Publications by authors named "Paul E Ashworth"

2 Publications

  • Page 1 of 1

New Model for the Assessment of Transcatheter Aortic Valve Replacement Devices in Sheep.

J Invest Surg 2020 Dec 28:1-10. Epub 2020 Dec 28.

Experimental Surgical Services Laboratory, Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA.

Background: Transcatheter aortic valve replacement (TAVR) is an effective therapy in treating high-risk patients suffering from aortic stenosis. Animal models used to evaluate safety and efficacy of TAVR devices prior to clinical use lack a stenotic aortic annulus, a critical impediment to long-term TAVR device evaluation. We sought to create a reproducible model of aortic stenosis using a modified aortic annuloplasty (MAA) procedure in sheep, followed by deployment and long-term evaluation of TAVR devices using this model.

Methods: Twelve sheep underwent the MAA procedure and were recovered. Transthoracic echocardiography (TTE) was used to monitor changes in the aortic annulus in the postoperative period. At 60 days post-MAA, Test group animals were anesthetized for TAVR insertion and Control animals underwent a necropsy. Test animals were recovered following TAVR insertion and observed for a postoperative period of 140 days.

Results: Twelve sheep survived the annuloplasty procedure and the 60-day recovery period. Gross examination of seven Control group animals revealed the implanted annuloplasty ring segments formed hard protrusions into the aortic annulus. Five sheep in the Test group underwent successful deployment of Abbott's experimental TAVR device without evidence of migration. Examination at 140 days post-TAVR insertion showed all devices tightly anchored within the modified aortic annulus.

Conclusions: The MAA procedure creates stenotic segments in the aortic annulus with adequate rigidity for anchorage and long-term evaluation of TAVR devices. This represents the first model that successfully mimics human aortic stenosis and provides a clinically relevant TAVR deployment platform for long-term evaluation in sheep.
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December 2020

Triglycidyl amine crosslinking combined with ethanol inhibits bioprosthetic heart valve calcification.

Ann Thorac Surg 2011 Sep;92(3):858-65

Division of Cardiology, The Children's Hospital of Philadelphia, and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4318, USA.

Background: One of the most important factors responsible for the calcific failure of bioprosthetic heart valves is glutaraldehyde crosslinking. Ethanol (EtOH) incubation after glutaraldehyde crosslinking has previously been reported to confer anticalcification efficacy for bioprostheses. The present studies investigated the anticalcification efficacy in vivo of the novel crosslinking agent, triglycidyl amine (TGA), with or without EtOH incubation, in comparison with glutaraldehyde.

Methods: The TGA crosslinking (±EtOH) was used to prepare porcine aortic valves for both rat subdermal implants and sheep mitral valve replacements, for comparisons with glutaraldehyde-fixed controls. Thermal denaturation temperature, an index of crosslinking, cholesterol extraction, and hydrodynamic properties were quantified. Explant endpoints included quantitative and morphologic assessment of calcification.

Results: Thermal denaturation temperatures after TGA were intermediate between unfixed and glutaraldehyde-fixed. EtOH incubation resulted in almost complete extraction of cholesterol from TGA or glutaraldehyde-fixed cusps. Rat subdermal explants (90 days) demonstrated that TGA-EtOH resulted in a significantly greater level of inhibition of calcification than other conditions. Thus, TGA-ethanol stent mounted porcine aortic valve bioprostheses were fabricated for comparisons with glutaraldehyde-pretreated controls. In hydrodynamic studies, TGA-EtOH bioprostheses had lower pressure gradients than glutaraldehyde-fixed. The TGA-ethanol bioprostheses used as mitral valve replacements in juvenile sheep (150 days) demonstrated significantly lower calcium levels in both explanted porcine aortic cusp and aortic wall samples compared with glutaraldehyde-fixed controls. However, TGA-EtOH sheep explants also demonstrated isolated calcific nodules and intracuspal hematomas.

Conclusions: The TGA-EtOH pretreatment of porcine aortic valves confers significant calcification resistance in both rat subdermal and sheep circulatory implants, but with associated structural instability.
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September 2011