A standardized education protocol significantly reduces traumatic injuries and syncope recurrence: an observational study in 316 patients with vasovagal syncope.

AIMS: The aim of this study was to assess the role of a non-pharmacological approach on the frequency of traumatic injuries and syncope recurrence in patients with vasovagal syncope and normal hearts. We report the experience in our syncope centre with a standardized education and teaching protocol for patients with vasovagal syncope. The treatment of vasovagal syncope is often complex and discouraging. Besides medical options, behaviour modification is a main component of therapy but has no statistical evidence to support its use. METHODS AND RESULTS: Between January 1999 and September 2006, we prospectively enrolled all patients with vasovagal syncope. The patients were counselled about the benign nature of their disease. Specific recommendations were made according to a standardized education protocol established at our syncope centre. A pre-/post-study was conducted to investigate the effectiveness of our approach on syncope recurrence and frequency of injury as the study endpoints. Complete follow-up data were available from 85% of the study population (316 of 371) after a mean time of 710 ± 286 days (mean age 50 years; standard deviation ± 18 years, 160 female). Eighty-seven patients (27.5%) had a syncope recurrence with 22 suffering an injury during syncope. During the follow-up period, the syncope burden per month was significantly reduced from 0.35 ± 0.03 at initial presentation to 0.08 ± 0.02 (P< 0.001). The frequency of traumatic syncope was significantly lower at the time of recurrence compared with the initial presentation (25 vs. 42%; McNemar's test P= 0.02). CONCLUSION: A standardized education protocol significantly reduces traumatic injuries and syncope recurrence in patients with vasovagal syncope.

Clopidogrel improves systemic endothelial nitric oxide bioavailability in patients with coronary artery disease: evidence for antioxidant and antiinflammatory effects.

BACKGROUND: Platelet stimulation and activation are known not only as prerequisite of clot formation but are increasingly recognized as important contributors to inflammation and vascular injury. The present study in patients with symptomatic coronary disease investigated whether platelet adenosine diphosphate receptor blockade by clopidogrel exerts beneficial effects on endothelial nitric oxide bioavailability, oxidative stress, and/or inflammatory status. METHODS AND RESULTS: One hundred three consecutive patients with symptomatic coronary disease and long-term aspirin therapy were studied. Endothelium-dependent and -independent vasodilation was determined measuring forearm blood flow (FBF)-responses to acetylcholine with and without N(G)-monomethyl-L-arginin (L-NMMA) and sodium nitroprusside, by using venous occlusion plethysmography. Patients were randomized to receive additional treatment with clopidogrel or placebo. Vascular function tests were repeated after 5 weeks and showed significant improvement of acetylcholine-induced vasodilatation and L-NMMA responses in the clopidogrel-added group (max. FBF from 9.8+/-0.3 to 14.7+/-0.4; L-NMMA-response from 3.7+/-0.1 to 6.8+/-0.3 mL/100 mL/min). In contrast, no significant changes were observed in the placebo group. Sodium nitroprusside-induced vasodilation was not changed in either group. Urinary excretion of 8-iso-prostaglandin F2alpha and plasma levels of hsCRP, sCD40L, and RANTES were reduced in patients on additional treatment with clopidogrel, but not in patients on placebo. CONCLUSIONS: Clopidogrel improves endothelial nitric oxide bioavailability and diminishes biomarkers of oxidant stress and inflammation in patients with symptomatic coronary artery disease, suggesting that beyond inhibition of platelet aggregation, adenosine phosphate receptor blockade may also have promising vasoprotective effects.

Myeloperoxidase enhances nitric oxide catabolism during myocardial ischemia and reperfusion.

Impaired microvascular function during myocardial ischemia and reperfusion is associated with recruitment of polymorphonuclear neutrophils (PMN) and has been attributed to decreased bioavailability of nitric oxide (NO). Whereas myeloperoxidase (MPO), a highly abundant, PMN-derived heme protein facilitates oxidative NO consumption and impairs vascular function in animal models of acute inflammation, its capacity to function in this regard during human myocardial ischemia and reperfusion remains unknown. Plasma samples from 30 consecutive patients (61 +/- 14 years, 80% male) presenting with acute myocardial infarction were collected 9 +/- 4 h after vessel recanalization and compared to plasma from healthy control subjects (n = 12). Plasma levels of MPO were higher in patients than in control subjects (1.4 +/- 0.9 vs 0.3 +/- 0.2 ng/mg protein, respectively, p < 0.0001). The addition of hydrogen peroxide to patient plasma resulted in accelerated rates of NO consumption compared to control subjects (0.53 +/- 0.25 vs 0.068 +/- 0.039 nM/s/mg protein, respectively, p < 0.0001). Myocardial tissue from patients with the same pathology revealed intense recruitment of MPO-positive PMN localized along infarct-related vessels as well as diffuse endothelial distribution of non-PMN-associated MPO immunoreactivity. Endothelium-dependent microvascular function, as assessed by an acetylcholine-dependent increase in forearm blood flow in 75 patients with symptomatic coronary artery disease, inversely correlated with MPO plasma levels (r = -0.75, p < 0.005). Plasma from patients undergoing myocardial reperfusion contained increased levels of MPO, which catalytically consumed NO in the presence of H(2)O(2). Given the correlation between intravascular MPO levels and forearm vasomotor function in patients with coronary artery disease, MPO appears to be an important modulator of vasomotor function in inflammatory vascular disease and a potential therapeutic target for treatment.