Advertisement

Journal of Artificial Organs

, Volume 21, Issue 2, pp 138–141 | Cite as

Differences in clotting parameters between species for preclinical large animal studies of cardiovascular devices

  • Toshihide Mizuno
  • Tomonori Tsukiya
  • Yoshiaki Takewa
  • Eisuke Tatsumi
Original Article Artificial Heart (Basic)

Abstract

Several species of domestic animals are used in preclinical studies evaluating the safety and feasibility of medical devices; however, the relevance of animal models to human health is often not clear. The purpose of this study was to compare the clotting parameters of animal models to determine which animals most adequately mimic human clotting parameters. The clotting parameters of the different species were assessed in whole blood by in vitro thromboelastography using the clotting activators, such as tissue factor (extrinsic clotting screening test, EXTEM®) and partial thromboplastin phospholipid (intrinsic clotting screening test, IINTEM®). The measurements were performed using normal blood samples from humans (n = 13), calves (n = 18), goats (n = 56) and pigs (n = 8). Extrinsic clotting time (CT) and the intrinsic CT were significantly prolonged in calves compared to humans (249.9 ± 91.3 and 376.4 ± 124.4 s vs. 63.5 ± 11.8 and 192.5 ± 29.0 s, respectively, p < 0.01). The maximum clot firmness (MCF) in domestic animals (EXTEM®: 77–87 mm, IINTEM®: 66–78 mm) was significantly higher than that of humans (EXTEM®: 59.1 ± 6.0 mm, IINTEM®: 58.8 ± 1.5 mm, p < 0.01), and calves and goats exhibited longer time to MCF (MCF-t) than did humans and pigs (p < 0.01). Our results show that there are relevant differences in the four species’ extrinsic and intrinsic clotting parameters. These cross-comparisons indicate that it is necessary to clarify characteristics of clotting properties in preclinical animal studies.

Keywords

Clotting Animals Thromboelastography Medical devices Preclinical study 

Notes

Acknowledgements

This work was supported by JSPS KAKENHI Grant Number JP17K10745.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

References

  1. 1.
    U.S. Department of Health and Human Services Food and Drug Administration Center for Devices and Radiological Health DoCDOoDE: Guidance for industry and FDA staff general considerations for animal studies for cardiovascular devices, 2010.Google Scholar
  2. 2.
    Monreal G, Sherwood LC, Sobieski MA, et al. Large animal models for left ventricular assist device research and development. Asaio J. 2014;60:2–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Suzuki Y, Yeung AC, Ikeno F. The pre-clinical animal model in the translational research of interventional cardiology. JACC Cardiovasc Interv. 2009;2:373–83.CrossRefPubMedGoogle Scholar
  4. 4.
    Dickneite G, Pragst I, Joch C, et al. Animal model and clinical evidence indicating low thrombogenic potential of fibrinogen concentrate (Haemocomplettan P). Blood Coagul Fibrinolysis. 2009;20:535–40.CrossRefPubMedGoogle Scholar
  5. 5.
    Bodary PF, Eitzman DT. Animal models of thrombosis. Curr Opin Hematol. 2009;16:342–6.CrossRefPubMedGoogle Scholar
  6. 6.
    Shanks N, Greek R, Greek J. Are animal models predictive for humans? Philos Ethics Humanit Med. 2009;4:2.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Pape A, Weber CF, Stein P, et al. ROTEM® and multiplate—a suitable tool for POC? ISBT Sci Ser. 2010;5:161–8.CrossRefGoogle Scholar
  8. 8.
    Munster AM, Olsen AK, Bladbjerg EM. Usefulness of human coagulation and fibrinolysis assays in domestic pigs. Comp Med. 2002;52:39–43.PubMedGoogle Scholar
  9. 9.
    Gross DR, Dewanjee MK, Zhai PY, et al. Successful prosthetic mitral valve implantation in pigs. Asaio J. 1997;43:M382–M6.CrossRefGoogle Scholar
  10. 10.
    Kramer NA, Kruger S, Schmitz S, et al. Preclinical evaluation of a novel fiber compound MR guidewire in vivo. Investig Radiol. 2009;44:390–7.CrossRefGoogle Scholar
  11. 11.
    Grandin T, Shivley C. How farm animals react and perceive stressful situations such as handling, restraint, and transport. Animals (Basel). 2015;5:1233–51.CrossRefGoogle Scholar
  12. 12.
    Tanaka H, Tsukiya T, Tatsumi E, et al. Initial in vivo evaluation of the newly developed axial flow turbo pump with hydrodynamic bearings. J Artif Organs. 2011;14:31–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Tuzun E, Roberts K, Cohn WE, et al. In vivo evaluation of investigation the Heart Ware centrifugal ventricular assist device. Texas Heart Inst J. 2007;34:406–11.Google Scholar
  14. 14.
    Alam MGS, Dobson H. Effect of various veterinary procedures on plasma-concentrations of cortisol, luteinizing-hormone and prostaglandin-F2-alpha metabolite in the cow. Vet Rec. 1986;118:7–10.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society for Artificial Organs 2017

Authors and Affiliations

  • Toshihide Mizuno
    • 1
  • Tomonori Tsukiya
    • 1
  • Yoshiaki Takewa
    • 1
  • Eisuke Tatsumi
    • 1
  1. 1.Department of Artificial OrgansNational Cerebral and Cardiovascular Center Research InstituteSuitaJapan

Personalised recommendations