ascorbic-acid and Cardiomyopathy--Dilated

In this study, we used spectral analysis to assess changes in respiratory recording variability during infusion of L-arginine and vitamin C, individually or together, in patients with chronic heart failure. We found that healthy subjects have a substantial ability to modulate sympathetic-mediated peripheral vascular resistance through endothelial synthesis of nitric oxide. Patients with chronic heart failure lose this ability.

Topics: Algorithms; Antioxidants; Arginine; Ascorbic Acid; Autonomic Nervous System; Cardiomyopathy, Dilated; Cross-Over Studies; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Respiration; Signal Processing, Computer-Assisted; Single-Blind Method; Vascular Resistance

Endothelial dysfunction has been described in patients with coronary artery disease (CAD) or chronic heart failure (CHF). Vitamin C administration leads to an improvement of endothelial function by reducing elevated levels of reactive oxygen species. It remains unclear, however, whether the degree of endothelial dysfunction caused by oxidative stress differs between CAD and CHF because of ischemic (ICM) or dilated cardiomyopathy (DCM).. In patients with CAD (n = 9; left ventricular ejection fraction [LVEF], 64% +/- 3%), ICM (n = 9; LVEF, 25% +/- 4%), DCM (n = 9; LVEF, 25% +/- 3%), and healthy subjects (HS; n = 5; LVEF, 66% +/- 5%) a change in internal radial artery diameter in response to acetylcholine (Ach; 15 and 30 microg/min) was measured with high-resolution ultrasound scanning during a co-infusion of normal saline or vitamin C (25 mg/min).. Ach-mediated vasodilation was blunted in patients with CHF (DCM, 90 +/- 20 microm; ICM, 86 +/- 20 microm) and patients with CAD (336 +/- 20 microm) as compared with HS (496 +/- 43 microm; P <.05 vs patients with DCM, ICM, CAD). Vitamin C co-infusion increased Ach-mediated vasodilation by 180 +/- 35 microm (to 270 +/- 30 microm) in DCM (P <.05 vs CAD, HS) and by 294 +/- 40 microm (to 380 +/- 20 microm) in ICM (P <.05 vs DCM, CAD, HS). In patients with CAD, vitamin C increased Ach-mediated vasodilation by 146 +/- 35 microm to normal values, whereas vascular diameter remained unchanged in HS (14 +/- 20 microm; P = not significant).. Acute vitamin C administration restored peripheral endothelial function in patients with CAD to normal values, whereas endothelial function remained attenuated in CHF, in particular in patients with DCM. These results suggest that in patients with CHF, factors other than oxidative stress (eg, cytokines) contribute to the pathologic endothelial function.

Topics: Acetylcholine; Aged; Ascorbic Acid; Cardiomyopathy, Dilated; Chronic Disease; Coronary Artery Disease; Drug Therapy, Combination; Endothelium, Vascular; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Nitroprusside; Oxidative Stress; Vasodilation; Vasodilator Agents

Inhibition of xanthine oxidase (XO) in failing hearts improves cardiac efficiency by an unknown mechanism. We hypothesized that this energetic effect is due to reduced oxidative stress and critically depends on nitric oxide synthase (NOS) activity, reflecting a balance between generation of nitric oxide (NO) and reactive oxygen species. In dogs with pacing-induced heart failure (HF), ascorbate (1000 mg) mimicked the beneficial energetic effects of allopurinol, increasing both contractility and efficiency, suggesting an antioxidant mechanism. Allopurinol had no additive effect beyond that of ascorbate. Crosstalk between XO and NOS signaling was assessed. NOS inhibition with N(G)-monomethyl-L-arginine (L-NMMA; 20 mg/kg) had no effect on basal contractility or efficiency in HF, but prevented the +26.2+/-3.5% and +66.5+/-17% enhancements of contractility and efficiency, respectively, observed with allopurinol alone. Similarly, improvements in contractility and energetics due to ascorbate were also inhibited by L-NMMA. Because of the observed NOS-XO crosstalk, we predicted that in normal hearts NOS inhibition would uncover a depression of energetics caused by XO activity. In normal conscious dogs, L-NMMA increased myocardial oxygen consumption (MVO2) while lowering left ventricular external work, reducing efficiency by 31.1+/-3.8% (P<0.005). Lowered efficiency was reversed by XO inhibition (allopurinol, 200 mg) or by ascorbate without affecting cardiac load or systemic hemodynamics. Single-cell immunofluorescence detected XO protein in cardiac myocytes that was enhanced in HF, consistent with autocrine signaling. These data show that both NOS and XO signaling systems participate in the regulation of myocardial mechanical efficiency and that upregulation of XO relative to NOS contributes to mechanoenergetic uncoupling in heart failure.

