Effects of carvedilol on oxidative stress and chronotropic response to exercise in patients with chronic heart failure.
BACKGROUND
Our previous studies suggest that the increase in heart rate from rest to peak exercise is reduced in patients with chronic heart failure (CHF) and this is associated with increased oxidative stress, as determined by malondialdehyde (MDA) plasma levels.


OBJECTIVE
To investigate the effects of carvedilol on the heart rate response to exercise and oxidative stress in patients with CHF.


RESULTS
Thirty stable NYHA classes II-III CHF patients received carvedilol therapy for 6 months, at a mean maintenance dose of 25 mg (range 6.25-50 mg/day). After treatment, the patients showed a significant improvement in their functional NYHA class (p=0.013), increased left ventricular ejection fraction (LVEF) (24+/-1.4% to 31+/-2.3%, p=0.003) and 6-min walk distance (499+/-18 to 534+/-18 m, p=0.03), without changes in the peak VO2. At baseline, norepinephrine (NE) plasma levels increased with exercise (510+/-51 to 2513+/-230 pg/mL, p<0.001), and these levels were not affected by carvedilol. Chronotropic responsiveness index (increase in heart rate divided by the increase in NE from rest to peak exercise) was not changed by carvedilol (0.049+/-0.001 to 0.042+/-0.001, p=0.6). MDA levels of CHF patients decreased after treatment with carvedilol (2.4+/-0.2 to 1.1+/-0.2 microM, p<0.001), without changes in antioxidant enzyme activities.


CONCLUSIONS
Carvedilol treatment in patients with CHF results in reduced oxidative stress without restoration of the chronotropic responsiveness index.
Castro
Pablo
P
Cardiovascular Diseases, Universidad Católica de Chile, Santiago, Chile. pcastro@med.puc.cl
Vukasovic
José Luis
JL
Chiong
Mario
M
Díaz-Araya
Guillermo
G
Alcaino
Hernán
H
Copaja
Miguel
M
Valenzuela
Rodrigo
R
Greig
Douglas
D
Pérez
Osvaldo
O
Corbalan
Ramón
R
Lavandero
Sergio
S
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005979:Glutathione Peroxidase / Q000032:analysis / Q000378:metabolism; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000201:enzymology*; D006334:Heart Function Tests; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D016014:Linear Models; D008297:Male; D008315:Malondialdehyde / Q000032:analysis / Q000378:metabolism; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011336:Probability; D011412:Propanolamines / Q000627:therapeutic use*; D011446:Prospective Studies; D015635:Radionuclide Ventriculography / Q000187:drug effects; D012720:Severity of Illness Index; D013318:Stroke Volume / Q000187:drug effects; D013482:Superoxide Dismutase / Q000032:analysis / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D009638:Norepinephrine