Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 38, Issue 5, Pages 755-766Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/0271678X17705567
Keywords
Collateral perfusion; hypertension; ischemic stroke; infarction; reperfusion
Categories
Funding
- National Institute of Neurologic Disorders and Stroke [NS093289]
- National Heart Lung and Blood Institute [P01 HL095488]
- Totman Medical Research Trust
- Cardiovascular Research Institute of Vermont
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Similar to patients with chronic hypertension, spontaneously hypertensive rats (SHR) develop fast core progression during middle cerebral artery occlusion (MCAO) resulting in large final infarct volumes. We investigated the effect of Sanguinate (TM) (SG), a PEGylated carboxyhemoglobin (COHb) gas transfer agent, on changes in collateral and reperfusion cerebral blood flow and brain injury in SHR during 2 h of MCAO. SG (8 mL/kg) or vehicle (n = 6-8/group) was infused i.v. after 30 or 90 min of ischemia with 2 h reperfusion. Multi-site laser Doppler probes simultaneously measured changes in core MCA and collateral flow during ischemia and reperfusion using a validated method. Brain injury was measured using TTC. Animals were anesthetized with choral hydrate. Collateral flow changed little in vehicle-treated SHR during ischemia (-8 +/- 9% vs. prior to infusion) whereas flow increased in SG-treated animals (29 +/- 10%; p < 0.05). In addition, SG improved reperfusion regardless of time of treatment; however, brain injury was smaller only with early treatment in SHR vs. vehicle (28.8 +/- 3.2% vs. 18.8 +/- 2.3%; p < 0.05). Limited collateral flow in SHR during MCAO is consistent with small penumbra and large infarction. The ability to increase collateral flow in SHR with SG suggests that this compound may be useful as an adjunct to endovascular therapy and extend the time window for treatment.
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