Evaluation of Complement Activation on Cardiopulmonary Bypass and in Retransfused Oxygenator and Shed Mediastinal Blood

Several methods of blood salvage are used in cardiac surgery. Our aim was to study, on the basis of complement activation, the quality of autologous blood products reinfused to the patient. Eleven patients with elective myocardial revascularisation were studied for: operative and cardiopulmonary bypass (CPB) data, hematology, blood chemistry and complement activation (C3a [des Arg] and terminal complement complex [TCC] or C5b-9 complex). Centrifugated oxygenator blood (COB) and shed mediastinal blood (SMB) samples were examined before reinfusion into the patient and the effect of this retransfusion on the systemic values. The activation pattern for C3a [des Arg] and TCC was similar. Thus only evaluation of C3a [des Arg] is reported. Anesthesia increased C3a [des Arg] two fold over baseline (85 +/- 64 vs. 161 +/-103 ng/ml [standardised]; ns)

The International Hypothermia Registry (IHR): Dieter's ESAO Winter Schools and Beat's International Hypothermia Registry.

Accidental hypothermia could be listed as an 'orphan disease,' since mild hypothermia is common but has no severe medical consequences, whereas severe hypothermia is rare and life-threatening. In order to increase our knowledge, find new outcome predictors, and propose better guidelines for the treatment of deep accidental hypothermia victims, we created the International Hypothermia Registry (IHR: https://www.hypothermia-registry.org), which will allow us to gather a large number of cases in order to achieve statistical significance and issue evidence-based recommendations

DOES IMPLANTATION SITE OF DRUG-ELUTING POLYMERS MATTER: SUBCUTANEOUS vs. AORTIC?.

Objectives: Drug-eluting degradable polymers represent a new direction in vascular surgery. Subcutaneous implantation in rats of vascular prostheses is a rapid and cost-effective screening model to assess the drug-elution effect and could to some extent be extrapolated to forecast results for vascular implantation. We therefore assessed the biologic and histologic response according to the implantation site. Materials & Methods: Polycaprolactone(PCL), paclitaxel-loaded PCL(PCL-PTX) and dexamethasone-loaded PCL(PCL-DXM) grafts were implanted subcutaneously(n=60) and in an infrarenal abdominal aortic replacement model(n=28) in rats for 1,3 and 12 weeks. At conclusion of the study histological analysis was performed in all groups and models. Results: Cellular graft invasion was analyzed by morphometry in the subcutaneous and aortic group revealing time differences of infiltration between PCL, PCL-PTX and PCL-DXM groups in both models. Cell infiltration was continuously increasing with time in the aortic model compared to the subcutaneous model(41% vs. 28% at 12 weeks). Morphological cell counting revealed major differences in fibroblast, macrophage and giant cell graft colonisation with time. Macrophages and giant cells increased more in the aortic compared to the subcutaneous model after 3 weeks but decreased in the drug-eluting groups. Other major findings were observed only in the aortic replacement such as extracellular matrix deposition and neo-angiogenesis. Conclusions: The subcutaneous polymer implant model can be used for screening, especially when drug-eluting effects are studied. However major histological differences are observed in cell type reaction and depth of cell penetration compared to the aortic replacement model. Thus our results demonstrate that no extrapolations should be made from a subcutaneous screening to a vascular implantation model

DOES IMPLANTATION SITE OF DRUG-ELUTING POLYMERS MATTER: SUBCUTANEOUS vs. AORTIC?

