Effects of a nitric oxide donor on and correlation of changes in cyclic nucleotide levels with experimental vasospasm.
OBJECTIVE
Vasospasm after subarachnoid hemorrhage (SAH) may result from hemoglobin-mediated removal of nitric oxide (NO) from the arterial wall. We tested the ability of the long-acting, water-soluble, NO donor (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-1,2-diolate (DETA/NO), delivered via continuous intracisternal infusion, to prevent vasospasm in a nonhuman primate model of SAH.


METHODS
First, vasorelaxation in response to DETA/NO was characterized in vitro by using monkey basilar artery rings under isometric tension. Next, monkeys were randomized to undergo angiography, unilateral SAH, and no treatment (SAH only, n = 4) or treatment with DETA/NO (1 mmol/L, 12 ml/d, n = 4) or decomposed DETA/NO (at the same dose, n = 4). Vasospasm was assessed by angiography, which was performed on Day 0 and Day 7. Levels of cyclic adenosine monophosphate and cyclic guanosine monophosphate (cGMP) were measured in cerebral arteries on Day 7.


RESULTS
DETA/NO produced significant relaxation of monkey arteries in vitro, which reached a maximum at concentrations of 10(-5) mol/L. In monkeys, angiography demonstrated significant vasospasm of the right intradural cerebral arteries in all three groups, with no significant difference in vasospasm among the groups (P > 0.05, analysis of variance). The ratios of cGMP or cyclic adenosine monophosphate levels in the right and left middle cerebral arteries were not different among the groups (P > 0.05, analysis of variance). There was no significant correlation between arterial cGMP contents and the severity of vasospasm.


CONCLUSIONS
DETA/NO did not prevent vasospasm. There was no correlation between the severity of vasospasm and cyclic adenosine monophosphate and cGMP levels in the cerebral arteries. These results suggest that events downstream of cyclic nucleotides may be abnormal during vasospasm.
Aihara
Yasuo
Y
Department of Surgery, Pritzker School of Medicine and University of Chicago Medical Center, Chicago, Illinois 60637, USA.
Jahromi
Babak S
BS
Yassari
Reza
R
Sayama
Tetsuro
T
Macdonald
R Loch
RL
D000818:Animals; D002533:Cerebral Angiography; D000242:Cyclic AMP / Q000097:blood*; D006152:Cyclic GMP / Q000097:blood*; D004195:Disease Models, Animal; D008252:Macaca fascicularis; D020768:Middle Cerebral Artery / Q000000981:diagnostic imaging / Q000187:drug effects; D020030:Nitric Oxide Donors / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013345:Subarachnoid Hemorrhage / Q000097:blood* / Q000150:complications* / Q000000981:diagnostic imaging; D014226:Triazenes / Q000627:therapeutic use*; D020301:Vasospasm, Intracranial / Q000097:blood* / Q000209:etiology / Q000517:prevention & control*
C105351:1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene; D020030:Nitric Oxide Donors; D014226:Triazenes; D000242:Cyclic AMP; D006152:Cyclic GMP