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Challenges in Perioperative Animal Care for Orthotopic Implantation of Tissue-Engineered Pulmonary Valves in the Ovine Model

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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Background:

Development of valvular substitutes meeting the performance criteria for surgical correction of congenital heart malformations is a major research challenge. The sheep is probably the most widely used animal model in heart valves regenerative medicine. Although the standard cardiopulmonary bypass (CPB) technique and various anesthetic and surgical protocols are reported to be feasible and safe, they are associated with significant morbidity and mortality rates. The premise of this paper is that the surgical technique itself, especially the perioperative animal care and management protocol, is essential for successful outcomes and survival.

Methods:

Ten juvenile and adult female sheep aged 7.8–37.5 months and weighing 32.0–58.0 kg underwent orthotopic implantation of tissue-engineered pulmonary valve conduits on beating heart under normothermic CPB. The animals were followed-up for 6 months before scheduled euthanasia.

Results:

Based on our observations, we established a guide for perioperative care, follow-up, and treatment containing information regarding the appropriate clinical, biological, and ultrasound examinations and recommendations for feasible and safe anesthetic, surgical, and euthanasia protocols. Specific recommendations were also included for perioperative care of juvenile versus adult sheep.

Conclusion:

The described surgical technique was feasible, with a low mortality rate and minimal surgical complications. The proposed anesthetic protocol was safe and effective, ensuring both adequate sedation and analgesia as well as rapid recovery from anesthesia without significant complications. The established guide for postoperative care, follow-up and treatment in sheep after open-heart surgery may help other research teams working in the field of heart valves tissue regeneration.

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Acknowledgments

This work was supported by a grant from the Competitiveness Operational Programme 2014-2020, Tissue engineering technologies for cardiac valve regeneration, valve-regen, ID:P_37_673, Mysmis code:103431, contract 50/05.09.2016, from grant 1P30GM131959 from NIGMS and from the Dempsey Endowment. We would like to thank Editage (www.editage.com) for English language editing.

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Author notes

  1. Hussam Al Hussein and Marius M. Harpa have contributed equally to this work.

Authors and Affiliations

  1. Tissue Engineering and Regenerative Medicine Laboratory “TERMLab”, The University of Medicine, Pharmacy, Science and Technology “George Emil Palade” of Tirgu Mures, 38 Gh. Marinescu Street, 540139, Tirgu Mures, Romania

    Hussam Al Hussein, Hamida Al Hussein, Carmen Sircuta, Ovidiu S. Cotoi, Ionela Movileanu, Dan Nistor, Bogdan Cordos, Radu Deac, Horatiu Suciu, Klara Brinzaniuc, Dan T. Simionescu & Marius M. Harpa

  2. The Emergency Institute for Cardiac Diseases and Transplantation of Tirgu Mures, 50 Gh. Marinescu Street, 540136, Tirgu Mures, Romania

    Hussam Al Hussein, Ionela Movileanu, Dan Nistor, Horatiu Suciu & Marius M. Harpa

  3. Clemson University, 306 Rhodes Annex, Clemson, SC, 29634, USA

    Dan T. Simionescu

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  1. Hussam Al Hussein
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Correspondence to Hamida Al Hussein.

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The authors have no financial conflicts of interest.

Ethical statement

All procedures and perioperative care of the experimental animals were performed in accordance with the “Guide for the care and use of laboratory animals” and Directive 2010/63/EU of the European Parliament on the protection of animals used for scientific purposes. Euthanasia was performed in compliance with the Convention on the experiments on live vertebrate animals and all the legal norms referring to the protection and welfare of animals: Law No. 9 of January 11, 2008 on the animals’ protection and Decision no. 19 of 01. July 2011 adopted by the National Council of the Veterinary Doctors College regarding the “Guide for the euthanasia of animals.” This work is part of a research grant conducted in accordance with the protocol no. 131/21.10.2016 approved by the Ethics Committee of the UMFST “George Emil Palade” of Tirgu Mures.

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Al Hussein, H., Al Hussein, H., Sircuta, C. et al. Challenges in Perioperative Animal Care for Orthotopic Implantation of Tissue-Engineered Pulmonary Valves in the Ovine Model. Tissue Eng Regen Med 17, 847–862 (2020). https://doi.org/10.1007/s13770-020-00285-1

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