Medicina / Ciências Médicas e da Saúde

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Modulação aguda da função cardíaca diastólica e suas implicações fisiopatológicas

 

Autor: Ricardo José Araújo Ladeiras Lopes
Orientador: Joaquim Adelino Correia Ferreira Leite Moreira

 

Mestrado Integrado em Medicina - Fisiologia

Faculdade de Medicina

Universidade do Porto
 

 

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Modulação aguda da função cardíaca diastólica e suas implicações fisiopatológicas

Resumo

Myocardial function is regulated by several acute and chronic neurohumoralmediators. Furthermore, mechanical stretch is also an important determinant of cardiacperformance. This work assessed the myocardial response to an acute stretch, with special emphasis in its diastolic arm. Rabbit papillary muscles were stretched from 92% to 100% of Lmax under basal conditions and in the presence of: i) an inhibitor of the Na + /H + exchanger (NHE) (amiloride); ii) an inhibitor of the reverse mode of the Na + /Ca 2+ exchanger (rNCX) (KB-R7943); iii) an inhibitor of PKC (chelerythrine); iv) an inhibitor of PKA (KT-5720); v) angiotensin-II (AngII); vi) an AT1 receptor antagonist(ZD-7155); vii) ZD-7155 plus an AT2 receptor antagonist (PD123,319); and viii) after two cycles of ischemic preconditioning (IP). The myocardial response to stretch was also studied under ischemic conditions in the absence or presence of: i) ZD-7155; ii) ZD-7155 plus PD123,319; and iii) after ischemic preconditioning. Acute stretch elicited immediate and delayed increases in active tension (AT). During ischemia AT decreased instead of increasing during the delayed response, but this deterioration was blunted by ZD-7155 and IP. Regarding diastolic function, after an immediate increase upon stretch, there was a significant and time-dependent decrease in passive tension. This decrease was attenuated with PKC inhibition and blunted during ischemia. The latter effect was prevented with AT1 antagonism. These results suggest that mechanical stretch elicits not only a systolic but also a diastolic adaptive response. Both responses are impaired during ischemia, but ischemic preconditioning and AT1 antagonism seem to partially prevent this deterioration.

 

Palavras chave: myocardial stretch; Frank-Starling mechanism; Anrep effect; diastole

 

 

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