Neuro- and cardioprotective effects of blockade of nitric oxide action by administration of methylene blue.
Methylene blue (MB), generic name methylthioninium (C(16)H(18)ClN(3) S . 3H(2)O), is a blue dye synthesized in 1876 by Heinrich Caro for use as a textile dye and used in the laboratory and clinically since the 1890s, with well-known toxicity and pharmacokinetics. It has experimentally proven neuroprotective and cardioprotective effects in a porcine model of global ischemia-reperfusion in experimental cardiac arrest. This effect has been attributed to MB's blocking effect on nitric oxide synthase and guanylyl cyclase, the latter blocking the synthesis of the second messenger of nitric oxide. The physiological effects during reperfusion include stabilization of the systemic circulation without significantly increased total peripheral resistance, moderately increased cerebral cortical blood flow, a decrease of lipid peroxidation and inflammation, and less anoxic tissue injury in the brain and the heart. The last two effects are recorded as less increase in plasma concentrations of astroglial protein S-100beta, as well as troponin I and creatine kinase isoenzyme MB, respectively.
Wiklund
Lars
L
Department of Surgical Sciences, Uppsala University Hospital, SE-75185 Uppsala, Sweden. lars.wiklund@surgsci.uu.se
Basu
Samar
S
Miclescu
Adriana
A
Wiklund
Per
P
Ronquist
Gunnar
G
Sharma
Hari Shanker
HS
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D052279:Creatine Kinase, MB Form / Q000378:metabolism; D015237:Dinoprost / Q000097:blood; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000266:history; D049672:History, 19th Century; D008751:Methylene Blue / Q000008:administration & dosage* / Q000737:chemistry / Q000266:history; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism*; D015425:Myocardial Reperfusion / Q000379:methods; D009414:Nerve Growth Factors / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D011897:Random Allocation; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood; D016019:Survival Analysis; D013552:Swine; D013997:Time Factors; D019210:Troponin I / Q000378:metabolism
D004791:Enzyme Inhibitors; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D019210:Troponin I; D009569:Nitric Oxide; D015237:Dinoprost; D052279:Creatine Kinase, MB Form; D008751:Methylene Blue