The H-PVR patients have stiffening of both pulmonary and systemic arteries, preserved transpulmonary BNP uptake, but diminished cGMP release, which is reversible by the administration of sildenafil. This study provides in vivo evidence that phosphodiesterase 5A inhibition restores sensitivity of pulmonary vasculature to endogenous cGMP-dependent vasodilators.

Aim: The aim of our cross-sectional study was to assess the relationships between body iron stores, oxidative stress, impaired insulin sensitivity and carotid atherosclerosis in a cohort of healthy men in primary prevention of cardiovascular disease. Methods: We examined 151 volunteers, aged 35– 60 years. Anthropometric parameters, markers of metabolic syndrome, insulin resistance, inflammatory markers, parameters of oxidative stress and intima-media thickness of common carotid artery were measured. Results: Ferritin correlated positively with waist circumference, body mass index, impaired insulin sensitivity, plasma triglycerides and inversely with high-density lipoprotein cholesterol. We observed positive correlations between ferritin, oxidized lowdensity lipoprotein and advanced oxidation protein products after adjustment for age, waist circumference, body mass index and measured inflammatory markers (high-sensitivity C-reactive protein, fibrinogen, interleukin-6 and tumor necrosis factor-α). There were no significant associations between ferritin and intima-media thickness or markers of endothelial dysfunction. In a stepwise multiple regression analysis, triglycerides, waist circumference and elevated transaminases were independent determinants of the serum ferritin level. Conclusion: Our results provide evidence for a relationship between plasma ferritin and oxidative modification of lipids as well as proteins in vivo. Higher body iron stores may contribute to impaired insulin sensitivity through increased oxidative stress in a cohort of healthy men.

Our study showed a clear association of body iron stores expressed by the TfR/F ratio with asymptomatic carotid atherosclerosis. TfR/F further exhibited an independent positive correlation with fibrinogen and a negative correlation with sCD163 and IL-8.

In some patients, heart failure (HF) is associated with increased pulmonary vascular resistance (PVR). The magnitude and the reversibility of PVR elevation affect the HF management. Sildenafil has been recently recognized as potent PVR-lowering drug in HF. The aim of the study was to compare hemodynamic effects and pulmonary selectivity of sildenafil to prostaglandin E1 (PGE1). Right-heart catheterization was performed in 13 euvolemic advanced HF patients with elevated PVR (6.3±2 Wood´s units). Hemodynamic parameters were measured at the baseline, during i.v. infusion of PGE1 (alprostadil 200 ng∙kg-1∙min-1) and after 40 mg oral dose of sildenafil. Both drugs similarly reduced systemic vascular resistance (SVR), but sildenafil had higher effect on PVR (–28 % vs. –49 %, p=0.05) and transpulmonary pressure gradient than PGE1. The PVR/SVR ratio – an index of pulmonary selectivity, did not change after PGE1 (p=0.7) but it decreased by –32 % (p=0.004) after sildenafil. Both drugs similarly reduced pulmonary artery mean and wedge pressures and increased cardiac index (+27 % and +28 %). Sildenafil led more often to transplant-acceptable PVR while causing smaller drop of mean systemic pressure than PGE1. In conclusion, vasodilatatory effects of sildenafil in patients with heart failure are more pronounced in pulmonary than in systemic circulation.

Common ghrelin variants may have an effect on changes in biochemical and anthropometric parameters in hemodialyzed patients over time and could be used in the future to plan individualized therapy.