[Show abstract][Hide abstract] ABSTRACT: To test the local delivery of sirolimus nanoparticles following percutaneous transluminal coronary angioplasty (PTCA) to treat in-stent restenosis (ISR) in a swine model.
Coronary bare-metal stent (BMS) implantation reduces major adverse cardiac events when compared with PTCA; however, ISR rates remain high.
Eighteen swine underwent BMS deployment guided by intravascular ultrasound (IVUS). Of these, 16 developed ISR (1 stent/swine) and underwent angioplasty with a noncompliant balloon (PTCA-NC). The animals were then randomized into four groups for local infusion of sirolimus nanoparticles through a porous balloon catheter, as follows: (1) PTCA-NC alone (control); (2) PTCA-NC + (polylactic acid)-based nanoparticle formulation (anionic 1); (3) PTCA-NC + (polylactic-co-glycolic acid)-based nanoparticle formulation (anionic 2); and (4) PTCA-NC + Eudragit RS nanoparticle formulation (cationic). Coronary angiography and IVUS follow-up were performed 28 days after ISR treatment.
There was one episode of acute coronary occlusion with the cationic formulation. Late area loss was similar in all groups at 28 days according to IVUS. However, luminal volume loss (control = 20.7%, anionic 1 = 4.0%, anionic 2 = 6.7%, cationic = 9.6%; P = 0.01) and neointimal volume gain (control = 68.7%, anionic 1 = 17.4%, anionic 2 = 29.5%, cationic = 31.2%; P = 0.019) were significantly reduced in all treatment groups, especially in anionic 1.
PTCA-NC followed by local infusion of sirolimus nanoparticles was safe and efficacious to reduce neointima in this model, and this strategy may be a promising treatment for BMS ISR. Further studies are required to validate this method in humans.
Full-text · Article · Feb 2013 · Catheterization and Cardiovascular Interventions
[Show abstract][Hide abstract] ABSTRACT: Statins have anti-inflammatory and antiproliferative properties irrespective of their cholesterol-lowering effects. The aim of the present study was to evaluate a simvastatin-eluting stent (SimvES) in the treatment of de novo coronary lesions.
Forty-two patients with de novo coronary artery lesions were assigned to SimvES, bare-metal stent (BMS) or everolimus-eluting stent (EES) implantation followed by intravascular ultrasound (IVUS) for neointimal quantitative analysis. Six months later, quantitative coronary angiography (QCA) and IVUS were repeated. QCA showed no binary restenosis, a mean in-stent late loss of 1.05 ± 0.25 mm (BMS, 1.12 ± 0.48 mm; EES, 0.20 ± 0.16 mm) and a diameter stenosis of 33.5 ± 7.1% (BMS, 35.5 ± 15.30%; EES, 7.2 ± 3.12%). Control IVUS showed a mean in-stent obstruction of 18.3 ± 9.4% (BMS, 32.8 ± 19.1%; EES, 9.8 ± 2.4%) and a neointimal volume index of 1.58 ± 0.75 mm(3)/mm (BMS, 2.93 ± 1.76 mm(3)/mm; EES, 0.80 ± 0.16 mm(3)/mm). Thrombus, late incomplete apposition and major adverse cardiac events were not observed.
In this sample of patients with de novo coronary lesions, the use of a SimvES was not related to major adverse cardiac events, but it was associated with a higher level of neointimal proliferation than expected.
Full-text · Article · Feb 2012 · Circulation Journal
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: There are several experimental animal models, but, the swine model is the most similar to human anatomic and physiologic characteristics. Therefore, this study was carried out to develop and implement an experimental protocol of vascular neointimal hyperplasia induction in swine, aiming at creating vascular injury techniques simulating restenosis. METHOD: From August 2006 to March 2009, 69 young Large White swine underwent coronary angiography followed by vascular injury and implantation of 102 oversized stents guided by intravascular ultrasound. After 28 days a new coronary angiography and intravascular ultrasound was performed. RESULTS: The minimal luminal diameter and the minimal luminal area immediately after the stent deployment in the group treated with an oversized stent were significantly higher when compared to the control group (3.5 ± 0.3 mm vs. 3 ± 0.2 mm, P < 0.0001 and 40.7 ± 0.3 mm2 vs. 30.2 ± 0.2 mm2, P < 0.0001). The binary restenosis rate in the group treated with an oversized stent was 92% (69/75 stents), whereas it was 12% (3/25 stents) in the control group, with a statistically significant difference (P < 0.0001). The neointimal hyperplasia volume was significantly higher in the group treated with an oversized stent in comparison to the control group (5.9 ± 0.8 mm3/stent mm vs. 1.8 ± 0.7 mm3/stent mm, P < 0.0001). CONCLUSION: The proposed experimental model of neointimal proliferation induction in swine is effective in inducing instent hyperplasia, and therefore it may be used for the study of the pathophysiologic mechanisms of in-stent restenosis as well as for therapeutic purposes, such as the evaluations of new drugs, new devices and new drug-eluting stents for the prevention and treatment of in-stent restenosis.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Reuse of dental and medical devices is a worldwide common practice, and our country is not an exception; its aim is to reduce procedural costs. PTCA insufflation devices (or manometers) are frequently re-sterilized for clinical reuse purposes. Evaluations of their physical and mechanical properties are not described in current literature. OBJECTIVE: Determine if the physical and functional characteristics of insufflation devices are maintained after reuse processing, as well as establish their life span. Methods: This was a prospective longitudinal study, carried out at university hospital in Porto Alegre, RS, Brazil. From November 2007 to March 2008, all new insufflation devices were included and separated in two different groups: Group A devices were evaluated immediately after their first use and Group B devices were evaluated after subsequent uses. RESULTS: Of the 36 devices, 11 (30.6%) were discarded after the first use due to severe mechanical or functional problems. Of the remaining devices, only 8 (32%) in Group A and 6 (24%) in Group B kept totally preserved functionality. These devices presented significant changes, even though they were mild, in measurements after 12 atm. Mean reuse rate was 1.7 ± 1.2 times. CONCLUSIONS: Results showed that about 30% of PTCA insufflation devices were not in working conditions after the first use. Only a quarter of the remaining devices maintained intact functional characteristics to the end of their life span.
[Show abstract][Hide abstract] ABSTRACT: Vulnerable Atherosclerotic Coronary Plaque: Current Status Coronary artery disease (CAD) progression includes chronic and stable coronary syndromes (stable angina), acute coronary syndromes (unstable angina or acute myocardial infarction) and even sudden death from cardiovascular nature. The more obvious characteristics that help us distinguish patients with acute coronary syndromes from those with stable CAD are: 1) complex coronary stenosis; 2) fissured coronary plaques; 3) recent thrombosis; and 4) plaque inflammation. The shift from an asymptomatic, stable lesion to a fissured, unstable plaque involves many complex mechanisms. The purpose of the authors is to carry out a critical review of the vulnerable atherosclerotic coronary plaque mechanisms, as well as development and rupture physiopathological mechanisms. The concept of vulnerable patient will also be reviewed, with comments on diagnostics tools (widely accepted or experimental) and perspectives for treatment options. DESCRIPTORS: Arteriosclerosis, pathology. Arterial occlusive diseases. Coronary disease. Myocardial ischemia.