Systemic complement depletion inhibits experimental cerebral vasospasm.
OBJECTIVE
Cerebral vasospasm is the leading cause of morbidity and mortality in patients who are hospitalized because of aneurysmal subarachnoid hemorrhage (SAH). Recent work has suggested that activation of the complement cascade contributes to the development of cerebral vasospasm. To further examine this hypothesis, a rabbit model of SAH was employed.


METHODS
Two milliliters of autologous arterial blood was injected into the region of the perimesencephalic cistern. Forty-eight hours after SAH was induced, intravital perfusion-fixation was performed. Morphometric analysis of the basilar artery was used to assess the extent of cerebral vasospasm after pretreatment with the complement depleting agent, cobra venom factor (CVF), or vehicle. Rabbits were randomized to one of four groups: 1) sham (n = 5); 2) sham + CVF (n = 4); 3) SAH (n = 10); or 4) SAH + CVF (n = 7). Twenty-four hours before induction of SAH, the animals received either 100 units/kg CVF or vehicle. The total hemolytic potential of the serum confirmed a significant (P < 0.05) reduction in serum complement activity 24 hours after the administration of CVF.


RESULTS
Pretreatment with CVF significantly (P < 0.0083) reduced the extent of vasospasm, as assessed by lumen diameter from 393.9 +/- 100.1 microns (mean +/- standard deviation) in the SAH group to 510.7 +/- 72.8 microns in the SAH + CVF group, when compared with the sham (594.5 +/- 27.9 microns) and sham + CVF (587.7 +/- 47.3 microns) groups.


CONCLUSIONS
The results suggest a role for complement activation in SAH.
German
J W
JW
Department of Surgery, University of Vermont College of Medicine, Burlington, USA.
Gross
C E
CE
Giclas
P
P
Watral
W
W
Bednar
M M
MM
D000818:Animals; D001488:Basilar Artery / Q000276:immunology / Q000473:pathology; D003167:Complement Activation / Q000276:immunology*; D003165:Complement System Proteins / Q000502:physiology*; D004546:Elapid Venoms / Q000494:pharmacology; D005260:Female; D002546:Ischemic Attack, Transient / Q000276:immunology* / Q000473:pathology; D008297:Male; D011817:Rabbits; D013345:Subarachnoid Hemorrhage / Q000276:immunology* / Q000473:pathology
D004546:Elapid Venoms; C016310:cobra venom factor; D003165:Complement System Proteins