fibrin and Coronary-Stenosis

FFR-rFVIIa is an inactivated recombinant factor VIIa (rFVIIa) that inhibits the binding of factor VIIa to tissue factor (TF). It has been shown to prevent TF-induced thrombosis in animals. The present study is a substudy of the Active Site Inhibited Seven (ASIS) trial and examines the antithrombotic effect of 3 doses of FFR-rFVIIa in 24 patients undergoing percutaneous coronary intervention (PCI). Group 1 (n=9) received 400 microg/kg FFR-rFVIIa and 40 to 50 U/kg heparin, group 2 (n=7) received 200 microg/kg FFR-rFVIIa and 100 U/kg heparin, and group 3 (n=8) received 50 microg/kg FFR-rFVIIa and 100 U/kg heparin. Blood thrombogenicity was assessed as total thrombus area and fibrin deposition on the perfusion chamber at shear rate conditions typical of mild-moderate coronary stenosis. Baseline blood thrombogenicity was evaluated a day before PCI, after heparin administration. A second perfusion chamber study was performed just before PCI, 15 minutes after the administration of heparin and FFR-rFVIIa. Thrombus formation at a high shear rate was markedly reduced in groups 1 and 2 after drug administration, by 79% to 84% and 76% to 87%, respectively (P<0.004 [group 1], P<0.04 [group 2]). In group 3, moderate thrombus reduction of 46% to 48% was achieved (P<0.04). Fibrin deposition in all 3 groups was nearly eliminated after drug administration. Our data demonstrate that FFR-rFVIIa has a potent antithrombotic effect at different shear rates and severe arterial injury conditions.

Topics: Angioplasty, Balloon, Coronary; Animals; Blood Coagulation Tests; Coronary Stenosis; Double-Blind Method; Drug Administration Schedule; Factor VIIa; Female; Fibrin; Fibrinolytic Agents; Humans; Injections, Intravenous; Male; Middle Aged; Perfusion; Platelet Function Tests; Recombinant Fusion Proteins; Swine; Thromboplastin; Thrombosis

The advent of drug-eluting balloon (DEB) therapy has represented an important development in interventional cardiology. Nevertheless, preclinical data with this technology remain scant, and comparative studies have not previously been published. Bare metal stents were implanted in the coronary arteries of 15 pigs followed by balloon angioplasty. Animals were allocated to treatment with a 60-second inflation of one of four different balloon catheters: a conventional untreated plain angioplasty balloon (PBA, Biotronik AG), the Pantera Lux DEB (3.0 μg/mm2 paclitaxel; BTHC excipient, Biotronik AG), the Elutax DEB (2.0 μg/mm2 paclitaxel; no excipient; Aachen Resonance), or the SeQuent Please DEB (3.0 μg/mm2 paclitaxel; iopromide excipient: B. Braun). Twenty-eight days following balloon deployment, animals underwent repeat angiography for quantitative coronary angiography analysis and euthanasia for histopathologic assessment. By histology, the mean neointimal thickness was 0.44 ± 0.19 mm with PBA, 0.35 ± 0.13 mm with Pantera Lux , 0.61 ± 0.20 mm with Elutax , and 0.47 ± 0.21 mm with SeQuent Please DEB (p=0.02). In comparison with PBA, deployment of the Pantera Lux or the SeQuent Please DEB resulted in delayed healing characterised by significant increases in fibrin, neointimal cell vacuity and delayed re-endothelialisation. In conclusion, investigation of comparative DEB performance in a porcine model of advanced coronary restenosis reveals significant heterogeneity of neointimal suppression between the devices tested with numerically lowest values seen in the Pantera Lux group. On the other hand, evidence of delayed healing was observed in the most effective DEB groups.

Topics: Angioplasty, Balloon; Animals; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Disease Models, Animal; Drug-Eluting Stents; Endothelium, Vascular; Fibrin; Humans; Neointima; Paclitaxel; Swine; Wound Healing

Because of its low profile and biologically inert behavior, thin film nitinol (TFN) is ideally suited for use in construction of endovascular devices. We have developed a surface treatment for TFN designed to minimize platelet adhesion by creating a superhydrophilic surface. The hemocompatibility of expanded polytetrafluorethylene (ePTFE), untreated thin film nitinol (UTFN), and a surface treated superhydrophilic thin film nitinol (STFN) was compared using an in vitro circulation model with whole blood under flow conditions simulating a moderate arterial stenosis. Scanning electron microscopy analysis showed increased thrombus on ePTFE as compared to UTFN or STFN. Total blood product deposition was 6.3 ± 0.8 mg/cm(2) for ePTFE, 4.5 ± 2.3 mg/cm(2) for UTFN, and 2.9 ± 0.4 mg/cm(2) for STFN (n = 12, p < 0.01). ELISA assay for fibrin showed 326 ± 42 μg/cm(2) for ePTFE, 45.6 ± 7.4 μg/cm(2) for UTFN, and 194 ± 25 μg/cm(2) for STFN (n = 12, p < 0.01). Platelet deposition measured by fluorescent intensity was 79,000 20,000 AU/mm(2) for ePTFE, 810 ± 190 AU/mm(2) for UTFN, and 1600 ± 25 AU/mm(2) for STFN (n = 10, p < 0.01). Mass spectrometry demonstrated a larger number of proteins on ePTFE as compared to either thin film. UTFN and STFN appear to attract significantly less thrombus than ePTFE. Given TFN's low profile and our previously demonstrated ability to place TFN covered stents in vivo, it is an excellent candidate for use in next-generation endovascular stents grafts.

