Effect of Intrathecal Administration of Nitroglycerine in the Endothelin-1 Induced Rabbit Vasospasm Model

ABSTRACT

OBJECTIVE: Nitric oxide and endothelin-1 are two endothelium derived relaxing and constricting factors probably involved in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage. The aim of this study is to ascertain the effects of nitric oxide donor(nitroglycerine) to reverse endothelin-1 induced cerebral vasoconstriction in vivo, when administered to the adventitial side of the basilar artery exposed through a transclival approach and common carotid artery exposed through a transcervical approach. METHODS: The exposed arteries were subjected to pharmacological manipulations and direct observation of the changes of their sizes under surgical microscope. Measurements of blood pressure, pulse rate and cerebral blood flow using thermal diffusion flowmetry during the drug infusion were done. RESULTS: 1) Nitroglycerine rapidly and completely reversed endothelin-1-induced vasoconstriction. The average value for maximal vasoconstriction by endothelin-1/synthetic cerebrospinal fluid was 58.3% of baseline arterial diameter and occurred within 30 minutes. 2) The nitroglycerine administered via adventitial side of the blood vessel was not associated with any changes in systemic blood pressure nor other vital signs. 3) Same changes occurred in the common carotid artery, although the severity of the occurrence and reversal of vasospasm were not significant compared to those of basilar artery. CONCLUSION: Intrathecally administered nitroglycerine was effective in reversing cerebral vasoconstriction without causing systemic hypotension. These findings provides the potential for the development of targeted therapy to reverse cerebral vasospasm after subarachnoid hemorrhage using nitric oxide donors.