Comparison of of techniques for measuring +Gz tolerance in man.

Two objective methods and one subjective method for measuring +Gz tolerance (inertial vector in a head-to-foot direction) were compared on the human centrifuge. Direct eye-level blood pressure (Pa), blood flow velocity in the superficial temporal artery (Qta), and subjective visual symptoms were used to determine tolerance to rapid onset acceleration (1 G/s) on the USAFSAM human centrifuge. Seven "relaxed" subjects with extensive centrifuge experience were exposed to gradually increasing +Gz plateaus until the subject reported 100% loss of peripheral centrifuge gondola lights (PLL) and 50% loss of central light (CLD); viz., blackout. Zero forward Qta occurred 6 s (range 4-9 s) before subjective blackout and when mean eye-level blood pressure had reached 20 +/- 1 mmHg (SE). The results of this study indicate that flow changes in the superficial temporal artery reflect flow changes in the retinal circulation during +Gz stress.     

正加速度重复暴露后大鼠心室肌缝隙连接蛋白43表达及分布的改变

本文旨在探讨不同水平的一周重复多次正加速度( Gz)暴露后大鼠心室肌缝隙连接蛋白43(connexin 43, Cx43)表达及分布的改变.36只雄性Sprague-Dawley大鼠随机分为对照组、 6Gz组和 10Gz组,每组12只. Gz组大鼠分别暴露于 6Gz和 10Gz各3min,1次/d,共1周,分别于末次暴露后即刻、1d、3d、7d(各3只)取心室肌作免疫组织化学染色和Western blot分析,检测Cx43的表达和分布.免疫组织化学结果显示, Gz重复暴露可引起大鼠心室肌Cx43分布方式明显紊乱,Cx43在心肌细胞侧-侧连接处的表达明显增加,在心肌细胞端-端连接处的表达减少.Western Blot结果显示, 6Gz组与 10Gz组的Cx43蛋白表达量于末次暴露后即刻、1d、3d、7d与对照组相应时刻相比均明显减少(P<0.001),以暴露后即刻减少最为明显,且随着 Gz暴露时间的延长,表达逐渐恢复,但在暴露后7d,两组的Cx43表达量仍未恢复至对照组水平.Cx43蛋白表达的上述改变在 10Gz组比 6Gz组更为显著.以上结果提示 Gz重复暴露可引起大鼠心室肌Cx43表达量的一过性减少,分布方式明显紊乱,这种改变很可能是 Gz致心律失常发生的重要原因之一.     

Effect of water immersion on cardiopulmonary physiology at high gravity (+Gz)

We compared the cardiopulmonary physiology of eight subjects exposed to 1, 2, and 3 Gz during immersion (35 degrees C) to the heart level with control dry rides. Immersion should almost cancel the effects of gravity on systemic circulation and should leave the lung alone to gravitational influence. During steady-state breathing we measured ventilation, O2 consumption (VO2), CO2 production, end-tidal PCO2 (PACO2), and heart frequency (fH). Using CO2 rebreathing techniques, we measured cardiac output, functional residual capacity, equivalent lung tissue volume, and mixed venous O2 content, and we calculated arterial PCO2 (PaCO2). As Gz increased, ventilation, fH, and VO2 rose markedly, and PACO2 and PaCO2 decreased greatly in dry ride, but during immersion these variables changed very little in the same direction. Functional residual capacity was lower during immersion and decreased in both the dry and immersed states as Gz increased, probably reflecting closure effects. Cardiac output decreased as Gz increased in dry rides and was elevated and unaffected by Gz during immersion. We conclude that most of the changes we observed during acceleration are due to the effect on the systemic circulation, rather than to the effect on the lung itself.     

