Single High-dose Irradiation Research Articles

Observations of intracranial neoplasms treated with gamma knife radiosurgery

Object. The purpose of this study was to compare histopathological changes with imaging findings in different tumors after gamma knife radiosurgery (GKS). Methods. Five patients of a series of 220 treated with GKS underwent craniotomy for tumor removal 3 to 12 months after radiosurgery. There were two patients with multiple cerebral metastases, one with vestibular schwannoma, one with malignant glioma, and one with meningioma. A portion of normal brain tissue outside the prescription dose volume was acquired wherever possible to facilitate examination of the effects of radiosurgery. Histopathological and immunohistochemical investigations were performed. In addition to the routine hematoxylin and eosin and Mallory trichrome stains, immunohistochemical reactions were also performed for Factor VIII—associated antigen (FVIII) and CD34 antigen to study vascular endothelial effects of the irradiation. Endothelial cells of vessels in the normal brain tissue covering the tumor, outside of the prescription isodose volume, expressed marked CD34 and FVIII positivity. In the irradiated targeted tumor tissue samples, however, both reactions decreased remarkably. Conclusions. The results of the present immunohistochemical study provide support to the experimental hypothesis that vascular endothelial cells are the principal targets of single high-dose irradiation. The loss of central contrast enhancement of tumor tissue following radiosurgery might be consequence of the vascular damage.

Low dose fractionated radiation (LDFRT) inhibits estrogen response element (ERE) and progesterone response element (PRE) binding activity: a potential molecular mechanism of ldfrt mediated sensitization

Purpose/Objective: We performed studies using p53 wild-type (BG-1) and p53-mutant (SW626) ovarian cancer cell lines: (1) To compare the Taxotere potentiating effects of single high dose radiation (>1 Gy) versus hyper radiation sensitivity (HRS) inducing low dose fractionated radiation (LDFRT) and (2) to understand the molecular mechanism of LDFRT mediated chemopotentiating effects.

Stereotactic single high dose irradiation of lung tumors under respiratory gating

Purpose: To investigate the feasibility of a stereotactic single high dose irradiation of lung tumors under respiratory gating and the clinical response. Methods and materials: Twenty-three malignant lung tumors less than 40 mm in diameter were treated by a single fractional irradiation. Results and discussion: Local regrowth was seen in three of ten tumors irradiated less than 30 Gy, the minimal dose. Only one regrowth was observed in the tumors treated by 30 Gy of with a follow up length of 3–24 months. Apparently 30 Gy is able to control the lung tumors with a diameter less than 40 mm.

Changes in plasma gelsolin concentration during acute oxidant lung injury in mice.

Oxidant stress may contribute to acute lung injury under some circumstances. The rapid depletion of plasma gelsolin following major trauma in patients who subsequently develop respiratory distress suggests that this actin-scavenging protein might protect against delayed pulmonary complications. The specific aim of these experiments was to explore the temporal and quantitative relationship between gelsolin levels and lung damage. Gelsolin levels were measured in three murine models of oxidant injury: immunotargeting of pulmonary endothelium with an H2O2-generating enzyme; continuous exposure to >95% O2; and single high-dose thoracic radiation. The degree of lung injury was inversely related to gelsolin levels in mice treated with glucose oxidase-conjugated antibodies against platelet endothelial cell adhesion molecule-1 (p <0.0001). By 60-72 hours of hyperoxic exposure, gelsolin levels had dropped precipitously in all mice who sustained major lung damage (p <0.0001), establishing a quantitative association between gelsolin concentration and hyperoxic lung injury (r = -0.72; 95% confidence interval: ?0.81 to ?0.59). Gelsolin levels modestly but progressively fell in irradiated mice over the 3 days following treatment (p = 0.012) despite the development of only microscopic lung damage during this timeframe. These findings are consistent with the hypothesis that gelsolin depletion is involved in the pathogenesis of acute oxidant lung injury.

