Jose R. Altonaga

Coating titanium implants with bioglass and with hydroxyapatite: A comparative study in sheep

Summary.This study compares the osteointegration of titanium implants coated with bioglass (Biovetro GSB formula) and with hydroxyapatite (HAP). Twenty-four bioglass-coated and 24 HAP-coated cylinders were implanted in the femoral diaphyses of sheep, and examined after 2, 4, 6, 8, 12, and 16 weeks. The HAP coating gave a stronger and earlier fixation to the bone than did bioglass. Bioglass formed a tissue interface which showed a macrophage reaction with little new bone formation activity. In contrast, HAP, showed intense new bone formation, with highly mineralised osseous trabeculae in the neighbourhood of the interface.Résumé.Le but de cette étude expérimentale est de comparer l’ostéointégration d’implants en titane recouverts de bioverre (Biovetro GSD) et ceux recouverts d’hydroxyapatite (HAP). 24 cylindres recouverts de bioverre et 24 recouverts d’hydroxyapatite ont été implantés dans la diaphyse fémoral du mouton, puis examinés à 2, 4, 6, 8, 12 et 16 semaines de l’implantation. Les implants recouverts d’hydroxyapatite montrent une fixation à l’os plus précoce et plus solide que ceux recouverts de bioverre. Le bioverre a étéà l’origine d’un tissu d’interface os-implant avec présence d’une réaction macrophagique avec petite activité de formation d’os nouveau. L’hydroxyapatite en revanche, est à l’origine d’une formation assez intense d’os nouveau avec des trabécules bien minéralisés au voisinage de l’interface os-implant.

Closed-chest experimental porcine model of acute myocardial infarction-reperfusion

INTRODUCTION Progress in cardiovascular regenerative medicine research requires the availability of appropriate experimental animal models that are as close to humans as feasible. Our objective was to assess the validity of a porcine endovascular model of myocardial infarction and reperfusion. METHODS Fifteen domestic pigs (Large White race) were anesthetized and pre-medicated with amiodarone. Endovascular fluoroscopy-guided coronary procedures were performed to occlude the mid-left anterior descending artery using a coronary angioplasty balloon. Occlusion was confirmed by angiography and electrocardiography. After 75 min the balloon catheter system was withdrawn and the presence of reperfusion flow was verified. The animals were sacrificed after 1 and 2 weeks of follow-up, the hearts were explanted, and the extent of myocardial infarction with respect to the left ventricle was quantified. RESULTS Overall survival rate was 67%. Five animals died prematurely: 3 showing signs of heart failure, 1 had reperfusion failure (final TIMI flow grade 1) and 1 succumbed to acute stress. The most common adverse event was ventricular fibrillation (87% of the animals) and defibrillation was effective in all affected animals. The extent of myocardial infarct in the animals followed-up for 1 and 2 weeks was similar (20.4+/-4.3% vs. 20.9+/-2.8%, respectively; p=0.8) but was significantly greater in the animals that died prematurely (29.5+/-3.6%, p=0.02). CONCLUSIONS The endovascular porcine model we have explored constitutes a feasible and reproducible alternative for the evaluation of human myocardial infarction and reperfusion.

Time Course of Reendothelialization of Stents in a Normal Coronary Swine Model Characterization and Quantification

Late thrombosis of coronary drug-eluting stents is an infrequent but serious complication of percutaneous transluminal coronary angioplasty. The best predictor of this event is the lack of endothelialization of stent struts. The objective of this study is to characterize and quantify the time course of endothelialization of different stents implanted in nonatherosclerotic swine coronary arteries. Thirty-three Carbofilm-coated stents were implanted percutaneously in 11 anesthetized domestic, crossbred pigs (weight 25 ± 3 kg, 2 months old). Each animal received 1 stainless steel stent (SS), 1 cobalt-chromium stent (CCS), and 1 tacrolimus-eluting stent (TES) in each coronary artery. Follow-up periods were 1 day (n = 9 stents), 3 days (n = 9 stents), and 7 days (n = 15 stents). Longitudinal sections of the stented vessels were examined using scanning electron microscopy. At 1 day, there was scarce, patchy endothelialization with areas of fibrin; the endothelialization rate was similar for all the stents (SS, 29% ± 23%; CCS, 29% ± 24%; TES, 31% ± 25%; P = .9). At 3 days, there were more endothelial cells but with immature features and giant cells over fibrin; the endothelialization was greater in SS and CCS than in TES (SS, 79% ± 14%; CCS, 81% ± 17%; TES, 46% ± 9%; P = .007). At 7 days, arteries showed better endothelialization with few giant cells; the endothelialization was greater in SS and CCS than in TES (SS, 95% ± 4%; CCS, 98% ± 4%; TES, 79% ± 9%; P = .01). In conclusion, the described model is useful for the analysis of endothelialization of coronary stents and facilitates measurement of its rate of formation and characterization of the involved cell types.

