2-(amino)oleic-acid and Aortic-Diseases

Bifunctional amines were previously found to act as bridging molecules between the terminal ends of incomplete glutaraldehyde (GA) cross-links. The additional cross-links thus formed between -NH2 groups of tissue were seen to significantly inhibit bioprosthetic calcification. In the current study, the potential ability of alpha-amino oleic acid (AOA) to act as a bridging molecule between -NH2- and COOH-dependent cross-links was hypothesized to similarly augment the anticalcification effect of the AOA molecule.. Porcine aortic wall tissue from Medtronic Freestyle valve bioprostheses incorporating the AOA anticalcification process additionally underwent carboxyl-group cross-linking with Jeffamine (poly[propylene glyco]-bis-[aminopropyl ether]) using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC). Tissue was subdermally implanted into 5-week-old Long-Evans rats for 60 days. Standard 0.2% GA-fixed tissue served as a control. To further assess the impact of storage solution on AOA tissue, samples were either stored in GA (0.2%GA) or EDC (25 mmol/L carbodiimide) before implantation. Tissue calcification was assessed by atomic absorption spectroscopy and histochemical staining.. Aldehyde end-capping with AOA achieved only a modest reduction of calcification in GA-treated aortic wall tissue (-20.0%; p < 0.05). Replacing GA with EDC as a storage solution led to a further 32.4% (p < 0.01) mitigation of calcification in Freestyle tissue. Incorporating an intermediate EDC/Jeffamine cross-linking step achieved a distinct additional reduction of calcification by 40.4% (p < 0.05). Overall, aortic wall calcification was 59.7% (p < 0.0001) lower if commercial Freestyle tissue underwent an additional EDC/Jeffamine cross-linking step and subsequent storage in EDC. Relative to control GA-fixed tissue, this represented a 67.8% (p < 0.0001) reduction. Incorporation of AOA was essential for the beneficial effect of the additional EDC/Jeffamine cross-linking step.. Potentially utilizing both the amino- and the carboxyl moieties of AOA for tissue binding dramatically reduces aortic wall calcification of GA-fixed tissue.

Topics: Animals; Aorta, Thoracic; Aortic Diseases; Bioprosthesis; Calcinosis; Drug Synergism; Ethyldimethylaminopropyl Carbodiimide; Fixatives; Glutaral; Male; Oleic Acids; Rats; Rats, Long-Evans

New anticalcification treatments for stentless bioprostheses have not yet been compared independently.. The No-reacts (Biocor), AOA (Medtronic Freestyle), and BiLinx (SJM Toronto SPV II) methods were studied and compared with a control group. Aortic valve leaflet and aortic root tissue was subcutaneously implanted in 60 male, 21-days-old Sprague-Dawley rats. Calcium content was quantified using inductively coupled plasma spectrophotometry.. No infections occurred. Low levels of calcium were measured in aortic valve leaflet tissue for all methods (0.4 to 1.5 mg/g dry weight) in comparison to the control group (225 mg/g), p < 0.01. Calcification of aortic root tissue was low in the Bilinx group (2.4 mg/g, p < 0.01), whereas calcium levels were high in all other groups (104 to 127 mg/g).. Calcification of aortic valve leaflets was significantly reduced by all new anticalcification treatments, whereas aortic root calcification was only reduced by inhibition of cellular calcification (BiLinx). Maximum anticalcification properties of both leaflet and aortic root are important, as these are considered a functional unit in stentless bioprostheses.

Topics: Aluminum Chloride; Aluminum Compounds; Animals; Aorta, Thoracic; Aortic Diseases; Aortic Valve; Astringents; Bioprosthesis; Calcinosis; Calcium; Chlorides; Coated Materials, Biocompatible; Disease Models, Animal; Drug Combinations; Ethanol; Fixatives; Follow-Up Studies; Glutaral; Heart Valve Diseases; Heart Valve Prosthesis; Male; Oleic Acids; Prosthesis Design; Rats; Rats, Sprague-Dawley; Solvents; Stainless Steel; Surface-Active Agents