The effect of ritanserin, a 5-HT2 receptor antagonist, on ischemic cerebral blood flow and infarct volume in rat middle cerebral artery occlusion.
OBJECTIVE
In a previous study from our laboratory, ritanserin, a specific 5-HT2 serotonin receptor antagonist, reduced ischemic damage in the setting of transient global ischemia. In this study, we examined the effect of ritanserin on ischemic cerebral blood flow, systemic blood pressure, and infarct volume in the model of permanent focal ischemia with brain temperature controlled at 35.0 degrees C to 36.0 degrees C.


METHODS
Thirty-seven male Sprague-Dawley rats were used. The right middle cerebral artery was permanently occluded. Ritanserin (8 mg/kg) or vehicle was continuously administered intravenously for 90 minutes starting 10 minutes after middle cerebral artery occlusion. Cerebral blood flow was monitored by laser Doppler flowmetry in the ischemic cortex before and for 2 hours after arterial occlusion. Brains were perfusion-fixed 3 days later, and infarct volumes were measured.


RESULTS
Mean arterial blood pressure was not affected by treatment. In the vehicle and ritanserin groups, mean ischemic cerebral blood flow (percent of preischemic values) was 34.6 +/- 14.7% (mean +/- SD) and 26.6 +/- 15.0%, respectively. Hemispheric infarct volumes were 119.3 +/- 49.4 mm3 and 136.6 +/- 49.6 mm3, respectively. No significant differences were recognized.


CONCLUSIONS
Intravenous administration of ritanserin did not affect mean arterial blood pressure or cerebral blood flow in the ischemic region during the acute phase of ischemia. No protective effect of ritanserin was apparent in the setting of permanent focal ischemia when treatment was begun shortly after the onset of ischemia.
Takagi
K
K
Department of Neurology, University of Miami School of Medicine, FL 33101.
Ginsberg
M D
MD
Globus
M Y
MY
Busto
R
R
Dietrich
W D
WD
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology*; D002536:Cerebral Arteries; D002540:Cerebral Cortex / Q000098:blood supply / Q000473:pathology; D002544:Cerebral Infarction / Q000473:pathology* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003342:Corpus Striatum / Q000098:blood supply / Q000473:pathology; D018492:Dopamine Antagonists; D007262:Infusions, Intravenous; D008297:Male; D011674:Pulse / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D016713:Ritanserin / Q000008:administration & dosage / Q000494:pharmacology*
D018492:Dopamine Antagonists; D016713:Ritanserin