Real-time hemodynamic response and mitochondrial function changes with intracarotid mannitol injection

Shailendra Joshi, Rajinder Singh-Moon, Mei Wang, Jeffrey N. Bruce, Irving J. Bigio, Avraham Mayevsky

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Disruption of blood brain barrier (BBB) is used to enhance chemotherapeutic drug delivery. The purpose of this study was to understand the time course of hemodynamic and metabolic response to intraarterial (IA) mannitol infusions in order to optimize the delivery of drugs for treating brain tumors. Principal results: We compared hemodynamic response, EEG changes, and mitochondrial function as judged by relative changes in tissue NADH concentrations, after intracarotid (IC) infusion of equal volumes of normal saline and mannitol in our rabbit IC drug delivery model. We observed significantly greater, though transient, hyperemic response to IC infusion of mannitol compared to normal saline. Infusion of mannitol also resulted in a greater increase in tissue NADH concentrations relative to the baseline. These hemodynamic, and metabolic changes returned to baseline within 5 min of mannitol injection. Conclusion: Significant, though transient, changes in blood flow and brain metabolism occur with IA mannitol infusion. The observed transient hyperemia would suggest that intravenous (IV) chemotherapy should be administered either just before, or concurrent with IA mannitol injections. On the other hand, IA chemotherapy should be delayed until the peak hyperemic response has subsided.

Original languageEnglish
Pages (from-to)42-51
Number of pages10
JournalBrain Research
Volume1549
DOIs
StatePublished - 26 Feb 2014

Bibliographical note

Funding Information:
This work was supported by the National Cancer Institute , NIH R01 Grants CA-127500 , and R01-CA-138643 , SJ.

Keywords

  • Blood brain barrier
  • Intraarterial chemotherapy
  • Intracarotid
  • Ischemia
  • Mannitol
  • Nicotinamide adenine dinucleotide
  • Ultraviolet spectroscopy

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