gms | German Medical Science

Objective: Cerebral vasospasm (CVS) is a reversible vessel contraction in response to subarachnoid haemorrhage (SAH). D-penicillamin (D-pen) catalyses a variety of metals. Therefore it is used treating heavy metal intoxications, Wilson’s disease and rheumatoid arthritis (RA). Iatrogenic myasthenia gravis (MG) may occur during D-pen treatment of autoimmune diseases, esp. RA. We planned to investigate D-pen effects on CVS in rabbits undergoing autologous blood injection into the cerebellomedullary cistern (CC) in order to constitute SAH.

Method: Study group consisted of 30 rabbits, divided into 4 groups. Sole basilar angio was performed in group 1, basilar angio following intra peritoneal D-pen application for 3 weeks in group 2, SAH by blood injection into CC in group 3, and SAH following intraperitoneal D-pen application for 3 weeks in group 4. We evaluated CVS by angio, vascular degeneration by electron microscopic (EM) examination of the basilar artery, free O₂ radicals by investigating superoxide dismutase and malondialdehyde levels, MG by electromyography (EMG) and EM of the orbicularis oculi muscles.

Results: A significant decrease in free O₂ radicals was observed in both D-pen treated groups. Basilar angio in groups 1, 2 revealed only minimal CVS. In group 3 (SAH -D-pen.) basilar artery constriction of 50% was observed after 30min, followed by some dilatation after 120min and again 50% CVS after 180min. In group 4 (SAH +D-pen.) a similar pattern of CVS was found: 50% after 30min and still nearly 40% after 180min. MG did not develop in our subjects. EMG and EM of the orbicularis oculi muscles in D-pen treated groups were found to be normal. EM of the basilar artery in group 1, 2 was normal. In group 3 we observed splitting of endothelial cells, chromatin aggregation, cytoplasmatic vacuolisation, mitochondrial edema, splitting in endothelial connections, thickening in elastic lamina and changes in smooth muscles. SAH-triggered changes were less pronounced in EM examination of group 4 basilar arteries.

Conclusions: These findings indicate that treatment with D-penicillamine does not prevent or reverse CVS in this model of SAH. A slight 10% dilatation of the basilar artery at 180min may be attributed to a decrease of free O₂ radicals. EM examination of basilar arteries after SAH induction revealed less changes in D-pen treated groups, may be due to the chelate forming effect of penicillamine by removing transitional metals from the vessel wall, decreasing O₂ radicals and preventing inflammation.