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  • Effect of early Sanguinate (PEGylated carboxyhemoglobin bovine) infusion on cerebral blood flow to the ischemic core in experimental middle cerebral artery occlusion

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Basic science
Original research
Effect of early Sanguinate (PEGylated carboxyhemoglobin bovine) infusion on cerebral blood flow to the ischemic core in experimental middle cerebral artery occlusion
  1. Gregory A Christoforidis1,
  2. Niloufar Saadat2,
  3. Mira Liu2,
  4. Yong Ik Jeong2,
  5. Steven Roth3,
  6. Marek Niekrasz4,
  7. Timothy Carroll2
  1. 1 Radiology, Mount Carmel Health System, Columbus, Ohio, USA
  2. 2 Radiology, University of Chicago Division of the Biological Sciences, Chicago, Illinois, USA
  3. 3 Anesthesiology, University of Illinois at Chicago, Chicago, Illinois, USA
  4. 4 Animal Research Center, University of Chicago Division of the Biological Sciences, Chicago, Illinois, USA
  1. Correspondence to Dr Gregory A Christoforidis, Radiology, Mount Carmel Health System, Columbus, OH 43222, USA; gchristofo{at}yahoo.com

Abstract

Background Sanguinate, a bovine PEGylated carboxyhemoglobin-based oxygen carrier with vasodilatory, oncotic and anti-inflammatory properties designed to release oxygen in hypoxic tissue, was tested to determine if it improves infarct volume, collateral recruitment and blood flow to the ischemic core in hyperacute middle cerebral artery occlusion (MCAO).

Methods Under an IACUC approved protocol, 14 mongrel dogs underwent endovascular permanent MCAO. Seven received Sanguinate (8 mL/kg) intravenously over 10 min starting 30 min following MCAO and seven received a similar volume of normal saline. Relative cerebral blood flow (rCBF) was assessed using neutron-activated microspheres prior to MCAO, 30 min following MCAO and 30 min following intervention. Pial collateral recruitment was scored and measured by arterial arrival time (AAT) immediately prior to post-MCAO microsphere injection. Diffusion-weighted 3T MRI was used to assess infarct volume approximately 2 hours after MCAO.

Results Mean infarct volumes for control and Sanguinate-treated subjects were 4739 mm3 and 2585 mm3 (p=0.0443; r2=0.687), respectively. Following intervention, rCBF values were 0.340 for controls and 0.715 in the Sanguinate group (r2=0.536; p=0.0064). Pial collateral scores improved only in Sanguinate-treated subjects and AAT decreased by a mean of 0.314 s in treated subjects and increased by a mean of 0.438 s in controls (p<0.0276).

Conclusion Preliminary results indicate that topload bolus administration of Sanguinate in hyperacute ischemic stroke significantly improves infarct volume, pial collateral recruitment and CBF in experimental MCAO immediately following its administration.

  • stroke
  • blood flow
  • angiography
  • MRI

Data availability statement

Data are available upon reasonable request. Not applicable.

https://doi.org/10.1136/neurintsurg-2021-018239

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    Data availability statement

    Data are available upon reasonable request. Not applicable.

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    Footnotes

    • Contributors GAC: conception and design of the work, planning of the work, data collection, data analysis and interpretation, drafting the article, critical revision of the article, final approval of the version to be published and guarantor responsible for the overall content. NS: data collection, planning of the work, data collection, data analysis, approval of the version to be published. ML: data collection, data analysis, approval of the version to be published. YIJ: data collection, data analysis, approval of the version to be published. SR: conception or design of the work, data analysis and interpretation, critical revision of the article, approval of the version to be published. MN: conception or design of the work, planning of the work, data collection, approval of the version to be published. TC: conception and design of the work, planning of the work, data collection, data analysis and interpretation, critical revision of the article, final approval of the version to be published. No one else who fulfils the criteria by ICMJE recommendations has been excluded as an author.

    • Funding Grant support: NIH R01-NS093908 (National Institutes of Health).

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.