Interleukins and inflammatory markers in in-stent restenosis after femoral percutaneous transluminal angioplasty.

BACKGROUND: Inflammatory activity may influence results of percutaneous transluminal angioplasty (PTA). The purpose of this study was to evaluate the relationship between (1) proinflammatory markers (interleukin [IL]-6, IL-8, tumor necrosis factor α (TNF-α), and highly sensitive C-reactive protein [CRP]); (2) type 1 T helper cell marker (IL-12); and (3) Type 2 T helper cell marker (transforming growth factor-ß [TGF-ß]) and in-stent restenosis, 6 months after femoral PTA with stent implantation. METHODS: We performed a single-center prospective study with 26 patients with peripheral artery disease requiring PTA and stenting. As control, we studied 26 patients who were submitted to diagnostic angiography. Serum samples were collected before stent implantation, 24 hr and 6 months after the procedure. To detect restenosis, a new angiography was obtained at 6 months. RESULTS: Restenosis was observed in 10 (38.5%) patients who underwent PTA and stenting. There was a trend to increased levels of IL-6, TNF-α, TGF-ß, and IL-12 24 hr after PTA and stenting compared with pretreatment. IL-8 levels showed a statistically significant reduction 24 hours after versus pretreatment (P < 0.05), 6 months vs. pretreatment, and 6 months vs. 24 hr (P < 0.01). There was no statistical difference between cytokine levels when comparing restenosis and no restenosis groups. CRP levels were already high at pretreatment. CONCLUSIONS: No inflammatory marker was independently identified as risk factor for in-stent restenosis, 6 months after femoral PTA with stent implantation. The question that remains is whether acute phase reactants will be clinically useful to predict the individual risk for in-stent restenosis.

Characterization of the kallikrein-kinin system, metalloproteinases, and their tissue inhibitors in the in-stent restenosis after peripheral percutaneous angioplasty.

BACKGROUND: The kallikrein-kinin system (KKS) has several direct and indirect effects on cells and cellular mediators involved in the inflammatory process. Studies about inflammation on percutaneous transluminal angioplasty with stent (PTA/stent) to treat peripheral arterial disease (PAD) in humans are scarce. The matrix metalloproteinases (MMPs) are calcium-dependent zinc-containing endopeptidases expressed in various cells and tissues such as fibroblasts, inflammatory cells, and, smooth muscle cells. Changes in the extracellular matrix (ECM) take place in the pathogenesis of many cardiovascular pathologies. MMPs and their inhibitors (tissue inhibitors of metalloproteinases [TIMPs]) are crucial in ECM remodeling in both physiologic and pathologic conditions. The aim of this study was to evaluate the role of the KKS and the MMP metabolism, which are important mediators that may contribute to tissue repair, in the process of arterial restenosis due to intimal hyperplasia in the femoropopliteal segment with the aim of developing new interventions. METHODS: Thirty-nine consecutive patients were selected (regardless of ethnic group, age, or sex) for revascularization, who underwent PTA/stent of the femoropopliteal segment. Twenty-five patients with the same clinical characteristics who were scheduled for diagnostic angiography but not subjected to PTA/nitinol stent were also selected. The concentrations in blood of total and kininogen fractions were evaluated using immunoenzymatic methods. Plasma kallikrein was evaluated by the colorimetric method. Tissue kallikrein was evaluated by the spectrophotometric method. The activity of kininase II was measured by fluorometric analysis. Quantification of MMPs was performed by zymography, which is an electrophoresis technique, and TIMPs were measured by enzyme-linked immunosorbent assay. RESULTS: Among the 31 patients who completed the survey, there were 10 cases of angiographically defined restenosis of >50%, and 21 cases without restenosis. There was an increase in the concentrations of the substrates (high-molecular-weight kininogens and lower molecular weight kininogens) and enzymes (plasma and tissue kallikrein) in patients with restenosis, indicating activation of this inflammatory pathway in these patients. The activity of kininase II was not significantly different between the groups of patients studied. There were no statistical differences between restenosis and no restenosis patients for both MMPs and TIMPs dosage, but there is an upward trend of MMPs in time 6 months in patients with restenosis. CONCLUSIONS: With the aim of identifying factors contributing to restenosis after endovascular intervention, this study showed evidence of high activation of the KKS in the pathologic inflammatory process of PTA/stent restenosis. In the other hand, it could not show participation of metalloproteinase metabolism in PTA/stent restenosis.