Clinical outcomes of 3D conformal hypofractionated single high-dose radiotherapy for one or two lung tumors using a stereotactic body frame

Purpose: This study was performed to evaluate the clinical outcomes of three-dimensional (3D) conformal hypofractionated single high-dose radiotherapy for one or two lung tumors using a stereotactic body frame.Methods and Materials: Forty patients who were treated between July 1998 and November 2000 and were followed for >10 months were included in this study. Of the 40 patients, 31 had primary lung cancer and 9 had metastatic lung cancer. The primary lung cancer was staged as T1N0M0, T2N0M0, and T3N0M0 in 19, 8, and 4 patients, respectively. The primary sites of metastatic lung cancer were the colon in 4, tongue in 2, and osteosarcoma, lung cancer, and hepatocellular carcinoma in 1 each. 3D treatment planning was performed to maintain the target dose homogeneity within 15% and to decrease the irradiated lung volume from >20 Gy to <25%. All patients were irradiated using a stereotactic body frame and received 4 times 10–12 Gy single high-dose radiation at the isocenter during a period of 5–13 days (median 12).Results: The initial 3 patients received 40, and the remaining 37 patients received 48 Gy after dose escalation. Of the 33 tumors followed >6 months, 6 tumors (18%) disappeared completely after treatment. Twenty-five tumors (76%) decreased in size by 30% or more after treatment. Therefore, 31 tumors (94%) showed a local response. During the follow-up of 4–37 months (median 19), no pulmonary complications greater than National Cancer Institute-Common Toxicity Criteria Grade 2 were noted. Of the 16 patients with histologically confirmed T1N0M0 primary lung cancer who received 48 Gy, all tumors were locally controlled during the follow-up of 6–36 months (median = 19). In 9 tumors with lung metastases that were irradiated with 48 Gy in total, 2 tumors did not show a local response. Finally, 3 tumors (33%) with lung metastases relapsed locally at 6–12 months (median 7) after treatment during the follow-up of 3–29 months (median 18).Conclusion: 3D conformal hypofractionated single high-dose radiotherapy of 48 Gy in 4 fractions using a stereotactic body frame was useful for the treatment of lung tumors.

Expression of TNF-alpha and TGF-beta 1 in the rat brain after a single high-dose irradiation.

Cytokines and growth factors are important regulatory proteins controlling the growth and differentiation of normal and malignant glial cells. In this study, we investigated the expression and origin of tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta 1 (TGF-beta 1) in the subacute brain injury after a single high-dose irradiation using 60 Sprague-Dawley rats. The right cerebral hemispheres of rats were exposed to a single 10 Gy dose of gamma rays using Ir-192. The radiation effect was assessed at 1 week, 2 weeks, 4 weeks, 6 weeks, and 8 weeks after irradiation, and the results were compared with those in sham operation group. Histological changes characteristic of radiation injury were correlated with the duration after the single dose irradiation. The loss of cortical thickness also increased with the lapse of time after irradiation. The TNF-alpha expression in the irradiated cerebral hemispheres was significantly increased compared with that in the sham operation group. TGF-beta 1 expression was also increased in the irradiated hemispheres. Immunohistochemical study revealed that TGF-beta 1 was expressed predominantly by infiltrating macrophages and astrocytes around the necrotic areas. These findings indicate that TNF-alpha and TGF-beta 1 may play prominent roles in the radiation injuries after a single high-dose irradiation.

Single dose radiation is more effective for the UV-induced activation and proliferation of melanocytes than fractionated dose radiation.

