Electrophysiological and Pathological Impact of Medium-Dose External Carbon Ion and Proton Beam Radiation on the Left Ventricle in an Animal Model.

Background Medium-dose (25 gray) x-ray radiation therapy has recently been performed on patients with refractory ventricular tachyarrhythmias. Unlike x-ray, carbon ion and proton beam radiation can deliver most of their energy to the target tissues. This study investigated the electrophysiological and pathological changes caused by medium-dose carbon ion and proton beam radiation in the left ventricle (LV). Methods and Results External beam radiation in the whole LV was performed in 32 rabbits. A total of 9 rabbits were not irradiated (control). At the 3-month or 6-month follow-up, the animals underwent an open-chest electrophysiological study and were euthanized for histological analyses. No acute death occurred. Significant LV dysfunction was not seen. The surface ECG revealed a significant reduction in the P and QRS wave voltages in the radiation groups. The electrophysiological study showed that the local conduction times in each LV site were significantly longer and that the local LV bipolar voltages were significantly lower in the radiation groups than in the control rabbits. Histologically, apoptosis, fibrotic changes, and a decrease in the expression of the connexin 43 protein were seen in the LV myocardium. These changes were obvious at 3 months, and the effects were sustained 6 months after radiation. No histological changes were seen in the coronary artery and esophagus, but partial radiation pneumonitis was observed. Conclusions Medium-dose carbon ion and proton beam radiation in the whole LV resulted in a significant electrophysiological disturbance and pathological changes in the myocardium. Radiation of the arrhythmogenic substrate would modify the electrical status and potentially induce the antiarrhythmic effect.

Intraperitoneal injection of (-)-Epigallocatechin-3-gallate protects against light-induced photoreceptor degeneration in the mouse retina.

PURPOSE: (-)-epigallocatechin-3-gallate (EGCG), a major catechin component of green tea, is reported to delay or prevent certain forms of cancer, arthritis, cardiovascular disease, and neurodegenerative disorders. In this study, we determined if systemically administered EGCG could protect the retina against light damage (LD) in mice. METHODS: BALB/cJ mice were treated with either EGCG or saline via intraperitoneal (IP) injection, and then placed under constant cool white light-emitting diode (LED) light (10,000 lux) for 5 h. Retinal structure and function were evaluated using optical coherence tomography (OCT), histology, and electroretinography (ERG) 7 days after LD. In addition, the mRNAs of several oxidative stress genes were quantified by qPCR before LD and 24 h after LD. RESULTS: OCT and photomicrographs of mouse retinas showed morphologic protection of photoreceptors. Mice in the EGCG group had significantly higher ERG amplitudes for all three wave types compared with mice in the saline control group, which indicated that EGCG protected retinal function. Furthermore, qPCR results showed that EGCG administration can increase the mRNA level of the antioxidant gene Sod2 before LD and 24 h after LD. CONCLUSIONS: The IP injection of EGCG attenuated the detrimental effects of bright light on the retinas of BALB/cJ mice by protecting the structure and function of the retina.

A standardized Hippophae extract (SBL-1) counters neuronal tissue injuries and changes in neurotransmitters: implications in radiation protection.

