Shailendra Joshi1, Rajinder Singh-Moon2, Mei Wang2, Jeffrey N Bruce3, Irving J Bigio4, Avraham Mayevsky5. 1. Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, NY, USA. Electronic address: sj121@columbia.edu. 2. Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, NY, USA. 3. Department of Neurological Surgery, College of Physicians and Surgeons of Columbia University, New York, NY, USA. 4. Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA. 5. Faculty of Life Sciences, Bar Ilan University, Ramat Gan 52900, Israel.
Abstract
UNLABELLED: 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 5min 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.
UNLABELLED: 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 5min 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.
Authors: Edward Neuwelt; N Joan Abbott; Lauren Abrey; William A Banks; Brian Blakley; Thomas Davis; Britta Engelhardt; Paula Grammas; Maiken Nedergaard; John Nutt; William Pardridge; Gary A Rosenberg; Quentin Smith; Lester R Drewes Journal: Lancet Neurol Date: 2008-01 Impact factor: 44.182
Authors: Johann N R Cooke; Jason A Ellis; Shaolie Hossain; Juliane Nguyen; Jeffrey N Bruce; Shailendra Joshi Journal: Drug Deliv Transl Res Date: 2016-10 Impact factor: 4.617
Authors: Vesa Kiviniemi; Vesa Korhonen; Jukka Kortelainen; Seppo Rytky; Tuija Keinänen; Timo Tuovinen; Matti Isokangas; Eila Sonkajärvi; Topi Siniluoto; Juha Nikkinen; Seppo Alahuhta; Osmo Tervonen; Taina Turpeenniemi-Hujanen; Teemu Myllylä; Outi Kuittinen; Juha Voipio Journal: PLoS One Date: 2017-03-20 Impact factor: 3.240