高原脑损伤血脑屏障变化的实验研究

目的：了解高原条件下颅脑损伤后血脑屏障（ｂｌｏｏｄ－ｂｒａｉｎｂａｒｉｅｒ，ＢＢＢ）变化的特点．方法：采用自由落体致伤法（致伤冲量为１２００ｇ·ｃｍ）造成颅脑损伤模型．ＢＢＢ变化的定性测定采用伊文氏蓝（ｅｖａｎｓｂｌｕｅ，ＥＢ）染色，利用荧光比色法测定组织中ＥＢ含量来定量代表ＢＢＢ通透性变化，同时电镜观察毛细血管的病理改变．结果：高原脑损伤后局部损伤区出现蓝染带较早且范围宽．脑组织中ＥＢ含量较平原损伤时含量有非常显著的增高．脑组织中毛细血管损伤严重，以基底膜破坏明显，其周围有大量的水肿液．结论：高原低压低氧条件可加重颅脑ＢＢＢ损伤破坏，通透性增高．     

Simplified, noninvasive PET measurement of blood-brain barrier permeability

Blood-brain barrier (BBB) permeability to [68Ga]EDTA was measured by positron emission tomography (PET) in four normal volunteers and in 11 patients with brain tumors. A unidirectional transfer constant, Ki, was calculated applying multiple-time graphical analysis (MTGA). This method allows the detection of backflux from brain to blood and, by generalization, the measurement of the constant Kb (brain to blood). Furthermore, the need for an independent measurement of the intravascular tracer is obviated: MTGA itself provides an estimate of the cerebral plasma volume (Vp). In the four normal volunteers the Ki was 3.0 +/- 0.8 X 10(-4) ml g-1 min-1 (mean +/- SD) and the Vp 0.034 +/- 0.007 ml g-1. A net increase in Ki up to a maximum of 121.0 X 10(-4) ml g-1 min-1 (correspondent value of Kb = 0.025 min-1) as well as an increase of Vp was observed in malignant tumors. The input function was calculated using both the [68Ga]EDTA concentration in sequential arterial blood samples and, noninvasively, the activity derived from the superior sagittal sinus image. The values of Ki and Vp from these two calculations were in good agreement. The application of MTGA to PET permits the evaluation of passage of substances across the BBB without making assumptions about the compartments in which the tracer distributes.     

急性中、重度低压缺氧对大鼠血脑屏障通透性的影响

目的 观察急性中、重度低压缺氧条件下,大鼠血脑屏障通透性的变化特点,为阐明低压缺氧作用下脑功能障碍的可能机理提供生理学依据。方法 选择雄性ＳＤ大鼠１８只,随机分为对照组、５０００ｍ及８０００ｍ急性低压缺氧暴露组。实验组动物于低压舱内,以２０ｍ／ｓ的速率上升,至５０００ｍ（或８０００ｍ）,停留５ｈ,而后以２０ｍ／ｓ的速率下降至地面,出舱后立即经心脏灌注硝酸镧固定液,开颅取脑,制成切片,置透射电镜下观     

Recompression during decompression and effects on bubble formation in the pig

INTRODUCTION: There is a relationship between gas bubble formation in the vascular system and serious decompression sickness. Hence, control of the formation of vascular bubbles should allow safer decompression procedures. METHODS: There were 12 pigs that were randomly divided into an experimental group (EXP) and a control group (CTR) of 6 animals each. The pigs were compressed to 500 kPa (5 ATA) in a dry hyperbaric chamber and held for 90 min bottom time breathing air. CTR animals were decompressed according to a modified USN dive profile requiring four stops. EXP followed the same profile except that a 5-min recompression of 50 kPa (0.5 ATA) was added at the end of each of the last three decompression stops before ascending to the next stop depth. RESULTS: All CTR animals developed bubbles, compared with only one animal in EXP. The number of bubbles detected during and after the dive was 0.02 +/- 0.02 bubbles x cm(-2) in CTR, while the number of bubbles detected in EXP were 0.0009 +/- 0.005 bubbles x cm(-2); the difference was highly significant. CONCLUSION: By brief recompression during late decompression stops, the amount of bubbles was reduced. Our findings give further support for a gas phase model of decompression.     

