fibrin and Hyperlipoproteinemia-Type-II

This study sought to compare the effect of paclitaxel-coated balloon (PCB) concentration on tissue levels and vascular healing using 3 different PCB technologies (In.Pact Pacific = 3 μg/mm(2), Lutonix = 2 μg/mm(2) and Ranger = 2 μg/mm(2)) in the experimental setting.. The optimal therapeutic dose for PCB use has not been determined yet.. Paclitaxel tissue levels were measured up to 60 days following PCB inflation (Ranger and In.Pact Pacific) in the superficial femoral artery of healthy swine (18 swine, 36 vessels). The familial hypercholesterolemic swine model of superficial femoral artery in-stent restenosis (6 swine, 24 vessels) was used in the efficacy study. Two weeks following bare-metal stent implantation, each in-stent restenosis site was randomly treated with a PCB or an uncoated control balloon (Sterling). Quantitative vascular analysis and histology evaluation was performed 28 days following PCB treatment.. All PCB technologies displayed comparable paclitaxel tissue levels 4 h following balloon inflation. At 28 days, all PCB had achieved therapeutic tissue levels; however, the In.Pact PCB resulted in higher tissue concentrations than did the other PCB groups at all time points. Neointimal inhibition by histology was decreased in all PCB groups compared with the control group, with a greater decrease in the In.Pact group. However, the neointima was more mature and contained less peri-strut fibrin deposits in both 2-μg/mm(2) PCB groups.. Compared with the clinically established PCB dose, lower-dose PCB technologies achieve lower long-term tissue levels but comparable degrees of neointimal inhibition and fewer fibrin deposits. The impact of these findings in restenosis reduction and clinical outcomes needs to be further investigated.

Topics: Animals; Cardiovascular Agents; Coated Materials, Biocompatible; Constriction, Pathologic; Disease Models, Animal; Endovascular Procedures; Femoral Artery; Fibrin; Hyperlipoproteinemia Type II; Metals; Neointima; Paclitaxel; Peripheral Arterial Disease; Radiography; Stents; Swine; Tissue Distribution; Vascular Access Devices; Wound Healing

Peri-strut low-intensity area (PLI) is a common imaging finding during the evaluation of in-stent neointima using optical coherence tomography (OCT). We aimed to determine the biological significance of PLI by comparing in-vivo OCT images with the corresponding histological sections obtained from the familial hypercholesterolemic swine model of coronary stenosis.. A total of 26 coronary vessels of nine familial hypercholesterolemic swine were injured with 30% balloon overstretch and then immediately followed by everolimus eluting or bare metal stent placement at 20% overstretch. At 30 days, all stented vessels were subjected to in-vivo OCT analysis and were harvested for histological evaluation. For OCT analysis, stent cross-sections (three per stent) were categorized into presence (PLI+) or absence (PLI-) of PLI. In histology, inflammation and fibrin deposition were scored semiquantitatively from 0 (none) to 3 (severe).. PLI was found in 64.9% of stent sections. Peri-strut inflammation was more frequently observed in OCT sections PLI (+) compared with PLI (-) (56.0 vs. 7.4%, P=0.01). In contrast, peri-strut fibrin deposits was similar in both groups (PLI+=58.0% vs. PLI-=59.3%, P=0.94). Histological neointimal thickness was significantly higher in PLI (+) sections (mean±SE: 0.68±0.06 vs. 0.34±0.02 mm; P<0.01), yielding a higher percent area stenosis compared with PLI (-) (mean±SE: 59.0±4.4 vs. 34.1±2.2%, P<0.01). The PLI diagnostic sensitivity and specificity for inflammation were 80 and 76.1%, respectively (>56% PLI, area under the curve=0.86, P<0.01), whereas for fibrin deposition, the sensitivity and specificity were 42.2 and 76.1%, respectively (area under the curve=0.56, P=NS). Area under the receiver operating characteristic curve was significantly higher for identifying inflammation than fibrin (0.86 vs. 0.56, P<0.01). The severity of PLI correlated with the neointimal thickness when assessed by OCT (R=0.79, P<0.001).. The presence of PLI in OCT correlates with neointimal thickness and appears to have a diagnostic value in the recognition of peri-strut inflammation, therefore possibly serving as a surrogate for in-vivo assessment of stent efficacy.

