HISTIDINE ATTENUATES CEREBRAL VASOSPASM IN A RABBIT MODEL OF SUBARACHNOID HEMORRHAGE

BACKGROUND Free radical generation following hemolysis of a subarachno id blood clot is believed to be a key component in the development of cerebral vasospasm. Histidine, an essential amino acid with free radic al scavenging characteristics, was examined for its effects on cerebra l vasospasm. METHODS An experimental rabbit model of subarachnoid hemo rrhage-induced vasospasm was used in which autologous arterial blood w as injected into the cisterna magna. Basilar arteries were removed fol lowing perfusion-fixation two days after the injection of blood, and t heir cross-sectional luminal areas were measured using computerized im age analysis. Rabbits received intravenous injections of L-histidine o r vehicle starting 30 min prior to induction of subarachnoid hemorrhag e (SAH), with additional injections given four times per day for the n ext 2 days. RESULTS The luminal area of arteries from animals treated with histidine (50 mg/kg/dose or 100 mg/kg/dose) were significantly la rger than those from vehicle-treated animals. Relative to the SAH-only groups (mean cross-sectional area = 106.8 x 10(3) mu m(2)), vasoconst riction was attenuated by 31% in the low dose treatment group (180.0 x 10(3) mu m(2)) and by 52% in the high dose treatment group (227.4 x 1 0(3) mu m(2)). Mean luminal area of control basilar arteries was 340.5 x 10(3) mu m(2). CONCLUSIONS These findings demonstrate that histidin e reduces the amount of cerebral vasospasm occurring subsequent to exp erimental SAH. It is suggested that the free radical scavenging charac teristics of histidine, particularly its ability to scavenge singlet o xygen, may be responsible for the reduction in vasospasm.