Endothelialization of Nonapposed Stent Struts Located over the Origin of a Side Branch: Results with Different Carbofilm‐Coated Stents

OBJECTIVE To evaluate the degree of endothelialization of the nonapposed struts located at the ostia of side branches. BACKGROUND Endothelialization of coronary stents has got considerable relevance because of the phenomenon of late thrombosis. Bifurcation location and incomplete stent apposition have been linked to this complication. METHODS Domestic pigs (n = 11; weight: 25 +/- 3 kg) were anesthetized and had one stent per coronary artery implanted: one stainless steel (Tecnic), one cobalt-chromium (Chrono), and one tacrolimus-eluting stent (Janus), all of them being Carbofilm-coated (Sorin). One, three, or seven days postprocedure, the pigs were sacrificed, the hearts explanted, and longitudinal sections examined by surface electron microscopy to quantify the percentage of the strut endothelialized over the branches and in the total surface. RESULTS Forty-four side branches (25 stents) that had stent struts over their origin were evaluated. Different patterns of endothelialization were observed, from the total absence to the complete endothelialization. There were no significant differences in relation to type of stent or to the artery treated. The predictors of higher percentage of endothelialization were the ratio of metal to branch diameter (P = 0.04) and better endothelialization in the rest of the stent (P = 0.0002), only this parameter maintaining significant correlation (P = 0.03) in multivariate analysis. CONCLUSIONS Carbofilm-coated stent struts located over the origin of side branches follow the pattern of endothelialization for the rest of the stent, even in the case of tacrolimus-eluting stent.

La reestenosis en el stent depende del daño vascular inducido. ¿Son válidos los modelos experimentales actuales de análisis de los stents farmacoactivos?

INTRODUCTION AND OBJECTIVES Drug-eluting stents are useful for preventing restenosis, but the patho-physiological processes involved in the proliferative response after implantation are still not known in detail. The aim of this study is to compare the coronary vascular histomorphometry after implanting drug-eluting stents and bare metal stents in a swine model. METHODS Sixty stents were randomly implanted in 20 Large White female pigs with a ratio of baremetal/drug-eluting stents of 1:2. After 28 days, euthanasia and histomorphometry were performed. We defined the vessel injury score in accordance to whether the internal elastic lamina was intact or ruptured. RESULTS There were no differences between drug-eluting stents and bare metal stents in the intact internal elastic lamina group regarding neointimal area or % restenosis (1.3 [1.1-2.2]) vs 2.0 [1.3-2.5] mm²; P=.6; and 14.0 [12.1-20.8] vs 22.2 [14.1-23.3] %; P=.5). We assessed statistically significant differences for the ruptured internal elastic lamina group, (neointimal area 1.2 [0.8-2.0] vs 2.9 [2.3-3.7] mm²; P=.001 and % restenosis 16.63 [11.2-23.5] vs 30.4 [26.4-45.7] %; P=.001). CONCLUSIONS In our swine model, we did not find any differences between proliferative response of drug-eluting stents and bare metal stents when the internal elastic lamina is intact; differences are only found when vascular injury is deeper.

Preclinical Evaluation of Coronary Stents: Focus on Safety Issues

In recent years, we have witnessed a revolution in the treatment of coronary artery disease. The development and improvement of drug eluting stents (DES) have lowered the incidence of restenosis to one-digit figures. In the search for a superior efficacy, animal models have played a key role. The classical swine model of coronary stenting remains the preferred model to measure restenosis, although the rabbit iliac artery stenting has become an accepted alternative. After widespread clinical use of DES, an unforeseen complication arose: late stent thrombosis. In a back-to-bench step, some data from animal models helped to explain the phenomenon. A delayed and incomplete vascular healing was detected. Toxic and hypersensitivity reactions to polymers and/or drugs seem to be the underlying causes. So, translational research focused on the safety aspect of these devices: development of better drug carriers as absorbable polymers or fully bioresorbable scaffolds, selection of different drugs and assessment of the re-endothelialization process. We review and evaluate the efficacy and safety of coronary stents in different animal models. Further improvements in this field such as, the selection of better animal models (e.g. hyperlipidemic, diabetic, atherosclerotic) that closely mimic the clinical setting and longer follow-up periods to detect late complications are also discussed.

