Prophylactic Intra-Arterial Injection of Vasodilator for Asymptomatic Vasospasm Converts the Patient to Symptomatic Vasospasm due to Severe Microcirculatory Imbalance

Object. The strategy to treat asymptomatic angiographic vasospasm following subarachnoid hemorrhage (SAH) is controversial. In this study we review our consecutive vasospasm series and discuss an adequate treatment strategy for asymptomatic vasospasm. Methods. From January 2007 to December 2012 we treated 281 aneurysmal SAH cases, with postoperative angiography performed 9 ± 2 days after the onset of SAH. Four asymptomatic cases received intra-arterial (IA) injection of vasodilator due to angiographic vasospasm. All cases improved vasospasm immediately following intervention. But all cases turned symptomatic within 48 hours. We retrospectively analyzed the time-density angiography curve and calculated the time to peak (TTP), mean transit time (MTT), and relative blood flow (rBF). Relative blood flow was calculated as follows. The integration of the value of the time-density curve for the artery was divided by the same value for the internal carotid artery multiplied by the MTT. Results. The decrease in TTP and MTT for the etiologic artery was similar to that of the nonetiologic artery. But the improvement in rBF for the etiologic artery and nonetiologic artery was 10% and 17%, respectively. Blood supply to the spastic artery decreased due to iatrogenic steal. Conclusion. Prophylactic IA injection of vasodilator in cases of asymptomatic vasospasm can produce symptomatic vasospasm

The Role of Arterioles and the Microcirculation in the Development of Vasospasm after Aneurysmal SAH

Cerebral vasospasm of the major cerebral arteries, which is characterized by angiographic narrowing of those vessels, had been recognized as a main contributor to delayed cerebral ischemia (DCI) in subarachnoid hemorrhage (SAH) patients. However, the CONSCIOUS-1 trial revealed that clazosentan could not improve mortality or clinical outcome in spite of successful reduction of relative risk in angiographic vasospasm. This result indicates that the pathophysiology underlying DCI is multifactorial and that other pathophysiological factors, which are independent of angiographic vasospasm, can contribute to the outcome. Recent studies have focused on microcirculatory disturbance, such as microthrombosis and arteriolar constriction, as a factor affecting cerebral ischemia after SAH. Reports detecting microthrombosis and arteriolar constriction will be reviewed, and the role of the microcirculation on cerebral ischemia during vasospasm after SAH will be discussed

EFFECT OF A FREE RADICAL SCAVENGER, EDARAVONE, IN THE TREATMENT OF PATIENTS WITH ANEURYSMAL SUBARACHNOID HEMORRHAGE

Abstract OBJECTIVE It is hypothesized that cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) is induced by free radicals released from a subarachnoid clot. This study therefore investigated the effect of a new free radical scavenger, edaravone, in the treatment of patients with aneurysmal SAH. METHODS Ninety-one patients with aneurysmal SAH participated in this study and were randomized into a control group (n = 42) and an edaravone-treated group (n = 49). The difference between the 2 groups in terms of incidence of delayed ischemic neurological deficits (DINDs) and cerebral infarction caused by vasospasm, and Glasgow Outcome Scale score at 3 months after SAH were statistically analyzed. RESULTS The incidence of DINDs was 21% in the control group and 10% in the edaravone-treated group, yet there was no statistically significant difference between the 2 groups (P = 0.118). In patients with DINDs, the incidence of cerebral infarction caused by vasospasm was 66% in the control group and 0% in the edaravone-treated group (P = 0.028), whereas the incidence of poor outcome caused by vasospasm was 71% in the control group and 0% in the edaravone-treated group (P = 0.046). CONCLUSION We found a trend toward a lesser incidence of DINDs and a lesser incidence of poor outcome caused by cerebral vasospasm in edaravone-treated patients. It might therefore be suggested that edaravone is a useful agent for the treatment of aneurysmal SAH

Suppression of the Rho/Rho-Kinase Pathway and Prevention of Cerebral Vasospasm by Combination Treatment with Statin and Fasudil After Subarachnoid Hemorrhage in Rabbit

The Rho/Rho-kinase pathway is considered important in the pathogenesis of sustained smooth muscle cell contraction during cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). The aims of this study were to investigate whether combination treatment, with pitavastatin as an inhibitor of RhoA and fasudil as an inhibitor of Rho-kinase, prevents the cerebral vasospasm. SAH was simulated using the double-hemorrhage rabbit model, and pitavastatin, or fasudil, or both (combination treatment) were administrated. The basilar artery (BA) cross-sectional area only in the combination treatment group was statistically larger than in the SAH group (p < 0.05). BA Rho-kinase, as measured by ELISA, was statistically reduced only in the combination treatment group compared with the SAH group (p < 0.05). In the other two treatment groups, pitavastatin or fasudil treatment group showed larger BA cross-sectional areas and lower value for BA Rho-kinase, but there were no statistically significant differences compared with the SAH group. The expression of endothelial nitric oxide synthase (eNOS), evaluated by immunohistochemistry in the pitavastatin group and the combination group, was higher than in the SAH group. Results indicate that combination treatment could extensively prevent cerebral vasospasm due to the synergic effect of combining pitavastatin and fasudil on the Rho/Rho-kinase pathway and on eNOS.Open Access Articl