Endovascular treatment for acute aortic syndrome.

BACKGROUND: The term "acute aortic syndrome" (AAS) includes conditions of high mortality, such as ruptured aneurysm, pseudoaneurysm and, aortic dissection. Open surgery for these cases has demonstrated unsatisfactory results, and endovascular treatment has become an excellent alternative. METHODS: We performed a retrospective review of patients with AAS who underwent endovascular treatment in our emergency department from July 2009 to February 2011. They represent 64% (16 of 25) of all patients with AAS seen during this period. RESULTS: Sixteen patients underwent endovascular treatment: eight ruptured aneurysms, six aortic dissections, one nonruptured painful aneurysm, and one pseudoaneurysm. No intramural hematoma or penetrating atherosclerotic ulcer was found. The mean age was 64.3 years, and arterial hypertension (100%) and smoking (64.7%) were the major comorbidities. Technical success rate was 93%, and overall 30-day mortality was 6.25%. CONCLUSION: Endovascular treatment for AAS was feasible. Technical success, 30-day mortality, hospital stay, and procedure time were similar to those of the other series reported in the literature, and the endovascular approach has became the main technique for AAS in our hospital.

Inhibitory effect of sildenafil on rat duodenal contractility in vitro: putative cGMP involvement.

1. Sildenafil citrate (Viagratrade mark; Pfizer, Sandwich, Kent, UK), a phosphodiesterase 5 inhibitor, rises cGMP levels in smooth muscle cells. It relaxes both vascular and visceral smooth muscle. In order to assess the intestinal effects of sildenafil, we decided to investigate its actions on rat duodenal motor activity in vitro. 2. In isolated duodenal segments maintained in Tyrode's solution, sildenafil exhibited a concentration-dependent antispasmodic effect on acetylcholine (ACh)-induced phasic contractions, with an IC50 value of 26.7 micromol/L (95% confidence interval (CI) 2.0-55.3 micromol/L). 3. Sildenafil also relaxed the carbamylcholine (CCh)-induced sustained contraction with an IC(50) of 16.2 micromol/L (95% CI 9.5-27.6 micromol/L). Sildenafil produced significant additional relaxation of 25.2 +/- 8.1% of the CCh-induced contraction, beyond basal tone. 4. Sildenafil reduced the amplitude of spontaneous duodenal contractions with an EC50 of 9.6 micromol/L (95% CI 5.7-16.2 micromol/L). This effect was significantly more potent than the effects of zaprinast and papaverine, which also reduced duodenal contractions with EC50 values of 91.6 micromol/L (95% CI 46.0-182.2 micromol/L) and 78.5 micromol/L (95% CI 37.1-166.3 micromol/L), respectively. 5. In preparations treated previously with methylene blue (10 micromol/L) or 1H-[1,2,4]oxadiazolo(4,3-a)quinoxalin-1-one (ODQ; 10 micromol/L), the EC50 values for the sildenafil effect were significantly increased to 39.0 micromol/L (95% CI 23.9-63.4 micromol/L) and 43.8 micromol/L (95% CI 24.5-78.3 micromol/L), respectively. These values were significantly greater than those obtained with sildenafil alone. 6. In conclusion, sildenafil has myorelaxant and antispasmodic effects on rat duodenal segments in vitro. The contractile inhibitory effect of sildenafil on rat isolated duodenum is probably due to intracellular cGMP accumulation as a result of its decreased degradation.