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Real-time hemodynamic response and mitochondrial function changes with intracarotid mannitol injection
Shailendra Joshi1, Rajinder Singh-Moon1, Mei Wang1
1Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, NY, USA.
Brain Research
|January 21, 2014
Summary
Intraarterial (IA) mannitol infusions transiently increase blood flow and alter brain metabolism, impacting chemotherapy delivery for brain tumors. Timing is crucial for optimizing drug efficacy.
Area of Science:
- Neuroscience
- Pharmacology
- Biomedical Engineering
Background:
- Blood-brain barrier (BBB) disruption enhances chemotherapeutic drug delivery.
- Optimizing drug delivery for brain tumors requires understanding responses to BBB-disrupting agents.
Purpose of the Study:
- To investigate the time course of hemodynamic and metabolic changes following intraarterial (IA) mannitol infusions.
- To provide data for optimizing chemotherapeutic drug delivery strategies for brain tumors.
Main Methods:
- Comparison of hemodynamic and metabolic responses (tissue NADH) to intracarotid (IC) infusion of mannitol versus normal saline in a rabbit model.
- Evaluation of electroencephalogram (EEG) changes.
Main Results:
- Mannitol infusion caused a significantly greater, transient hyperemic response compared to normal saline.
- Mannitol increased tissue NADH concentrations, indicating altered mitochondrial function.
- Hemodynamic and metabolic changes returned to baseline within 5 minutes.
Conclusions:
- Intraarterial mannitol induces significant, transient changes in cerebral blood flow and brain metabolism.
- Intravenous chemotherapy should be administered concurrently with or just before IA mannitol.
- Intraarterial chemotherapy should be timed after the peak hyperemic response to mannitol subsides.