Topics: Alloys; Blood Platelets; Blood Proteins; Coronary Stenosis; Fibrin; Hemorheology; Humans; Mass Spectrometry; Materials Testing; Microscopy, Electron, Scanning; Microscopy, Fluorescence; Thrombosis

We set out to compare the effectiveness of platelet aggregation therapy in association with the development of in-stent neointimal hyperplasia in porcine coronary arteries.. Thirty-two pigs underwent coronary stenting with bare-metal stents under general anaesthesia. One hundred milligrams of aspirin and loading doses of either 300 mg clopidogrel (group C, n=13) or 2 x 500 mg ticlopidine (group T, n=19) were administered before intervention. During the follow-up, the animals received a daily dose of 100 mg aspirin and 75 mg clopidogrel or 2 x 250 mg ticlopidine, respectively. After 4 weeks, the histopathological and histomorphometric parameters of the explanted stented coronaries were assessed. Levels of circulating cytokines and platelet activation factors were measured. ADP-induced and collagen-induced aggregation was measured immediately before stenting and then every 3rd day. The aggregation profiles were calculated and correlated with the histological parameters.. The fibrin deposition scores and inflammation scores were higher in group T than in group C, with similar injury scores. Endothelialization was complete in both groups. A significantly lower neointimal area (1.08+/-0.36 vs. 1.58+/-0.5, group C vs. T, P=0.026) and percentage of area stenosis (29.8+/-12.1 vs. 44.3+/-16.3, group C vs. T, P=0.032) were observed in group C. The loading dose of clopidogrel significantly reduced the platelet activation parameters before the first angiography as compared with ticlopidone. Clopidogrel treatment resulted in a significantly better aggregation profile relative to ticlopidine (mean ADP-induced aggregation: 28.4+/-9.1 vs. 52.5+/-12.0%, P<0.001). Significant (P<0.05) positive linear correlations were observed between the ADP-induced aggregation profile and the neointimal area (r=0.584), percentage of area stenosis (r=0.666), inflammation (r=0.476) and fibrin deposition (r=0.496).. The effectiveness of dual antiplatelet therapy plays an important role in the inhibition of in-stent neointimal hyperplasia.

Topics: Adenosine Diphosphate; Angioplasty, Balloon, Coronary; Animals; Aspirin; Cell Proliferation; Clopidogrel; Collagen; Coronary Angiography; Coronary Stenosis; Coronary Vessels; Cytokines; Disease Models, Animal; Drug Therapy, Combination; Fibrin; Hyperplasia; Inflammation Mediators; Metals; P-Selectin; Platelet Activating Factor; Platelet Aggregation; Platelet Aggregation Inhibitors; Prosthesis Design; Stents; Swine; Ticlopidine; Time Factors; Tunica Intima

We sought to investigate the benefit, predictors of procedural success, and safety of pre-procedural intra-coronary fibrin-specific lytic infusion (ICL) in patients with failed prior percutaneous coronary intervention (PCI) for chronic total occlusions (CTO).. Percutaneous coronary intervention for CTO remains a challenge with a high incidence of procedural failure secondary to inability to cross the occlusion with the guidewire.. Eighty-five patients who underwent unsuccessful PCI procedures of CTO (more than three months' duration) had a repeat attempt of recanalization with the use of pre-procedural ICL. Patients received a weight-adjusted dose of either alteplase (tPA) (2 to 5 mg/h) or tenecteplase (TNK) (0.5 mg/h) for a total of 8 h. The total dose of ICL therapy was infused split between the guiding catheter and an intracoronary infusion catheter. A step-down multivariate logistic regression analysis was completed to determine the best predictors of procedural success. In-hospital major adverse cardiac events (MACE) including myocardial infarction, acute reocclusion, stroke, and death, as well as bleeding complications, were also examined.. The procedure was successful in 46 of 85 cases (54%). Four of 85 (5%) contained dissections that did not result in perforations, tamponade, or MACE. The incidence of groin complications was 7 of 85 (8%) and of bleeding complications requiring transfusions was 3 of 85 (3.5%). On multivariate analysis, predictors of success were tapering morphology (odds ratio, 15.5; 95% confidence interval, 3.73 to 63; p = 0.0002) and lack of bridging collaterals (odds ratio, 5.08; 95% confidence interval, 1.53 to 17; p = 0.008).. Intracoronary infusion of fibrin-specific thrombolytic therapy may provide a valuable and safe option for facilitating percutaneous revascularization of CTO.

Topics: Angioplasty, Balloon, Coronary; Cardiac Catheterization; Chronic Disease; Coronary Angiography; Coronary Stenosis; Female; Fibrin; Fibrinolytic Agents; Humans; Male; Middle Aged; Preoperative Care; Reoperation; Treatment Failure