A growing body of evidence supports the existence of a tissue-based renin-angiotensin system (RAS) in the vasculature, but the functional capacity of vascular RAS was not investigated in humans. In 28 normotensive healthy control subjects, the metabolism of angiotensins through vascular tissue was investigated in normal, low, and high sodium diets by the measurement of arterial-venous gradient of endogenous angiotensin (Ang) I and Ang II in two different vascular beds (forearm and leg), combined with the study of 125I-Ang I and 125I-Ang II kinetics. In normal sodium diet subjects, forearm vascular tissue extracted 36+/-6% of 125I-Ang I and 30+/-5% of 125I-Ang II and added 14.9+/-5.1 fmol x 100 mL(-1) x min(-1) of de novo formed Ang I and 6.2+/-2.8 fmol x 100 mL(-1) x min(-1) of Ang II to antecubital venous blood. Fractional conversion of 125I-Ang I through forearm vascular tissue was about 12%. Low sodium diet increased (P<.01) plasma renin activity, whereas de novo Ang I and Ang II formation by forearm vascular tissue became undetectable. Angiotensin degradation (33+/-7% for Ang I and 30+/-7% for Ang II) was unchanged, and vascular fractional conversion of 125I-Ang I decreased from 12% to 6% (P<.01). In high sodium diet subjects, plasma renin activity decreased, and de novo Ang I and Ang II formation by forearm vascular tissue increased to 22 and 14 fmol x 100 mL(-1) x min(-1), respectively (P<.01). Angiotensin degradation did not significantly change, whereas fractional conversion of 125I-Ang I increased from 12% to 20% (P<.01). Leg vascular tissue functional activities of RAS paralleled those of forearm vascular tissue both at baseline and during different sodium intake. These results provide consistent evidence for the existence of a functional tissue-based RAS in vascular tissue of humans. The opposite changes of plasma renin activity and vascular angiotensin formation indicate that vascular RAS is independent from but related to circulating RAS.

These results provide evidence for the existence of a functional cardiac RAS independent of but related to the circulating RAS.

Defibrotide is a polydeoxyribonucleotide-derived anti-ischemic drug with multiple sites of action involving both plasmatic and cellular targets. This agent has been demonstrated to produce profibrinolytic, cytoprotective, and vaso-facilatory actions. Since monocytes are increased in the mediation of some of the pathophysiologic responses seen in ischemic disorders, the functional properties of these cells were investigated in experimental conditions to evaluate their behavior during resting and stimulated states. Defibrotide was supplemented in these systems to determine its modulatory action. In this investigation Defibrotide was found to decrease the PAI-1 levels and may indicate that this may be the mechanism for its profibrinolytic actions. Defibrotide was also found to reduce the procoagulant activity of monocytes in these experimental settings. Both PAI and procoagulant factors play an important role in the pathophysiology of inflammation, DIC, and ischemia. Defibrotide induced reduction of these two factors represents the mechanism whereby this agent produces its therapeutic action.

The measurement of fibrinogen (Fg) plasma levels is one of the more frequently performed tests in clinical practice, usually by clotting assay. However, for the diagnosis of dysfibrinogenemia the use of an immunological assay is necessary to compare total and clottable protein. Little information is available on the range of the ratio clottable (C) Fg/immunological (I) Fg levels in normal population. This study aimed at evaluating the CFg/IFg ratio in 70 control subjects (age range 17-74 years – group A), in 57 acute patients (age range 17-79 years – group B) and in 14 pregnant women (age range 27-41 years, pregnancy weeks 30-40 – group C), as a physiologic model of hyperfibrinogenemia. CFg was assayed on citrated plasma by the Clauss clotting method and IFg was assayed by radial immunodiffusion technique. In the three groups, CFg/IFg ratios were not significantly different (respectively group A 0.98 ± 0.17, group B 1.02 ± 0.18 and group C 1.01 ± 0.11), whereas both CFg (310 ± 45 mg/dl) and IFg (326 ± 70mg/dl) levels were lower (p < 0.001) in control subjects than in patients (CFg 556 ± 92 mg/dl; IFg 561 ± 121 mg/dl) and in pregnant women (CFg 530 ± 65 mg/dl; IFg 530 ± 77 mg/dl). The analysis of the relationship between CFg and IFg in the three groups (group A: y = 11.53 + 1.01x, r = 0.64, p < 0.001; group B: y = 68.72 + 0.88x, r = 0.67, p < 0.001; group C: y = 71.59 + 0.87x, r = 0.73, p < 0.01) indicates that a good correlation exists (p < 0.001) for values of fibrinogenemia ranging from 180 to over 700 mg/dl. A reference range of CFg/IFg (mean ± 2 SD in group A) was 0.64-1.32. These data could be of practical importance for a rapid screening of dysfibrinogenemias.

Euglobulin lysis time is a global test for the study of fibrinolysis. The aim of this study was to evaluate the influence of storage of plasma and euglobulin precipitates on euglobulin lysis time, by testing samples stored in different conditions. In 20 healthy subjects, euglobulin lysis time was measured by (1) euglobulin precipitates prepared within 90 minutes from blood withdrawal (reference euglobulin lysis time); (2) euglobulin precipitates obtained from platelet-poor plasma stored for 24 hours at either -80 degrees C or at -20 degrees C; (3) euglobulin precipitates frozen for 24 hours at either -80 degrees C or at -20 degrees C; (4) euglobulin precipitates dissolved in Owren's buffer and frozen for 24 hours at either -80 degrees C or at -20 degrees C. Euglobulin lysis time measured on euglobulin precipitates dissolved in Owren's buffer and stored at -20 degrees C and at -80 degrees C, and euglobulin lysis time measured on platelet-poor plasma stored at -20 degrees C were significantly longer than the reference euglobulin lysis time (at least P < .05). On the contrary, no changes were observed in euglobulin lysis time measured on platelet-poor plasma stored at -80 degrees C, and on euglobulin precipitates undissolved and stored at -20 degrees C and at -80 degrees C versus reference euglobulin lysis time. The pattern was similar in samples obtained both before and after venous occlusion. These data indicate that the freezing of samples of platelet-poor plasma or euglobulin precipitates at -80 degrees C and of euglobulin precipitates at -20 degrees C makes the simultaneous determination of a large number of samples collected at different times the previous day possible.