Correlation between MRI, computed tomographic findings and clinical signs in a case of ovine coenurosis

COENUROSIS, commonly referred to as gid, is a parasitic disease produced by the larval stage of the tapeworm Taenia multiceps (Soulsby 1982). The adults are found in the small intestine of the definitive hosts such as the dog, fox, coyote and jackal. The metacestode, a coenurus, develops in the brain and spinal cord of sheep, other ungulates, cats (Smith and others 1988) and non-human primates (Clark 1969), and has

Surgical induced models of joint degeneration in the ovine stifle: Magnetic resonance imaging and histological assessment

BACKGROUND The purposes of this study were to (1) validate and assess the reliability of a modified magnetic resonance semi-quantitative score (sheep Magnetic Resonance osteoarthritis Knee Score (sMOAKS)) to evaluate joint degeneration in the ovine knee and to (2) investigate whether the transection of the anterior cruciate ligament (ACL), isolated or in combination with meniscal injuries, reproduce the degenerative changes described in the meniscectomized sheep. METHODS Twenty sheep were randomly subjected to one of the following injuries to induce osteoarthritis (OA): ACL transection (ACLt), mid-body transection of the medial meniscus, ACLt combined with complete medial meniscectomy and complete medial meniscectomy. OA assessment was performed eight weeks postoperatively with sMOAKS, Mankin and Osteoarthritis Research Society International (OARSI) histological scores. RESULTS sMOAKS showed very good to excellent reliability (kappa=0.61 to 1.0) for the majority of features evaluated. sMOAKS revealed small differences between groups (p<0.05) being the ACLt group the most affected. We observed a strong positive correlation between the three scales in the evaluation of femoro-tibial articular cartilage (AC) (r=0.829, r=0.917, r=0.879). CONCLUSIONS sMOAKS is a reliable semi-quantitative Magnetic Resonance (MR) scale to evaluate and quantify the effect of different OA induction lesions in the ovine knee and presents a high correlation with Mankin and OARSI scales in the evaluation of femoro-tibial AC. Although minor differences were observed between the different surgical procedures for the induction of OA, ACLt proved to be the intervention that produced the highest amount of degeneration eight weeks postoperatively. LEVEL OF EVIDENCE II.

Anestesia en el modelo animal de investigación cardiovascular

Preclinical cardiovascular research employs of a wide range of animal models, including large and small animals and a variety of species. Selecting a species for use as an animal model is one of the most important decisions that has to be taken before starting a biomedical study. The appropriate choice of anesthesia increases the survival rate and improves animal welfare, both of which increase the ethical acceptability of this kind of research and ensure that the experimental models are used as efficiently as possible. This review discusses the specific characteristics of the different animal models used in cardiovascular research from the point of view of anesthesia and analgesia and, in each case, describes the most appropriate techniques, drugs and dosages.

Safety and Efficacy of New Biodegradable Polymer-based Sirolimus-Eluting Stents in a Preclinical Model

INTRODUCTION AND OBJECTIVES New drug-eluting stents (DES) designed to overcome the limitations of existing devices should initially be tested in preclinical studies. Our objective was to analyze the safety and efficacy of new biodegradable polymer-based DES compared with bare-metal stents (BMS) and commercially available DES in a model of normal porcine coronary arteries. METHODS We randomly implanted 101 stents (BMS and biodegradable polymer-based sirolimus-eluting stents: 3 test stent iterations [BD1, BD2, and BD3], Orsiro, Biomime and Biomatrix) in the coronary arteries of 34 domestic pigs. Angiographic and histomorphometric studies were conducted 1 month (n = 83) and 3 months (n = 18) later. RESULTS The stents were implanted at a stent/artery ratio of 1.31 ± 0.21, with no significant differences between groups. At 1 month, the new test stents (BD1, BD2 and BD3) showed less late loss and angiographic restenosis, as well as lower histologic restenosis and neointimal area (P < .0005), than the BMS. There were no differences in endothelialization, vascular injury, or inflammation between the new test stents and BMS, although the new stents showed higher fibrin deposition (P = .0006). At 3 months, all these differences disappeared, except for a lower neointimal area with the new BD1 stent (P = .027). No differences at any time point were observed between the new test stents and commercially available controls. CONCLUSIONS In this preclinical model, the new biodegradable polymer-based DES studied showed less restenosis than BMS and no significant differences in safety or efficacy vs commercially available DES.