Abstract
BACKGROUND: Propofol has been shown to attenuate neuronal injury in a number of experimental conditions. However, its effect in models of cerebral ischemia after subarachnoid hemorrhage (SAH) remains controversial.
OBJECTIVE: To explore the effects of intracisternal injection of HX0507, a water-soluble propofol prodrug, on basilar artery spasm and brain tissue injury in a rabbit model of SAH.
DESIGN, TIME AND SETTING: A randomized, controlled, in vivo animal experiment based on behavior and morphology. The study was performed at the Laboratory of Anesthesiology and Critical Care Medicine, West China Hospital, Sichuan University from April to December 2007.
MATERIALS: HX0507 was provided by the Laboratory of Anesthesiology and Critical Care Medicine, West China Hospital of Sichuan University.
METHODS: A total of 30 healthy, male, New Zealand rabbits were randomly assigned to sham-operation, SAH-control, and SAH-HX0507 groups, with 10 animals in each group. The single-hemorrhage SAH model was established by injecting autologous arterial blood (1.0 mL/kg) into the cisterna magna in the SAH-control and SAH-HX0507 groups, while the sham-operation group was injected with normal saline (1.0 mL/kg). Thirty minutes after injection, the sham-operation and SAH-control groups were injected with normal saline (0.1 mL/kg) into the cisterna magna, while the SAH-HX0507 group received an injection of HX0507 (4.8 mg/kg).
MAIN OUTCOME MEASURES: The cross-sectional area and corrugation coefficients of basilar arteries and hippocampal CA1 neuronal densities were measured 48 hours after SAH (peak stage of vasospasm) using the Computer-Assisted Stereological Toolbox system. The ultrastructural structure of the basilar artery wall was examined by transmission electron microscopy. In addition, neurological behavioral impairment was evaluated by appetite score at pre-SAH, and 1 and 2 days after SAH.
RESULTS: The cross-sectional area of basilar arteries and hippocampal CA1 neuronal densities, as well as ultrastructural structure scores of the SAH-control group were significantly less than the other groups (P < 0.01 or P < 0.05), while the corrugation coefficients of basilar arteries and appetite score 2 days after SAH were significantly greater than the other groups (P < 0.01 or P < 0.05). The appetite score 1 day after modeling was remarkably greater than the SAH-control group (P < 0.05). However, no significant difference was determined between the sham-operation and SAH-HX0507 groups (P > 0.05).
CONCLUSION: Intracisternal administration of HX0507 attenuated basilar artery vasospasm and hippocampal ischemic injury in a rabbit model of SAH.
Key Words: HX0507; subarachnoid hemorrhage; basilar artery vasospasm