Chiara Montano

Nitric-oxide mediated effects of transdermal capsaicin patches on the ischemic threshold in patients with stable coronary disease.

Background Capsaicin has been shown to exert direct vasodilating effects through increased calcitonin gene-related peptide (CGRP) release. However, no data exist on its effect following systemic administration in humans. Methods Twelve male patients with stable coronary disease and a persistently positive exercise were selected for study. According to a double blind, placebo-controlled, cross-over study, patients were randomized to placebo or 3 g oleic capsaicin-containing patches, on 2 different days and with a 2-day interval between treatments. Patients performed treadmill exercise testing according to the Bruce protocol. Time to 1 mm ST segment depression and to peak exercise, maximal ST segment depression, and the number of ECG leads showing diagnostic changes were also measured. Blood samples for nitric oxide (NO) and CGRP were drawn at baseline, 2, 6, and 24 hours after exercise. Results On placebo, all patients had a positive ECG during exercise test. Only 1 patient experienced angina, on both treatments. With capsaicin, 1 patient had a negative exercise, while 8 patients significantly increased time to 1 mm ST depression from 328 ± 167 to 401 ± 174 seconds (P = 0.01). Of the remaining patients, 1 did not show any changes and 2 showed a worse ischemic threshold when on capsaicin. CGRP levels were not significantly different between placebo and capsaicin treatment. Conversely, when on capsaicin, NO significantly increased at 6 hours. Conclusions Transdermal capsaicin may improve ischemic threshold in patients with stable coronary disease, probably through arteriolar vasodilation. Increased capsaicin-induced NO availability could represent the principal mechanism of action.

Differential Long-term Effects of Carvedilol on Proinflammatory and Antiinflammatory Cytokines, Asymmetric Dimethylarginine, and Left Ventricular Function in Patients With Heart Failure

Neuroendocrine/inflammatory and endothelial functions have been indicated as crucial for heart failure (HF) patients. We evaluated relation in HF patients among cytokines and asymmetric dimethylarginine (ADMA) and left ventricular ejection fraction (LVEF) at baseline and after long-term administration of carvedilol. Interleukin 10 (IL-10), interleukin 18 (IL-18), and ADMA were measured in 22 NYHA class II to IV HF patients at baseline and after 40 ± 14 months of carvedilol treatment. Patients were divided into 2 groups according to whether, after treatment with carvedilol, LVEF had increased at least 5% (responders) or less than 5% (non-responders). In responders (11 of 22 patients), LVEF increased from 38 ± 6% to 50 ± 7%, (P < 0.001); in non-responders, it decreased from 36 ± 9% to 31 ± 6%, (P = 0.02); NYHA class significantly decreased in both groups. IL-18 decreased in responders (from 586.4 ± 128 to 183.13 ± 64.4 pg/mL; P < 0.001) and in non-responders (from 529.3 ± 116.25 to 142.4 ± 58.9 pg/mL; P < 0.001). IL-10 increased in responders (from 0.49 ± 0.25 to 2.01 ± 1.01 pg/mL; P < 0.001) and in non-responders (from 0.64 ± 0.31 to 1.33 ± 0.59 pg/mL; P < 0.001). Conversely, ADMA levels decreased only in responders (from 0.67 ± 0.16 to 0.44 ± 0.15 μmol/L; P < 0.001), and an inverse correlation was observed between basal ADMA levels and changes in LVEF after treatment. In HF patients, carvedilol appears to reduce symptoms and the expression of inflammation, regardless of the LV functional response. In those patients showing improvement of LVEF, the reduction of inflammation is paralleled by a reduction of ADMA. We surmise that carvedilol could be effective at various independent levels as a result of possible pleiotropic effects of this agent.

A high carbohydrate meal yields a lower ischemic threshold than a high fat meal in patients with stable coronary disease

OBJECTIVE To assess the ischemic threshold and stress-induced left ventricular dysfunction after high fat (HFM) and high carbohydrate (HCM) meals in patients with stable coronary disease. METHODS Twelve patients (68 ± 7 years) underwent stress (treadmill exercise testing) echocardiography after fasting (8h), after HFM and HCM (2h). Time to 1mm ST-segment depression (time to 1mm) and stress wall motion score index (WMSI) were evaluated. Before eating and just before exercise testing glucose, insulin, triglycerides, total cholesterol and FFA levels were measured. RESULTS Results are expressed as medians (Q1-Q3). HFM did not affect exercise variables compared to fasting, whereas HCM reduced the ischemic threshold [time to 1mm from 376 (343-493) to 297 (180-420) s, p = 0.003]. Compared to fasting [1.47 (1.31-1.66)], stress WMSI was higher after HCM [1.56 (1.44-1.69)] (p = 0.04) but not after HFM [1.56 (1.30-1.63)]. Glycemia and insulinemia were significantly higher after HCM, compared to fasting and HFM. CONCLUSIONS In patients with coronary disease, exercise testing after a high carbohydrate meal results in a lower ischemic threshold and greater ischemia magnitude. Conversely, compared to fasting, a high fat meal does not induce additional detrimental effects. Hyperglycemia and hyperinsulinemia were the only metabolic determinants identified as potential metabolic mechanisms of this phenomenon.