CONTEXT: Effects of a radioprotective, standardized leaf extract (code SBL-1) from traditional medicinal plant, sea buckthorn [Hippophae rhamnoides L. (Elaeagnaceae)], on neurotransmitters and brain injuries in rats showing radiation-induced conditioned taste aversion (CTA), are not known. Understanding CTA in rats is important because its process is considered parallel to nausea and vomiting in humans. OBJECTIVE: This study investigated the levels of neurotransmitters, antioxidant defences and histological changes in rats showing radiation CTA, and their modification by SBL-1. MATERIALS AND METHODS: The inbred male Sprague-Dawley rats (age 65 days, weighing 190 ± 10 g) were used. Saccharin-preferring rats were selected using standard procedure and divided into groups. Group I (untreated control) was administered sterile water, group II was 60Co-γ-irradiated (2 Gy), and group III was administered SBL-1 before irradiation. Observations were recorded up to day 5. RESULTS: Irradiation (2 Gy) caused (i) non-recoverable CTA (≥ 64.7 ± 5.0%); (ii) degenerative changes in cerebral cortex, amygdala and hippocampus; (iii) increases in brain dopamine (DA, 63.4%), norepinephrine (NE, 157%), epinephrine (E, 233%), plasma NE (103%) and E (160%); and (iv) decreases in brain superoxide dismutase (67%), catalase (60%) and glutathione (51%). SBL-1 treatment (12 mg/kg body weight) 30 min before irradiation (i) countered brain injuries, (ii) reduced CTA (38.7 ± 3.0%, day 1) and (iii) normalized brain DA, NE, E, superoxide dismutase, catalase and CTA from day 3 onwards. DISCUSSION AND CONCLUSION: Radiation CTA was coupled with brain injuries, disturbances in neurotransmitters and antioxidant defences. SBL-1 pretreatment countered these disturbances, indicating neuroprotective action.

Dose-dependent short- and long-term effects of ionizing irradiation on neural stem cells in murine hippocampal tissue cultures: neuroprotective potential of resveratrol.

INTRODUCTION: Radiation therapy plays an essential role in the treatment of brain tumors, but neurocognitive deficits remain a significant risk, especially in pediatric patients. In recent trials, hippocampal sparing techniques are applied to reduce these adverse effects. Here, we investigate dose-dependent effects of ionizing radiation (IR) on juvenile hippocampal neurogenesis. Additionally, we evaluate the radioprotective potential of resveratrol, a plant polyphenol recognized for its bifunctional tumor-preventive and anticancer effects. METHODS: Organotypic entorhinal-hippocampal slice cultures from transgenic nestin-CFPnuc C57BL/J6 mice, postnatal days 3-6, were irradiated on a X-ray machine (4.5, 8, 12, and 16 Gy, single doses) after about 2 weeks. Nestin-positive neural stem cells were counted at a confocal live imaging microscope 0, 2, 4, 14, 25, and 42 days after IR. Resveratrol (15 µmol/L) was added 2 hr before and 24 hr after IR. Proliferation and cell death were assessed by BrdU pulse label, 48 hr after and by propidium iodide staining 96 hr after IR. GFAP- and NeuN-positive cells were counted 42 days after IR in cryosectioned immunofluorescence-stained slices. RESULTS: The observed age-related changes of nestin-positive stem cells in the organotypic slice culture model resembled the reduction of neural stem cells in vivo. IR (4.5-16 Gy) led to a dose-dependent damage of the neural stem cell pool in the dentate gyrus. No recovery was seen within 42 days after doses from 4.5 Gy onward. The decline of nestin-positive cells was paralleled by increased cell death and decreased proliferation. The number of GFAP-positive cells was significantly enhanced. No significant change was detected in the overall NeuN-positive cell population, whereas the number of newborn, NeuN/BrdU double-positive neurons was reduced. Resveratrol treatment reversed the irradiation-induced decline of neural stem cells. CONCLUSION: The neuroprotective action of resveratrol on irradiated hippocampal tissue warrants further investigation as a possible supplement to hippocampal sparing procedures.

Chronic exposure to broadband noise at moderate sound pressure levels spatially shifts tone-evoked responses in the rat auditory midbrain.

