Disrupted serotonergic and sympathoadrenal systems in patients with chronic heart failure may serve as new therapeutic targets and novel biomarkers to assess severity, progression and response to treatment.

BACKGROUND: It is well established that the serotonergic system (SS) plays important roles in the pathogenesis of cardiovascular diseases. However, the impact of serotonin and its inter-relation with the sympathoadrenal system (SAS) in chronic heart failure (CHF) is poorly understood. METHODS: Utilizing high-performance liquid chromatography with electrochemical detection, we determined blood plasma levels of serotonin (5-hydroxy-triptamine, [5-HT](p)), 5- hydroxy-indole-acetic acid ([5-HIAA](p)), epinephrine ([E](p)), norepinephrine ([NE](p)), 3,4-dihydroxy-L-phenyl-alanine ([DOPA](p)), dopamine ([DA](p)) and the platelet concentration of serotonin ([5-HT](pt)) in CHF patients with different morphofunctional alterations of myocardium. The morphofunctional alterations included diastolic dysfunction (DD), diastolic dysfunction with left ventricular hypertrophy (DD&LVH), and diastolic and systolic dysfunction (D&SD). RESULTS: All CHF groups showed significant rises of [5-HT](p) and [5-HT](pt). DD&LVH and D&SD individuals also had increased [5-HIAA](p). Levels of SAS blood biomarkers were also significantly changed. The correlation between SS and SAS was increased in CHF and corresponded with disease severity. CONCLUSIONS: These results clearly demonstrate that in CHF patients significant changes in SS and SAS occur, which are thought to relate to the morphofunctional alterations of myocardium. The observed changes in the levels of these biomarkers may serve as potential surrogates to monitor severity of disease, to evaluate response to drug treatment, and as a rational basis for new therapeutic approaches.

Varicose disease affects the P2 receptor-mediated responses of human greater saphenous vein.

The aim of the present study was to investigate in vitro the differences in P2 receptor mediated responses of human greater saphenous vein (GSV) taken from patients with varicose disease and obliterating atherosclerosis. Samples of the inguinal part of the GSV were taken from the patients who underwent phlebectomia operation due to varicose disease (n=9, VD group) or femoropoplitea bypass operation using auto-vein due to obliterating atherosclerosis of lower extremities (n=11, OA group). The mechanical responses of the isolated segments of GSV to P2 receptor agonists were tested using standard organ-bath technique. ATP (10(-6)-10(-4) M), ADP (10(-6)-10(-4) M) and alpha,betamethyleneATP (10(-8)-10(-5) M) caused concentration-dependent contractions of the veins of both groups, the latter agonist being approximately tenfold more active than first two. ATP at all concentrations tested, alpha,betamethyleneATP at concentrations of 10(-6) and 10(-5) M and ADP at a concentration of 10(-6) M produced significantly higher contractions of the GSV taken from OA group than from VD group. UTP (10(-6)-10(-4) M) caused concentration-dependent contractions of the veins taken from OA group, while in VD group this agonist was virtually without effect. Adenosine (10(-6)-10(-4) M) and 2-methylthio-ATP (10(-7)-10(-5) M) had no significant contractile activity in this tissue in both groups. It is concluded from this study that there are P2 receptor and adrenoceptor mediated contractions in human greater saphenous veins, which are impaired by varicose disease, in contrast to contractions produced by histamine and carbachol which are, if anything, enhanced.