Effect of vitamin C and L-NMMA on the inotropic response to dobutamine in patients with heart failure.
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 the 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. The peak positive rate of change of LV pressure (LV +dP/dt) was measured in response to intravenous dobutamine (Dob-1). After recontrol, intracoronary N(G)-monomethyl-L-arginine (l-NMMA) was infused before reinfusion of dobutamine (L-NMMA + Dob-2). Finally, intracoronary vitamin C was infused in addition to intracoronary L-NMMA and dobutamine (L-NMMA + Dob-2 + vitamin C). Intracoronary L-NMMA alone had no effect on LV +dP/dt. After a stable inotropic response to intracoronary L-NMMA and dobutamine was established, the addition of intracoronary vitamin C resulted in a modest but significant increase in LV +dP/dt. The change in LV +dP/dt in response to dobutamine alone was 25 +/- 5%, with intracoronary L-NMMA, 27 +/- 6%, and with intracoronary L-NMMA plus vitamin C, 37 +/- 5% (P < 0.05 vs. Dob-1 and L-NMMA + Dob-2). These findings demonstrate that an interaction between endogenous NO and redox environment exists and exerts some influence on stimulated contractility in HF.
Mak
Susanna
S
Cardiovascular Clinical Research Laboratory, Div. of Cardiology, Mount Sinai Hospital, 600 University Ave., Rm. 1543, Toronto, Ontario, Canada M5G 1X5.
Overgaard
Christopher B
CB
Newton
Gary E
GE
D001205:Ascorbic Acid / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000008:administration & dosage; D004280:Dobutamine / Q000008:administration & dosage*; D004338:Drug Combinations; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000503:physiopathology* / Q000517:prevention & control; D019323:omega-N-Methylarginine / Q000008:administration & dosage*
D002316:Cardiotonic Agents; D004338:Drug Combinations; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D004280:Dobutamine; D019001:Nitric Oxide Synthase; D001205:Ascorbic Acid