Noise-induced hearing disorders are a significant public health concern. One cause of such disorders is exposure to high sound pressure levels (SPLs) above 85 dBA for eight hours/day. High SPL exposures occur in occupational and recreational settings and affect a substantial proportion of the population. However, an even larger proportion is exposed to more moderate SPLs for longer durations. Therefore, there is significant need to better understand the impact of chronic, moderate SPL exposures on auditory processing, especially in the absence of hearing loss. In this study, we applied functional magnetic resonance imaging (fMRI) with tonal acoustic stimulation on an established broadband rat exposure model (65 dB SPL, 30 kHz low-pass, 60 days). The auditory midbrain response of exposed subjects to 7 kHz stimulation (within exposure bandwidth) shifts dorsolaterally to regions that typically respond to lower stimulation frequencies. This shift is quantified by a region of interest analysis that shows that fMRI signals are higher in the dorsolateral midbrain of exposed subjects and in the ventromedial midbrain of control subjects (p<0.05). Also, the center of the responsive region in exposed subjects shifts dorsally relative to that of controls (p<0.05). A similar statistically significant shift (p<0.01) is observed using 40 kHz stimulation (above exposure bandwidth). The results suggest that high frequency midbrain regions above the exposure bandwidth spatially expand due to exposure. This expansion shifts lower frequency regions dorsolaterally. Similar observations have previously been made in the rat auditory cortex. Therefore, moderate SPL exposures affect auditory processing at multiple levels, from the auditory cortex to the midbrain.

Osseointegration of implants in irradiated bone with and without hyperbaric oxygen treatment: an experimental study in rat Tibiae.

PURPOSE: Hyperbaric oxygen (HBO) has been recommended to enhance implant osseointegration in irradiated bone. The aim of this study was to further investigate the effects of HBO on implant integration in irradiated bone tissue. MATERIALS AND METHODS: The present study was an experimental intraindividual study in 16 rats. A single fraction of 20 Gy external irradiation was applied to one rat hind leg, while the other served as a nonirradiated control. Three days after radiation, two implants were inserted in each tibial tuberosity. The rats were divided into two groups: non-HBO treated (group 1) and HBO treated (group 2). Five weeks after radiation, removal torque tests were performed. Implants with surrounding tissue were processed to undecalcified cut and ground sections for histomorphometric evaluations of bone-to-implant contact and bone area. Retrieved bones were also investigated with dual-energy x-ray absorptiometry. RESULTS: The non-HBO treated rats (group 1) demonstrated higher, but not statistically significantly higher, values in the nonirradiated leg for all investigated parameters compared to the HBO-treated rats (group 2). However, the mean value for bone area was significantly higher in the irradiated sides compared to the nonirradiated control sides. CONCLUSIONS: In the present study, HBO treatment did not have a significant impact on osseointegration of implants in irradiated bone.

Mitigation of lung injury after accidental exposure to radiation.

There is a serious need to develop effective mitigators against accidental radiation exposures. In radiation accidents, many people may receive nonuniform whole-body or partial-body irradiation. The lung is one of the more radiosensitive organs, demonstrating pneumonitis and fibrosis that are believed to develop at least partially because of radiation-induced chronic inflammation. Here we addressed the crucial questions of how damage to the lung can be mitigated and whether the response is affected by irradiation to the rest of the body. We examined the widely used dietary supplement genistein given at two dietary levels (750 or 3750 mg/kg) to Fischer rats irradiated with 12 Gy to the lung or 8 Gy to the lung + 4 Gy to the whole body excluding the head and tail (whole torso). We found that genistein had promising mitigating effects on oxidative damage, pneumonitis and fibrosis even at late times (36 weeks) when drug treatment was initiated 1 week after irradiation and stopped at 28 weeks postirradiation. The higher dose of genistein showed no greater beneficial effect. Combined lung and whole-torso irradiation caused more lung-related severe morbidity resulting in euthanasia of the animals than lung irradiation alone.

Renin-Angiotensin system suppression mitigates experimental radiation pneumonitis.

