O paradoxo arritmogênico do transplante de células tronco pós infarto de miocárdio
Arquivos
Data
2023
Autores
Seibt, Larissa Emília 
Orientadores
Serra, Andrey Jorge
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Objetivo: Examinar a repercussão antiarrtimica das células tronco mesenquimais (CMT) do tecido adiposo (CTMAs) em animais com infarto de miocárdio (IM). Métodos: O estudo contemplou três grupos experimentais: sham, submetido a cirurgia simulada para induzir IM e injeção intramiocárdica de solução salina; IMS, infartado por oclusão de coronariana e submetido a injeção intramiocárdica de solução salina; IM+CTMAs, infartado por oclusão coronariana submetido a injeção intramiocárdica de CTMAs. As injeções foram realizadas três dias após as cirurgias e o experimento de inducibilidade arritmogênica conduzido no quinto dia de experimentação; todos os animais foram autanasiados no quinto dia de expeirmtno para coleta e congelamento do miocárdio infartado e remoto. Foram analisados estresse oxidativo miocárdico, teor miocárdico de diferentes tipos de colágeno, conexinas e citocinas inflamatórias sabidamente envolvidas na gênese da arritmia ventricular pó-IM. Resultados: Apenas 35% dos animais do grupo IM-CTMAs desenvolveram arritmias ventriculares, enquanto a no grupo IMS foi de 65%. A proporção de taquicardia ventricular (TV) não sustentada (TVNS), sustentada (TVS) e fibrilação ventricular (FV) foi semelhante entre os grupos IM e IM+CTMAs, porém animais com CTMAs tiveram TV de menor duração. As CTMAs preveniram o aumento de IL-1β nas áreas distintas do miocárdio. Houve maior carbonilação e teor de 4-hidroxinonenal (4-HNE, um marcador de lipoperoxidação) no miocárdio das ratas infartadas, porém, as CTMAs atenuaram o aumento do 4-HNE na área infartada. O IM reduziu o conteúdo de conexina 43 na área remota, mas sem modificação na área infartada. Interessante, o transplante de CTMAs elevou o teor conexina 43 na área remota, inclusive acima dos níveis identificados para o grupo Sham. Conclusão: As CTMAs têm ação protetora para o desenvolvimento de arritmias, porém, não impetra benefícios expressivos para os animais que desenvolveram arritmias ventriculares. É possível pensar que a cardioproteção das CTMAs envolva ações anti-inflamatórias/oxidantes e melhora na formação de junções comunicantes.
Objective: To examine the antiarrhythmic repercussion of mesenchymal stem cells (TMCs) of adipose tissue (MSCs) in animals with myocardial infarction (MI). Methods: The study included three experimental groups: sham, submitted to sham surgery to induce MI and intramyocardial injection of saline; IMS, infarcted by coronary occlusion and submitted to intramyocardial injection of saline; MI+CTMAs, infarcted by coronary occlusion submitted to intramyocardial injection of MSCs. The injections were performed three days after the surgeries and the arrhythmogenic inducibility experiment was conducted on the fifth day of experimentation; All animals were autanasized on the fifth day of experiential for collection and freezing of the infarcted and remote myocardium. Myocardial oxidative stress, myocardial content of different types of collagen, connexins and inflammatory cytokines known to be involved in the genesis of ventricular arrhythmia after MI were analyzed. Results: Only 35% of the animals in the IM-CTMAs group developed ventricular arrhythmias, while the one in the IMS group was 65%. The proportion of non-sustained ventricular tachycardia (VT), sustained tachycardia (SVT) and ventricular fibrillation (VF) was similar between the MI and MI+MSC groups, but animals with MSCs had shorter duration VT. The MSCs prevented the increase of IL-1β in the distinct areas of the myocardium. There was higher carbonylation and content of 4-hydroxynonenal (4-HNE, a marker of lipoperoxidation) in the myocardium of the infarcted rats, however, the MSCs attenuated the increase of 4-HNE in the infarcted area. MI reduced the connexin content 43 in the remote area, but without modification in the infarcted area. Interestingly, the transplantation of CTMAs raised the connexin content 43 in the remote area, even above the levels identified for the Sham group. Conclusion: MSCs have a protective action for the development of arrhythmias, but do not imply significant benefits for animals that have developed ventricular arrhythmias. It is possible to think that the cardioprotection of MSCs involves anti-inflammatory/oxidizing actions and improvement in the formation of communicating junctions.
Objective: To examine the antiarrhythmic repercussion of mesenchymal stem cells (TMCs) of adipose tissue (MSCs) in animals with myocardial infarction (MI). Methods: The study included three experimental groups: sham, submitted to sham surgery to induce MI and intramyocardial injection of saline; IMS, infarcted by coronary occlusion and submitted to intramyocardial injection of saline; MI+CTMAs, infarcted by coronary occlusion submitted to intramyocardial injection of MSCs. The injections were performed three days after the surgeries and the arrhythmogenic inducibility experiment was conducted on the fifth day of experimentation; All animals were autanasized on the fifth day of experiential for collection and freezing of the infarcted and remote myocardium. Myocardial oxidative stress, myocardial content of different types of collagen, connexins and inflammatory cytokines known to be involved in the genesis of ventricular arrhythmia after MI were analyzed. Results: Only 35% of the animals in the IM-CTMAs group developed ventricular arrhythmias, while the one in the IMS group was 65%. The proportion of non-sustained ventricular tachycardia (VT), sustained tachycardia (SVT) and ventricular fibrillation (VF) was similar between the MI and MI+MSC groups, but animals with MSCs had shorter duration VT. The MSCs prevented the increase of IL-1β in the distinct areas of the myocardium. There was higher carbonylation and content of 4-hydroxynonenal (4-HNE, a marker of lipoperoxidation) in the myocardium of the infarcted rats, however, the MSCs attenuated the increase of 4-HNE in the infarcted area. MI reduced the connexin content 43 in the remote area, but without modification in the infarcted area. Interestingly, the transplantation of CTMAs raised the connexin content 43 in the remote area, even above the levels identified for the Sham group. Conclusion: MSCs have a protective action for the development of arrhythmias, but do not imply significant benefits for animals that have developed ventricular arrhythmias. It is possible to think that the cardioprotection of MSCs involves anti-inflammatory/oxidizing actions and improvement in the formation of communicating junctions.