Synergic activity of combined prostacyclin: dimethyl sulfoxide in experimental brain ischemia.
We examined whether drugs that block calcium, prostaglandins, free radicals, and endorphin release could modify cerebral blood flow or nerve tissue pathology following a focal cerebrovascular lesion. Cats were randomly divided into six groups and were subjected to standard middle cerebral artery occlusion (MCAO) performed using a transorbital approach. One hour after MCAO, cats received the following compounds intravenously: (i) saline (CS), 1.5 mL/kg or polyethylene glycol, 300 micrograms (CP); (ii) naloxone (NX), 2 mg/kg; (iii) nimodipine (NM), 1 microgram.kg-1.min-1 x 60 min; (iv) dimethyl sulfoxide (DS), 0.9 g/kg in a 40% solution; (v) prostacyclin (PGI2), 200 ng.kg-1.min-1 for 60 min; or (vi) DS-PGI2 combined. At 1-h intervals, local CBF was recorded from the cortical tissue proximal and distal to the MCAO site using the hydrogen clearance method. Five hours after MCAO, cortical tissue was removed for catecholamine histofluorescence or perfused for tyrosine hydroxylase immunoreactive axon examination. Treatment with NX, NM, CP, or CS had no effect on either CBF or cortical tissue neurotransmitter morphology. PGI2 showed a transiently modest but significant increase of CBF, while DS provided moderate protection of catecholaminergic fibers and increased CBF by 27% after MCAO. The combination of DS-PGI2 resulted in significant cytoprotection of cortical catecholaminergic fibers and generated a sustained CBF increase of 68% of control values. These findings suggest that combining DS with PGI2 can yield a synergic effect with respect to cortical neurotransmitter and CBF protection after MCAO.
de la Torre
J C
JC
Division of Neurological Surgery, University of Ottawa, Ont., Canada.
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D002245:Carbon Dioxide / Q000378:metabolism; D002415:Cats; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004121:Dimethyl Sulfoxide / Q000627:therapeutic use*; D004357:Drug Synergism; D011464:Epoprostenol / Q000627:therapeutic use*; D005260:Female; D008297:Male; D009270:Naloxone / Q000627:therapeutic use; D009553:Nimodipine / Q000627:therapeutic use; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D009435:Synaptic Transmission / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002245:Carbon Dioxide; D009270:Naloxone; D009553:Nimodipine; D011464:Epoprostenol; D014446:Tyrosine 3-Monooxygenase; D004121:Dimethyl Sulfoxide