Literature DB >> 20692430

Surgical and nonsurgical complications of a pig to baboon heterotopic heart transplantation model.

P C Corcoran1, K A Horvath, A K Singh, R F Hoyt, M L Thomas, M A Eckhaus, M M Mohiuddin.   

Abstract

A modified immunosuppressive regimen, developed at the National Institutes of Health, has been employed in a large animal model of heterotopic cardiac xenotransplantation. Graft survival has been prolonged, but despite this, our recipients have succumbed to various surgical or nonsurgical complications. Herein, we have described different complications and management strategies. The most common complication was hypercoagulability (HC) after transplantation, causing thrombosis of both small and large vasculature, ultimately leading to graft loss. While managing this complication we discovered that there was a delicate balance between HC and consumptive coagulopathy (CC). CC encountered in some recipient baboons was not able to be reversed by stopping anticoagulation and administering multiple blood transfusions. Some complications had iatrogenic components. To monitor the animals, a solid state left ventricular telemetry probe was placed directly into the transplanted heart via the apex. Induction of hypocoagulable states by continuous heparin infusion led to uncontrollable intra-abdominal bleeding in 1 baboon from this apical site. This occurrence necessitated securing the probe more tightly with multiple purse strings and 4-quadrant pledgeted stay sutures. One instance of cardiac rupture originated from a lateral wall infarction site. Earlier studies have shown infections to be uniformly fatal in this transplant model. However, owing to the telemetry placement, infections were identified early by temperature spikes that were treated promptly with antibiotics. We had several cases of wound dehiscence due to recipients disrupting the suture line. These complications were promptly resolved by either re-approximating the wound or finding distractions for the baboon. A few of the most common problems we faced in our earlier experiments were related to the jacket, tether, and infusion pumps. It was difficult to keep the jackets on some baboons and the tether had to be modified several times before we assured long-term success. Infusion catheter replacement resulted in transplant heart venous obstruction and thrombosis from a right common femoral venous line. Homeostatic perturbations such as HC and CC and baboon-induced wound complications comprised most complications. Major bleeding and death due to telemetry implantation and infarct rupture occurred in 2 baboons. Despite the variety of complications, we achieved significant graft prolongation in this model. Copyright 2010 Elsevier Inc. All rights reserved.

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Year:  2010        PMID: 20692430      PMCID: PMC2919494          DOI: 10.1016/j.transproceed.2010.05.116

Source DB:  PubMed          Journal:  Transplant Proc        ISSN: 0041-1345            Impact factor:   1.066


  8 in total

1.  Anti-CD154 monoclonal antibody and thromboembolism.

Authors:  L Buhler; I P Alwayn; J Z Appel; S C Robson; D K Cooper
Journal:  Transplantation       Date:  2001-02-15       Impact factor: 4.939

2.  Disseminated intravascular coagulation in association with the delayed rejection of pig-to-baboon renal xenografts.

Authors:  F L Ierino; T Kozlowski; J B Siegel; A Shimizu; R B Colvin; P T Banerjee; D K Cooper; A B Cosimi; F H Bach; D H Sachs; S C Robson
Journal:  Transplantation       Date:  1998-12-15       Impact factor: 4.939

3.  Cardiac xenotransplantation: progress toward the clinic.

Authors:  Christopher G A McGregor; Sumeet S Teotia; Guerard W Byrne; Marian G Michaels; Jack M Risdahl; Johannes M Schirmer; Henry D Tazelaar; Randall C Walker; John S Logan
Journal:  Transplantation       Date:  2004-12-15       Impact factor: 4.939

4.  Technique for heterotopic pig heart xenotransplantation in primates.

Authors:  D H Adams; R H Chen; A Kadner; S Naficy
Journal:  Ann Thorac Surg       Date:  1999-07       Impact factor: 4.330

5.  Porcine hematopoietic cell xenotransplantation in nonhuman primates is complicated by thrombotic microangiopathy.

Authors:  L Bühler; C Goepfert; H Kitamura; M Basker; S Gojo; I P Alwayn; Q Chang; J D Down; H Tsai; R Wise; D H Sachs; D K Cooper; S C Robson; R Sackstein
Journal:  Bone Marrow Transplant       Date:  2001-06       Impact factor: 5.483

6.  Babesia as a complication of immunosuppression following pig-to-baboon heart transplantation.

Authors:  Mohamed Ezzelarab; Peter Yeh; Robert Wagner; David K C Cooper
Journal:  Xenotransplantation       Date:  2007-03       Impact factor: 3.907

7.  Coagulation and thrombotic disorders associated with pig organ and hematopoietic cell transplantation in nonhuman primates.

