Treatment with 17β‐estradiol protects donor heart against brain death effects in female rat

Abstract

The viability of donor organs is reduced by hemodynamic and immunologic alterations caused by brain death (BD). Female rats show higher heart inflammation associated with the reduction in female sex hormones after BD. This study investigated the effect of 17b-estradiol (E2) on BD-induced cardiac damage in female rats. Groups of female Wistar rats were assigned: Sham-operation (Sham), brain death (BD), treatment with E2 (50 lg/ml, 2 ml/h) 3 h after BD (E2-T3), or immediately after BD confirmation (E2-T0). White blood cell (WBC) count was analyzed; cytokines and troponin-I were quantified. Heart histopathological changes and expression of endothelial nitric oxide synthase, endothelin-1, intercellular adhesion molecule-1, BCL-2, and caspase-3 were evaluated. Cardiac function was continuously assessed for 6 h by left ventricular pressure-volume loop analysis. E2 decreased the BD-induced median serum concentration of troponin-I (BD:864.2 vs. E2-T0:401.4; P = 0.009), increased BCL-2 (BD:0.086 vs. E2-T0:0.158; P = 0.0278) and eNOS median expression in the cardiac tissue (BD:0.001 vs. E2-T0:0.03 and E2-T3:0.0175; P < 0.0001), and decreased caspase-3 (BD:0.025 vs. E2-T0:0.006 and E2-T3:0.019; P = 0.006), WBC counts, leukocyte infiltration, and hemorrhage. 17b-estradiol treatment was effective in reducing cardiac tissue damage in brain-dead female rats owing to its ability to reduce leukocyte infiltration and prevent cardiomyocyte apoptosis.

Protective role of 17β-estradiol treatment in renal injury on female rats submitted to brain death

“…Previous studies have shown a higher inflammatory female condition in relation to male donor, which was correlated with acute estradiol reduction following BD (5)(6)(7). In BD female rats, treatment with E2 efficiently reduced heart and lung injury, modulated inflammatory cell infiltration, enhanced release of chemokines, and suppressed cardiomyocyte apoptosis (8,9). Female sex hormone concentrations acute reduction after BD may occur probably due to interruption of the hypothalamic-pituitary-ovary axis and affects the control of several nonreproductive tissues including the immune system (5).…”

“…The E2 treatment was based on previous studies (8,9), using the same model of BD, in which both treated groups presented similar increases in serum estradiol levels after the end of E2 infusion compared to the BD group (BD =68.2±8, E2-T0 =1,713.5±44.7, E2-T3 =1,717.9±29.2 pg/mL; P<0.05).…”

“…Female sex hormone concentrations acute reduction after BD may occur probably due to interruption of the hypothalamic-pituitary-ovary axis and affects the control of several nonreproductive tissues including the immune system (5). The treatment applied here was based on previous study and the aim was to use a low therapeutic dose and maintain high serum E2 concentration during the studied period (8).…”

“…In order to evaluate the cell death pathway, we based our evaluation in the expression of pro-apoptotic protein, caspase-3 and the expression of anti-apoptotic protein, BCL-2, as previously studied in the heart (8). With respect to the expression of the apoptotic protein, Caspase-3, higher values were found in the BD group in protein (Figure 5A).…”

“…In female rats, BD results in more edema, hemorrhagic foci and recruitment of inflammatory cells to lungs and heart (6). 17β-estradiol (E2) treatment is able to prevent heart injury caused by BD in female rats (8). Moreover, previous results pointed to E2 therapeutic effects reducing the release of chemokines, hindering cell traffic into female rat lungs (9).…”