PURPOSE: To find the mitigators of pneumonitis induced by moderate doses of thoracic radiation (10-15 Gy). METHODS AND MATERIALS: Unanesthetized WAG/RijCmcr female rats received a single dose of X-irradiation (10, 12, or 15 Gy at 1.615 Gy/min) to the thorax. Captopril (an angiotensin-converting enzyme inhibitor) or losartan (an angiotensin receptor blocker) was administered in the drinking water after irradiation. Pulmonary structure and function were assessed after 8 weeks in randomly selected rats by evaluating the breathing rate, ex vivo vascular reactivity, and histopathologic findings. Survival analysis was undertaken on all animals, except those scheduled for death. RESULTS: Survival after a dose of 10 Gy to the thorax was not different from that of unirradiated rats for

High-dose selenium for the mitigation of radiation injury: a pilot study in a rat model.

The purpose of this study was to evaluate in an animal model the safety and efficacy of dietary supplementation with high doses of selenium for the mitigation of the type of radiation injury that might be sustained during a nuclear accident or an act of radiological terrorism. Age-matched male rats were exposed to 10 Gy (single dose) of total-body irradiation (TBI) followed by a syngeneic bone marrow transplant, then randomized to standard drinking water or drinking water supplemented with sodium selenite or seleno-l-methionine. At 21 weeks after TBI, most rats on standard drinking water had severe renal failure with a mean blood urea nitrogen (BUN) level of 124 +/- 29 mg/dl (geometric mean +/- SE) whereas rats on selenium-supplemented drinking water (100 microg/day) had a mean BUN level of 67 +/- 12 mg/dl. The mitigating effect of selenium was confirmed by histopathological analyses. None of the animals on high-dose selenium showed signs of selenium toxicity. Our results suggest that dietary supplementation with high-dose selenium may provide a safe, effective and practical way to mitigate radiation injury to kidneys.

Drinking water supplementation with ascorbate is not protective against UVR-B-induced cataract in the guinea pig.

PURPOSE: To study if ascorbate supplementation decreases ultraviolet radiation (UVR)-induced cataract development in the guinea pig. METHODS: Sixty 6-9-week-old pigmented guinea pigs received drinking water supplemented with or without 5.5 mm l-ascorbate for 4 weeks. After supplementation, 40 animals were exposed unilaterally in vivo under anaesthesia to 80 kJ/m(2) UVR-B. One day later, the animals were killed and lenses were extracted. Degree of cataract was quantified by measurement of intensity of forward lens light scattering. Lens ascorbate concentration was determined with high-performance liquid chromatography (HPLC) with UVR detection at 254 nm. Twenty animals were used as non-exposed control. RESULTS: Supplementation increased lens ascorbate concentration significantly. In UVR-exposed animals, mean 95% confidence intervals (CIs) for animal-averaged lens ascorbate concentration (micromol/g wet weight lens) were 0.54 +/- 0.07 (no ascorbate) and 0.83 +/- 0.05 (5.5 mm ascorbate). In non-exposed control animals, mean 95% CIs for animal-averaged lens ascorbate concentration (micromol/g wet weight lens) were 0.72 +/- 0.12 (0 mm ascorbate) and 0.90 +/- 0.15 (5.5 mm ascorbate). All non-exposed lenses were devoid of cataract. Superficial anterior cataract developed in all UVR-exposed lenses. The lens light scattering was 39.2 +/- 14.1 milli transformed equivalent diazepam concentration (m(tEDC)) without and 35.9 +/- 14.0 m(tEDC) with ascorbate supplementation. CONCLUSION: Superficial anterior cataract develops in lenses exposed to UVR-B. Ascorbate supplementation is non-toxic to both UVR-B-exposed lenses and non-exposed control lenses. Ascorbate supplementation does not reduce in vivo lens forward light scattering secondary to UVR-B exposure in the guinea pig.

[Disorders in rat's higher nervous activity in the course of chronic gamma-irradiation].

Investigations of early disorders in rat's higher nervous activity in the course of chronic gamma-irradiation (elaboration of the conditioned defensive reflex of avoidance "under the ray") showed that already in 10-15 minutes since the beginning of exposure (total dose of approx. 0.75-1.15 Gy) the conditioned reflex parameters degraded significantly with a general trend toward an increased excitation and disruption of active inhibition in the higher sections of the central nervous system (CNS). The most dramatic disorders occurred in the middle of the period of exposure (total dose of approx. 4-5 Gy). There were some individual differences in the CNS functional reaction to irradiation.