To establish whether the effect of fractionating radiation modifies the effects of ultraviolet (UV) radiation on epidermal melanocytes, we compared the clinical and histological effects of single high dose radiation against repeated intermediate to low dose radiation on epidermal melanocytes. Three minimal erythema UV doses (MED) were administered to three sites on the buttocks of healthy volunteers. One site was irradiated with 0.5 MED UV every day for 6 consecutive days, another site was irradiated with 1 MED UV every second day, and a third site received a single dose of radiation with 3 MED UV. The treatment was replicated on the other buttock. For the evaluation of UV-induced erythema and pigmentation, erythema and melanin indices were measured at 2 and 14 days post-irradiation. For purposes of histological evaluation, tissue specimens taken from each irradiated site at 2 and 14 days post-irradiation and were stained with monoclonal antibodies against Mel-5, HMB-45 and tyrosinase. Fontana-Masson silver staining, DOPA staining and split DOPA reactions were also performed. At 14 days post-irradiation, UV radiation induced melanocyte activation, proliferation and melanogenesis in proportion to the radiation dose administered to each fraction. The most prominent responses were observed after single high doses of radiation. When the total administered dose is identical, fractionation of radiation dose diminishes the effects of UV radiation on epidermal melanocytes. Furthermore, long, uninterrupted doses of UV radiation were found to more effective in inducing melanogenesis and melanocyte activation.

Clinical outcomes of 3-D conformal hypofractionated single high dose radiotherapy for one or two lung tumors using a stereotactic body frame

Purpose: This study was performed to evaluate the clinical outcomes of three-dimensional (3-D) conformal hypofractionated single high dose radiotherapy for one or two lung tumors using a stereotactic body frame. Materials and Methods: Forty patients who were treated between July 1998 and November 2000, and were followed up longer than 4 months were included in this study. Thirty-one patients had primary lung cancer, and the other nine had metastatic lung cancer. The primary lung cancer was staged as T1N0M0, T2N0M0, and T3N0M0 in 19, 8, and 4 patients, respectively, and of the 31 primary lung cancer patients, 20 were inoperable, and the other 11 refused operations. All patients with primary lung cancer had a solitary pulmonary nodule less than 40 mm in diameter without any mediastinal lymph nodal involvement. The histology was adenocarcinoma in 18, squamous cell carcinoma in 9, small cell carcinoma in 1, and unconfirmed in 3 patients. The primary sites of metastatic lung cancer were colon cancer in 5, tongue cancer in 2, osteosarcoma and hepatocellular carcinoma in one patient each. Three patients with metastatic lung cancer had two tumors. The Performance Status was better than WHO grade-2 in all patients. Three-dimensional treatment planning was performed to establish the number of non-coplanar beams to maintain the target dose homogeneity within 15%, and to decrease the irradiated lung volume >20 Gy to less than 25%. All patients were irradiated using a stereotactic body frame and received 4 times 10-12 Gy single high dose radiation at the isocenter over a period of 5-13 (median=12) days. Results: Thirty-eight patients were treated with 6-10 non-coplanar static beams and the other 2 patients were treated with 7 arcs of dynamic arc conformal therapy. Forty Gy was irradiated in the initial 3 patients, and 48 Gy was irradiated in the remaining 37 patients after dose escalation. During the follow-up of 4-31 (Median=14) months, no pulmonary complications greater than an NCI-CTC criteria of grade 2 were noted. However, CT pulmonary changes (NCI-CTC criteria Grade 1) were confirmed in 90% of the patients without any severe symptoms. In addition, 36 (90%) tumors were locally controlled without any symptomatic complications. Of the 16 patients with histologically confirmed T1N0M0 stage primary lung cancer ( 11 adenocarcinomas, 4 squamous cell carcinoma and 1 small cell carcinoma ) who received 48 Gy, all tumors were locally controlled for the follow-up of 4-28months (median=12). In one patient cancer recurred in hilar lymph nodes and in the opposite lung at 6 months, and in the other two patients bone metastases were noted at 6 and 15 months without local recurrence. One patient died during the follow-up period due to intercurrent cause. Thus, the one-year local control rate was 100%, and the one-year cumulative overall survival rate was 93%, respectively. In 9 tumors with liver metastases that were irradiated with 48Gy in total, 3 tumors (33%) relapsed locally at 6-12 (median=9) months after treatment. Primary tumors other than lung tumors recurred in two patients. Conclusion: Based on the initial clinical results, we consider that 3-D conformal hypofractionated single high dose radiotherapy of 48 Gy in 4 fractions using a stereotactic body frame was safe and useful for the treatment of primary T1N0M0 stage lung tumors. Dose escalation might be necessary for patients with metastatic lung tumor.

