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ALTEPLASE AND METHYLPREDNISOLONE ASSOCIATED TREATMENT MODULATE MICROCIRCULATION AND INFLAMMATION ON BRAIN DEATH
Lucas Ferreira da Anunciação1, Marina Vidal-Dos-Santos, Caio Medeiros Fernandes
1Laboratorio de Cirurgia Cardiovascular e Fisiopatologia da Circulação (LIM-11), Instituto do Coração (INCOR), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Alteplase treatment improved microcirculation and prevented platelet aggregation in brain-dead rats. Combination therapy with methylprednisolone further reduced inflammation, suggesting potential for donor organ quality preservation.
Area of Science:
- Organ preservation research
- Translational medicine
Background:
- Brain death (BD) induces systemic inflammation and coagulation issues, impairing organ quality for transplantation.
- Fibrinolytic therapy is explored to mitigate these detrimental effects.
Purpose of the Study:
- To evaluate the efficacy of alteplase, alone and with methylprednisolone, in preserving organ quality after inducing brain death.
- To assess the impact on microcirculation, inflammation, and coagulation.
Main Methods:
- Wistar rats underwent brain death induction and were randomized into sham, BD, alteplase (rTPA), and alteplase+methylprednisolone (rTPA+P) groups.
- Mesenteric microcirculation, inflammatory mediators, platelet aggregation, coagulation, and histology were analyzed.
Main Results:
- Alteplase improved mesenteric microcirculatory flow and reduced platelet aggregation, potentially via increased vascular density and decreased endothelin-1.
- Combined therapy significantly modulated the inflammatory cascade (reduced IL-6, IL-10, VEGF) and improved leukocyte-endothelial interactions.
- Alteplase showed no detectable organ damage.
Conclusions:
- Alteplase effectively prevents platelet aggregation and enhances microcirculation in brain-dead subjects.
- Combination with methylprednisolone further modulates the inflammatory response.
- These findings indicate alteplase's potential to improve the quality of organs from brain-dead donors.