Topics: Allopurinol; Animals; Antioxidants; Ascorbic Acid; Cardiac Pacing, Artificial; Cardiomyopathy, Dilated; Dogs; Energy Metabolism; Fluorescent Antibody Technique; Free Radical Scavengers; Hemodynamics; Infusions, Intravenous; Myocardial Contraction; Myocardium; Nitric Oxide Synthase; omega-N-Methylarginine; Signal Transduction; Xanthine Oxidase

In patients with idiopathic dilated cardiomyopathy, endothelium vasomotor function is disturbed. Increased oxidative stress and the consecutive formation of oxygen free radicals have been implicated as one possibility for this observation, suggesting that nitric oxide (NO) is inactivated by oxygen free radicals. We tested the hypothesis that the antioxidant, vitamin C, may improve endothelial function in idiopathic dilated cardiomyopathy. In 11 patients, the endothelium-dependent vasomotor response of the left anterior descending coronary artery to intracoronary acetylcholine (ACh) infusion (1/2 x 10(-6) mol/L, 1/4 x 10(-5) mol/L; respectively) was determined before and immediately after intravenous infusion of 3 g of vitamin C. Coronary cross-sectional diameter was obtained by quantitative coronary angiography, average peak velocity was measured by an intracoronary Doppler flow wire, and coronary blood flow (CBF) was calculated. Maximum cross-sectional diameter was determined after administration of nitroglycerin. Dose-dependent ACh showed a decrease in cross-sectional diameter (-5% to -7%, p <0.05) and an increase in average peak velocity (+16% to +25%, p <0.05); the CBF was unchanged (+1% to -2%, p = NS). After vitamin C infusion, the cross-sectional diameter increased in a dose-dependent manner from +11% to +15%, the average peak velocity increased from +20% to + 41% (p <0.05), and the CBF increased from +38% to + 82% (p <0.01, p <0.001, respectively). Thus, patients with idiopathic dilated cardiomyopathy had endothelial dysfunction, and administration of vitamin C reversed endothelium-dependent dysfunction.

Topics: Antioxidants; Ascorbic Acid; Cardiomyopathy, Dilated; Coronary Angiography; Coronary Vessels; Endothelium, Vascular; Female; Free Radical Scavengers; Hemodynamics; Humans; Male; Middle Aged; Regional Blood Flow

To assess degree of oxidative stress and antioxidant concentrations in dogs with idiopathic dilated cardiomyopathy (IDCM).. Prospective study.. 18 dogs with IDCM and 16 healthy control dogs.. Concentrations of malondialdehyde (an indicator of oxidative stress); vitamins A, C, and E; glutathione peroxidase; and superoxide dismutase were measured.. Glutathione peroxidase concentration was significantly increased in dogs with IDCM, compared with control dogs. Vitamin A and superoxide dismutase concentrations were not significantly different between groups. A negative correlation was found between disease severity and plasma vitamin E concentration. Disease severity was not correlated with concentrations of other antioxidants. Medications did not significantly affect oxidant or antioxidant concentrations.. The change in glutathione peroxidase concentration and the correlation between vitamin E concentration and disease severity suggest that the oxidant-antioxidant system may play a role in development of IDCM.

Topics: Animals; Antioxidants; Ascorbic Acid; Cardiomyopathy, Dilated; Chromatography, High Pressure Liquid; Colorimetry; Dog Diseases; Dogs; Electrocardiography; Female; Glutathione Peroxidase; Male; Malondialdehyde; Oxidative Stress; Prospective Studies; Statistics, Nonparametric; Superoxide Dismutase; Vitamin A; Vitamin E

Impaired endothelium-dependent vasodilation has been reported to play an important role in the pathogenesis of cardiovascular diseases such as coronary artery disease (CAD) and congestive heart failure (CHF). However, the precise mechanism of endothelial dysfunction has not been elucidated in these conditions. To evaluate the role of oxidative stress in endothelial dysfunction, the effect of antioxidant ascorbic acid on brachial flow-mediated, endothelium-dependent vasodilation during reactive hyperemia and nitroglycerin-induced endothelium-independent vasodilation was examined with high resolution ultrasound in 12 patients with CHF caused by idiopathic dilated cardiomyopathy without established coronary atherosclerosis and in 10 patients with CAD. Flow-mediated vasodilation in CHF (4.4+/-0.5%) and CAD (4.0 - 0.8%) was significantly (p <0.05) attenuated compared with that in 10 control subjects (9.6+/-0.9%). However, nitroglycerin-induced vasodilation was similar in 3 groups (13.7+/-1.3% in control, 13.9+/-1.1% in CHF, 12.7+/-1.4% in CAD). Ascorbic acid could significantly improve flow-mediated vasodilation only in patients with CAD (9.1+/-0.9%) but not with CHF (5.6+/-0.6%), and had no influence on nitroglycerin-induced vasodilation (13.6+/-1.1% in CHF, 14.0+/-1.3% in CAD). These results suggest that, in brachial circulation, augmented oxidative stress mainly leads to endothelial dysfunction in CAD but not in CHF caused by idiopathic dilated cardiomyopathy.

Topics: Adult; Aged; Angina Pectoris; Ascorbic Acid; Blood Flow Velocity; Brachial Artery; Cardiomyopathy, Dilated; Coronary Disease; Endothelium, Vascular; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Nitroglycerin; Reproducibility of Results; Ultrasonography, Doppler; Vasodilation; Vasodilator Agents