The evaluation of the 3D treatment planning in stereotactic hypofractionated single high dose radiotherapy for lung tumor

The evaluation of the 3D treatment planning in stereotactic hypofractionated single high dose radiotherapy for lung tumor

The effects of continuous and single-dose radiation on choline uptake in organotypic tissue slice cultures of rabbit hippocampus

The objective of the present study was to determine the time-dependent course of choline uptake in mature organotypic slice cultures of rabbit hippocampal formation and to assess the effects of continuous and single high-dose irradiation on choline uptake in cultivated slices in vitro. Transverse slices of hippocampus were dynamically incubated in a cerebrospinal fluid-like culture medium for 72 h. To study the changes in choline uptake longitudinally, the slice cultures were processed with 0.1 µ M [3H]-choline, and tritium accumulation was counted. Two different gamma irradiation sources (125I seeds and a clinical 60Co source) were used as representative models of interstitial radiosurgery and other radiosurgical techniques. A total dose of approximately 6000 cGy was delivered to the brain slices in one session or in a continuous, relatively low-dose rate fashion, and their effects on high-affinity choline uptake were examined. In another set of experiments with 125I, 5 µM hemicholinium-3 was used in choline uptake procedures as a competitive high-affinity choline uptake inhibitor. The results can be summarized as follows: (1) in the control group of the hippocampal tissue culture, there was a significant increase in tritium accumulation values from 0 to 48 h and a decrease thereafter; (2) continuous 125I irradiation caused a highly significant depression of the accumulation of tritium compared to that observed in the control group throughout its application for 72 h; (3) there was no significant change in the accumulation of tritium in the slices after single high-dose rate irradiation with a 60Co source; and (4) 5 µM hemicholinium significantly depressed the accumulation of tritium in both the control and the 125I-irradiated groups, and there was no longer a difference between 125I-irradiated and control groups when both groups were treated with hemicholinium. These results demonstrate that the delivery of continuous but relatively low-dose rate gamma irradiation is more efficacious than single high-dose external irradiation on high-affinity choline uptake in hippocampal nervous tissue. The results also indicate that continuous irradiation specifically affected the high-affinity energy-dependent choline uptake mechanism, whereas nonspecific choline uptake did not seem to be disturbed. [Neurol Res 2001; 23: 669-675]

Early effects of PRS-irradiation for 9L gliosarcoma: characterization of interphase cell death.

We characterized the interphase cell death of 9L gliosarcoma after high-dose-rate, low-energy photon irradiation using the Photon Radiosurgery System (PRS), a novel device for interstitial radiotherapy. Within 24 hours after irradiation with a dose of 18 Gray, 22.0% of cells underwent metabolic cell death, whereas dead cells in controls stayed less than 5.0% (p<0.005). In the majority of sensitive cells, loss of membrane integrity preceded the lethal morphological changes. The response was dose-dependent over the range of 9-18 Gray, but saturation was obtained over 18 Gray. On the other hand, a significant (p < 0.01) increase in the number of TUNEL-positive cells with apoptotic morphology was detected 6-24 hours after irradiation, but the fraction remained 1.9-2.1% of the population and was independent of the doses between 9 and 25 Gray. Apoptotic cells were rarely observed in the control cells (0.3-0.6%). Our data indicate that single high-dose irradiation induces both necrotic and apoptotic interphase cell death in 9L gliosarcoma, but rapid cell death mostly occurs through the non-apoptotic pathway.

