Michel Bonneau

Familial hypercholesterolaemic downsized pig with human-like coronary atherosclerosis: a model for preclinical studies.

Aims: A manageable and reproducible large animal model of human-like coronary atherosclerosis is l acking but highly needed for translational research in percutaneous coronary interventions and imaging. Farm pigs with familial hypercholesterolaemia develop advanced atherosclerosis in two to three years but then weigh >200 kg making them impractical and costly. We aimed at down-sizing this pig and accelerating coronary plaque development to make the model more useful and affordable. Methods and results: Familial hypercholesterolaemic farm pigs were downsized by crossing them with smaller pigs while preserving their hypercholesterolaemic trait ascribed to a mutation in the low density lipoprotein receptor. We accelerated coronary plaque development by atherogenic diet feeding whereby plasma total cholesterol rose to >20 mmol/l (>800 mg/dl). We further accelerated coronary plaque development site-specifically by inflicting coronary artery balloon injury. Both spontaneously developed and balloon accelerated coronary plaques mirrored pertinent human plaque features, including a large necrotic core covered by a thin and inflamed fibrous cap as seen in the most common type of thrombosis-prone (vulnerable) plaque in humans. Associated vulnerable plaque features included neovascularisation, intraplaque haemorrhage, and expansive remodelling. Conclusions: This human-like porcine model of coronary atherosclerosis is practical and highly relevant for translational research in percutaneous coronary interventions and imaging.

Dual time-of-flight photoelectron-photoion spectrometry on a magnetic bottle-molecular beam apparatus

Abstract A supersonic molecular beam experiment uncluding a standard “magnetic bottle” TOF photoelectron spectrometer and a TOF ion mass spectrometer has been constructed with the goal of performimg MPI studies of cooled molecules and clusters. The supersonic beam characteristics have been tested by using several pure or mixed rare-gas expansions. A rotational temperature of about 0.5 K was measured from the rotational contours of the S 1 ←S 0 transition of aniline, demonstrating the qualities of the molecular beam in the interaction region. The capability of the apparatus to form van der Waals clusters and to mass analyze them was checked by performing (1+1) REMPI on fluorostyrene—(Ar) n and aniline—(Ar) n clusters formed in a helium/argon mixture expansion. The sensitivity of the photoelectron detection was measured by recording the photoelectron spectrum of a pure xenon expansion via a (3+2) photon ionization process.

Kinetics of endothelialization of the multilayer flow modulator and single-layer arterial stents.

The multilayer flow modulator (MFM; Cardiatis, Isnes, Belgium) is a self-expandable mesh of braided cobalt alloy wires, used for treatment of aortic and peripheral aneurysms. To further improve our understanding of this novel technology, the endothelialization kinetics of the MFM was investigated and compared with those of two marketed single-layer stents. Five porcine animal models were used in which a total of 19 stents were implanted in the iliac and carotid arteries between one and five weeks before sacrifice. All 19 stents were successfully delivered. For all devices, nonsignificant signs of inflammation or thrombosis were noted, and there was no evidence of local intolerance. The MFM developed a thin layer of endothelial cells earlier and was associated with less neointimal development than the two single-layer stents. A differing phenomenon of integration was also revealed and hypothesized as endothelialization from adhesion of circulating endothelial progenitor cells, as well as adhesion from the arterial wall, and also by the differences in trauma exposed to the arterial wall.

Assessment of Biocompatibility of the Multilayer Flow Modulator withDiffering Thread Designs

