2-(amino)oleic-acid and Disease-Models--Animal

Durability remains the main problem of all bioprosthetic valves, and calcification is the major cause of failure. New tissue treatment processes are expected to reduce mineralization. A comparative animal study was undertaken to evaluate the behavior of a new-generation porcine bioprosthesis in contrast with a first-generation porcine bioprosthesis. The primary goal was to evaluate the efficacy of alpha-amino-oleic acid as an anticalcification treatment.. Seventeen Targhee sheep (aged 4.5-7 months) had a mitral valve replacement with a Mosaic or Hancock Standard. The animals were followed up to 20 weeks (144.1 +/- 4.0 days vs 144.3 +/- 8.2 days) and then euthanized as scheduled. After gross examination, the explants were radiographed for the presence of calcification. The central portions were preserved for histologic examination, and the remainder of the sample was analyzed for quantitative calcium content by atomic absorption spectroscopy.. Four Mosaic sheep were excluded because of perioperative surgical mortality. The remaining 13 were enrolled in the study (9 Mosaic and 4 Hancock Standard). The mean calcium content was 1.97 +/- 2.21 microg/mg tissue weight for Mosaic versus 8.36 +/- 4.12 microg/mg for Hancock Standard valves (P < .01). Mild fibrous tissue overgrowth and fibrinous lining were observed regardless the xenograft type.. The low level of calcification in the Mosaic versus Hancock Standard xenografts confirms the efficacy of alpha-amino-oleic acid treatment in mitigating mineralization. A longer durability is expected with the clinical use of the Mosaic porcine valve.

Topics: Animals; Bioprosthesis; Calcinosis; Cardiovascular Agents; Disease Models, Animal; Heart Valve Diseases; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Mitral Valve; Models, Cardiovascular; Oleic Acid; Oleic Acids; Sheep

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

New anticalcificant treatments have been developed because tissue calcification is a major contributing factor for bioprosthetic valve failure.. Aortic valve leaflet and aortic root tissue samples from stentless bioprostheses treated with No-React (Biocor, Belo Horizonte, Brazil), AOA (Medtronic freestyle, Minneapolis, MN), and BiLinx (St. Jude Medical, St. Paul, MN) were compared to a control group by subcutaneous implantation in 60 male weanling Sprague-Dawley rats.. Calcium levels were in the range of 0.3 to 2.2 mg/g dry tissue at 3 and 12 weeks in all three treated aortic valve leaflet implants. The BiLinx treatment proved anticalcificant effectiveness on aortic root samples as well. There were statistically significant differences for valve leaflet tissue samples: No-React = AOA < BiLinx < < Control and for aortic root tissue samples: BiLinx < < AOA < Control = No-React.. Calcification of aortic valve leaflets was significantly reduced by all new anticalcificant treatments. Inhibition of cellular calcification (BiLinx) resulted in additional reduction of aortic root calcification. Maximum anticalcificant properties upon both leaflet and aortic root is important as these are considered a functional unit in stentless bioprostheses.

Topics: Aluminum; Animals; Aortic Valve; Bioprosthesis; Calcinosis; Calcium; Disease Models, Animal; Durapatite; Ethanol; Fixatives; Glutaral; Heart Valve Prosthesis; Male; Oleic Acids; Prosthesis Design; Prosthesis Failure; Rats; Rats, Sprague-Dawley; Spectrophotometry; Surface-Active Agents

Postimplant calcific degeneration is a frequent cause of clinical failure of glutaraldehyde crosslinked porcine aortic valve bioprostheses. We demonstrated previously in rat subdermal and circulatory implants that alpha-amino oleic acid used as a bioprosthesis pretreatment was highly effective in mitigating aortic valve cusp but not aortic wall calcification. In this study we investigated the feasibility of synergistically applying two proven anticalcification agents (alpha-amino oleic acid and FeCl3) as pretreatments for mitigating both bioprosthetic cusp and aortic wall calcification. alpha-Amino oleic acid is hypothesized to prevent calcification by disrupting calcium phosphate formation kinetics, whereas suppression of alkaline phosphatase activity and ferric-phosphate complexation at a cellular membrane initiation sites may be important factors in ferric ion's inhibition of calcification. In vivo implant studies (21-day rat subdermal model) indicated that individually FeCl3 (0.01 or 0.1 M for 24 h) or alpha-amino oleic acid (saturated solution) treatments were equally effective in mitigating cuspal calcification (tissue calcium levels: 30.2 +/- 10.2, 29.8 +/- 2.7, and 31.6 +/- 7.8 micrograms/mg tissue, respectively). However, sequential application of first alpha-amino oleic acid and then FeCl3 synergistically reduced aortic wall calcification more effectively than either of the agents alone. The benefit of a synergistic application of two anticalcification treatments, alpha-amino oleic acid and FeCl3, was demonstrated. However, the synergistic effect was observed on aortic wall only at a higher FeCl3 concentration. (i.e., 0.1 M).

Topics: Animals; Aorta; Calcinosis; Chlorides; Disease Models, Animal; Equipment Failure; Ferric Compounds; Heart Valve Prosthesis; Oleic Acids; Rats; Swine

Alpha-aminooleic acid (AOA), a potent, non-toxic and biocompatible anticalcification agent, has been shown to be effective for glutaraldehyde-fixed valves in rat and juvenile sheep models, and is used for the treatment of Medtronic heart valve bioprostheses currently in clinical trials. In the pre-clinical sheep study of a stentless aortic root, the treatment with AOA prevented calcification of the cusps, but not of the wall. The experiments described in this manuscript were designed to investigate a possible relationship between the binding of AOA and the differential treatment efficacy in the cusp and the wall, and to improve the anticalcification effect of the AOA treatment in the wall. Glutaraldehyde-fixed porcine roots were treated with [14C]-AOA for binding studies, and with non-radioactive AOA for calcification studies for rat subdermal implants. The results indicate that a) the AOA treatment did reduce wall calcification, but only temporarily, b) the low efficacy of the AOA treatment on the wall was probably due to the limited penetration of AOA, and c) increasing the volume of the AOA solution during treatment significantly increased the content of AOA in the wall, and significantly decreased wall calcification. This study suggests that AOA efficacy in the wall may be hindered because of the physical characteristics of the wall, and that wall calcification may be prevented by developing methods aimed at increasing AOA penetration into the wall.

Topics: Animals; Bioprosthesis; Calcinosis; Disease Models, Animal; Heart Valve Prosthesis; Male; Oleic Acids; Rats; Rats, Sprague-Dawley; Sheep; Solutions; Swine