Chronic Ovine Studies Demonstrate Low Thromboembolic Risk in the Penn State Infant Ventricular Assist Device

Branka Lukic, Joseph Clark, Jenelle Izer, Timothy K. Cooper, Heidi A. Finicle, Joshua Cysyk, Bradly Doxtater, Eric Yeager, John Reibson, Raymond K. Newswanger, Patrick Leibich, Kirby Bletcher, William Weiss

Research output: Contribution to journalArticle

Abstract

Mechanical circulatory support for children under 6 years of age remains a challenge. This article describes the preclinical status and the results of recent animal testing with the Penn State Infant Left Ventricular Assist Device (VAD). The objectives have been to 1) demonstrate acceptably low thromboembolic risk to support Food and Drug Administration approval, 2) challenge the device by using minimal to no anticoagulation in order to identify any design or manufacturing weaknesses, and 3) improve our understanding of device thrombogenicity in the ovine animal model, using multicomponent measurements of the coagulation system and renal ischemia quantification, in order to better correlate animal results with human results.The Infant VAD was implanted as a left VAD (LVAD) in 18-29 kg lambs. Twelve LVAD and five surgical sham animals were electively terminated after approximately 30 or 60 days. Anticoagulation was by unfractionated heparin targeting thromboelastography R times of 2x normal (n = 6) or 1x normal (n = 6) resulting in negligible heparin activity as measured by anti-Xa assay (<0.1 IU/ml). Platelet inhibitors were not used.There were no clinically evident strokes or evidence of end organ dysfunction in any of the 12 electively terminated LVAD studies. The degree of renal ischemic lesions in device animals was not significantly different than that found in five surgical sham studies, demonstrating minimal device thromboembolism.In summary, these results in a challenging animal test protocol support the conclusion that the Penn State Infant VAD has a low thromboembolic risk and may allow lower levels of anticoagulation.

Original languageEnglish (US)
Pages (from-to)371-379
Number of pages9
JournalASAIO journal (American Society for Artificial Internal Organs : 1992)
Volume65
Issue number4
DOIs
StatePublished - May 1 2019

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Heart-Assist Devices
Sheep
Animals
Equipment and Supplies
Left ventricular assist devices
Heparin
Thrombelastography
Kidney
Drug Approval
Platelet Aggregation Inhibitors
Thromboembolism
United States Food and Drug Administration
Platelets
Coagulation
Ischemia
Animal Models
Stroke
Assays
Testing

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Biomedical Engineering

Cite this

Lukic, Branka ; Clark, Joseph ; Izer, Jenelle ; Cooper, Timothy K. ; Finicle, Heidi A. ; Cysyk, Joshua ; Doxtater, Bradly ; Yeager, Eric ; Reibson, John ; Newswanger, Raymond K. ; Leibich, Patrick ; Bletcher, Kirby ; Weiss, William. / Chronic Ovine Studies Demonstrate Low Thromboembolic Risk in the Penn State Infant Ventricular Assist Device. In: ASAIO journal (American Society for Artificial Internal Organs : 1992). 2019 ; Vol. 65, No. 4. pp. 371-379.
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Chronic Ovine Studies Demonstrate Low Thromboembolic Risk in the Penn State Infant Ventricular Assist Device. / Lukic, Branka; Clark, Joseph; Izer, Jenelle; Cooper, Timothy K.; Finicle, Heidi A.; Cysyk, Joshua; Doxtater, Bradly; Yeager, Eric; Reibson, John; Newswanger, Raymond K.; Leibich, Patrick; Bletcher, Kirby; Weiss, William.

In: ASAIO journal (American Society for Artificial Internal Organs : 1992), Vol. 65, No. 4, 01.05.2019, p. 371-379.

Research output: Contribution to journalArticle

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AU - Yeager, Eric

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AU - Bletcher, Kirby

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