Non-invasive measurement of pulmonary artery pressure in humans with simulated altitude-induced venous gas emboli

BACKGROUND: Decompression to simulated altitude causes super-saturation of nitrogen desolved in body tissues and can result in venous gas emboli (VGE), which are usually "cleared" in the lung. Large intravenous boli of air administered to animals increase pulmonary artery pressure (PAP), and may induce cross-over of gas to the left side of the heart (creating dangerous arterial gas emboli). This study was conducted to determine whether high VGE grades induced at simulated altitude elevate PAP in humans. METHODS: Eight human subjects with subclinical tricuspid regurgitation were exposed to simulated altitude of > or = 24,000 ft (7315 m) for up to 4 h. Systolic PAP was derived from Doppler ultrasound echo imaging measurements of peak flow velocity of the regurgitant jet. VGE was rated using the Spencer scale. A technique of "bubble titration" was employed with changes in exercise and altitude to maintain sufficient bubbles without decompression sickness. RESULTS: All subjects developed grade III-IV VGE, but 3 developed decompression sickness, resulting in earlier termination. Pre-exposure systolic PAP averaged 24.4 +/- 1.3 (SE) mm Hg. After 1, 2, 3 and 4 h, systolic PAP was 23.7 +/- 1.2 (n = 8), 23.4 +/- 1.1 (n = 8), 23.3 +/- 1.0 (n = 6), and 25.9 +/- 0.6 (n = 5) mm Hg, respectively. Systolic PAP remained unchanged, in spite of bubble grades III-IV for up to 4 h. CONCLUSION: As systolic PAP did not increase with hypobaric exposures that created substantial VGE, the bubble loading was not sufficient to overwhelm the lung clearing capacity. The risk of high PAP resulting in VGE cross-over is low during typical operational altitude exposures.     

Pathological animal models in the experimental evaluation of tumour microvasculature with magnetic resonance imaging

PURPOSE: The purpose of this study was to evaluate the applications of magnetic resonance imaging (MRI), and in particular, dynamic contrast-enhanced MRI (DCE-MRI), in the assessment of tumour microvasculature by means of animal tumour models evaluated before and after antiangiogenic treatment. MATERIALS AND METHODS: Forty-two MRI exams were performed with intravascular contrast media in 21 rats: tumours were induced by subcutaneous injection of colon carcinoma cells in 7 rats and mammary adenocarcinoma cells in 14 rats. Perfusion and permeability parameters of the implanted tumours were evaluated by using two contrast media (B22956/1 and Gd-DTPA37-albumin) to establish response to treatment with two different antiangiogenic drugs (tamoxifen and SU6668). These parameters were correlated with histology to obtain a radiological-histological map of tumour microvasculature. RESULTS: DCE-MRI revealed greater enhancement in the peripheral area than in the central area in all the examined animal models. In the mammary carcinoma experiment, vascular permeability measured by means of B22956/1 in the animals treated with the antiangiogenic drug (0.0043317+/-0.0040418 ml/min(-1)/ml(-1)) was significantly less than in untreated animals (0.0090460+/-0.0043680 ml/min(-1)/ml(-1)), whereas no significant difference was observed with Gd-DTPA-albumin (13.14+/-13.94 ml/min(-1)/ml(-1) in treated animals and 18.07+/-11.92 ml/min(-1)/ml(-1) in untreated animals). In the colon carcinoma experiment, mean permeability and perfusion decreased by 51% (from 5.2+/-1.1 to 2.5+/-0.8 ml/100 ml) and 59% (from 0.00165+/-5.1 to 0.0067+/-4.8 ml/min(-1)/ml(-1) of tissue), respectively, in all animals after antiangiogenic drug administration. CONCLUSIONS: DCE-MRI permits a noninvasive evaluation of tumour microcirculation and in particular of its dynamic characteristics and vascularity before and after antiangiogenic treatment.     

