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.
- blood flow
Data availability statement
Data are available upon reasonable request. Not applicable.
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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.
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