Effect of Folic Acid on Endothelial and Baroreceptor Function in Patients With Heart Failure

The randomized, double-blind, placebo-controlled study aim to evaluate the effect of 1-month therapy with folic acid (5 mg/day) on endothelial function and baroreceptor function in patients with heart failure. Endothelial function will be studied non-invasively with flow-mediated dilation while for eveluating baroreceptor function sympathetic nervous system activity will be measured directly with microneurography in baseline condition and during infusion of sodium-nitroprusside.

Endothelial and baroreceptor function are impaired in patients with heart failure. Impaired baroreflex control of the heart and peripheral circulation and endothelial dysfunction are thought to play an important pathophysiological role in chronic heart failure and confers a poor prognosis. In patients with essential hypertension we demonstrated an improvement in baroreceptor function after treatment with folic acid. Therefore, the aim of the present randomized, double-blind, placebo-controlled study was to evaluate endothelial function and baroreceptor function in patients with heart failure before and after 1-month therapy with folic acid (5 mg) or placebo. Endothelial function will be assessed with novel high-resolution ultrasound devices, which allows to investigate endothelial function in vivo. This method makes use of the property of the endothelium to release nitric oxide in response to shear stress and increased flow as previously described. Endothelium-dependent flow-mediated dilation (FMD) and endothelium-independent glycerol trinitrate (GTN) (0.4 mg sublingual, Nitrolingual Spray, Pohl-Boskamp, Germany)-induced vasodilation of the brachial artery will be assessed by a high-resolution ultrasound vessel wall tracking device with a 10 MHz linear array transducer . FMD of the brachial artery is induced by release of a wrist cuff inflated 50 mmHg above systolic pressure for 5 minutes. After sublingual GTN application, used as endothelium-independent stimulus, the diameter will be recorded every 30 seconds for 6 minutes. Multifiber recordings of muscle sympathetic nerve activity will be obtained from the peroneal nerve posterior to the fibular head with tungsten microelectrodes. The sympathetic nervous activity will be measured continuously together with ECG, respiration rate and blood pressure. Baroreceptor modulation of muscle sympathetic nerve activity and heart rate would be assessed by intravenous infusion of sodium nitroprusside.

Inclusion Criteria: Heart failure (min. NYHA ll, LVEF <50%) Not smokers Written informed consent Exclusion Criteria: Unstable heart failure Smoking Unstabile Angina Pectoris Endocrinologic disease such as Diabetes mellitus, Hypo- und Hyperthyroidism Alcohol abuse Epilepsia Treatment with folic acid antaponists Trimethoprim, Pyrimethamin, Methotrexat.. Participation to one other clinical Study within 1 Month