Venous gas emboli in normal and dehydrated rats following decompression from a saturation dive

INTRODUCTION: Dehydration may increase the risk for decompression sickness (DCS). Since DCS most probably is caused by endogenous gas phase formation, we hypothesized that decompression will induce more venous gas emboli (VGE) in dehydrated rats compared to controls. METHODS: Two groups of rats were pressurized to 0.5 MPa (5 ATA) on heliox for 16 h, and thereafter decompressed to atmospheric pressure at a rate of 0.3 MPa x min(-1). The nine control rats had free access to water ad libitum whereas the eight dehydrated rats were water-deprived for 48 h before decompression. During and after decompression, VGE was measured in the vena cava for 60 min with the Doppler technique and graded into six bubble grade (BG) categories. Body mass (BM), and food and water intake were registered daily, and venous blood samples were taken before and after pressure exposure. RESULTS: Serum osmolality and hematocrit increased significantly in dehydrated rats (306 +/- 5.2 to 315 +/- 7.3 mosmol x kg(-1) and 39.3 +/- 4.9 to 49.6 +/- 5.2%) but not in controls (300 +/- 8.9 to 303 +/- 6.7 mosmol x kg(-1) and 40.3 +/- 5.2 to 41.4 +/- 6.1%). Plasma volume decreased by 9.2% (P < 0.05) and 2.8% (n.s.) in dehydrated and control rats. VGE were detected in all control animals (average BG: 2.8 +/- 1.9), but only in four water-deprived rats (BG: 1.6 +/- 2.2). This difference was not significant. CONCLUSIONS: Our experiments do not support the idea that dehydration increases circulatory VGE.     

Exercise in the heat: effect of fluid ingestion on blood-brain barrier permeability

INTRODUCTION: This study examined changes in serum S100beta concentration, a peripheral marker of BBB permeability, in response to exercise in the heat with and without fluid ingestion. METHODS: Eight physically active males completed up to 90 min of intermittent exercise at a power output corresponding to 55% VO2peak in a warm environment (35 degrees C, 56% rh). Trials were completed with (F trial) and without (NF trial) the replacement of sweat losses. During the fluid trial, an aliquot of plain water was ingested at 15-min intervals to match the volume of sweat lost during the previous period of exercise. RESULTS: Exercise time was 80.7 +/- 13.0 min in the NF trial and 85.1 +/- 9.5 min in the F trial (P = 0.107). Fluid ingestion resulted in a smaller rise in core temperature (P = 0.050) and heart rate (P = 0.027) during the latter stages of exercise. Serum S100beta concentrations were 0.08 +/- 0.02 microg.L at rest, increasing to 0.20 +/- 0.06 microg.L at the end of exercise in the NF trial, with this response attenuated by the ingestion of fluid (0.13 +/- 0.03 microg.L; P = 0.046). Both serum sodium concentration (P < 0.001) and serum osmolality (P = 0.003) were significantly lower at the end of exercise in the F trial than in the NF trial. CONCLUSION: The results of this study demonstrate that water ingestion can limit exercise-induced increases in serum S100beta, consistent with the preservation of BBB integrity. It is possible that this response was mediated through the maintenance of lower extracellular osmolality late in exercise, thus potentially limiting the osmotically driven movement of fluid across the BBB.     

A strategy for increasing the brain uptake of a radioligand in animals: use of a drug that inhibits plasma protein binding

A positron-emitter labeled radioligand for the glycine-binding site of the N-methyl-D-aspartate (NMDA) receptor, [(11)C]L-703,717, was examined for its ability to penetrate the brain in animals by simultaneous use with drugs having high-affinity separate binding sites on human serum albumin. [(11)C]L-703,717 has poor blood-brain barrier (BBB) permeability because it binds tightly to plasma proteins. Co-injection of warfarin (50-200 mg/kg), a drug that binds to albumin and resembles L-703,717 in structure, dose-dependently enhanced the penetration by [(11)C]L-703,717 in mice, resulting in a five-fold increase in the brain radioactivity at 1 min after the injection. Drugs structurally unrelated to L-703,717, salicylate, phenol red, and L-tryptophan, were less effective or ineffective in increasing the uptake of [(11)C]L-703,717. These results suggest that the simultaneous use of a drug that inhibits the binding of a radioligand to plasma proteins is a useful way to overcome the poor BBB permeability of the radioligand triggered by its tight binding to plasma proteins. In brain distribution studies in rodents, it was found that, after the increase in brain uptake with warfarin, much of the glycine site antagonist accumulates in the cerebellum but its pharmacological specificity did not match the glycine site of NMDA receptors.     

