Innovative experimental animal models for real-time comparison of antithrombogenicity between two oxygenators using dual extracorporeal circulation circuits and indocyanine green fluorescence imaging.
COVID-19
antithrombotic comparison
dual extracorporeal circulation
experimental animal model
extracorporeal membrane oxygenation
indocyanine green fluorescence imaging
oxygenator
pulsatile flow
Journal
Artificial organs
ISSN: 1525-1594
Titre abrégé: Artif Organs
Pays: United States
ID NLM: 7802778
Informations de publication
Date de publication:
Jan 2023
Jan 2023
Historique:
revised:
08
07
2022
received:
13
05
2022
accepted:
02
08
2022
pubmed:
13
8
2022
medline:
4
1
2023
entrez:
12
8
2022
Statut:
ppublish
Résumé
Antithrombogenicity of extracorporeal membrane oxygenation (ECMO) devices, particularly oxygenators, is a current problem, with numerous studies and developments underway. However, there has been limited progress in developing methods to accurately compare the antithrombogenicity of oxygenators. Animal experiments are commonly conducted to evaluate the antithrombogenicity of devices; however, it is challenging to maintain a steady experimental environment. We propose an innovative experimental animal model to evaluate different devices in a constant experimental environment in real-time. This model uses two venous-arterial ECMO circuits attached to one animal (one by jugular vein and carotid artery, one by femoral vein and artery) and real-time assessment of thrombus formation in the oxygenator by indocyanine green (ICG) fluorescence imaging. Comparison studies were conducted using three pigs: one to compare different oxygenators (MERA vs. CAPIOX) (Case 1), and two to compare antithrombotic properties of the oxygenator (QUADROX) when used under different hydrodynamic conditions (continuous flow vs. pulsatile flow) (Cases 2 and 3). Thrombi, visualized using ICG imaging, appeared as black dots on a white background in each oxygenator. In Case 1, differences in the site of thrombus formation and rate of thrombus growth were observed in real-time in two oxygenators. In Case 2 and 3, the thrombus region was smaller in pulsatile than in continuous conditions. We devised an innovative experimental animal model for comparison of antithrombogenicity in ECMO circuits. This model enabled simultaneous evaluation of two different ECMO circuits under the same biological conditions and reduced the number of sacrificed experimental animals.
Sections du résumé
BACKGROUND
BACKGROUND
Antithrombogenicity of extracorporeal membrane oxygenation (ECMO) devices, particularly oxygenators, is a current problem, with numerous studies and developments underway. However, there has been limited progress in developing methods to accurately compare the antithrombogenicity of oxygenators. Animal experiments are commonly conducted to evaluate the antithrombogenicity of devices; however, it is challenging to maintain a steady experimental environment. We propose an innovative experimental animal model to evaluate different devices in a constant experimental environment in real-time.
METHODS
METHODS
This model uses two venous-arterial ECMO circuits attached to one animal (one by jugular vein and carotid artery, one by femoral vein and artery) and real-time assessment of thrombus formation in the oxygenator by indocyanine green (ICG) fluorescence imaging. Comparison studies were conducted using three pigs: one to compare different oxygenators (MERA vs. CAPIOX) (Case 1), and two to compare antithrombotic properties of the oxygenator (QUADROX) when used under different hydrodynamic conditions (continuous flow vs. pulsatile flow) (Cases 2 and 3).
RESULTS
RESULTS
Thrombi, visualized using ICG imaging, appeared as black dots on a white background in each oxygenator. In Case 1, differences in the site of thrombus formation and rate of thrombus growth were observed in real-time in two oxygenators. In Case 2 and 3, the thrombus region was smaller in pulsatile than in continuous conditions.
CONCLUSIONS
CONCLUSIONS
We devised an innovative experimental animal model for comparison of antithrombogenicity in ECMO circuits. This model enabled simultaneous evaluation of two different ECMO circuits under the same biological conditions and reduced the number of sacrificed experimental animals.
Substances chimiques
Indocyanine Green
IX6J1063HV
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
77-87Subventions
Organisme : Japan Society for the Promotion of Science KAKENHI
ID : JP21K08817
Organisme : Terumo Foundation for Life Sciences and Arts
ID : 20-III107
Informations de copyright
© 2022 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.
Références
Barbaro RP, MacLaren G, Boonstra PS, Iwashyna TJ, Slutsky AS, Fan E, et al. Extracorporeal membrane oxygenation support in COVID-19: an international cohort study of the Extracorporeal Life Support Organization registry. Lancet. 2020 Oct 10;396(10257):1071-8.
