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ABSTRACT

Title
Cardiac Rehabilitation On Sirt1 Activity In Patients With Heart Failure: Preliminary Data 
 
Authors
V. Conti1, G. Corbi2, G. Russomanno1, V. Simeon1, S. Latte3, P. Capogrosso1, N. Ferrara2, A. Filippelli1.

1 Dept of Exp Medicine, Second University of Naples, Naples
2 Dept of Health Sciences, Faculty of Medicine, University of Molise, Campobasso
3 Cardiology Division, San Gennaro Hospital, Naples
 
Abstract
 

 It is well established that supervised exercise training (ET) favorably influences the prognosis in patients with coronary artery disease (CAD). ET increases physical capacity, decreases symptoms and more importantly reduces the incidence of acute cardiac events, mortality and hospital readmission rates in CAD patients1. Many physical activity benefits for chronic heart failure (CHF) patients have been documented, such as improvements in physical capacity2. Recently it has been shown that in humans a moderate exercise is able to induce recovery of antioxidant defenses, whose expression changes with aging and cardiovascular diseases. The mechanisms that account for this cardioprotective effect are incompletely known.

Aim of this study was to evaluate in subjects with CHF whether a 4-weeks structered rehabilitation program was able to modify antioxidant potential of sera collected at baseline and after 4-weeks, in order to examine the mechanisms by which exercise improves cardiovascular function.

For this reason subjects with diagnosis of CHF (NYHA class II and III) were recruited at the Rehabilitation Ward in Cardiology Division of San Gennaro Hospital in Naples. On admission, patients underwent case history recording, clinical examination, electrocardiogram, chest X-Ray, echocardiogram, cardiopulmonary stress test, blood sample collection for routinary and experimental assessment. The rehabilitation program consisted in ET of 30' on cycloergometer, respiratory gymnastic and educational meetings, for a meantime of 4 weeks. For the exercise stress test, the ECG and BP were recorded every minute before, during, and after exercise. Exercise parameters included exercise duration, HR and BP at rest, peak exercise, 1st or 3rd minute after exercise, and metabolic equivalent. At baseline and after 4 weeks blood samples were collected and some variables were assessed (TBARS and 8-OHdG levels, SOD, Cat and SIRT1 activities). Moreover, sera collected by the patients at baseline and after 4 weeks rehabilitation were used to conditionate endothelial cells (ECs) in presence and absence of H2O2-induced oxidative stress. On these cells senescence (by beta-gal associated senescence) and proliferation (by MTT) were measured.

The study population consisted of 34 males (mean age 58,5±6,7 ys; SBP 142,85±6,8 mmHg; DBP 81,6±5,8 mmHg; HR 83,9±5 bpm) with, at admission, a prevalent diagnosis of post-ischemic CHF. After a 4 weeks rehabilitation program a significant reduction was found in stress test parameters: SBP max (p<0.0001) and DBP max (p=0.001) values, in HR (p<0.01) and stress test duration (p<0.0001). After 4 weeks of ET, a reduction in oxidative stress, as showed by decrease in TBARS and 8-OHdG serum levels (both p<0.02), and increase in antioxidant molecular defense expressed by increased SOD (p<0.005) and Cat (p=0.005) activities were found. These results were also associated to an increase of SIRT1 activity (p=0.001). Moreover, ECs conditioned with sera at baseline and after 4-weeks ET showed significant changes of proliferation and senescence in absence and presence of H2O2-induced oxidative stress.

These preliminary data show that ET in humans is able to modify the oxidative response and that a central role is played by SIRT1, a lifespan regulator.

1 Mora S, Cook N, Buring JE, Ridker PM, Lee IM . Physical activity and reduced risk of cardiovascular events: potential mediating mechanisms. Circulation 2007;116(19):2110-8

2 Carvalho VO, Guimarães GV. An overall view of physical exercise prescription and training monitoring for heart failure patients. Cardiol J 2010;17(6):644-9