Risk of decompression sickness during exposure to high cabin altitude after diving

BACKGROUND: Postdive altitude exposure increases the risk of decompression sickness (DCS). Certain training and operational situations may require U.S. Special Operations Forces (SOF) personnel to conduct high altitude parachute operations after diving. Problematically, the minimum safe preflight surface intervals (PFSI) between diving and high altitude flying are not known. METHODS: There were 102 healthy, male volunteers (34 +/- 10 [mean +/- SD] yr of age, 84.5 +/- 13.8 kg weight, 26.2 +/- 4.2 kg x m(-2) BMI) who completed simulated 60 fsw (feet of seawater)/60 min air dives preceding simulated 3-h flights at 25,000 ft to study DCS risk as a function of PFSI. Subjects were dry and at rest throughout. Oxygen was breathed for 30 min before and during flight in accordance with SOF protocols. Subjects were monitored for clinical signs of DCS and for venous gas emboli (VGE) using precordial Doppler ultrasound. DCS incidence was compared with Chi-squared; VGE onset time and time to maximum grade with one-way ANOVA (significance at p < 0.05). RESULTS: Three cases of DCS occurred in 155 subject-exposures: 1/35 and 0/24 in 2 and 3 h flight-only controls, respectively; 0/23, 1/37, and 1/36 for 24, 18, and 12 h dive-PFSI-flight profiles, respectively. DCS risk did not differ between profiles (chi2 [4] = 1.33; crit = 9.49). VGE were observed in 19% of flights. Neither VGE onset time nor time to max grade differed between profiles (82 +/- 38 min [p = 0.88] and 100 +/- 40 min [p = 0.68], respectively). CONCLUSION: Increased DCS risk was not detected as a result of dry, resting 60 fsw/60 min air dives conducted 24-12 h before a resting, 3-h oxygen-breathing 25,000 ft flight (following 30 min oxygen prebreathe). The current SOF-prescribed minimum PFSI of 24 h may be unnecessarily conservative.     

Kinetic analysis of 3'-deoxy-3'-18F-fluorothymidine in patients with gliomas.

3'-Deoxy-3'-fluorothymidine (FLT), a thymidine analog, is under investigation for monitoring cellular proliferation in gliomas, a potential measure of disease progression and response to therapy. Uptake may result from retention in the biosynthetic pathway or leakage via the disrupted blood-tumor barrier. Visual analysis or static measures of 18F-FLT uptake are problematic as transport and retention cannot be distinguished. METHODS: Twelve patients with primary brain tumors were imaged for 90 min of dynamic 18F-FLT PET with arterial blood sampling. Total blood activity was corrected for labeled metabolites to provide an FLT input function. A 2-tissue compartment, 4-rate-constant model was used to determine blood-to-tissue transport (K1) and metabolic flux (K(FLT)). Modeling results were compared with MR images of blood-brain barrier (BBB) breakdown revealed by gadolinium (Gd) contrast enhancement. Parametric image maps of K1 and K(FLT) were produced by a mixture analysis approach. RESULTS: Similar to prior work with 11C-thymidine, identifiability analysis showed that K1 (transport) and K(FLT) (flux) could be estimated independently for sufficiently high K1 values. However, estimation of K(FLT) was less robust at low K1 values, particularly those close to normal brain. K1 was higher for MRI contrast-enhancing (CE) tumors (0.053 +/- 0.029 mL/g/min) than noncontrast-enhancing (NCE) tumors (0.005 +/- 0.002 mL/g/min; P < 0.02), and K(FLT) was higher for high-grade tumors (0.018 +/- 0.008 mL/g/min, n = 9) than low-grade tumors (0.003 +/- 0.003 mL/g/min, n = 3; P < 0.01). The flux in NCE tumors was indistinguishable from contralateral normal brain (0.002 +/- 0.001 mL/g/min). For CE tumors, K1 was higher than K(FLT). Parametric images matched region-of-interest estimates of transport and flux. However, no patient has 18F-FLT uptake outside of the volume of increased permeability defined by MRI T1+Gd enhancement. CONCLUSION: Modeling analysis of 18F-FLT PET data yielded robust estimates of K1 and K(FLT) for enhancing tumors with sufficiently high K1 and provides a clearer understanding of the relationship between transport and retention of 18F-FLT in gliomas. In tumors that show breakdown of the BBB, transport dominates 18F-FLT uptake. Transport across the BBB and modest rates of 18F-FLT phosphorylation appear to limit the assessment of cellular proliferation using 18F-FLT to highly proliferative tumors with significant BBB breakdown.     