The expression of heat shock protein 70 in rat brain after +Gz exposure

To investigate the effect of +Gz exposure on the expression and distribution of heat shock protein 70 (HSP70) in rat brain. Methods: One hundred rats were randomly divided into control group, +2 Gz, +6 Gz and +10 Gz exposures groups. The +Gz group rats were exposed to +2 Gz, +4 Gz, +6 Gz and +10 Gz for 3 minute respectively. The expression of HSP70 in rat brain was measured by immunohistochemistry and West blot methods after +Gz exposure. Results: There was no HSP70 expression in the brains of control rats. In +2, +4. and +6 Gz groups, HSP70 was obviously expressed in cortex, hippocampus and pyriform cortex 6 h after exposures, and strongly expressed 1 d after exposure, and then had a tendency to decrease 2 d after exposure, and returned to control level 6 d after exposure. The expression of HSP70 after +6 Gz exposure was the strongest in all +Gz groups. In +10 GZ group, HSP70 protein was only weakly expressed in pyriform cortex after exposure. Conclusions: +Gz exposures may cause time-dependent HSP70 expression in rat brain.     

Medical monitoring during the NASA Artificial Gravity-Bed Rest Pilot Study

The NASA artificial gravity-bed rest pilot study (AGPS) was designed to investigate the efficacy of daily exposure to a +Gz acceleration gradient for counteracting the physiologic decrements induced by prolonged bed rest. Test subjects were continuously monitored by a physician for signs and symptoms of pre-syncope, motion sickness, and arrhythmias while on the centrifuge. In this article, we have summarized the medical monitoring observations that were made during the AGPS and included an assessment of the relative usefulness of the information provided by the various monitoring tools in making a decision to terminate a centrifuge spin.     

Right ventricular pressure response to +GZ acceleration stress

Measurements of right ventricular pressure in miniature swine were made at +Gz levels from +1 through +9 Gz. Polyethylene catheters were chronically placed in the cranial vena cava of five 2-yr-old female miniature swine (35-50 kg). The catheters were large enough to allow the introduction of a Millar pressure transducer into the venous system for placement in the right heart. The animals were fitted with an abdominal anti-G suit, restrained in a fiberglass couch, and exposed to the various +Gz levels on a centrifuge while fully conscious and unanesthetized. Right ventricular pressure and heart rate were measured during and for 2 min following 30-s exposures to each level of +Gz stress. The maximum right ventricular systolic pressure observed during +Gz was 200 Torr at +5 Gz with the maximum diastolic pressure being 88 Torr observed at +5 Gz. Mean heart rates were 200-210 beats/min at all levels of +Gz greater than or equal to +3 Gz when the animal remained stable. Mean maximum right ventricular pressures during +Gz stress were observed to increase through +5 Gz (85 Torr) and to decrease at higher levels of +Gz, indicating that through +5 Gz there is at least a partial compensation during acceleration stress. Decompensation in response to the stress began to occur during acceleration above +5 Gz with all animals decompensating during +9 Gz.     

Increased gravitational stress does not alter maximum expiratory flow

We measured maximum expiratory flow-volume (MEFV) curves in six seated subjects during normal (+1 Gz) and increased (+2 and +3 Gz) gravitational stress. Full MEFV curves, initiated at total lung capacity, were recorded, as were partial MEFV curves, initiated at approximately 60% of the vital capacity. Data were acquired in all subjects breathing air at +1 and +2 Gz; results were available for three subjects breathing 80% He-20% O2 at +1 and +2 Gz, and in two subjects, results were obtained at +3 Gz. Changes in gravitational stress were not associated with changes of either full or partial MEFV curves. The known increase in differences of regional lung volume and recoil caused by increased gravitational stress did not influence maximum expiratory flow. Though increased gravitational stress probably changed regional emptying sequences little during full MEFV maneuvers, substantial changes of emptying sequence were expected during partial maneuvers. It is possible that such changes in emptying sequence occurred but were not associated with changes in maximum flow because the latter was determined by choking in central airways common to all regions.     

