Effect of nimodipine on arachidonic acid metabolites after subarachnoid hemorrhage.
Arachidonic acid metabolites are under investigation as possible vasoactive agents involved in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage. Prostaglandins, as well as other vasoactive compounds, activate contractile proteins through utilization of extracellular bound Ca++ to the intracytoplasmic free fraction. Recently, calcium-antagonists, mainly Nimodipine, have been proposed for the prophylaxis and/or reversal of the ischemic damage caused by vasospasm. Nimodipine failed to reduce vasospasm incidence in a series of 30 patients admitted with diagnosis of subarachnoid hemorrhage from ruptured intracranial aneurysm. Nimodipine failed to reduce level of four arachidonate metabolites measured (prostaglandin D2, prostacyclin, thromboxane B2 and leukotriene C4) in lumbar and cisternal CSF. After subarachnoid hemorrhage there is a significant increase of CSF levels of arachidonate metabolites; in perianeurysmic cisterns level of prostaglandin D2, thromboxane B2 and leukotriene C4 are significantly higher than lumbar CSF levels. Moreover, cisternal CSF level of prostaglandin D2 and leukotriene C4 are significantly higher in patients with symptomatic vasospasm. Nimodipine did not significantly modify CFS level of arachidonate metabolites: this suggests that Nimodipine treatment, which definitely improves long-term results of patients for intracranial aneurysms, could exert its pharmacological action reducing Ca++ intake from the extracellular compartment and preventing a direct toxic effect of calcium, without a direct action against the release of vasoactive compounds.
D015121:6-Ketoprostaglandin F1 alpha / Q000134:cerebrospinal fluid; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000134:cerebrospinal fluid*; D006801:Humans; D009553:Nimodipine / Q000627:therapeutic use*; D015230:Prostaglandin D2; D011457:Prostaglandins D / Q000134:cerebrospinal fluid; D013189:SRS-A / Q000134:cerebrospinal fluid; D013345:Subarachnoid Hemorrhage / Q000134:cerebrospinal fluid* / Q000188:drug therapy; D013929:Thromboxane B2 / Q000134:cerebrospinal fluid
D001095:Arachidonic Acids; D011457:Prostaglandins D; D013189:SRS-A; D016718:Arachidonic Acid; D013929:Thromboxane B2; D009553:Nimodipine; D015121:6-Ketoprostaglandin F1 alpha; D015230:Prostaglandin D2