Propofol anesthesia compared to awake reduces infarct size in rats.
BACKGROUND
Propofol has not been studied directly in animals subject to cerebral ischemia in the conscious state. Strokes are usually induced in animals while they are anesthetized, making it difficult to eliminate anesthetic interactions as a complicating factor. Therefore, to compare the neuroprotective effects of propofol to the unanesthetized state, experiments were performed using a model that induces a stroke in the conscious rat.


METHODS
Cerebral ischemia was induced in awake Wistar rats by a local intracerebral injection of the potent vasoconstrictor endothelin. Four days before the strokes were induced, a guide cannula was implanted for the injection of endothelin. On the day of the experiment, endothelin (6.0 pmol in 3 microl) was injected into the striatum. Propofol (25 or 15 mg. kg-1. h-1) or intralipid (vehicle) were infused for 4 h starting immediately after the endothelin injection. In another series, the propofol infusion was begun 1 h after the endothelin injection and continued for 4 h. Three days later, the animals were killed, and the brains were sectioned and stained.


RESULTS
The propofol group (25 mg. kg-1. h-1) had a significantly reduced infarct size (0.7 +/- 0.21 mm3, first 4 h; 0.27 +/- 0.07 mm3, started 1 h after initiation of infarct) compared with the intralipid controls (3.40 +/- 0.53 mm3). To exclude a direct interaction between propofol and endothelin, in thiobutabarbital anesthetized rats, endothelin-induced cerebral vasoconstriction was examined using videomicroscopy, with or without propofol. Propofol had no effect on the magnitude or time course of the endothelin-induced vasoconstriction.


CONCLUSIONS
The results show that concurrent or delayed administration of propofol is neuroprotective.
Gelb
Adrian W
AW
Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada.
Bayona
Nestor A
NA
Wilson
John X
JX
Cechetto
David F
DF
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature; D001921:Brain / Q000187:drug effects / Q000502:physiology; D002544:Cerebral Infarction / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D016232:Endothelins / Q000494:pharmacology; D008297:Male; D018696:Neuroprotective Agents; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D020521:Stroke / Q000139:chemically induced / Q000473:pathology; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D018686:Anesthetics, Intravenous; D016232:Endothelins; D018696:Neuroprotective Agents; D014662:Vasoconstrictor Agents; D015742:Propofol