Application of multivariate statistical analysis to estimate +Gz tolerance based on the changes of hemodynamic parameters during lower body negative pressure (LBNP)

The application of lower body negative pressure (LBNP) is very useful method for simulation of +Gz stress and for evaluation of orthostatic reaction. The different physiological changes that occur during LBNP test and +Gz acceleration test are similar. Lategola and Trent found that supine LBNP exposure at the level of -50 mmHg may be equivalent to +2Gz in producing the changes of heart rate (HR). Polese and coworkers compared hemodynamic changes occurring during upright and supine LBNP at the levels to -70 mmHg with identical measurements made during accelerations to +2Gz, +3Gz, and +4Gz in the same subjects. They noted for example that HR changes during upright LBNP exceeded HR supine levels. Peak values of HR during +3Gz and +4Gz significantly exceeded HR levels during both kinds of LBNP, but HR values at +2Gz were equivalent to those at -40 mmHg of upright and -70 mmHg of supine LBNP. So, the present study was undertaken to evaluate adaptating responses to LBNP stimulus at the level of -60 mmHg, regulatory mechanisms of the circulatory system (central and peripheral) and to look for the possibility of +Gz tolerance prediction based on the changes of some hemodynamic parameters during LBNP.     

Tolerance of snakes to hypergravity

Sensitivity of carotid blood flow to increased gravitational force acting in the head-to-tail direction(+Gz) was studied in diverse species of snakes hypothesized to show adaptive variation of response. Tolerance to increased gravity was measured red as the maximum graded acceleration force at which carotid blood flow ceased and was shown to vary according to gravitational adaptation of species defined by their ecology and behavior. Multiple regression analysis showed that gravitational habitat, but not body length, had a significant effect on Gz tolerance. At the extremes, carotid blood flow decreased in response to increasing G force and approached zero near +1 Gz in aquatic and ground-dwelling species, whereas in climbing species carotid flow was maintained at forces in excess of +2 Gz. Tolerant (arboreal) species were able to withstand hypergravic forces of +2 to +3 Gz for periods up to 1 h without cessation of carotid blood flow or loss of body movement and tongue flicking. Data suggest that the relatively tight skin characteristic of tolerant species provides a natural antigravity suit and is of prime importance in counteracting Gz stress on blood circulation.     

Hemodynamics of miniature swine during +Gz stress with and without anti-G support

Nine unanesthetized, chronically instrumented, female miniature swine (MS) (avg wt, 39.7 kg) were exposed to head-to-tail inertial load (+Gz) levels of +3, +5, and +7 Gz for 60 s, with and without anti-G-suit inflation. Venous flow (VF) was measured by an electromagnetic flow sensor around the inferior thoracic vena cava at the diaphragm. Central venous pressure (CVP), abdominal venous pressure (AVP), eye-level blood pressure (ELBP), and esophageal pressure (EP) were also measured before, during, and after +Gz. There was a progressive significant decrease from control of both ELBP (P less than 0.001) and VF (P less than 0.05) during the three +Gz exposures, both with and without G-suit inflation. Without G-suit inflation, most of the MS were unable to tolerate +5 and +7 Gz. Although VF was significantly (P less than 0.02) improved by G-suit inflation during +Gz there was no significant difference in VF between the three +Gz levels, with or without G-suit inflation. The MS does a spontaneous straining maneuver (cyclic Valsalva) during +Gz with G-suit support. Using EP as a trigger, the data were grouped as strain or no strain (relaxation). A continuous AVP-to-CVP gradient existed during G-suit inflation, which increased dramatically during no strain with increasing +Gz, and was associated with an increase in VF. Thus, the majority of VF occurred during relaxation between strains, even though relaxation time was shortened as +Gz increased. Although ELBP is obviously dependent on cardiac output and venous return, the progressive reduction in ELBP with increased +Gz loads was not significantly related to changes in VF at the diaphragm which was maintained, although at a reduced rate, by the AVP-to-CVP gradient during G-suit inflation.     

