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


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 5min of mannitol injection.


CONCLUSIONS
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.
Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, NY, USA. Electronic address: sj121@columbia.edu.
Shailendra
S
Joshi
Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
Rajinder
R
Singh-Moon
Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
Mei
M
Wang
Department of Neurological Surgery, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
Jeffrey N
JN
Bruce
Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA.
Irving J
IJ
Bigio
Faculty of Life Sciences, Bar Ilan University, Ramat Gan 52900, Israel.
Avraham
A
Mayevsky
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D002339:Carotid Arteries; D004569:Electroencephalography; D006439:Hemodynamics / Q000187:drug effects*; D007269:Injections, Intra-Arterial; D008353:Mannitol / Q000008:administration & dosage*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D011817:Rabbits
D009243:NAD; D008353:Mannitol
Blood brain barrier; Intraarterial chemotherapy; Intracarotid; Ischemia; Mannitol; Nicotinamide adenine dinucleotide; Ultraviolet spectroscopy