Hyperbaric oxygen as a chemotherapy adjuvant in the treatment of metastatic lung tumors in a rat model
Hyperbaric oxygen as a chemotherapy adjuvant in the treatment of metastatic lung tumors in a rat model
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DOI：
10.1067/mtc.2003.90
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发表时间：
2003-01-01
影响因子：
6
通讯作者：
Spears, JR
中科院分区：
文献类型：
--
作者：
Petre, PM;Baciewicz, FA;Spears, JR
目的：这项研究的目的是检验高压氧水平增强肉瘤细胞系对阿霉素敏感性的假设在体外和体内在肺转移的大鼠模型中检测阿霉素（Adriamycin）的活性，并在大鼠模型中通过将水性氧直接注射到肺动脉中来测试混合静脉血动脉化的可行性。大鼠肉瘤（MCA-2）细胞在增加浓度的阿霉素（0.1-2.0 μ mol/L）的存在下孵育。在12小时的处理中，检查了有和没有高压氧预处理（3.7 atm绝对压力，持续1.5-3.5小时）的剂量依赖性毒性关系。在体内，向Sprague-Dawley大鼠（n = 24）静脉内注射10（6）个MCA-2细胞，并使肺肿瘤成熟14天。此时，将动物分为四组：对照组（未处理）、2 mg/kg阿霉素组、高压氧组（2 atm绝对压力下氧气30分钟）和高压氧加阿霉素组。给药后7天，计数肺结节数并测定肺重量。在另外的大鼠（n = 7），水氧（1毫升氧气/克生理盐水溶液）注入肺动脉，以确定是否动脉化的混合静脉血肺动脉氧合与高压舱（n = 7）。MCA-2细胞的细胞溶解（P <0.01）。高压氧联合阿霉素也显著降低了肺转移瘤的数量和肺重量（分别为P <0.01和P <0.01）。混合静脉血动脉化的可行性（> 100毫米汞柱）与水性氧infrations.Conclusions：高压氧增强阿霉素的化疗效果，在细胞培养和大鼠模型。水性氧输注可用于使混合静脉血达到与使用高压氧舱获得的水平相似的水平。
Objectives: The objectives of the study were to test the hypothesis that hyperbaric levels of oxygen enhance the sensitivity of a sarcoma cell line to doxorubicin (Adriamycin) both in vitro and in vivo in a rat model of pulmonary metastases and to test the feasibility of arterialization of mixed venous blood by direct injection of aqueous oxygen into the pulmonary artery in a rat model.Methods: Rat sarcoma (MCA-2) cells were incubated in the presence of increasing concentrations of doxorubicin (0.1-2.0 mumol/L). A dose-dependent toxicity relationship at 12 hours of treatment was examined with and without pretreatment with hyperbaric oxygen (3.7 atm absolute for 1.5-3.5 hours). In vivo, Sprague-Dawley rats (n = 24) were injected intravenously with 10(6) MCA-2 cells, and the lung tumors were allowed to mature for 14 days. At that time the animals were divided into four groups: control (no treatment), doxorubicin at 2 mg/kg, hyperbaric oxygen (oxygen at 2 atm absolute for 30 minutes), and hyperbaric oxygen plus doxorubicin. Seven days after treatment, the numbers of lung nodules were counted and the lung weights were determined. In additional rats (n = 7), aqueous oxygen (1 mL oxygen/g saline solution) was infused into the pulmonary artery to determine whether arterialization of mixed venous blood was comparable to pulmonary artery oxygenation with a hyperbaric chamber (n = 7).Results: Hyperbaric oxygen plus doxorubicin produced significantly greater. cytolysis of MCA-2 cells (P < .01) than did doxorubicin alone. Hyperbaric oxygen plus doxorubicin also significantly decreased the number of lung metastases and the lung weight relative to doxorubicin alone (P < .01 and P < .01, respectively). The feasibility of arterialization of mixed venous blood (> 100 mm Hg) with aqueous oxygen infusion was demonstrated.Conclusions: Hyperbaric oxygen enhanced the chemotherapeutic effect of doxorubicin both in cell culture and in the rat model. Aqueous oxygen infusion can be used to oxygenate mixed venous blood at levels similar to those obtained with the use of a hyperbaric chamber.