Lactic acid output of cat gastrocnemius-plantaris during repetitive twitch contractions

Because fatigable, white (FF) muscle fibers have been reported to have a greater glycolytic capacity and a lower oxidative capacity than fatigue-resistant, red (FR and SR) muscle fibers, it is generally supposed that FF muscle fibers produce and therefore release more lactic acid into the blood during contractions than FR and SR muscle fibers. To test this supposition, the net lactic acid output, L, and O2 uptake, VO2, were measured for the cat gastrocnemius-plantaris muscle during repetitive isometric contractions. The results obtained from this low metabolic capacity (FF, FR and SR muscles) were compared to results obtained previously in the high metabolic capacity (FR and SR muscles) of the same muscle group in the dog during similar contractions. Preliminary studies established that 1 twitch X 2 s-1 provided a similar VO2 pattern during the contractions of cat muscle as 4 twitches X s-1 produced in the dog muscle. The decline in VO2 over a 30-min period of contractions was 12 to 18%, as developed tension declined with fatigue. Thus, the contractions of the cat muscles were matched with the dog muscles in terms of the relative aerobic capacity and development of fatigue. During the 1 twitch X 2 s-1 twitches, the VO2 reached 24.4 +/- 1.41 (SE) microliter X g-1 X min-1 at 10 min of contractions. The VO2 declined to 21.3 +/- 2.3 microliter X g-1 X min-1 by 30 min. The VO2 and tension developed changed parallel to each other. The net L reached 0.21 +/- 0.06 mumol X g-1 X min-1 at 10 min and fell to 0.13 +/- 0.05 mumol X g-1 X min by 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

The influence of prior exercise at anaerobic threshold on decompression sickness.

This study was conducted to examine the effects of exercise prior to decompression on the incidence of altitude decompression sickness (DCS). In a balanced, two-period, crossover trial, 39 healthy individuals (29 males, 10 females) of mean (S.D.) age 32.5 (7.7) years and body mass index 23.7 (3.4) were each exposed twice, without denitrogenation, to an altitude of 6,400 m (21,000 ft) in a hypobaric chamber. Under the experimental condition, subjects exercised at their predetermined anaerobic threshold levels for 30 min each day for 3 d prior to altitude exposure; the other condition was a non-exercise control. Under both conditions, subjects performed exercise simulating space extravehicular activities at altitude for a period of 3 h, while breathing 100% oxygen. There were nine preferences (untied responses) for DCS, four under control and five under experimental conditions; all were Type I, pain-only bends. No carryover effect between exposures was detected, and the test for treatment differences showed p = 0.56 (95% confidence interval = 0.34-0.58) for symptoms. No significant difference in DCS preferences was found after subjects exercised up to their anaerobic threshold levels during the days prior to decompression.     

Bubble formation of aqueous humor and lens opacity during chamber flight

A transparent miniature decompression chamber was placed on the stage of a large-working zoom-stereo microscope so that the effect of decompression on the frog eye could be microscopically observed and photographed. It was found that chamber flight at a simulated altitude of 66,000 ft (20,117 m) or more caused bubble formation in aqueous humor and lens opacities in some of the experimental animals. On return to ground level, the bubbles either decreased in size or completely disappeared. The cataract could also regress after recompression to 1 atm. Such lens opacities may be termed altitude cataract, instead of asphyxial or anoxic cataract.     

The effect of repeated altitude exposures on the incidence of decompression sickness

INTRODUCTION: Repeated altitude exposures in a single day occur during special operations parachute training, hypobaric chamber training, unpressurized flight, and extravehicular space activity. Inconsistent and contradictory information exists regarding the risk of decompression sickness (DCS) during such hypobaric exposures. HYPOTHESIS: We hypothesized that four short exposures to altitude with and without ground intervals would result in a lower incidence of DCS than a single exposure of equal duration. METHODS: The 32 subjects were exposed to 3 different hypobaric exposures--condition A: 2 h continuous exposure (control); condition B: four 30-min exposures with descent/ascent but no ground interval between the exposures; condition C: four 30-min exposures with descent/ascent and 60 min of ground interval breathing air between exposures. All exposures were to 25,000 ft with 100% oxygen breathing. Subjects were observed for symptoms of DCS, and precordial monitoring of venous gas emboli (VGE) was accomplished with a SONOS 1000 echo-imaging system. RESULTS: DCS occurred in 19 subjects during A (mean onset 70+/-29 min), 7 subjects in B (60+/-34 min), and 2 subjects in C (40+/-18 min). There was a significant difference in DCS incidence between B and A (p = 0.0015) and C and A (p = 0.0002), but no significant difference between B and C. There were 28 cases of VGE in A (mean onset 30+/-23 min), 21 in B (41+/-35 min), and 21 in C (41+/-32 min) with a significant onset curve difference between B and A and between C and A, but not between B and C. Exposure A resulted in four cases of serious respiratory/neurological symptoms, while B had one and C had none. All symptoms resolved during recompression to ground level. CONCLUSION: Data indicate that repeated simulated altitude exposures to 25,000 ft significantly reduce DCS and VGE incidence compared with a single continuous altitude exposure.     

