Controlled release of lipopolysaccharide in the subarachnoid space of rabbits induces chronic vasospasm in the absence of blood

• Published in: Surgical neurology 2006-11, Vol.66 (5), p.463-469
• Main Authors: Recinos, Pablo F., Pradilla, Gustavo, Thai, Quoc-Anh, Perez, Marilyn, Hdeib, Alia M., Tamargo, Rafael J.
• Format: Article
• Language: English
• Subjects: Animals; Basilar Artery - drug effects; Basilar Artery - physiopathology; Blood Proteins - adverse effects; Blood Proteins - metabolism; Cerebral Arteries - drug effects; Cerebral Arteries - physiopathology; Chemotaxis, Leukocyte - drug effects; Chemotaxis, Leukocyte - physiology; Chronic Disease; Delayed-Action Preparations - administration & dosage; Delayed-Action Preparations - pharmacokinetics; Disease Models, Animal; Dose-Response Relationship, Drug; Encephalitis - etiology; Encephalitis - physiopathology; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Endotoxin; Inflammation Mediators - administration & dosage; Inflammation Mediators - metabolism; Inflammation Mediators - pharmacokinetics; Lipopolysaccharide; Lipopolysaccharides - administration & dosage; Lipopolysaccharides - metabolism; Lipopolysaccharides - pharmacokinetics; Polyvinyls - administration & dosage; Polyvinyls - chemistry; Polyvinyls - pharmacokinetics; Rabbit; Rabbits; Subarachnoid hemorrhage; Subarachnoid Hemorrhage - complications; Subarachnoid Hemorrhage - physiopathology; Subarachnoid Space - drug effects; Subarachnoid Space - physiopathology; Vascular Patency - drug effects; Vasoconstriction - drug effects; Vasoconstriction - physiology; Vasospasm; Vasospasm, Intracranial - etiology; Vasospasm, Intracranial - physiopathology
• ISSN: 0090-3019; 1879-3339
• DOI: 10.1016/j.surneu.2006.04.010

Leukocyte-endothelial cell interactions appear to play a role in the development of vasospasm after SAH. Using a purely inflammatory protein, LPS, we evaluated the effect of inflammation on the development of chronic vasospasm in the absence of blood and compared it to SAH-induced vasospasm in rabbits. Lipopolysaccharide was incorporated into EVAc polymers to produce 20% LPS/EVAc polymers (wt/wt). Rabbits (n = 23) were randomized to 4 experimental groups: (1) empty polymer (n = 6), (2) SAH (n = 5), (3) 0.7 mg/kg polymeric LPS dose (n = 6), and (4) 1.4 mg/kg polymeric LPS dose (n = 6). Blood and polymers were inserted into the cisterna magna. The rabbits were killed 3 days postoperatively, and the basilar arteries were harvested for morphometric analysis. Clinical response and lumen patencies were analyzed using ANOVA and a post hoc Newman-Keuls Multiple Comparisons test. Significant narrowing of the basilar artery was observed by insertion of 20% LPS/EVAc polymers into the subarachnoid space at a polymeric dose of 1.4 mg/kg (actual dose, 66 μg kg −1 d −1) (75.4% ± 4.2%; P < .01) and by SAH (80.3% ± 8.1%; P < .01) as compared with the empty polymer group. A trend toward narrowing was observed in the 0.7 mg/kg polymeric LPS dose group (actual dose, 33 μg kg −1 d −1) (85.2% ± 2.6%; P > .05). Symptoms associated with SAH were noted in 50% of the rabbits in the 0.7 mg/kg LPS group and in 100% of rabbits in the 1.4 mg/kg LPS group. Controlled release of LPS into the subarachnoid space of rabbits produced chronic vasospasm in a dose-dependent manner. At a polymeric dose of 1.4 mg/kg, LPS-induced vasospasm was equivalent to that induced by SAH. This suggests that LPS and SAH may induce vasospasm through similar mechanisms and provides further evidence that inflammation plays a central role in the etiology of chronic vasospasm.