title: Redox modulation of the inotropic response to dobutamine is impaired in patients with heart failure.
abstract: 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.
authors.affiliation: Bayer Cardiovascular Clinical Research Laboratory, Division of Cardiology, Mount Sinai Hospital, University of Toronto, Ontario, Canada.
authors.forename: Susanna
authors.initials: S
authors.lastname: Mak
authors.forename: Gary E
authors.initials: GE
authors.lastname: Newton
mesh_terms: D001205:Ascorbic Acid / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D004280:Dobutamine / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D006333:Heart Failure / Q000503:physiopathology*; D049692:History, Early Modern 1451-1600; D006801:Humans; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D010084:Oxidation-Reduction; D012016:Reference Values; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology
chemical_list: D002316:Cardiotonic Agents; D004280:Dobutamine; D001205:Ascorbic Acid