A systematic review of nitric oxide donors and L-arginine in experimental stroke; effects on infarct size and cerebral blood flow.
BACKGROUND
Nitric oxide (NO) is a candidate treatment for acute ischaemic stroke, however published studies in experimental stroke have given conflicting results.


METHODS
We performed a systematic review of published controlled studies of L-arginine (the precursor for NO) and NO donors in experimental stroke. Data were analysed using the Cochrane Collaboration Review Manager software. Standardised mean difference (SMD) and 95% confidence intervals (95% CI) were calculated.


RESULTS
Altogether, 25 studies(s) were identified. L-Arginine and NO donors reduced total cerebral infarct volume in permanent (SMD -1.21, 95% CI -1.69 to -0.73, p < 0.01, s = 10) and transient models of ischaemia (SMD -0.78, 95% CI -1.21 to -0.35, p < 0.01, s = 7). Drug administration increased cortical CBF in permanent (SMD +0.86, 95% CI 0.52-1.21, p < 0.01, s = 8) but not transient models (SMD +0.34, 95% CI -0.02 to 0.70, p = 0.07, s = 4).


CONCLUSIONS
Administration of NO in experimental stroke reduces stroke lesion volume in permanent and transient models. This may be mediated, in part, by increased cerebral perfusion in permanent models. These data support clinical trials in stroke patients, although the presence of a narrow therapeutic time window may be a limiting factor.
Willmot
Mark
M
Institute of Neuroscience, University of Nottingham, Nottingham, UK.
Gray
Laura
L
Gibson
Claire
C
Murphy
Sean
S
Bath
Philip M W
PM
D000818:Animals; D001120:Arginine / Q000627:therapeutic use*; D002544:Cerebral Infarction / Q000188:drug therapy*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D020030:Nitric Oxide Donors / Q000627:therapeutic use*; D011817:Rabbits; D051381:Rats; D013997:Time Factors
D020030:Nitric Oxide Donors; D001120:Arginine