ALTEPLASE AND METHYLPREDNISOLONE ASSOCIATED TREATMENT MODULATE MICROCIRCULATION AND INFLAMMATION ON BRAIN DEATH DONORS
Lucas Ferreira da Anunciação, Marina Vidal-Dos-Santos, Caio Medeiros Fernandes, Fernanda Yamamoto Ricardo-da-Silva, Mayara Munhoz de Assis Ramos, Brunella Valbão Flora Agostinho, Pedro Luiz Zonta de Freitas, Ana Cristina Breithaupt-Faloppa, Cristiano Jesus Correia, Luiz Felipe Pinho MoreiraIntroduction:
Brain death (BD) triggers systemic inflammation, platelet aggregation, and thrombus formation, which compromise organ quality. This study evaluated the effects of the fibrinolytic alteplase alone and in combination with methylprednisolone, following BD induction.
Methods:
Wistar rats were randomized into four groups: sham (animals without BD), BD (animals subjected to BD), rTPA (animals with BD and alteplase treatment), and rTPA+P (animals with BD and alteplase and methylprednisolone treatment). The analyzed parameters included mesenteric microcirculation perfusion, inflammatory mediators, platelet aggregation, coagulation, and histology.
Results:
Improvements in mesenteric microcirculatory flow following alteplase were observed. This effect is likely related to the modulatory action of alteplase on platelet aggregation, along with an increase in vascular density, which occurred in association with decrease of endothelin-1 levels. Combined therapy demonstrated an additional beneficial effect by modulating the inflammatory cascade, including significant reductions in IL-6, IL-10, and VEGF, as well as improving leukocyte-endothelial interactions in the mesentery. Importantly, alteplase did not cause detectable damage to any of the studied organs.
Conclusion:
Alteplase treatment prevented platelet aggregation and improved microcirculation. When combined with methylprednisolone, it also modulated the inflammatory response. These findings suggest that alteplase treatment has a potential benefit in maintaining the quality of brain-dead donors.