Navegando por Palavras-chave "Action potential"

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    Molecular mechanisms of cardiac electromechanical remodeling during Chagas disease: Role of TNF and TGF-beta
    (Elsevier Science London, 2017) Cruz, Jader Santos; Machado, Fabiana Simao; Ropert, Catherine; Roman-Campos, Danilo [UNIFESP]
    Chagas disease is caused by the trypanosomatid Trypanosoma cruzi, which chronically causes heart problems in up to 30% of infected patients. Chagas disease was initially restricted to Latin America. However, due to migratory events, this disease may become a serious worldwide health problem. During Chagas disease, many patients die of cardiac arrhythmia despite the apparent benefits of anti arrhythmic therapy (e.g., amiodarone). Here, we assimilate the cardiac form of Chagas disease to an inflammatory cardiac disease. Evidence from the literature, mostly provided using experimental models, supports this view and argues in favor of new strategies for treating cardiac arrhythmias in Chagas disease by modulating cytokine production and/or action. But the complex nature of myocardial inflammation underlies the need to better understand the molecular mechanisms of the inflammatory response during Chagas disease. Here, particular attention has been paid to tumor necrosis factor alpha (TNF) and transforming growth factor beta (TGF-beta) although other cytokines may be involved in the chagasic cardiomyopathy.
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    Pharmacological evaluation of R(+)-pulegone on cardiac excitability: Role of potassium current blockage and control of action potential waveform
    (Elsevier B.V., 2014-09-01) Santos-Miranda, Artur; Gondim, Antonio Nei; Rodrigues Menezes-Filho, Jose Evaldo; Lins Vasconcelos, Carla Marina; Cruz, Jader Santos; Roman-Campos, Danilo [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade Federal de Minas Gerais (UFMG); Univ Estado Bahia; Univ Fed Sergipe
    Introduction: R(+)-pulegone is a ketone monoterpene and it is the main constituent of essential oils in several plants. Previous studies provided some evidence that R(+)-pulegone may act on isolated cardiac myocytes. in this study, we evaluated in extended detail, the pharmacological effects of R(+)-pulegone on cardiac tissue.Methods: Using in vivo measurements of rat cardiac electrocardiogram (ECG) and patch-clamp technique in isolated myocytes we determinate the influence of R(+)-pulegone on cardiac excitability.Results: R(+)-pulegone delayed action potential repolarization (APR) in a concentration-dependent manner (EC50 = 775.7 +/- 1.48, 325.0 +/- 1.30, 469.3 +/- 1.91 mu M at 10, 50 and 90% of APR respectively). in line with prolongation of APR R(+)-pulegone, in a concentration-dependent manner, blocked distinct potassium current components (transient outward potassium current (I-to), rapid delayed rectifier potassium current (I-kr), inactivating steady state potassium current (I-ss) and inward rectifier potassium current (I-K1)) (EC50 = 1441 +/- 1.04; 605.0 +/- 1.22, 818.7 +/- 1.22; 1753 +/- 1.09 mu M for I-to, I-Kr, I-ss and I-K1, respectively). the inhibition occurred in a fast and reversible way, without changing the steady-state activation curve, but instead shifting to the left the steady-state inactivation curve (V-1/2 from -56.92 +/- 0.35 to 67.52 +/- 0.19 mV). in vivo infusion of 100 mg/kg R(+)-pulegone prolonged the QTc (similar to 40%) and PR (similar to 62%) interval along with reducing the heart rate by similar to 26%.Conclusion: Taken together, R(+)-pulegone prolongs the APR by inhibiting several cardiomyocyte current components in a concentration-dependent manner. This occurs through a direct block by R(+)pulegone of the channel pore, followed by a left shift on the steady state inactivation curve. Finally, R(+)-pulegone induced changes in some aspects of the ECG profile, which are in agreement with its effects on potassium channels of isolated cardiomyocytes. (C) 2014 Elsevier GmbH. All rights reserved.