Fractionated radiosurgery for 9L gliosarcoma in the rat brain

Purpose: Fractionated radiosurgery is being carried out in the clinic to improve the therapeutic ratio of single-dose radiosurgery using various fractionation schemes. Because there is a paucity of experimental radiobiological data in the literature on the tumor response and late-responding normal tissue of critical intracranial structures to radiosurgery, the present animal study was designed to compare the response following a single high dose of radiation with that obtained from calculated fractionated doses of radiosurgery. Methods and Materials: Male Fischer rats with 9L gliosarcoma growing in their brains were stereotactically irradiated and assayed for the tumor control rate and brain tissue damage. The radiation dose needed for 50% tumor control (TCD 50) was used as the endpoint of the efficacy of radiosurgery. Normal brain damage was measured histologically following a period of time over 270 days. Histological evaluation included hematoxylin–eosin (H & E), Luxol fast blue and periodic acid Schiff (LFB/PAS) for the presence of myelin and glial fibrillary acidic protein (GFAP) for the assessment of astrocytic re-activity. The optical density of optic nerves and chiasms staining with LFB/PAS was quantitatively measured using a computer image analysis to assess the magnitude of demyelination. Results: Radiosurgery (RS) was found to be more effective in curing small tumors than large tumors. The dose required to control 50% of the tumored animals for 120 days was 24, 31, and 40 Gy for 2-, 6-, and 12-day-old tumors, respectively. Using 12-day-old brain tumors, two fractions of 23.5 Gy and three fractions of 18.5 Gy were found to be equivalent to the single dose of 35 Gy for tumor control. For normal brain damages, the visual pathways including optic nerves and chiasm were found to be highly radiosensitive structures. A single dose of 35 Gy produced 100% severe optic neuropathy. The fractionated RS regimens spared substantial optic nerve damage. Conclusion: The present data provide a strong radiobiological rationale for the use of fractionated RS in the treatment of tumors located near critical normal structures, including visual pathways. The sparing effect of fractionated RS is greater for late-responding tissues, relative to the rapidly proliferating tumor tissues. This report also characterizes the dose/time tolerance relationship of optic neuropathy after single and fractionated RS.

Short- and long-term histopathological changes in the canine liver following single high dose intraoperative radiation therapy (IORT)

Purpose: The histopathological changes in the canine liver following single high-dose intraoperative radiation therapy (IORT) were investigated in order to establish the tolerance of liver tissue to IORT, thus providing a framework for clinical IORT treatment of patients with metastatic disease to the liver. Materials and methods: Following partial resection of the liver, IORT in doses of 10, 20, 25, or 30Gy was applied to the resection plane and a non-surgically manipulated part of the liver of 25 beagles. Results: There were no postoperative complications, and no morbidity or mortality during a maximal follow-up of 5 years. Dogs were killed at 3 months, and 1, 2, 3 and 5 years following IORT. Light microscopic examination revealed capsular thickening, severe parenchymal fibrosis, liver cell atrophy, and bile duct proliferation at the irradiated area 1-2 years following IORT. At 3-5 years, however, only mild parenchymal changes were found that consisted of slight periportal fibrosis, an incidental portal...

Delayed vascular injury after single high-dose irradiation in the rat brain: histologic immunohistochemical, and angiographic studies.

To investigate structural and functional changes in rats after focal brain irradiation by using histologic, immunohistochemical, and angiographic methods. Sixty rats were irradiated stereotactically with photons from a 15-MeV linear accelerator. Two collimators and single doses ranging from 20 to 100 Gy were used to treat stereotactically defined areas of 3.7- and 4.7-mm cross section (80% isodose) in the right frontal lobe. The dose-response relationship for the end-point necrosis at 19 months revealed a mean tolerance dose (D50) of 34.2 Gy (standard errors: +4.1, -3.7 Gy). Histologic, immunohistochemical, and angiographic examinations were performed to evaluate delayed radiation effects. All animals irradiated with 100 Gy developed radiation necrosis after 9 months. Microangiography and immunohistochemical fluorescence staining of the endothelial cells revealed dose-dependent vascular dilatation and rarefaction. Animals irradiated with 20-50 Gy showed no morphologic changes after 9 months. With irradiation of 30-50 Gy, histologic vascular changes that increased with dose were found after 19 months. At that time, no changes were detected after irradiation with 20 Gy with both field sizes and after irradiation with 30 Gy and the 2-mm collimator. Radiation-induced functional disturbances of the brain vasculature could be demonstrated by extravasation of contrast medium by using a microangiographic technique. The observed effect had a definite dependence on dose, volume, and time after treatment.

