Article
A preclinical randomized, blinded, placebo-controlled study of sodium nitrite as an adjunct to delayed thrombolysis for ischemic stroke
Erprobung von Nitrit als Zusatz zur verspäteten Thrombolyse nach ischämischem Schlaganfall – eine präklinische randomisierte plazebokontrollierte Doppelblindstudie
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Published: | May 30, 2008 |
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Objective: At present, stroke therapy using systemic thrombolysis is limited to the first three hours post ictus due to the risk of hemorrhagic events due to reperfusion injury. Sodium nitrite recently emerged as a promising radical nitric oxide donor and radical scavenger in myocardial reperfusion injury and liver transplantation. While there is anecdotal evidence for its use as a neuroprotectant in small animal studies, it is not known whether it is a clinically useful adjunct to thrombolysis after delayed ischemic stroke.
Methods: This randomized, blinded, placebo-controlled study evaluated intravenous sodium nitrite with recombinant tissue plasminogen activator (rtPA) in middle cerebral artery occlusion (MCAO) with 6 and 2 hours of ischemia followed by reperfusion in Sprague-Dawley rats (n=59). Serial magnetic resonance imaging (DWI, T1, T2 and perfusion imaging) and neurobehavioral assessment were used throughout the experiment to determine the effect of treatment. After 48 hours, the experiment was concluded with a histopathological workup.
Results: Nitrite treatment (6 hour group: 37.5μmol over 90 minutes; 2 hour group: 26.25 and 1.75 μmol over 60 minutes) did not reduce infarct volume 48 hours after MCAO compared to saline-treated placebo groups. Stroke progression from baseline to 48 hours, based on the apparent diffusion coefficient (ADC) and relative cerebral blood flow (rCBF) deficits before and after reperfusion and T2-weighted hyperintensity at 48 hours, did not differ between treated and control animals.
Conclusions: These results suggest that nitrite is not a protective adjuvant therapy to delayed rtPA administration following ischemic stroke in rats.