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Am J Physiol Heart Circ Physiol (October 9, 2003). doi:10.1152/ajpheart.00633.2003
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Submitted on July 7, 2003
Accepted on October 3, 2003

Redox Modulation of the Inotropic Response to Dobutamine is Impaired in Patients With Heart Failure

Susanna Mak1 and Gary E. Newton1*

1 Division of Cardiology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada

* To whom correspondence should be addressed. E-mail: GNewton{at}mtsinai.on.ca.

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 1) vitamin C would augment contractility in HF, and 2) this effect would be of greater magnitude in HF patients as compared to 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. LV peak +dP/dt (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. By 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 2 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. Absence of this effect in HF patients may suggest that normal redox responsiveness is lost in this disease state.




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