Platelet activation and platelet-derived growth factor (PDGF) play a pivotal role in the pathogenesis of atherosclerosis. Evidence has been accumulating that in the evolution of chronic arterial obstructive disease (CAOD) platelets are also crucially important. The aim of the present study was, therefore, to assess plasma levels of PDGF in patients with different degrees of CAOD according to Fontaine. Twenty patients (17 men, 3 women, mean age sixty-eight +/- seven years) with intermittent claudication (Fontaine stage II) entered the study and their PDGF levels were assessed by radioimmunoassay. Ten additional patients (7 men, 3 women, mean age seventy-three +/- seven years) with more severe CAOD (leg pain at rest/skin ulcers) were also studied. Ten healthy subjects (6 men, 4 women, mean age fifty-four +/- six years) comprised the control group. Patients in stage II were reinvestigated after sixty days of a "training" procedure. Patients with both intermittent claudication and more severe disease had higher levels of PDGF than controls (controls 165.9 +/- 119.1 pg/mL; Fontaine stage II 403.5 +/- 218.4; Fontaine stage III/IV 578.1 +/- 637.2: ANOVA P = 0.04) with no difference between the two groups of patients. After the training period, PDGF levels were significantly higher than at baseline (863.7 +/- 819.6 pg/mL vs 403.5 +/- 218.4) but without significant improvement of physical performance. The elevation of PDGF levels in blood from CAOD patients could be the result of marked platelet activation due to interaction with a widely damaged peripheral vasculature. The same was not true for coronary heart disease, in which normal values of PDGF in venous blood were found.(ABSTRACT TRUNCATED AT 250 WORDS)

Tumor necrosis factor alpha (TNF-alpha) is a cytokine that affects endothelial cells' function by changing their antithrombotic potential to a net procoagulant effect. Only a few data have so far been reported for the pathophysiologic role of TNF in vascular diseases in the involvement of microvessels and/or macrovessels and a prothrombotic state. In the present study the authors evaluated plasma TNF (and interleukin-1) levels in 20 patients with chronic arterial obstructive disease (CAOD) with intermittent claudication and 10 CAOD patients with more severe disease (pain at rest/skin ulcers). In addition, they studied 10 patients with Raynaud's phenomenon (RP), suspected to be secondary to a collagen disease. The control group consisted of 20 subjects matched for sex and age with the three groups of patients. TNF levels were assayed by enzyme-linked immunosorbent assay. The antigen levels of von Willebrand factor (vWF), tissue plasminogen activator (t-PA), and its inhibitor (PAI) were also determined as markers of release from the endothelium, while the fragment 1 + 2 of prothrombin (F1 + 2) and thrombin-antithrombin III (TAT) complexes were assessed as indexes of systemic thrombin generation. TNF levels were significantly higher in both groups of CAOD patients than in controls or RP patients, and the same was true for vWF. t-PA was significantly higher only in the CAOD subjects with more severe disease. No differences among groups were seen in PAI antigen/activity or thrombin generation. When data were corrected for age, TNF no longer differentiated CAOD patients from controls and RP subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: The clinical efficacy of iloprost, a stable analogue of prostacyclin, in patients with Raynaud's phenomenon (RP) has been widely reported. However, its mechanism of action is still unclear, and also unknown is why the benefit lasts for many weeks after therapy is discontinued. The aim of the present study was to learn what kind of microcirculatory changes occur in the skin of the affected hand one month after the end of iloprost treatment in patients with RP. Patients and Methods: Eleven subjects (8 women, 3 men, mean age forty-four years) with RP suspected to be secondary to a collagen disease entered the study and were infused with iloprost up to 2.0 ng/kg/minute for six hours on five consecutive days. At baseline and one month after treatment discontinuation, laser Doppler flowmetry, thermography, and computer-assisted video capillaroscopy of the affected hand were performed. Results: At the end of follow-up, the mean capillary density as recorded by video capillaroscopy was significantly increased as was the skin temperature in the different areas (fingertip, nailbed, tenar, hypotenar). In contrast, laser Doppler flowmetry revealed no significant changes after therapy. Comment: The improvement of vascularization of the skin and, therefore, the decrease in avascular areas in patients with RP suspected to be secondary to a connective tissue disease appear to be associated with enhancement of nutritional flow. Rather than rely on an angiogenetic effect of iloprost, these modifications may be related to the drug-induced normalization of the described dysfunctional arteriolar-venular anastomoses in the skin of RP patients through redistribution of flow.

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