prevent BD-induced RV dysfunction and the associated pathobiological changes. Methods: After randomized tacrolimus (n = 8; 0.05 mg·kg−1·day−1) or placebo (n = 9) pretreatment, pigs were assigned to a BD procedure and hemodynamically investigated 1, 3, 5, and 7 h after the Cushing reflex. After euthanasia, myocardial tissue was sampled for pathobiological evaluation. Seven pigs were used as controls. Results: Calcineurin inhibition prevented increases in pulmonary vascular resistance and RV-arterial decoupling induced by BD. BD was associated with an increased RV pro-apoptotic Bax-to-Bcl2 ratio and RV and LV apoptotic rates, which were prevented by tacrolimus. BD induced increased expression of the pro-inflammatory IL-6-to-IL-10 ratio, their related receptors, and vascular cell adhesion molecule-1 in both the RV and LV. These changes were prevented by tacrolimus. RV and LV neutrophil infiltration induced by BD was partly prevented by tacrolimus. BD was associated with decreased RV expression of the β-1 adrenergic receptor and sarcomere (myosin heavy chain [MYH]7-to-MYH6 ratio) components, while β-3 adrenergic receptor, nitric oxide-synthase 3, and glucose transporter 1 expression increased. These changes were prevented by tacrolimus. Conclusions: Brain death was associated with isolated RV dysfunction. Tacrolimus prevented RV dysfunction induced by BD through the inhibition of apoptosis and inflammation activation.

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