Background: The Multilayer Flow Modulator (MFM) (Cardiatis, Isnes, Belgium) is a self-expandable mesh of cobalt alloy wires used for the treatment of aortic aneurysms. The impact of design thread count and duration of implantation on the biocompatibility of the MFM in porcine animal models was assessed in this study. nMethods: Eight mini-piglets received 26 MFM devices (12 with 56 threads, 14 with 80-96 threads) in the iliac, carotid, and renal arteries. Animals were sacrificed and specimens explanted at 1, 3, and 6 months, at which time histological and ultrastructural analyses were carried out. nResults: The MFM was successfully deployed in 25 of the 26 implanted cases. The 56 thread devices were well tolerated locally and yielded fewer signs of inflammation and neo intimal hyperplasia. Percentage stenosis was 16.9% ± 5.1% for the 56 thread devices versus 33.4% ± 10.2% for the 80-96 thread devices (p=0.001) at 3 months, and 21.7% ± 9.9% for the 56 thread devices versus 33.6% ± 12.4% for the 80-96 thread devices (p=0.004) at 6 months. The 5 devices selected for SEM examination were well deployed, integrated into the vessel wall and endothelialized, and had patent side branches. nConclusions: No significant stenosis formation or inflammatory response was recorded in any of the implanted animals. The 80-96 thread devices elicited a greater intra-arterial response than the 56 thread devices, although the values for both groups remained within the normal range for stented carotid, renal, or iliac arteries. Further preclinical and clinical studies will extend assessment of the long-term safety and effectiveness of the MFM

Initiation d'un bassin transporté: l'exemple du ≪ sillon méso-hellénique ≫ au Tertiaire (Grèce)*

Abstract The Mesohellenic trough (MHT), northern Greece, is a Tertiary molassic piggy-back basin that formed in several stages. This evolution is related to the underthrusting of the external Hellenides below the internal Hellenides. Sedimentologic and tectonic studies of its western border allow us to reconstruct the first stages of the basin differentiation and to propose a new interpretation of the mechanisms at the origin of the MHT. The MHT is made of several overlapping individual basins that evolved successively through time, from west to east, starting in the Upper Eocene. These basins develop along the border of dissymetrical faulted flexures, which are controlled by the characteristics of the major tectonic units.

Study of human von Willebrand factor immunogenicity in pigs with severe von Willebrand disease.

Replacement therapy is the treatment of choice for patients with von Willebrand disease who are unresponsive to desmopressin. In order to prevent transmission of non-enveloped viruses, a solvent/detergent-treated plasma-derived von Willebrand factor available in France since 1989 has been subjected to additional removal/inactivation steps by 35 nm filtration and dry heating for 72 h at 80°C. This preclinical study evaluates the potential immunogenicity of this new product by comparing the antibodies raised in pigs affected with von Willebrand disease after intravenous injection of either a solvent/detergent-treated product or a triple-secured product. Our data showed that there is no difference between the two products in terms of the rate and intensity of the humoral response measured by both binding and neutralizing antibody levels. It was concluded that no antigenic alterations of von Willebrand factor molecules during the nanofiltration and final dry-heating steps were detected in our animal model.

Intrapulmonary artery balloon pulsation improves circulatory function after acute myocardial infarction in pigs

ABSTRACT Aim: To examine whether pulmonary artery balloon pulsation (PABP) could improve circulatory function in acute myocardial infarction (AMI) in pigs. Methods/results: Ten downsize pigs were sedated and ventilated. AMI was induced by inserting a plug into the left anterior descending artery. A pulsation balloon was placed in the pulmonary artery in all animals. In the treatment group (TG), pulsations began when life-threatening arrhythmia or > 30% drop in mean blood pressure (MBP) or > 40% decrease in cardiac output compared to baseline occurred. Pulsation rate was 120/min, independent of the heartbeat, maintained for 10 min. The control group (CG) received no pulsation. In the TG (n = 5), mean BP after the AMI improved by 7 ± 12 mmHg after 150 min while in the CG, MBP decreased by 17 ± 25 mmHg, P < 0.05; coronary perfusion pressure improved by 8 ± 7 mmHg in the TG but decreased by 15 ± 12 in the CG (P < 0.05). In the CG, cardiac output did not change but in the TG it improved from 3.5 ± 0.9 after the AMI to 4.2 ± 1.1 l/min 150 min after AMI (P < 0.05). The TG required 1.8 ± 0.4 electric shocks for ventricular fibrillation versus 0.8 ± 0.4 in the pulsation group (P < 0.05). Conclusion: PABP could be useful in the management of AMI due to improved mean arterial BP, coronary perfusion pressure, cardiac output and electrical stability. The mechanism of this effect remains to be determined.