The Influence of Anesthetic Choice, PaCO2, and Other Factors on Osmotic Blood-Brain Barrier Disruption in Rats with Brain Tumor Xenografts
| Autor: | Gary Sexton, Michael A. Pagel, Edward A. Neuwelt, Steven A. Fiamengo, Christopher I. McCormick, Laura G. Remsen |
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| Rok vydání: | 1999 |
| Předmět: |
Antimetabolites
Antineoplastic Partial Pressure Transplantation Heterologous Brain tumor Nitrous Oxide Blood–brain barrier Tritium chemistry.chemical_compound Rats Nude Pharmacokinetics medicine Animals Humans Mannitol Propofol Evans Blue Isoflurane business.industry Brain Neoplasms Osmolar Concentration Carbon Dioxide medicine.disease Arabinose Diuretics Osmotic Rats Transplantation Oxygen medicine.anatomical_structure Methotrexate Anesthesiology and Pain Medicine chemistry Blood-Brain Barrier Anesthesia Anesthetic Anesthetics Inhalation Female business Anesthetics Intravenous medicine.drug |
| Zdroj: | Anesthesia & Analgesia. 88:559-567 |
| ISSN: | 0003-2999 |
| DOI: | 10.1213/00000539-199903000-00018 |
| Popis: | UNLABELLED Increasing the delivery of therapeutic drugs to the brain improves outcome for patients with brain tumors. Osmotic opening of the blood-brain barrier (BBB) can markedly increase drug delivery, but achieving consistent, good quality BBB disruption (BBBD) is essential. We evaluated four experiments compared with our standard isoflurane/O2 protocol to improve the quality and consistency of BBBD and drug delivery to brain tumor and normal brain in a rat model. Success of BBBD was assessed qualitatively with the large molecular weight marker Evans blue albumin and quantitatively by measuring delivery of the low molecular weight marker [3H]-methotrexate. With isoflurane/O2 anesthesia, the effects of two BBBD drugs of different osmolalities were evaluated at two different infusion rates and infusion durations. Arabinose was superior to saline (P = 0.006) in obtaining consistent Evans blue staining in 16 of 24 animals, and it significantly increased [3H]-methotrexate delivery compared with saline in the tumor (0.388 +/- 0.03 vs 0.135 +/-0.04; P = 0.0001), brain around the tumor (0.269 +/- 0.03 vs 0.035 +/- 0.03; P = 0.0001), brain distant to the tumor (0.445 +/- 0.05 vs 0.034 +/- 0.07; P = 0.001), and opposite hemisphere (0.024 +/- 0.00 vs 0.016 +/- 0.00; P = 0.0452). Forty seconds was better than 30 s (P = 0.0372) for drug delivery to the tumor. Under isoflurane/O2 anesthesia (n = 30), maintaining hypocarbia was better than hypercarbia (P = 0.025) for attaining good BBBD. A propofol/ N2O regimen was compared with the isoflurane/O2 regimen, altering blood pressure, heart rate, and PaCO2 as covariates (n = 48). Propofol/N2O was superior to isoflurane/O2 by both qualitative and quantitative measures (P < 0.0001). Neurotoxicity and neuropathology with the propofol/N2O regimen was evaluated, and none was found. These data support the use of propofol/N2O along with maintaining hypocarbia to optimize BBBD in animals with tumors. IMPLICATIONS Propofol/N2O anesthesia may be better than isoflurane/O2 for optimizing osmotic blood-brain barrier disruption for delivery of chemotherapeutic drugs to brain tumor and normal brain. |
| Databáze: | OpenAIRE |
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