Submitted on May 5, 2005
Accepted on July 15, 2005
The Effect of Vitamin C and L-NMMA on the Inotropic Response to Dobutamine in Patients With Heart Failure
Susanna Mak1, Christopher B Overgaard1, and Gary E Newton1*
1 Department of Medicine, Divsion of Cardiology, Mount Sinai Hospital, Toronto, Ontario, Canada
* To whom correspondence should be addressed. E-mail: gnewton{at}mtsinai.on.ca.
The positive effect of vitamin C on left ventricular (LV) inotropic responses to dobutamine, observed in patients with preserved LV function, is lost in heart failure (HF). We tested the hypothesis that, in HF, endogenous nitric oxide (NO) opposes the positive effect of vitamin C on adrenergically-stimulated contractility by examining effects of vitamin C on dobutamine responses during NO synthase inhibition. In 11 HF patients, a micromanometer-tipped catheter was inserted into the LV and an infusion catheter was positioned in the left main coronary artery. Left ventricular peak +dP/dt (LV +dP/dt) was measured in response to intravenous dobutamine (Dob-1). After recontrol, intracoronary (IC) NG-monomethyl-L-arginine (L-NMMA) was infused, prior to re-infusion of dobutamine (L-NMMA + Dob-2). Finally, IC vitamin C was infused in addition to IC L-NMMA and dobutamine (L-NMMA + Dob-2 + vit C). IC L-NMMA alone had no effect on LV +dP/dt. After establishing a stable inotropic response to IC L-NMMA and dobutamine, the addition of IC vitamin C resulted in a significant increase in LV+dP/dt. The change in LV +dP/dt in response to dobutamine alone was 25 ± 5%, with IC L-NMMA was 27 ± 6%, and with IC L-NMMA and vitamin C was 37 ± 5% (p<0.05 versus Dob-1 and L-NMMA + Dob-2). These findings demonstrate an interaction between endogenous NO and redox environment exists and exerts some influence on stimulated contractility in HF.
