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Snap-shots of thoracic transplantation

Tuesday September 13, 2022 - 16:25 to 17:25

Room: F

337.4 Tacrolimus for prevention of right and left ventriculo-arterial coupling changes in experimental brain death

Asmae Belhaj, Belgium

Head of depatment
Cardiovascular, thoracic surgery and Lung transplantation
CHU UcL Namur


Tacrolimus for prevention of right and left ventriculo-arterial coupling changes in experimental brain death

Asmae Belhaj1,2, Laurence Dewachter2, Benoit Rondelet1,2.

11Department of Cardio-Vascular, Thoracic Surgery and Lung Transplantation, CHU UCL Namur, Université Catholique de Louvain, Yvoir, Belgium; 2Laboratory of Physiology and Pharmacology, Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium

Purpose: Right ventricular (RV) dysfunction remains the leading cause of early mortality after cardiac transplantation. Tacrolimus (FK506) is an immune suppressor that could preserve heart function via its anti-inflammation effect in animal models.

We sought to determine whether Tacrolimus might prevent brain death-induced RV dysfunction, and biological changes in myocarditis caused by BD acting on inflammation and apoptosis.   

Methods and Results: After randomisation to placebo (n=9) or to Tacrolimus (n=8; 0.05, seventeen pigs were assigned to a brain death procedure. One, three, five and seven hours after Cushing reflex, the animals underwent hemodynamic evaluation. After euthanasia of the animals, myocardial tissue was sampled. This was repeated in a control group (n=7). Seven hours after Cushing reflex, brain death had resulted in increased pulmonary artery pressure (29±2 versus 19±1 mmHg) and in a 33%-decreased RV ratio of end-systolic to pulmonary arterial elastances (Ees/Ea), while left ventriculo (LV)-arterial coupling did not change. This was prevented by Tacrolimus. Brain death-induced RV dysfunction was associated with increased RV expression of interleukin(IL)-6/IL-10, IL-1β, receptors for IL-1 and IL-6, b-3 adrenergic receptor, Toll-like receptor (TLR)-4  and neutrophil infiltration, while b-1 adrenergic receptor, TLR-2 and NLR family pyrin-domain-containing-3  expressions decreased. RV but not LV apoptosis was confirmed by TUNEL staining. Tacrolimus pre-treatment prevented RV-arterial uncoupling and changes in  RV expression of IL-1 R, IL-6 R, RV apoptosis, as well as in neutrophil infiltration. 

Conclusions: Brain death-induced isolated RV dysfunction is associated with RV activation of inflammation and apoptosis, partly limited by Tacrolimus.

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