Gz重力作用下脑循环的改变

为了研究 Gz重力作用下脑循环的改变,10名被试者在半径为6米的人体离心机上承受了 G_Z超重作用。实验记录了心电、上臂血压、心振动图和脑阻抗图。发现,随着超重值的增加,心率、心输出量、上臂血压和外周循环阻力逐渐增大,计算得到的头部眼水平的平均动脉血压逐渐下降,脑阻抗图波高和波形发生明显改变。并对重要的生理指标和脑循环调节机制进行了分析和讨论。结果表明,尽管机体内存在许多补偿机制,但在G值较高时,由于不能完全代偿血液静水压效应的影响,脑循环还是可能发生明显的改变。     

A new evaluation method for +Gz tolerance with loratadine by using a near-infrared spectroscopy

Background

Loratadine (Claritin^®), an over the counter antihistamine in U.S. and UK, is acceptable for use without adverse side effects by aircrew with mild or moderate allergic or other situations requiring an antihistamine. Although +Gz (head to foot direction) tolerance testing for aircrew with loratadine has not been documented in the published literature, it is commonly accepted that loratadine dose not effect +Gz tolerance. The purpose of this study was to offer and validate a new evaluation method for +Gz tolerance testing with loratadine by using a near-infrared spectroscopy (NIRS).

Methods

A double-blind, placebo-controlled, randomized, crossover protocol was used to administer 10 mg of loratadine or placebo in nine healthy subjects. The subjects didn't wear anti-G suit. The +Gz exposure profiles consisted of, in series, a gradual onset ran (0.1 G·sec^-1) to the subject's visual end-point (peripheral light loss) or loss of consciousness (GLOC), and rapid onset run (1.0 G·sec^-1) to the subject's same end-point. In this study, G-level tolerance was defined as the +Gz level at visual end-point and/or at GLOC. As a subject's G-duration tolerance, we measured the total time (seconds) during rapid onset run. Otherwise, to confirm the effect of loratadine on +Gz tolerance, we measured the cerebral NIRS variables (hemoglobin concentration changes and tissue oxygenation index) as a new quantitative method for +Gz tolerance during a centrifuge experiments.

Results

No significant differences were observed in +Gz tolerance (+Gz level, duration time and NIRS variables) between subjects taking loratadine and placebo.

Conclusion

Our results demonstrate that loratadine has no detectable effect on +Gz tolerance by using a new method with cerebral NIRS variables and the traditional method with +Gz level and duration time. This study represents the first use of a quantitative parameter such as cerebral NIRS variables to assess the effects of a drug on acceleration tolerance.

     

The mechanism [correction of mehanism] of spatial [correction of spetial] orientation in conditions of G-stress

Six test subjects were subjected to lateral (+Gy) and longitudinal-lateral (+Gz/+Gy) accelerations in a centrifuge with a rotation radius of 6.55 m. During rotation, test subjects were instructed to indicate the position of subjective visual vertical. Results of this study demonstrated that during exposure to +Gy and +Gz/+Gy accelerations, the direction of the indicated subjective vertical approached the direction of the resultant acceleration vector when the lateral component increased. This observed effect decreases with an increase of the longitudinal component of the acceleration. It was suggested that exposure to (i.e. "pulling") high lateral acceleration (up to 2-3 Gy) in highly maneuverable aircraft can hinder spatial orientation of a pilot due to this persistent illusory spatial position as reported above. Our analysis showed that the process of spatial orientation under the conditions of G-load influence becomes more difficult and it is depending on the compromise between visual and vestibular-proprioceptive inputs. On account of this finding, it may be proposed that under conditions of G-load influence, pilots that rely primarily on visual perception may be exposed to higher risk of spatial disorientation.     

Limitations of Stroke Volume Estimation by Non-Invasive Blood Pressure Monitoring in Hypergravity

Background

Altitude and gravity changes during aeromedical evacuations induce exacerbated cardiovascular responses in unstable patients. Non-invasive cardiac output monitoring is difficult to perform in this environment with limited access to the patient. We evaluated the feasibility and accuracy of stroke volume estimation by finger photoplethysmography (SVp) in hypergravity.