Nagaoka E, Arai H, Ugawa T, Masuda T, Ochiai K, Tamaoka M, et al. Efficacy of multidisciplinary team approach with extracorporeal membrane oxygenation for COVID-19 in a low volume ECMO center. Artif Organs. 2021 Sep;45(9):1061-7.
Durak K, Kersten A, Grottke O, Zayat R, Dreher M, Autschbach R, et al. Thromboembolic and bleeding events in COVID-19 patients receiving extracorporeal membrane oxygenation. Thorac Cardiovasc Surg. 2021 Sep;69(6):526-36.
Yusuff H, Zochios V, Brodie D. Thrombosis and coagulopathy in COVID-19 patients requiring extracorporeal membrane oxygenation. ASAIO J. 2020 Aug;66(8):844-6.
Wakisaka Y, Taenaka Y, Araki K, Chikanari K, Nakatani T, Baba Y, et al. Effects of self washout structure on the antithrombogenicity and the hemolytic properties of a centrifugal pump. Artif Organs. 1997 Feb;21(2):148-53.
Naito N, Ukita R, Wilbs J, Wu K, Lin X, Carleton NM, et al. Combination of polycarboxybetaine coating and factor XII inhibitor reduces clot formation while preserving normal tissue coagulation during extracorporeal life support. Biomaterials. 2021 May;272:120778.
Sarode DN, Roy S. In vitro models for thrombogenicity testing of blood-recirculating medical devices. Expert Rev Med Devices. 2019 Jul;16(7):603-16.
Wakisaka Y, Taenaka Y, Tatsumi E, Araki K, Masuzawa T, Nakatani T, et al. Improvement in antithrombogenicity in a centrifugal pump with self wash-out structure for long-term use. ASAIO J. 1995 Jul-Sep;41(3):M350-5.
Sakurai H, Fujiwara T, Ohuchi K, Hijikata W, Inoue Y, Seki H, et al. Novel application of indocyanine green fluorescence imaging for real-time detection of thrombus in a membrane oxygenator. Artif Organs. 2021 Oct;45(10):1173-82.
Moroi M, Force M, Wang S, Kunselman AR, Ündar A. In vitro comparison of pediatric oxygenators with and without integrated arterial filters in maintaining optimal hemodynamic stability and managing gaseous microemboli. Artif Organs. 2018 Apr;42(4):420-31.
Iida M, Shiono M, Orime Y, Nakata K, Hata M, Sezai A, et al. A newly developed silicone-coated membrane oxygenator for long-term cardiopulmonary bypass and cardiac support. Artif Organs. 1997 Jul;21(7):755-9.
Guan Y, Su X, McCoach R, Wise R, Kunselman A, Undar A. Evaluation of Quadrox-i adult hollow fiber oxygenator with integrated arterial filter. J Extra Corpor Technol. 2010 Jun;42(2):134-8.
Iizuka K, Katagiri N, Takewa Y, Tsukiya T, Mizuno T, Itamochi Y, et al. Evaluation of the novel centrifugal pump, CAPIOX SL, in chronic large animal experiments. Artif Organs. 2018 Aug;42(8):835-41.
Yamane T, Kosaka R, Nishida M, Maruyama O, Yamamoto Y, Kuwana K, et al. Enhancement of hemocompatibility of the MERA monopivot centrifugal pump: toward medium-term use. Artif Organs. 2013 Feb;37(2):217-21.
Hijikata W, Shinshi T, Asama J, Li L, Hoshi H, Takatani S, et al. A magnetically levitated centrifugal blood pump with a simple-structured disposable pump head. Artif Organs. 2008 Jul;32(7):531-40.
Nagaoka E, Fujiwara T, Kitao T, Sakota D, Shinshi T, Arai H, et al. MedTech Mag-Lev, single-use, extracorporeal magnetically levitated centrifugal blood pump for mid-term circulatory support. ASAIO J. 2013 May-Jun;59(3):246-52.
Fujiwara T, Nagaoka E, Watanabe T, Miyagi N, Kitao T, Sakota D, et al. New generation extracorporeal membrane oxygenation with MedTech Mag-Lev, a single-use, magnetically levitated, centrifugal blood pump: preclinical evaluation in calves. Artif Organs. 2013 May;37(5):447-56.
Reuthebuch O, Häussler A, Genoni M, Tavakoli R, Odavic D, Kadner A, et al. Novadaq SPY: intraoperative quality assessment in off-pump coronary artery bypass grafting. Chest. 2004 Feb;125(2):418-24.
