Systemic administration of phosphodiesterase V inhibitor, sildenafil citrate, for attenuation of cerebral vasospasm after experimental subarachnoid hemorrhage.

OBJECTIVE

One of the phosphodiesterase isoenzymes, Type V (PDE V), specifically hydrolyzes cyclic guanosine monophosphate to cause vasoconstriction. This study analyses the effect of PDE V inhibition with sildenafil citrate (SC) on cerebral vasospasm and its effect on apoptotic changes of the vascular endothelium.

METHODS

Twenty-four rabbits were divided into four groups. The first group was composed of sham-surgery animals. The second group was the subarachnoid hemorrhage (SAH) group, in which cerebral vasospasm was induced. In the third group, sham-surgery rabbits were treated with SC. In the fourth group, animals were treated with SC after SAH. SC was administered for 48 hours, 0.7 mg/kg, three times per day in Groups 3 and 4. Basilar artery lumen circumferences were measured in all groups by computerized image analysis. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) method was used to evaluate the rate of apoptosis between SAH and SC-treated SAH groups. Results were compared by analysis of variance and paired t tests, and P values less than 0.05 were considered significant.

RESULTS

Basilar artery circumferences between groups were significantly different (P < 0.001). SC (0.7 mg/kg, three times per d) significantly dilated the basilar arteries in both the sham-surgery group (2370 +/- 233 microm; P = 0.039) and the SAH group (2142 +/- 195 microm; P = 0.006) after 48 hours of treatment. The TUNEL method for apoptosis revealed that actual numbers of the apoptotic endothelial cells per cross section after SAH in the control (no treatment) (73 +/- 2) and SC-treated (0.7 mg/kg) groups(76 +/- 3) were not significantly different (P > 0.05).

CONCLUSIONS

The vasodilatory effect of SC was observed to be significant on normal cerebral vessels and after SAH-induced vasospasm. SC did not prevent apoptosis of the endothelium in our study, which suggests that prevention of apoptosis is not necessary in the treatment of cerebral vasospasm.