Progenitor cell injury after irradiation to the developing brain can be modulated by mild hypothermia or hyperthermia.

Ionizing radiation induced acute cell death in the dentate gyrus subgranular zone (SGZ) and the subventricular zone (SVZ). Hypomyelination was also observed. The effects of mild hypothermia and hyperthermia for 4 h after irradiation (IR) were studied in postnatal day 9 rats. One hemisphere was irradiated with a single dose of 8 Gy and animals were randomized to normothermia (rectal temperature 36 degrees C for 4 h), hypothermia (32 degrees C for 4 h) or hyperthermia (39 degrees C for 4 h). Cellular injury, e.g. chromatin condensation and nitrotyrosine formation, appeared to proceed faster when the body temperature was higher. Caspase-3 activation was more pronounced in the hyperthermia group and nuclear translocation of p53 was less pronounced in the hypothermia group 6 h after IR. In the SVZ the loss of nestin-positive progenitors was more pronounced (48%) and the size was smaller (45%) in the hyperthermia group 7 days post-IR. Myelination was not different after hypo- or hyperthermia. This is the first report to demonstrate that hypothermia may be beneficial and that hyperthermia may aggravate the adverse side-effects after radiation therapy to the developing brain.

Study on the effects of Guiqi Oral Liquid in promoting recovery of hematopoiesis in acute irradiation injured mice.

OBJECTIVE: To explore the effects and possible mechanisms of Guiqi Oral Liquid (GQOL) on the recovery of hematopoiesis in acute irradiation injured mice. METHODS: The acute irradiation injured mice were randomly divided into 2 groups: the treated group and the control group, and also a normal control group was set up with 6 mice in it receiving no treatment. After the mice in the former two groups were irradiated by 6.0 Gy (60)Co gamma-ray, every one of them was given 0.4 ml GQOL or saline in equal volume through a gastric tube twice a day for 14 days. On the 4th, 8th and 14th day after irradiation, the bone marrow mononuclear cells (BMMNC) and megakaryocytes in bone marrow tissues of the mice were counted, the proportion of hematopoietic tissues (by area) was measured, and the expression of adhesion molecules, CD44 and CD54, in bone marrow were estimated by immunochemistry. The colony forming unit of spleen (CFU-S) in the mice were counted on the 8th day after irradiation. RESULTS: On the 4th, 8th, 14th day after irradiation, the count of BMMNC and megakaryocyte, and the proportion of hematopoietic tissues in the treated group were higher than those in the control group (P < 0.01 or P < 0.05). CD44 and CD54 expression in the treated group were higher than those in the control group on the 4th and 8th day (P < 0.01), but near normal on the 14th day (P < 0.01). On the 8th day, CFU-S count in the treated group was higher than that in the control group (P < 0.01). CONCLUSION: GQOL can regulate the expression of adhesion molecules, CD44 and CD54, in the bone marrow of the acute irradiation injured mice, which may be one of the mechanisms of GQOL in accelerating the early phase hematopoiesis recovery of mice.

[Regenerative capacity of muscle tissue and thymus state in irradiated rats exposed to long-term He-Ne laser radiation]. / Regeneratsionnaia sposobnost' myshechnoi tkani i sostoianie timusa u obluchennykh krys v usloviiakh prolongirovannogo vozdeistviia izlucheniia gelii-neonovogo lazera.

We studied the effect of He-Ne laser on regeneration of damaged gastrocnemius muscle in rats irradiated at 6 Gy in conditions of fractional laser energy spread (10 exposures, 3 min for each limb, within 30 days after the operation; 2-3 exposures weekly; 2.5-3.0 mW/cm2 power density; and 9.0-10.8 J/cm2 total dose per animal). Laser radiation stimulated regenerative activity of the skeletal muscle and favored a more even distribution of load on the thymus (a smooth decrease in its weight and slow aplasia). The level of chromosomal aberrations in the thymocytes demonstrated certain instability although remained lower as compared to the control during the whole observation period (60 days).