Objectives: Drug-eluting degradable polymers represent a new direction in vascular surgery. Subcutaneous implantation in rats of vascular prostheses is a rapid and cost-effective screening model to assess the drug-elution effect and could to some extent be extrapolated to forecast results for vascular implantation. We therefore assessed the biologic and histologic response according to the implantation site. Materials & Methods: Polycaprolactone(PCL), paclitaxel-loaded PCL(PCL-PTX) and dexamethasone-loaded PCL(PCL-DXM) grafts were implanted subcutaneously(n=60) and in an infrarenal abdominal aortic replacement model(n=28) in rats for 1,3 and 12 weeks. At conclusion of the study histological analysis was performed in all groups and models. Results: Cellular graft invasion was analyzed by morphometry in the subcutaneous and aortic group revealing time differences of infiltration between PCL, PCL-PTX and PCL-DXM groups in both models. Cell infiltration was continuously increasing with time in the aortic model compared to the subcutaneous model(41% vs. 28% at 12 weeks). Morphological cell counting revealed major differences in fibroblast, macrophage and giant cell graft colonisation with time. Macrophages and giant cells increased more in the aortic compared to the subcutaneous model after 3 weeks but decreased in the drug-eluting groups. Other major findings were observed only in the aortic replacement such as extracellular matrix deposition and neo-angiogenesis. Conclusions: The subcutaneous polymer implant model can be used for screening, especially when drug-eluting effects are studied. However major histological differences are observed in cell type reaction and depth of cell penetration compared to the aortic replacement model. Thus our results demonstrate that no extrapolations should be made from a subcutaneous screening to a vascular implantation model

Mucin Covalently Bonded to Microfibers Improves the Patency of Vascular Grafts

Due to high incidence of vascular bypass procedures, an unmet need for suitable vessel replacements exists, especially for small-diameter (<6 mm) vascular grafts. Here, we developed a novel, bilayered, synthetic vascular graft of 1-mm diameter that consisted of a microfibrous luminal layer and a nanofibrous outer layer, which was tailored to possess the same mechanical property as native arteries. We then chemically modified the scaffold with mucin, a glycoprotein lubricant on the surface of epithelial tissues, by either passive adsorption or covalent bonding using the di-amino-poly(ethylene glycol) linker to microfibers. Under static and physiological flow conditions, conjugated mucin was more stable than adsorbed mucin on the surfaces. Mucin could slightly inhibit blood clotting, and mucin coating suppressed platelet adhesion on microfibrous scaffolds. In the rat common carotid artery anastomosis model, grafts with conjugated mucin, but not adsorbed mucin, exhibited excellent patency and higher cell infiltration into the graft walls. Mucin, which can be easily obtained from autologous sources, offers a novel method for improving the hemocompatibility and surface lubrication of vascular grafts and many other implants

Paclitaxel-eluting biodegradable synthetic vascular prostheses: a step towards reduction of neointima formation?

BACKGROUND: Clinical small-caliber vascular prostheses are unsatisfactory. Reasons for failure are early thrombosis and late intimal hyperplasia. We thus prepared biodegradable small-caliber vascular prostheses using electrospun polycaprolactone (PCL) with slow-releasing paclitaxel (PTX), an antiproliferative drug. METHODS AND RESULTS: PCL solutions containing PTX were used to prepare nonwoven nanofibre-based 2-mm ID prostheses. Mechanical morphological properties and drug loading, distribution, and release were studied in vitro. Infrarenal abdominal aortic replacement was carried out with nondrug-loaded and drug-loaded prostheses in 18 rats and followed for 6 months. Patency, stenosis, tissue reaction, and drug effect on endothelialization, vascular remodeling, and neointima formation were studied in vivo. In vitro prostheses showed controlled morphology mimicking extracellular matrix with mechanical properties similar to those of native vessels. PTX-loaded grafts with suitable mechanical properties and controlled drug-release were obtained by factorial design. In vivo, both groups showed 100% patency, no stenosis, and no aneurysmal dilatation. Endothelial coverage and cell ingrowth were significantly reduced at 3 weeks and delayed at 12 and 24 weeks in PTX grafts, but as envisioned, neointima formation was significantly reduced in these grafts at 12 weeks and delayed at 6 months. CONCLUSIONS: Biodegradable, electrospun, nanofibre, polycaprolactone prostheses are promising because in vitro they maintain their mechanical properties (regardless of PTX loading), and in vivo show good patency, reendothelialize, and remodel with autologous cells. PTX loading delays endothelialization and cellular ingrowth. Conversely, it reduces neointima formation until the end point of our study and thus may be an interesting option for small caliber vascular grafts