Prevention of cerebral vasospasm by actinomycin D

The role of endothelin, a newly found vasoconstrictor peptide, is examined in the pathogenesis of cerebral vasospasm after experimental subarachnoid hemorrhage (SAH) in the dog. Endothelin immunoreactivity was overexpressed in the endothelium of the vasospastic basilar artery. Because endothelin synthesis is regulated at the messenger ribonucleic acid transcription level, the effect of actinomycin D, a ribonucleic acid synthesis inhibitor, was studied as a means of preventing vasospasm. It was found that treatment with intravenous actinomycin D for 5 days beginning on the day of SAH completely inhibited the development of vasospasm. This novel experimental therapy may lead not only to the elucidation of the pathogenesis of cerebral vasospasm but also to the availability of a prophylactic adjuvant therapy for patients with SAH.