Novel radioprotectant drugs for sparing radiation-induced damage to the physis.

PURPOSE: To determine if pentoxifylline, interleukin 1alpha, selenium and misoprostol can minimize damage to physeal longitudinal growth during single radiation dose exposure in an animal model. MATERIALS AND METHODS: Eighty-seven weanling Sprague-Dawley rats were randomized into 15 drug/dose groups. All groups received a single 17.5-Gy gamma-irradiation exposure to the right knee, the left limb serving as an internal control. Pentoxifylline was injected 30 min before exposure, sodium selenite and interleukin 1alpha 24 h before exposure and misoprostol 2 h before exposure. Positive controls received 17.5 Gy. At 6 weeks, animals were sacrificed, the hind limb lengths were measured and detailed histomorphometric analysis was performed. RESULTS: Statistically significant reductions (p < or = 0.03) in mean limb length discrepancy compared with irradiation alone were seen following administration of pentoxifylline (50 mg kg(-1)), interleukin 1alpha (15 mcg kg(-1)), selenium (5 mg kg(-1)) and misoprostol (20 mg kg(-1)). Histomorphometric endpoints and growth rate remained altered at 6 weeks despite treatment, but length discrepancy reduction was highly correlated with the appearance of regenerative clones. CONCLUSIONS: Each drug reduced the amount of anticipated growth arrest in the animal model and some compared favourably in magnitude with that previously demonstrated for the established radioprotectant drug amifostine. Restoration of growth appears related to appearance of regenerative clones.

Heat effects on the retina.

BACKGROUND AND OBJECTIVE: To study the heat and power dissipation effect of anintraocular electronic heater on the retina. The determination of thermal parameters that are nonharmful to the retina will aid in the development of an implantable intraocular electronic retinal prosthesis. MATERIALS AND METHODS: In dogs, five different retinal areas were touched with a custom intraocular heater probe (1.4 x 1.4 x 1.0 mm) for 1 second while the heater dissipated 0 (control), 10, 20, 50, or 100 mW. In a second protocol, the heater was mechanically held in the vitreous cavity while dissipating 500 mW for 2 hours while monitoring intraocular temperature. The animals were observed for 4 weeks with serial fundus photography and electroretinography. The procedure was then repeated in the fellow eye. The dogs were killed and both eyes were enucleated and submitted for histology. RESULTS: In experiments using protocol 1, heater settings of 50 mW or higher caused an immediate visible whitening of the retinal tissue. Histologically, this damage was evident only if the eyeswere immediately enucleated. Permanent damage was caused by heater settings of 100 mW or higher. Under protocol 2, no ophthalmologic, electroretinography, or histologic differences were noted between the groups. Temperature increases of 5 degrees C in the vitreous and 2 degrees C near the retina were noted. CONCLUSIONS: The liquid environment of the eye acts as a heat sink that is capable of dissipating a significant amount of power. An electronic chip positioned away from the retina can run at considerably higher powers than a chip positioned on the retinal surface.

[Cytokines as agents for the early pathogenetic therapy of radiation injuries. Their efficacy and mechanism of action]. / Tsitokiny kak sredstva rannei patogeneticheskoi terapii radiatsionnykh povrezhdenii. Effektivnost' i mekhanizm deistviia.

It has been shown in experiments with three species of laboratory animals that an early administration (during the first hours following irradiation) of human recombinant interleukins 1 alpha and 1 beta separately (to mice, rats) or in combination with antibiotic therapy (dogs) substantially increases survivability, favours a more rapid regeneration of the cellular content of the bone marrow and peripheral blood, intensifies the processes of endogenous colony formation and DNA synthesis in the bone marrow and liver and lowers the expressivity of radiation-induced endotoxemia. The significance of using cytokines in the system of remedial measures in radiation pathology is discussed.

