[The effect on the tumor vessel permeability by hyperosmotic blood brain barrier disruption].
The limited effect of chemotherapy on malignant brain tumors has been related to tumor cell insensitivity to the drugs and to their ineffectual delivery to the tumor. The studies by Groothuis and Neuwelt et al have shown that the studies of tumor vessel permeability show considerable variability in different areas of tumors and between different tumor models. The present studies used the 9L gliosarcoma model in Fischer 344 rats to evaluate the increase of tumor vessel permeability by osmotic BBB opening on drug delivery to the tumor, brain adjacent to tumor (BAT), and brain distant to tumor using cis-diamminedichloroplatinum (CDDP) as a chemotherapeutic agent which was water soluble and rarely permeable to BBB. In addition the difference of delivery to normal brain and tumor tissue were studied on intravenous or intracarotid administration of cisplatin with or without intracarotid infusion of graded (20%, 25%) hyperosmolar mannitol. Evans blue, which binds to plasma albumin, was used to provide a visual marker of BBB opening. 20% or 25% hyperosmolar mannitol infusion to right internal carotid artery for BBB disruption was done at 0.12 ml/sec for 30 sec with controlled respiration after temporally clipping of right common carotid artery. Then cis-diamminedichloroplatinum (CDDP) was infused at 0.5 mg/ml/100 gr (body weight). In control studies isotonic saline instead of mannitol was infused to intracarotid artery at identical rate and volume. In 14 9L gliosarcoma bearing rats and 3 normal rats cis-diamminedichloroplatinum (CDDP) delivery to tumor and normal brain.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001812:Blood-Brain Barrier; D001932:Brain Neoplasms / Q000098:blood supply / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects; D002945:Cisplatin / Q000493:pharmacokinetics*; D005910:Glioma / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
D008353:Mannitol; D002945:Cisplatin