Intraarterial infusion of high-concentration papaverine damages cerebral arteries in rats.
OBJECTIVE
To determine the appropriate concentration of papaverine for therapeutic intraarterial infusion against cerebral vasospasm.


METHODS
We investigated histopathologic changes in cerebral arteries and brain tissue of normal Wistar rats that had received infusions of papaverine via the carotid artery. Rats were infused with 0.20 mL papaverine (concentration, 0.4% to 4.0%) via the internal carotid artery. Injury to the vascular wall was evaluated by transmission electron microscopy; pathologic changes in cerebral tissue were studied by light microscopy.


RESULTS
Neither brain necrosis nor brain edema was seen under light microscopy at any concentration. At 4.0% papaverine concentration, degeneration of endothelial cells and medial smooth muscle, including vacuole formation, was observed under electron microscopy. At 1.4% concentration, degeneration of endothelial cells was seen. Extravasation of Evans blue dye was noted when drug concentration exceeded 1.4%. At 0.8% concentration, no histopathologic change was noted.


CONCLUSIONS
On the basis of these results, we recommend a papaverine concentration of 0.8% or less for intraarterial infusion.
Yoshimura
S
S
Department of Neurosurgery, National Cardiovascular Center, Osaka, Japan.
Hashimoto
N
N
Goto
Y
Y
Sampei
K
K
Tsukahara
T
T
Iihara
K
K
D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D005070:Evans Blue; D005119:Extravasation of Diagnostic and Therapeutic Materials; D007261:Infusions, Intra-Arterial; D002546:Ischemic Attack, Transient / Q000188:drug therapy; D008297:Male; D010208:Papaverine / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000633:toxicity*
D014665:Vasodilator Agents; D005070:Evans Blue; D010208:Papaverine