Download presentation
Presentation is loading. Please wait.
Published byDorcas Mary Logan Modified over 6 years ago
1
Bioengineered human and allogeneic pulmonary valve conduits chronically implanted orthotopically in baboons: Hemodynamic performance and immunologic consequences Richard A. Hopkins, MD, Arthur A. Bert, MD, Stephen L. Hilbert, PhD, MD, Rachael W. Quinn, PhD, Kathleen M. Brasky, VMD, William B. Drake, MD, Gary K. Lofland, MD The Journal of Thoracic and Cardiovascular Surgery Volume 145, Issue 4, Pages e3 (April 2013) DOI: /j.jtcvs Copyright © 2013 The American Association for Thoracic Surgery Terms and Conditions
2
Figure 1 Dobutamine echocardiography results after chronic implantation of human and baboon bioengineered and control valves. Source species and process preparation for each group are noted. Porcine valves (light blue) were glutaraldehyde crosslinked stentless valves (Medtronic Freestyle; Medtronic Inc, Minneapolis, Minn). Transvalvular gradients were uniformly lower for all bioengineered valves (red) at rest and during dobutamine challenge compared with the clinical reference valves (green) (A). The human bioengineered valves (orange) functionally had low gradients and normal indexed EOA at maximum dobutamine stimulation (B). *P ≤ PV, Pulmonary valve; BEV, bioengineered valve; RVCO, right ventricular cardiac output. The Journal of Thoracic and Cardiovascular Surgery , e3DOI: ( /j.jtcvs ) Copyright © 2013 The American Association for Thoracic Surgery Terms and Conditions
3
Figure 2 Examples of PRA time curves. A, Animal 3 received a cryopreserved allograft and developed both class I and II PRAs by week 3, sustained through 10 weeks. B, Animal 9 received a bioengineered allograft, did not elevate to class II, and was the only bioengineered allograft recipient in which class I increased at all. Titer returned to zero by 10 weeks. C, Animal 13 received a human bioengineered valve that provoked class II antibodies at week 7 but returned to baseline by weeks 26 and 27; no class I antibodies were detected. These serial measurements demonstrate the potential difficulties in interpretation of random isolated PRA titer measurements after tissue transplants. PRA, Panel-reactive antibody; Pre, preoperatively; Post, immediately after surgery. The Journal of Thoracic and Cardiovascular Surgery , e3DOI: ( /j.jtcvs ) Copyright © 2013 The American Association for Thoracic Surgery Terms and Conditions
4
Figure 3 Implanted valve sizes. Nomogram of BSA normalized human pediatric pulmonary valve annulus diameters derived from 14,128 normal pediatric transthoracic echocardiograms archived in the Children’s Mercy Cardiac Database and on which the 14 implanted valve annulus diameters measured by TEE at baseline after implant surgery (day 0) are graphed (green dots). Note that all but 3 were above the 50% median; the smallest valve for the recipient size was a baboon bioengineered valve (number 8). An inadvertent “downsizing” bias would not explain the greater functional deterioration of the cryopreserved valves. Numbers identify recipient animals for each valve as identified in Table 2. PV, Pulmonary valve. The Journal of Thoracic and Cardiovascular Surgery , e3DOI: ( /j.jtcvs ) Copyright © 2013 The American Association for Thoracic Surgery Terms and Conditions
5
Figure E1 Relative primate homology. Time domain is estimated with fossil or mtDNA evidence . Primates first appeared as fossils dated to c. 95 million years ago. The depicted divergences represent generalized combinations of physical anthropological findings and computational algorithms based on genetic sequencing data. Of the Old World monkeys, the baboon has the most genomic homology to humans. Data from multiple sources, including Raaum RL, Sterner KN, Noviello CM, Stewart C-B, Disotell TR. Catarrhine primate divergence dates estimated from complete mitochondrial genomes: concordance with fossil and nuclear DNA evidence. J Hum Evol. 2005;48: Adapted with permission from material provided by Jeffrey Rogers, PhD, SNPRC. Ma, Million years ago. The Journal of Thoracic and Cardiovascular Surgery , e3DOI: ( /j.jtcvs ) Copyright © 2013 The American Association for Thoracic Surgery Terms and Conditions
6
Figure E2 C-reactive protein serum titers for each animal consistently peaked 1 week postoperatively, indicating classic proinflammatory effects of surgery and cardiopulmonary bypass. Pre, Preoperatively; Post, immediately after surgery. The Journal of Thoracic and Cardiovascular Surgery , e3DOI: ( /j.jtcvs ) Copyright © 2013 The American Association for Thoracic Surgery Terms and Conditions
7
Figure E3 Histopathology examples of inflammatory infiltrate grades. Histologic and immunohistochemical stains of pulmonary valves. A, Histologic section of cryopreserved human pulmonary valve explanted at 10 weeks (H&E, magnification 2.5×) exemplifying a microscopic field that would rate a mild inflammation score. Elsewhere in the specimen, areas of marked inflammation were observed; thus, the overall score for this valve explant was “marked” (animal number 5, Table 2). B, Immunohistochemical stain for B-cells (red, alkaline phosphatase, magnification 10×) within the conduit wall inflammatory infiltrate shown in A. C, Histologic section of cryopreserved Papio pulmonary valve explanted at 10 weeks (H&E, magnification 2.5×) exemplifying a score of “marked” inflammation (animal 4). D, Immunohistochemical stain for B-cells (red, alkaline phosphatase, magnification 10×) within the inflammatory infiltrate in the conduit of PRA+ recipient in C. The Journal of Thoracic and Cardiovascular Surgery , e3DOI: ( /j.jtcvs ) Copyright © 2013 The American Association for Thoracic Surgery Terms and Conditions
Similar presentations
© 2025 SlidePlayer.com. Inc.
All rights reserved.