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Am J Physiol Heart Circ Physiol 286: H789-H795, 2004. First published October 9, 2003; doi:10.1152/ajpheart.00633.2003
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Redox modulation of the inotropic response to dobutamine is impaired in patients with heart failure

Susanna Mak and Gary E. Newton

Bayer Cardiovascular Clinical Research Laboratory, Division of Cardiology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada M5G 1X5

Submitted 7 July 2003 ; accepted in final form 3 October 2003

It has been suggested that oxidative stress contributes to impaired left ventricular (LV) contractility in the setting of heart failure (HF). To test this hypothesis, we studied the effect of an antioxidant on contractility at rest and in response to dobutamine in 10 HF patients. We hypothesized that vitamin C would augment contractility in HF and that this effect would be of a greater magnitude in HF patients compared with patients with normal LV (NLV) function. Data from 10 patients with NLV function who participated in this study are included in this report and have been published elsewhere. A micromanometer-tipped catheter was introduced into the LV. In the experimental protocol, an infusion catheter was positioned in the left main coronary artery. The peak positive rate of change of LV pressure (LV +dP/dt) was measured in response to the intravenous infusion of dobutamine before and during the intracoronary infusion of vitamin C (96 mg/min). Vitamin C had no effect on basal LV +dP/dt in either HF or NLV groups. The infusion of vitamin C augmented the LV +dP/dt response to dobutamine by 22 ± 4% in the NLV function group. In contrast, vitamin C had no effect on the inotropic response to dobutamine in the HF group. In the control protocol, without vitamin C, no differences were observed between responses to two sequential dobutamine infusions in either group (HF, n = 11; NLV, n = 9). Therefore, a positive effect of vitamin C on contractility was limited to patients with NLV function. The absence of this effect in HF patients may suggest that normal redox responsiveness is lost in this disease state.

antioxidants; contractility; receptors; {beta}-adrenergic



Address for reprint requests and other correspondence: G. E. Newton, Div. of Cardiology, Mount Sinai Hospital, 600 University Ave., Rm. 1614, Toronto, Ontario, Canada M5G 1X5 (E-mail: gnewton{at}mtsinai.on.ca).




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Thermogenic responsiveness to {beta}-adrenergic stimulation is augmented in exercising versus sedentary adults: role of oxidative stress
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Am. J. Physiol. Heart Circ. Physiol.Home page
S. Mak, C. B. Overgaard, and G. E. Newton
Effect of vitamin C and L-NMMA on the inotropic response to dobutamine in patients with heart failure
Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2424 - H2428.
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