Kitai T, Inomoto T, Miwa M, Shikayama T. Fluorescence navigation with indocyanine green for detecting sentinel lymph nodes in breast cancer. Breast Cancer. 2005;12(3):211-5.
Desmettre T, Devoisselle JM, Mordon S. Fluorescence properties and metabolic features of indocyanine green (ICG) as related to angiography. Surv Ophthalmol. 2000 Jul-Aug;45(1):15-27.
Hamamatsu Photonics K.K. Blood vessels observation camera system. Hamamatsu: The Company; c1953-2022 [cited 2022 Jun 16]. Available from: https://www.hamamatsu.com/us/en/product/life-science-and-medical-systems/blood-vessels-observation-camera-system/C10935-400.html
Kessler U, Grau T, Gronchi F, Berger S, Brandt S, Bracht H, et al. Comparison of porcine and human coagulation by thrombelastometry. Thromb Res. 2011;128:477-82.
Park CH, Nishimura K, Yamada T, Mizuhara H, Akamatsu T, Tsukiya T, et al. A magnetically suspended centrifugal pump. In vitro and in vivo assessment. ASAIO J. 1995 Jul-Sep;41(3):M345-50.
Maruyama O, Tomari Y, Sugiyama D, Nishida M, Tsutsui T, Yamane T. Simple in vitro testing method for antithrombogenic evaluation of centrifugal blood pumps. ASAIO J. 2009 Jul-Aug;55(4):314-22.
Murashige T, Hijikata W. Mechanical antithrombogenic properties by vibrational excitation of the impeller in a magnetically levitated centrifugal blood pump. Artif Organs. 2019 Sep;43(9):849-59.
Brockhaus MK, Behbahani MJ, Muris F, Jansen SV, Schmitz-Rode T, Steinseifer U, et al. In-vitro thrombogenicity testing of pulsatile mechanical circulatory support systems: design and proof-of-concept. Artif Organs. 2021;45:1513-21.
Robinson NB, Krieger K, Khan FM, Huffman W, Chang M, Naik A, et al. The current state of animal models in research: a review. Int J Surg. 2019 Dec;72:9-13.
Fujiwara T, Sakota D, Ohuchi K, Endo S, Tahara T, Murashige T, et al. Optical dynamic analysis of thrombus inside a centrifugal blood pump during extracorporeal mechanical circulatory support in a porcine model. Artif Organs. 2017 Oct;41(10):893-903.
Seki H, Fujiwara T, Hijikata W, Murashige T, Tahara T, Yokota S, et al. Evaluation of real-time thrombus detection method in a magnetically levitated centrifugal blood pump using a porcine left ventricular assist circulation model. Artif Organs. 2021 Jul;45(7):726-35.
Urlesberger B, Zobel G, Rödl S, Dacar D, Friehs I, Leschnik B, et al. Activation of the clotting system: heparin-coated versus non coated systems for extracorporeal circulation. Int J Artif Organs. 1997 Dec;20(12):708-12.
Magkoutas K, Rebholz M, Sündermann S, Alogna A, Faragli A, Falk V, et al. Control of ventricular unloading using an electrocardiogram-synchronized. Artif Organs. 2020 Oct;44(10):E394-405.
Voigt I, Spangenberg T, Ibrahim T, Bradaric C, Viertel A, Tallone EM, et al. Efficacy and safety of ECG-synchronized pulsatile extracorporeal membrane oxygenation in the clinical setting: the SynCor trial. Artif Organs. 2022 Mar;46(3):387-97.
Kuroda T, Miyamoto T, Miyagi C, Polakowski AR, Flick CR, Kuban BD, et al. Pulsatility hemodynamics during speed modulation of continuous-flow total. Artif Organs. 2022;46:1555-63.
Spratt EH, Melrose D, Bellhouse B, Badolato A, Thompson R. Evaluation of a membrane oxygenator for clinical cardiopulmonary bypass. Trans Am Soc Artif Intern Organs. 1981;27:285-8.
Syed A, Kerdi S, Qamar A. Bioengineering progress in lung assist devices. Bioengineering (Basel). 2021 Jun 28;8(7):89.
Schraven L, Kaesler A, Flege C, Kopp R, Schmitz-Rode T, Steinseifer U, et al. Effects of pulsatile blood flow on oxygenator performance. Artif Organs. 2018 Apr;42(4):410-9.
Krabatsch T, Netuka I, Schmitto JD, Zimpfer D, Garbade J, Rao V, et al. Heartmate 3 fully magnetically levitated left ventricular assist device for the treatment of advanced heart failure -1 year results from the Ce mark trial. J Cardiothorac Surg. 2017 Apr 4;12(1):23.