Effects of atrial natriuretic peptide on glomerular filtration rate in essential hypertension: a radionuclide study.

A number of studies show that atrial natriuretic peptide (ANP) raises renal sodium excretion with a concomitant increase in glomerular filtration rate (GFR) in both experimental animals and normal humans. Studies using indirect evaluation of GFR have provided less consistent results in hypertensive patients. We studied the effects of intravenously administered (iv) alpha-human ANP on GFR in patients with hypertension by a radionuclide technique using technetium 99m diethylenetriaminepenta-acetic acid. In six patients (ANP group), GFR was determined under control conditions, during iv ANP (initial bolus of 0.5 micrograms/kg followed by a 21-min maintenance infusion at 0.05 micrograms.kg-1.min-1) and during a recovery phase. In six other patients (control group), GFR was determined under control conditions, during saline iv infusion and during recovery. The two groups did not differ with respect to age, sex, basal blood pressure, heart rate or GFR. In the ANP group, the infusion of the peptide induced a significant decrease of mean blood pressure (from 133 +/- 5 to 120 +/- 5 mmHg, P less than 0.01), no change in heart rate and a significant increase in GFR (from 104 +/- 4 to 125 +/- 5 ml/min, P less than 0.01). During recovery, blood pressure, heart rate and GFR were not different from the values recorded under control conditions. No changes in blood pressure, heart rate or GFR (from 106 +/- 5 to 108 +/- 5 ml/min, n.s.) were detected during saline infusion in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)     

血管内皮生长因子在高原暴露下血脑屏障通透性改变中的作用及其与脑水肿的关系

目的:探讨血管内皮生长因子(VEGF)在高原暴露下血脑屏障(BBB)通透性改变中的作用及与脑水肿的关系。方法:将大鼠暴露于高原不同海拔下,应用RT-PCR测定脑组织内VEGFmRNA转录水平和双抗体夹心ELISA法测定脑内VEGF蛋白含量,应用比色法测定伊文思蓝(EB)的透过率以确定BBB通透性的变化,脑湿干比重法测定脑含水量百分率。结果:高原暴露下,大鼠脑内VEGF和VEGFmRNA的表达随着海拔增高而增高,随着时间延长而增高,以暴露于5 000 m的特高海拔区第9天增高最明显。与此同时,脑内EB含量和脑内含水量增高。脑内VEGF活性与脑内EB含量和脑含水量之间明显相关。结论:VEGF是高原环境下BBB通透性增高的重要因素。     

Decompression sickness risk model: development and validation by 150 prospective hypobaric exposures

INTRODUCTION: High altitude exposure has an inherent risk of altitude decompression sickness (DCS). A predictive DCS model was needed to reduce operational risk. To be operationally acceptable, such a theoretical model would need to be validated in the laboratory using human subjects. METHODS: The Air Force Research Laboratory (AFRL) has conducted numerous studies on human subjects exposed to simulated altitudes in hypobaric chambers. The database from those studies was used to develop a statistical altitude DCS model. In addition, a bubble growth model was developed using a finite difference method to solve for bubble radius as a function of time. The bubble growth model, integrated with the statistical model, constitutes the AFRL DCS Risk Assessment Model. Validation of the model was accomplished by comparing computer predictions of DCS risk with results from subsequent prospective human subject exposures. There were five exposure profiles, not previously found in the database, covering a wide parameter of ranges of altitude (18,000-35,000 ft), exposure time (180-360 min), prebreathe time (0-90 min), and activity level (rest-strenuous) that were used. The subjects were monitored for DCS symptoms and venous gas emboli. RESULTS: There were 30 subjects who were exposed to each of the 5 altitude profiles. The DCS incidence onset curves predicted by the model were not significantly different from the experimental values for all scenarios tested and were generally within +/- 5% of the actual values. CONCLUSION: A predictive altitude DCS model was successfully developed and validated.     