Topics: Animals; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Disease Models, Animal; Drug-Eluting Stents; Fibrin; Graft Occlusion, Vascular; Hyperlipoproteinemia Type II; Hyperplasia; Inflammation; Male; Neointima; Stents; Swine; Tomography, Optical Coherence

We investigated the effects of high plasma lipid levels on platelet adhesion and platelet thrombus formation in nonanticoagulated human blood on collagen fibrils at an arterial wall shear rate of 2600 seconds-1. Nonanticoagulated blood was drawn directly at a flow rate of 10 mL/min for 3 minutes from an antecubital vein of patients with type IIa (n = 5) and type IIb (n = 4) hyperlipoproteinemia over purified human type III collagen fibrils that were positioned on a plastic coverslip in a parallel-plate perfusion chamber. Results were compared with those obtained in healthy individuals with normal lipid plasma levels (n = 9). Blood-collagen interactions were quantified by morphometry as platelet-collagen adhesion, thrombus volume, and fibrin deposition. Platelet-collagen adhesion in the two groups of patients was significantly higher than in healthy individuals (70.7 [61.2 to 82.0] and 70.3 [66.4 to 81.0] in types IIa and IIb patients, respectively, versus 51.2 [44.5 to 68.6] in control subjects; P < .05. All values are percent median [range]). In contrast, the thrombus volume was similar in the three groups (11.3 [8.0 to 13.0], 9.6 [6.4 to 15.3], and 10.2 [6.8 to 16.1] microns3/microns2 [range], respectively). Differences in fibrin deposition were not observed. Thus, it appears that platelet-collagen adhesion is augmented in patients with type IIa and IIb hyperlipoproteinemia, indicating that the process of thrombogenesis is hastened in these patients.

Topics: Adult; Aged; Blood Coagulation; Cholesterol; Cholesterol, LDL; Cholesterol, VLDL; Collagen; Female; Fibrin; Humans; Hyperlipoproteinemia Type II; Male; Middle Aged; Platelet Adhesiveness; Triglycerides

The aim of the study was to evaluate the direct influence of lipid parameters (total and HDL-cholesterol, triglycerides and total lipids) on the rheologic-coagulative pattern. We studied blood rheological properties--blood (BV), plasmatic (PV), and seric (SV) viscosity, whole blood (WBF) and red cell (RCF) filterability--and some coagulative factors--fibrinogen (Fib), levels of clotting factor VII (fVIIc) and VIII (fVIIIc) activity--in 156 men aged 40-54 years; 87 patients had type II hyperlipoproteinemia (46 type IIa and 41 type IIb) and 69 were normolipemic controls. Smokers, patients with arterial hypertension, diabetes mellitus or cardiovascular clinical manifestations were excluded. Type IIb hyperlipoproteinemic patients had increased blood viscosity (shear rate 225 sec-1, p. less than 0.01), which was positively correlated with triglycerides and fibrinogen concentration. Levels of fibrinogen, fVIIc and fVIIIc activity did not differ significantly in hyperlipemic patients and controls, although fVIIc activity and fibrinogen were both positively related with lipid parameters. These data suggest that, in absence of other major risk factors, the alterations of the rheologic-coagulative pattern are mainly dependent on the severity of the lipid disorder.

Topics: Adult; Blood Coagulation; Blood Viscosity; Factor VII; Factor VIII; Fibrin; Humans; Hyperlipoproteinemia Type II; Lipids; Lipoproteins; Male; Middle Aged