Short- and long-term histopathological changes in the canine liver following single high-dose intraoperative radiation therapy (IORT)

Purpose: The histopathological changes in the canine liver following single high-dose intraoperative radiation therapy (IORT) were investigated in order to establish the tolerance of liver tissue to IORT, thus providing a framework for clinical IORT treatment of patients with metastatic disease to the liver. Materials and methods: Following partial resection of the liver, IORT in doses of 10, 20, 25, or 30Gy was applied to the resection plane and a non-surgically manipulated part of the liver of 25 beagles. Results: There were no postoperative complications, and no morbidity or mortality during a maximal follow-up of 5 years. Dogs were killed at 3 months, and 1, 2, 3 and 5 years following IORT. Light microscopic examination revealed capsular thickening, severe parenchymal fibrosis, liver cell atrophy, and bile duct proliferation at the irradiated area 1-2 years following IORT. At 3-5 years, however, only mild parenchymal changes were found that consisted of slight periportal fibrosis, an incidental portal-central fibrous septum and vascular changes with endothelial proliferation and focal arteriolar hyalinosis. Conclusions: This study demonstrated that following partial hepatic resection, IORT to the liver in the canine model can be applied safely, without short- or long-term treatment morbidity. Although doses up to 30Gy resulted in severe local tissue damage 1-2 years following IORT, these changes were largely reversible due to hepatic regeneration.

Delayed vascular injury after single high dose irradiation in the rat brain: Histological, immunohistochemical, and microangiographic studies

Delayed vascular injury after single high dose irradiation in the rat brain: Histological, immunohistochemical, and microangiographic studies

Palliative intraoperative irradiation of recurrent neck lymph node metastases in the head and neck area

In the course of a malignant tumor disease, metastases in the regional lymph nodes commonly are linked with poor prognosis. Especially in cases of recurrence after surgery and radiation therapy, curative management of the disease can rarely be achieved. Therefore several palliative treatment modalities have been developed. Intraoperative radiation therapy represents one of them it allows a single high-dose irradiation of a region which, in light of the global tumor disorder, cannot be cured by surgical intervention. METHODS/ PATIENTS: Between 1989 and 1994, 70 patients with recurrent metastases in the head and neck lymph nodes were treated with IORT in the ENT Department of the University Hospital Aachen in collaboration with the Radiation Department. Since some patients were irradiated up to four times, 91 operations (77 under general anesthesia and 14 under local anesthesia) and irradiations were performed. During the procedure each, patient had to be transported twice from the standard operating suite to the radiation unit and back. Regarding the palliative intention of IORT in these cases, we mainly evaluated parameters which had an influence on quality of life of the patients: duration of hospitalization, pain treatment, removal of necrotic tumor mass, and safety of treatment. Depending on the general condition, the patients stayed in the hospital for 3-56 days (median: 10 days). In almost every case, mental and to some extent physical integrity was restored for some time after the disfiguring tumor on the neck had been removed. In nearly 90%, pain treatment could be reduced (e.g., discontinuation of opiate treatment) or further progression could be avoided (74%). Despite the transportation only few complications occurred, which primarily involved healing disturbances (n = 8), fistulas (n = 3), and edemas of the arm (n = 2; after primary treatment of breast cancer). There was no serious infection observed under prophylactic antibiotic treatment in 74% of the cases. Local tumor control (LTC), which only was of minor interest in this treatment group, was possible depending on the extent of tumor resection that could be achieved during the surgical approach: R0 resection = > 50% LTC/R1 resection = > 40% LTC/R2 resection (72.5% of the cases) = > 24.8% LTC. Follow-up of the surviving patients lasted 6-26 months (mean: 14.4 months) but generally did not allow an exact assessment of the time of tumor control. IORT of recurrent metastases in the head and neck region in our opinion represents an effective alternative for palliative treatment. Important aspects of the patients' quality of life could be improved, and patients were then able to take part in social life again for some time. On the other hand tumor control was not to be expected since in most of the cases only an incomplete tumor resection was achieved. However, the extent of resection substantially affects local tumor control in the head and neck region.