Prophylactic high dose methylprednisolone fails to treat severe decompression sickness in swine

INTRODUCTION: Controlled decompression from saturation conditions is not always an option, particularly in a disabled submarine scenario. Hypothesis Prophylactic high dose methylprednisolone (MP) would improve outcome in severe cases of decompression sickness (DCS). METHODS: Littermate pairs of male Yorkshire swine (n = 86, mean weight +/- SE = 19.3 +/- 0.2 kg) were randomized to one of three groups, then compressed on air to 4.3 ATA (33 msw) for 22 h and brought directly to surface pressure (1 ATA) at 0.9 ATA x min(-1). The MP-50 group received i.v. infusion of 50 mg x kg(-1) of MP dissolved in 60 cc normal saline (NS) immediately prior to the hyperbaric exposure. The NS group received 60 cc NS i.v. immediately prior to the hyperbaric exposure. The MP-10 group received i.v. infusion of 10 mg x kg(-1) MP dissolved in 60 cc NS during the hyperbaric exposure, 7 h before the decompression. RESULTS: Outcomes of severe DCS and death were recorded. NS group: 14 DCS, 4 died; MP-50 group: 19 DCS, 12 died; MP-10 group: 19 DCS, 10 died. Compared with the NS group, logistic regression analysis suggested that animals in the MP-10 group were more likely to get severe DCS and to die (p < 0.01) and animals in the MP-50 group were more likely to die from their disease (p < 0.01). DISCUSSION: Prophylactic high dose MP exerts no protective effect against severe DCS and actually worsens mortality in this model. An earlier group of untreated controls (UC, n = 44, 30 DCS, 11 died, mean weight +/- SE = 19.9 +/- 0.3 kg) exposed to the same profile was also available for analysis. Comparison of the UC and NS animals suggested that pre-dive NS treatment may protect against severe DCS.     

Influence of blood-brain barrier permeability on O-(2-<Superscript>18</Superscript>F-fluoroethyl)-L-tyrosine uptake in rat gliomas

Purpose

O-(2-¹⁸F-fluoroethyl)-L-tyrosine (¹⁸F-FET) is an established tracer for the diagnosis of brain tumors with PET. This study investigates the influence of blood-brain barrier (BBB) permeability on ¹⁸F-FET uptake in two rat glioma models and one human xenograft model.

Methods

F98 glioma, 9L gliosarcoma or human U87 glioblastoma cells were implanted into the striatum of 56 Fischer or RNU rats. Thereafter, animals were divided into a control group and a group receiving injections of the glucocorticoid dexamethasone (Dex). After 12-13 days of tumor growth animals received injection of Evans blue dye (EBD) to visualize BBB disturbance and underwent ¹⁸F-FET PET followed by autoradiography. Time activity curves, standardized uptake values (SUV) and Tumor-to-brain ratios (TBR) of ¹⁸F-FET uptake [18-61 min post injection (p.i.)] were evaluated using a volume-of-Interest (VOI) analysis. BBB disturbance was quantitatively evaluated by EBD fluorescence. The membrane gaps of blood vessel endothelial tight junctions were measured using electron microscopy to visualize ultrastructural BBB alterations in one untreated and one Dex treated F98 glioma. Data were analyzed by two-way ANOVAs.

Results

In Dex treated animals EBD extravasation was significantly reduced in 9L (P?<?0.001) and U87 (P?=?0.008) models and showed a trend in F98 models (P?=?0.053). In contrast, no significant differences of ¹⁸F-FET uptake were observed between Dex treated animals and control group except a decrease of the TBR in the 9L tumor model in PET (P?<?0.01). Ultrastructural evaluation of tumor blood vessel endothelia revealed significant reduction of the cleft diameter between endothelial cells after Dex treatment in F98 model (P?=?0.010).

Conclusion

Despite a considerable reduction of BBB permeability in rat gliomas after Dex treatment, no relevant changes of ¹⁸F-FET uptake were noted in this experimental study. Thus, ¹⁸F-FET uptake in gliomas appears to be widely independent of the permeability of the BBB.