Supplemental dietary arginine accelerates intestinal mucosal regeneration and enhances bacterial clearance following radiation enteritis in rats.

BACKGROUND: Arginine is a dibasic amino acid with significant metabolic and immunologic, effects especially in trauma and stress situations. Arginine supplementation has been shown to promote wound healing and improve immune system. We designed a study to evaluate the effects of supplemental dietary arginine on intestinal mucosal recovery and bacterial translocation and bacterial clearance after induction of radiation injury in rats. METHODS: Twenty-one male Sprague-Dawley rats were subjected to a single dose of 1100 rads of abdominal X radiation. Rats were divided into three groups; the first group received diet enriched with 2% arginine, the second group with 4% arginine, and the third group with isonitrogenous 4% glycine. Rats were sacrificed 7 days after the radiation. Blood was drawn for arginine levels and mesenteric lymph nodes were harvested for quantitative aerobic and anaerobic cultures. Segments of ileum and jejunum were evaluated for villous height, number of villi per centimeter of intestine, and the number of mucous cells per villous. RESULTS AND CONCLUSIONS: Arginine is absorbed reliably from the gut following oral administration. Dietary 4% arginine supplementation enhanced bacterial clearance from mesenteric lymph nodes compared to 2% arginine and 4% glycine supplemented diet following radiation enteritis in rats. Four percent arginine resulted in clear improvement in intestinal mucosal recovery when compared to 2% arginine and 4% glycine after abdominal irradiation in rats.

Late response to whole-lung irradiation alone and with whole-body hyperthermia in dogs.

The late effects of whole-lung irradiation with and without whole-body hyperthermia were studied in beagle dogs. The reference doses ranged from 18 to 49.5 Gy given in 1.5-Gy fractions over 6 weeks. Whole-body hyperthermia was given in three 2-h treatments to a deep rectal temperature of 42.0 degrees C. Radiation was given simultaneously with hyperthermia on those days. Physiological and histopathological responses were evaluated. Physiological changes included decreases in cardiac output, systemic blood pressure, dynamic compliance and serotonin uptake. Early changes included an increase in extravascular water and total protein in the lavage. These changes were considered mild, were compensated for and occurred only in dogs receiving doses of 40.5 Gy or greater given in 1.5-Gy fractions over 6 weeks. Histopathological changes were typical of irradiated lung and included pleural fibrosis, interstitial fibrosis, fibrotic foci, and peribronchial and perivascular fibrosis. There was no enhancement of late injury to lung by hyperthermia seen in this study.

[The role of the vasoconstrictor effect in realizing the radioprotective properties of indralin in experiments on dogs]. / Rol' vazokonstriktornogo éffekta v realizatsii protivoluchevykh svoistv indralina v opytakh na sobakakh.

In the experiments on dogs, the role of a pharmacological circulatory hypoxia in the mechanism of radioprotective effect of indraline and mexamine was studied. Angiography revealed 20-40% vasoconstriction of major arteries of legs of animals, of pelvis and abdomen caused by mexamine (10 mg/kg) and the absence of a significant effect of indraline. Disruption of a regional blood circulation in the marrow and spleen (40-50% and 70-80%, respectively) was caused by indraline to the same extent as by mexamine. For indraline, a decrease in pO2 in the marrow was about 50%. With these hemodynamic disturbances, indraline showed 80 to 100% radioprotective effect, while mexamine was inefficient. Acute hypoxic hypoxia (5-7% O2) increased a post-radiation survival rate for dogs by 40%. The radioprotective effect of indraline was blocked by tropaphen and reduced in cases of breathing with pure oxygen. Splenectomy has no effect on radioprotective properties of indraline. Thus, a hypothesis of the mechanism of a radioprotective effect of alpha-adrenomimetics was proposed.