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01-01-2008 | lab. investigation-human/animal tissue

Transient cerebral hypoperfusion enhances intraarterial carmustine deposition into brain tissue

Authors: Shailendra Joshi, Mei Wang, Joshua J. Etu, Raymond F. Suckow, Thomas B. Cooper, Steven J. Feinmark, Jeffrey N. Bruce, Robert L. Fine

Published in: Journal of Neuro-Oncology | Issue 2/2008

Abstract

We hypothesized that bolus injections of lipid soluble chemotherapeutic drugs during transient cerebral hypoperfusion could significantly boost regional drug delivery. In the first two groups of New Zealand White rabbits we measured brain tissue carmustine concentrations after intravenous infusion, intraarterial infusion with normal perfusion, and after intraarterial injections during transient cerebral hypoperfusion. In the third group of animals we assessed the safety of the technique by assessing electroencephalographic changes for 6 h after flow arrest carmustine administration and subsequent histological examination. The brain tissue carmustine concentrations were fivefold to sevenfold higher when the drug was injected during cerebral hypoperfusion compared to a conventional intracarotid infusion (68.4 ± 24.5 vs. 14.2 ± 8.3 μg/g, n = 5 each, respectively, P < 0.0001). The brain tissue carmustine concentrations (y) were a linear function of the bolus dose (x) injected during cerebral hypoperfusion, y = 10.4 × x − 21 (R = 0.84, P < 0.001). Stable EEGs were recorded several hours after flow arrest carmustine exposure and histological examinations did not reveal any gross evidence of cerebral injury. Transient cerebral hypoperfusion during intraarterial bolus injection of carmustine significantly increases drug delivery. Clinical techniques that decrease CBF, such as, transient arterial occlusion by balloon tipped catheters, hyperventilation, hypothermia, induced hypotension, or transient circulatory arrest, could enhance intraarterial drug delivery to the brain. We believe that the mechanisms for improved drug delivery is the decrease in drug dilution by reduced or absent blood flow, decreased protein binding and a longer time for high concentrations of free drugs to transit through the blood brain barrier.

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Title: Transient cerebral hypoperfusion enhances intraarterial carmustine deposition into brain tissue
Authors: Shailendra Joshi
Mei Wang
Joshua J. Etu
Raymond F. Suckow
Thomas B. Cooper
Steven J. Feinmark
Jeffrey N. Bruce
Robert L. Fine
Publication date: 01-01-2008
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 2/2008
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-007-9450-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Transient cerebral hypoperfusion enhances intraarterial carmustine deposition into brain tissue

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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