O processo inflamatório após a indução de infarto agudo do miocárdio é atenuado por treinamento físico prévio em ratos - análise dos mecanismos de cardioproteção induzida com o exercício

Marilia Harumi Higuchi dos Santos

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Author(s):	Marilia Harumi Higuchi dos Santos Total Authors: 1
Document type:	Doctoral Thesis
Press:	São Paulo.
Institution:	Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ)
Defense date:	2010-02-08
Examining board members:	Raul Cavalcante Maranhão; Edimar Alcides Bocchi; Sandra Helena Poliselli Farsky; Jose Antonio Franchini Ramires; Paulo José Ferreira Tucci
Advisor:	Raul Cavalcante Maranhão
Abstract
Exercise is a well recognized protective factor for cardiovascular morbidity and mortality. In spite of extensive data from epidemiologic studies and intervention, the subjacent cardioprotective mechanisms of exercise are still non clear. Some authors believe that the physical training induces development of more resistant myocardial fibers against external injuries and increased vascularization. Also, exercise seems to influence the modulation of the immune system. The understanding of mechanisms by which the exercise acts in the acute myocardial infarction (MI) progression may bring a better comprehension of different clinical outcome in apparently similar individuals. The knowledge of which molecules and systems are involved in this cardioprotection and how they mediate and integrate the stress myocardial response may help future therapies. The objective of the present work is to test the hypothesis that the occurrence of MI in previously trained animals is associated with a better post MI ventricular function, major vascularization, in association with lower expression of inflammatory markers and of metabolic modulators, and less apoptosis. Material and Methods: Sessions of 60 min/day, 05 days/week, for 08 weeks were applied in the exercised group. After this period, the exercised and sedentary animals were randomized to surgery for myocardial infarction, through the ligature of left coronary artery (EI and SI, respectively), or control surgery (ES and SS, respectively), followed by a 04 week sedentary period. The left ventricular function was obtained by the echocardiography as also the infarct size. Immunohistochemistry was used for detection of PPAR-α, PPAR-γ, TNF-α, NF-kB, ad α-actin, and the results were quantified in an image analysis system by automatic collor detection. TUNEL technique was used for detection of apoptosis. Three regions of the heart were studied: infarcted (I), peri-infarcted (P), and non infarcted myocardium (M). Results: Infarction-related mortality was higher in SI comparing to EI group (25% vs 12%; P < 0.05), without differences in MI size. Compared to EI, SI group exhibited lower shortening fraction, higher apoptosis rate and higher local levels of inflammatory markers, such as NF-kB and TNF-α at I. SI group showed negative correlations between the quantities of PPARs and inflammatory cytokines: a) PPAR-α at M vs TNF-α at I (R:-0.826, P=0.005); b) PPAR-α vs NF-kB at I (R: -0.576, P=0.02) and P (R:-0.505, P=0.03); c) TNF-α at I vs PPAR-α and PPAR-γ at M (R:-0.826, P=0.005 e R:-0.786, P=0.02); d) NF-kB at I vs PPAR-α at M (R:-0.576, P=0.01); and e) NF-kB at P vs PPAR-α at M (R:-0.505, P=0.03). There was a positive correlation between NF-kB vs PPAR-γ at P (R: 0.596, P=0.02). The arteriolar density did not differ between the two infarcted groups. However, the exercised infarcted group showed a negative correlation between the arteriolar density at I and PPAR-γ at P (R:-0.76, P=0.02). Conclusion: These findings support the hypothesis that the occurrence of MI in previously trained animals is followed by lower local inflammatory markers, better ventricular function, and possibly a better interrelationship between modulators of the energetic metabolism and of the immune system. (AU)

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