Image-oriented planning of minimally invasive conformal irradiation of the head-neck area

Modern imaging techniques are a substantial part of treatment planning for minimally invasive radiotherapeutic procedures. The aim is three-dimensional assessment of the target volume and adjacent critical structures. In this paper, we report on our clinical experience with a precise system for stereotactic image correlation. Hereby, the advantages of each imaging modality can be combined. Precise immobilization of the patient is a prerequisite. The immobilization method has an accuracy of less than 1 mm. This method was evaluated in a clinical study in which a tumor control rate of 93% was achieved in patients with brain metastases after stereotactic single high dose radiotherapy. This indicated the excellent reliability of this treatment planning method. The integration of functional image information, such as blood flow or activation of cerebral cortical areas, will be evaluated in the future.

Effect of In Vivo Heart Irradiation on the Development of Antioxidant Defenses and Cardiac Functions in the Rat

During radiotherapy of thoracic tumors, the heart is often included in the primary treatment volume, and chronic impairment of myocardial function occurs. The cellular biomolecules are altered directly by radiation or damaged indirectly by free radical production. The purpose of this investigation was to evaluate the biochemical and functional responses of the rat heart to a single high dose of radiation. The effect of 20 Gy local X irradiation was determined in the heart of Wistar rats under general anesthesia. Mechanical performances were measured in vitro using an isolated perfused working heart model, and cardiac antioxidant defenses were also evaluated. Hearts were studied at 1 and 4 months after irradiation. This single dose of radiation induced a marked drop in the mechanical activity of the rat heart: aortic output was significantly reduced (18% less than control values) at 1 month postirradiation and remained depressed for the rest of the experimental period (21% less than control 4 months after treatment). This suggests the development of myocardial failure after irradiation. The decline of functional parameters was associated with changes in antioxidant defenses. The decrease in cardiac levels of vitamin E (-30%) was associated with an increase in the levels of Mn-SOD and glutathione peroxidase (+45.5% and +32%, respectively, at 4 months postirradiation). However, cardiac vitamin C and catalase levels remained constant. Since these antioxidant defenses were activated relatively long after irradiation, it is suggested that this was probably due to the production of free radical species associated with the development of inflammation.

The use of oxygenobarotherapy for treatment respiratory and cardio-vascular deaseases

Radiation effects are mediated in part by the generation of oxygen-derived free radicals and hydrogen peroxide. Membrane polyunsaturated fatty acids are important biological targets of these toxic molecules which cause lipid peroxidation. Radiation damage to DNA is also known to result in base hydroperoxides, especially thymidine hydroperoxide. Glutathione (GSH) is known to inhibit lipid peroxidation both chemically and through its interaction with the selenium-dependent glutathione peroxidase (GSH-Px). Although cytosolic GSH-Px can metabolize organic lipid peroxides in solution, it cannot metabolize phospholipid peroxides in micelles. This may be due to the interference of phase differences between the aqueous cytosol and the membrane, or the result of steric hinderance. Recent studies have suggested the presence of a membrane-bound GSH-dependent peroxidase system. We examined the cytosolic versus membrane-associated GSH-Px, in various tissues of mice on a selenium and vitamin E deficient diet, and found significant differences among organs in the distribution of enzyme activity in these two subcellular fractions. The effect of single high-dose whole body irradiation did not appear to be related to the activity of these enzymes.