Infarct reduction by the platelet activating factor antagonist apafant in rats.
OBJECTIVE
Recent findings suggest a key role for platelet activating factor in neuroinjury. For this reason we evaluated the effects of the platelet activating factor antagonist apafant (4-(2-chlorophenyl)-9-methyl-2[3(4-morpholinyl)-3-propanol-1- yl[6H-thieno[3.2-f[[1.2.4]triazolo]4,3-1]]1.4]diazepine on farct volume and local cerebral blood flow following irreversible occlusion of the left middle cerebral artery in rats to assess the direct and vascular components of apafant's action.


METHODS
We measured infarct volume 48 hours after middle cerebral artery occlusion. The effect of multiple doses of apafant (30 mg/kg p.o.) was tested in both pretreatment (n = 8) and posttreatment (n = 8) groups. In the pretreatment group apafant was given 30 minutes before and 2, 6, and 18 hours after occlusion. Rats of the posttreatment group received apafant 1, 6, and 18 hours after middle cerebral artery occlusion. We also examined the effect of a single dose of apafant given 30 minutes prior to occlusion (n = 9) on local cerebral blood flow determined 2 hours after middle cerebral artery occlusion.


RESULTS
Both regimens of apafant effectively decreased infarct volume. The reduction in cortical infarct volume was 59% (p less than 0.01; H test, U test) when the rats were treated before and after vessel occlusion whereas the decrease was 47% (p less than 0.05; H test, U test) when treatment began 1 hour after occlusion. Apafant did not change local cerebral blood flow after occlusion compared with controls.


CONCLUSIONS
We suggest that the cytoprotection afforded by apafant occurs mainly via a direct effect on brain tissue and has no major vascular component.
Bielenberg
G W
GW
Institut für Pharmakologie und Toxikologie, Fachbereich Pharmazie, Philipps-Universität, Marburg, FRG.
Wagener
G
G
Beck
T
T
D000818:Animals; D001381:Azepines / Q000627:therapeutic use*; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D051381:Rats; D011916:Rats, Inbred F344; D014230:Triazoles / Q000627:therapeutic use*
D001381:Azepines; D010972:Platelet Activating Factor; D014230:Triazoles; C052518:WEB 2086