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Poster Abstract PresentationsSession Title: Poster Session I

Abstract 193: Antithrombin Perfluorocarbon Nanoparticles Ameliorate Renal Injury Following Transient Warm Ischemia

Chandu Vemuri, Junjie Chen, Rohun U Palekar, John S Allen, Xiaoxia Yang, Hiuying Zhang, Samuel A Wickline
Arteriosclerosis, Thrombosis, and Vascular Biology. 2014;34:A193
Chandu Vemuri
Surgery (Vascular), Washington Univ in St Louis, St Louis, MO
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Junjie Chen
Surgery (Vascular), Washington Univ in St Louis, St Louis, MO
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Rohun U Palekar
Surgery (Vascular), Washington Univ in St Louis, St Louis, MO
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John S Allen
Surgery (Vascular), Washington Univ in St Louis, St Louis, MO
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Xiaoxia Yang
Surgery (Vascular), Washington Univ in St Louis, St Louis, MO
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Hiuying Zhang
Surgery (Vascular), Washington Univ in St Louis, St Louis, MO
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Samuel A Wickline
Surgery (Vascular), Washington Univ in St Louis, St Louis, MO
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Abstract

Objective: Thrombin mediated microvascular thrombosis plays a crucial role in the pathogenesis of acute renal reperfusion injury following transient ischemia. We hypothesize that anti-thrombin nanoparticles will ameliorate acute renal injury by inhibiting microvascular thrombosis.

Methods: Adult, male Sprague Dawley rats were randomized into two groups of 5 to receive tail vein injections of saline or nanoparticles loaded with Phe[D]-Pro-Arg-Chloromethylketone (NP-PPACK). Immediately following injection, all animals underwent operative bilateral renal artery occlusion to create 45 minutes of warm ischemia, followed by restoration of renal blood flow. Blood samples were drawn daily and animals were euthanized on day 1 or 7 for histologic analysis of kidney injury (H&E, TUNEL and thrombin staining).

Results: Histologic analysis of renal tissue revealed significant apoptosis, necrosis and thrombin accumulation 1 day after ischemia-reperfusion, confirming acute kidney injury. The peak creatinine (mg/dl) on day 1 was significantly lower in NP-PPACK treated animals (0.57 +/- 0.07 (SEM)) than in saline treated controls (1.40 +/- 0.20 (SEM); p-value <0.01). Furthermore, animals treated with NP-PPACK continued to exhibit less renal dysfunction for 7 days after injury (Figure 1).

Conclusion: Histologically confirmed intrarenal thrombosis was detected one day after ischemia-reperfusion injury. Targeted inhibition of thrombin with NP-PPACK prevented a decline in renal function following transient occlusion. Future work will focus on defining the underlying mechanisms of this effect.


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Key Words:
  • Acute Kidney Injury
  • Nanoparticle
  • Thrombosis
  • Author Disclosures: C. Vemuri: None. J. Chen: None. R.U. Palekar: None. J.S. Allen: None. X. Yang: None. H. Zhang: None. S.A. Wickline: Research Grant; Modest; U54:HL 112303, RO1: HL 073646, R21: DK 095555. Ownership Interest; Modest; AcuPlaq, L.L.C..

  • © 2014 by American Heart Association, Inc.
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May 2014, Volume 34, Issue Suppl 1
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    Abstract 193: Antithrombin Perfluorocarbon Nanoparticles Ameliorate Renal Injury Following Transient Warm Ischemia
    Chandu Vemuri, Junjie Chen, Rohun U Palekar, John S Allen, Xiaoxia Yang, Hiuying Zhang and Samuel A Wickline
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2014;34:A193, originally published September 3, 2014

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    Abstract 193: Antithrombin Perfluorocarbon Nanoparticles Ameliorate Renal Injury Following Transient Warm Ischemia
    Chandu Vemuri, Junjie Chen, Rohun U Palekar, John S Allen, Xiaoxia Yang, Hiuying Zhang and Samuel A Wickline
    Arteriosclerosis, Thrombosis, and Vascular Biology. 2014;34:A193, originally published September 3, 2014
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