Subarachnoid hemorrhage and the distribution of drugs delivered into the cerebrospinal fluid. Laboratory investigation.
OBJECTIVE
Investigators in experimental and clinical studies have used the intrathecal route to deliver drugs to prevent or treat vasospasm. However, a clot near an artery or arteries after subarachnoid hemorrhage (SAH) may hamper distribution and limit the effects of intrathecally delivered compounds. In a primate model of right middle cerebral artery (MCA) SAH, the authors examined the distribution of Isovue-M 300 and 3% Evans blue after infusion into the cisterna magna CSF.


METHODS
Ten cynomolgus monkeys were assigned to SAH and sham SAH surgery groups (5 in each group). Monkeys received CSF injections as long as 28 days after SAH and were killed 3 hours after the contrast/Evans blue injection. The authors assessed the distribution of contrast material on serial CT within 2 hours after contrast injection and during autopsy within 3 hours after Evans blue staining.


RESULTS
Computed tomography cisternographies showed no contrast in the vicinity of the right MCA (p < 0.05 compared with left); the distribution of contrast surrounding the entire right cerebral hemisphere was substantially reduced. Postmortem analysis demonstrated much less Evans blue staining of the right hemisphere surface compared with the left. Furthermore, the Evans blue dye did not penetrate into the right sylvian fissure, which occurred surrounding the left MCA. The authors observed the same pattern of changes and differences in contrast distribution between SAH and sham SAH animals and between the right and the left hemispheres on Days 1, 3, 7, 14, 21, and 28 after SAH.


CONCLUSIONS
Intrathecal drug distribution is substantially limited by SAH. Thus, when using intrathecal drug delivery after SAH, vasoactive drugs are unlikely to reach the arteries that are at the highest risk of delayed cerebral vasospasm.
Pluta
Ryszard M
RM
Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1414, USA. plutar@ninds.nih.gov
Butman
John A
JA
Schatlo
Bawarjan
B
Johnson
Dennis L
DL
Oldfield
Edward H
EH
D000818:Animals; D002946:Cisterna Magna / Q000378:metabolism; D004396:Coloring Agents / Q000493:pharmacokinetics; D003287:Contrast Media / Q000493:pharmacokinetics; D005070:Evans Blue / Q000493:pharmacokinetics; D007091:Image Processing, Computer-Assisted; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D007278:Injections, Spinal; D007479:Iopamidol / Q000493:pharmacokinetics; D008252:Macaca fascicularis; D004364:Pharmaceutical Preparations / Q000134:cerebrospinal fluid* / Q000378:metabolism; D013345:Subarachnoid Hemorrhage / Q000134:cerebrospinal fluid* / Q000378:metabolism; D015912:Thrombolytic Therapy; D014057:Tomography, X-Ray Computed; D020301:Vasospasm, Intracranial / Q000503:physiopathology
D004396:Coloring Agents; D003287:Contrast Media; D004364:Pharmaceutical Preparations; D005070:Evans Blue; D007479:Iopamidol