Histidine attenuates cerebral vasospasm in a rabbit model of subarachnoid hemorrhage.
BACKGROUND
Free radical generation following hemolysis of a subarachnoid blood clot is believed to be a key component in the development of cerebral vasospasm. Histidine, an essential amino acid with free radical scavenging characteristics, was examined for its effects on cerebral vasospasm.


METHODS
An experimental rabbit model of subarachnoid hemorrhage-induced vasospasm was used in which autologous arterial blood was injected into the cisterna magna. Basilar arteries were removed following perfusion-fixation two days after the injection of blood, and their cross-sectional luminal areas were measured using computerized image analysis. Rabbits received intravenous injections of L-histidine or vehicle starting 30 min prior to induction of subarachnoid hemorrhage (SAH), with additional injections given four times per day for the next 2 days.


RESULTS
The luminal area of arteries from animals treated with histidine (50 mg/kg/dose or 100 mg/kg/dose) were significantly larger than those from vehicle-treated animals. Relative to the SAH-only groups (mean cross-sectional area = 106.8 x 10(3) microns 2), vasoconstriction was attenuated by 31% in the low dose treatment group (180.0 x 10(3) microns 2) and by 52% in the high dose treatment group (227.4 x 10(3) microns 2). Mean luminal area of control basilar arteries was 340.5 x 10(3) microns 2.


CONCLUSIONS
These findings demonstrate that histidine reduces the amount of cerebral vasospasm occurring subsequent to experimental SAH. It is suggested that the free radical scavenging characteristics of histidine, particularly its ability to scavenge singlet oxygen, may be responsible for the reduction in vasospasm.
Fadel
M M
MM
Department of Neurological Surgery, University of Virginia, Charlottesville 22908, USA.
Foley
P L
PL
Kassell
N F
NF
Lee
K S
KS
D000818:Animals; D004195:Disease Models, Animal; D005609:Free Radicals / Q000378:metabolism*; D006639:Histidine / Q000627:therapeutic use*; D017665:Hydroxyl Radical / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D008297:Male; D011817:Rabbits; D011897:Random Allocation; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
D005609:Free Radicals; D013481:Superoxides; D017665:Hydroxyl Radical; D006639:Histidine