Authors:  L Bühler; M Basker; I P Alwayn; C Goepfert; H Kitamura; T Kawai; S Gojo; T Kozlowski; F L Ierino; M Awwad; D H Sachs; R Sackstein; S C Robson; D K Cooper
Journal:  Transplantation       Date:  2000-11-15       Impact factor: 4.939

8.  Prevention, detection, and management of early bacterial and fungal infections in a preclinical cardiac xenotransplantation model that achieves prolonged survival.

Authors:  Sumeet S Teotia; Randall C Walker; Johannes M Schirmer; Henry D Tazelaar; Marian G Michaels; Jack M Risdahl; Guerard W Byrne; John S Logan; Christopher G A McGregor
Journal:  Xenotransplantation       Date:  2005-03       Impact factor: 3.907

  8 in total
  10 in total

1.  B-cell depletion extends the survival of GTKO.hCD46Tg pig heart xenografts in baboons for up to 8 months.

Authors:  M M Mohiuddin; P C Corcoran; A K Singh; A Azimzadeh; R F Hoyt; M L Thomas; M A Eckhaus; C Seavey; D Ayares; R N Pierson; K A Horvath
Journal:  Am J Transplant       Date:  2011-11-09       Impact factor: 8.086

2.  Novel technique for retroperitoneal implantation of telemetry transmitters for physiologic monitoring in Göttingen minipigs (Sus scrofa domesticus).

Authors:  Scott Willens; David M Cox; Ernest H Braue; Todd M Myers; Matthew D Wegner
Journal:  Comp Med       Date:  2014-12       Impact factor: 0.982

Review 3.  Therapeutic issues in the treatment of vascularized xenotransplants using gal-knockout donors in nonhuman primates.

Authors:  Burcin Ekser; Goutham Kumar; Massimiliano Veroux; David K C Cooper
Journal:  Curr Opin Organ Transplant       Date:  2011-04       Impact factor: 2.640

Review 4.  New concepts of immune modulation in xenotransplantation.

Authors:  Vikas Satyananda; Hidetaka Hara; Mohamed B Ezzelarab; Carol Phelps; David Ayares; David K C Cooper
Journal:  Transplantation       Date:  2013-12-15       Impact factor: 4.939

5.  Cell size and velocity of injection are major determinants of the safety of intracarotid stem cell transplantation.

Authors:  Miroslaw Janowski; Agatha Lyczek; Charla Engels; Jiadi Xu; Barbara Lukomska; Jeff W M Bulte; Piotr Walczak
Journal:  J Cereb Blood Flow Metab       Date:  2013-03-13       Impact factor: 6.200

6.  Genetically engineered pigs and target-specific immunomodulation provide significant graft survival and hope for clinical cardiac xenotransplantation.

Authors:  Muhammad M Mohiuddin; Avneesh K Singh; Philip C Corcoran; Robert F Hoyt; Marvin L Thomas; David Ayares; Keith A Horvath
Journal:  J Thorac Cardiovasc Surg       Date:  2014-06-06       Impact factor: 5.209

7.  Human dominant-negative class II transactivator transgenic pigs - effect on the human anti-pig T-cell immune response and immune status.

Authors:  Hidetaka Hara; William Witt; Tanner Crossley; Cassandra Long; Kumiko Isse; Liming Fan; Carol J Phelps; David Ayares; David K C Cooper; Yifan Dai; Thomas E Starzl
Journal:  Immunology       Date:  2013-09       Impact factor: 7.397

8.  Role of anti-CD40 antibody-mediated costimulation blockade on non-Gal antibody production and heterotopic cardiac xenograft survival in a GTKO.hCD46Tg pig-to-baboon model.

Authors:  Muhammad M Mohiuddin; Avneesh K Singh; Philip C Corcoran; Robert F Hoyt; Marvin L Thomas; Billeta G T Lewis; Michael Eckhaus; Nicole L Dabkowski; Aaron J Belli; Keith A Reimann; David Ayares; Keith A Horvath
Journal:  Xenotransplantation       Date:  2013-10-29       Impact factor: 3.907

Review 9.  Porcine to Human Heart Transplantation: Is Clinical Application Now Appropriate?

Authors:  Christopher G A McGregor; Guerard W Byrne
Journal:  J Immunol Res       Date:  2017-11-07       Impact factor: 4.818

10.  Intra-Abdominal Heterotopic Cardiac Xenotransplantation: Pearls and Pitfalls.

Authors:  Laura DiChiacchio; Avneesh K Singh; Joshua L Chan; Nicole M Shockcor; Tianshu Zhang; Billeta G Lewis; David Ayares; Philip Corcoran; Keith A Horvath; Muhammad M Mohiuddin
Journal:  Front Cardiovasc Med       Date:  2019-07-25
  10 in total

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