Validity of D-penicillamine in experimental cerebral vasospasm therapy

Abstract

Background: Cerebral vasospasm is a reversible vessel constriction following subarachnoid hemorrhage. Immunoreactive and inflammatory mechanisms induce long-term vasoconstriction and vessel dilatation inhibition. We hypothesized that D-penicillamine depresses this process given that it reduces the concentration of free oxygen (O2) radicals. We evaluated the effects of D-penicillamine on cerebral vasospasm in rabbits induced with subarachnoid hemorrhage, achieved by autologous blood injection in the basal cistern. Materials and methods: Four experimental groups were studied: Group 1: basilar angiography, Group 2: basilar angiography + D-penicillamine, Group 3: subarachnoid hemorrhage (SAH), and Group 4: SAH + D-penicillamine. Vessel diameter and cerebral vasospasm were evaluated angiographically in each group. Vascular degeneration was studied by electron microscopy of the basilar artery. Free O2 radicals were investigated based on measurements of the levels of vascular superoxide dismutase and malondialdehyde. Myasthenia gravis–like side effects of D-penicillamine application were analyzed by electromyography and electron microscopy of the orbicularis oculi muscle. Results: We detected a 9.03% decrease in basilar artery constriction in Group 4 compared with Group 3. In addition, levels of free O2 radicals were reduced in Groups 2 and 4. Application of D-penicillamine resulted in the prevention of basilar artery wall degeneration, without myasthenia gravis–like side effects. Conclusion: Our study indicated that D-penicillamine application induced vasodilatation and had anti-inflammatory effects.

Keywords

• D-penicillamine
• Micro vasospasm
• Cerebral vasospasm
• Subarachnoid hemorrhage
• Oxygen radical