Nitrite does not provide additional protection to thrombolysis in a rat model of stroke with delayed reperfusion
Graduate School of Biomedical Sciences
Life Sciences | Medicine and Health Sciences
An adjuvant therapy to prolong the therapeutic window for stroke patients is urgently needed. This randomized, blinded, placebo-controlled study investigated adjuvant intravenous sodium nitrite with recombinant tissue plasminogen activator (rtPA) in middle cerebral artery occlusion (MCAO) with 6 and 2 h of ischemia followed by reperfusion in Sprague-Dawley rats (n=59). Quantitative diffusion, T(1)-, T(2)-weighted, and semiquantitative perfusion imaging were performed before and after reperfusion and at 48 h after ischemia to determine the spatiotemporal evolution of stroke. After 48 h animals were killed and examined to evaluate infarct size and evidence of hemorrhagic transformation. Factor VIII immunostaining was performed to assess vessel morphology. Nitrite treatment (6 h group: 37.5 micromol for more than 90 mins; 2 h group: 26.25 and 1.75 micromol for more than 60 mins) did not reduce infarct volume 48 h after MCAO compared with saline-treated placebo groups after 6 or 2 h of MCAO. Stroke progression from baseline to 48 h, based on the apparent diffusion coefficient and relative cerebral blood flow deficits before and after reperfusion and T(2)-weighted hyperintensity at 48 h, did not differ between treated and control animals. These results suggest that nitrite is not a protective adjuvant therapy to delayed rtPA administration after ischemic stroke in rats.
DOI of Published Version
J Cereb Blood Flow Metab. 2008 Mar;28(3):482-9. Epub 2007 Aug 8. Link to article on publisher's site
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
Schatlo B, Henning EC, Pluta RM, Latour LL, Golpayegani N, Merrill MJ, Lewin N, Chen Y, Oldfield EH. (2007). Nitrite does not provide additional protection to thrombolysis in a rat model of stroke with delayed reperfusion. Morningside Graduate School of Biomedical Sciences Student Publications. https://doi.org/10.1038/sj.jcbfm.9600542. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/444