Methods

Finger arterial blood pressure (ABP) waveforms were recorded continuously in ten healthy subjects before, during and after exposure to +Gz accelerations in a human centrifuge. The protocol consisted of a 2-min and 8-min exposure up to +4 Gz. SVp was computed from ABP using Liljestrand, systolic area, and Windkessel algorithms, and compared with reference values measured by echocardiography (SVe) before and after the centrifuge runs.

Results

The ABP signal could be used in 83.3% of cases. After calibration with echocardiography, SVp changes did not differ from SVe and values were linearly correlated (p<0.001). The three algorithms gave comparable SVp. Reproducibility between SVp and SVe was the best with the systolic area algorithm (limits of agreement −20.5 and +38.3 ml).

Conclusions

Non-invasive ABP photoplethysmographic monitoring is an interesting technique to estimate relative stroke volume changes in moderate and sustained hypergravity. This method may aid physicians for aeronautic patient monitoring.     

Expression of c-fos, c-jun and HSP70 mRNA in rat brain following high acceleration stress

Rats exposed to high +Gz forces in a small animal centrifuge (SAC) exhibit loss of neuronal function (isoelectric EEG), termed G-induced loss of consciousness (G-LOC). This phenomenon is presumably due to a reduction in cerebral blood flow (CBF) or ischemia. Ischemia induces various metabolic and physiologic changes including expression of immediate early genes (IEGs) in the brain. Expression of IEGs have been suggested to be reliable markers for neuronal response to external stimuli or stress. In the present study expression of IEGs c-fos, c-jun and stress response gene HSP70 were measured in the brains of rats subjected to six 30 s exposures of +22.5Gz in a small animal centrifuge. The level of c-fos, HSP70 and beta-actin mRNA were measured by both Northern blot and RT-PCR. Expression of c-jun was measured only by RT-PCR. Expression of c-fos and c-jun was significantly stimulated at 0.5, 15, 30 and 60 min post-centrifugation. The level of HSP70 mRNA was significantly higher only at 60 and 180 min post-centrifugation. Measurement of metabolities showed a significant increase in lactate and a decrease in Cr-P level at 30 s and 15 min post-centrifugation, respectively. Lactate, but not Cr-P and ATP levels were restored to control levels by 60 min post-centrifugation. It is concluded that the transient expression of c-fos, c-jun and HSP70 mRNA is stimulated by repeated ischemic/reperfusion episodes induced by high acceleration stress.     

Loss of consciousness as criterion of +Gz tolerance at Institute of Aviation Medicine MMA during +Gz acceleration selective test

+Gz induced loss of consciousness (G-LOC) is one of the most serious threats to aircrews flying high performance fighter aircraft. From the early beginning of use of our Centrifuge, use in selection was primary task. As a functional "endpoints" we use criteria: loss of peripheral vision, extreme pulse rate (above 180 b.p.m.), arrhythmias and loss of consciousness. The key-method in selection the candidate who tolerates +Gz stress on the best way is selection by common selective centrifuge "Test of linear increasing of acceleration" (TOLIA). We used gradual onset rate (GOR--0.1 G/s) and maximum/peak value: +5.5 Gz, +6.0 Gz and 7.0 Gz. Applied peak value depends on the goal of the test. The lowest peak value is for candidates planned for Air Academy, higher peak value is for those pilots planned for training to supersonic combat aircrafts and the highest peak value is for pilots who are planned to fly High performance combat aircrafts. We examined 2192 candidates in the last 20 years. Eleven subjects experienced G-LOC episodes. All episodes of G-LOC had occurred occasionally and without warning symptoms (loss of peripheral vision, gray out, blackout). The percentage of subjects having G-LOC episodes was 0.50%. Nine subjects experienced G-LOC during primary selection (+5.5 Gz), one G-LOC were observed at secondary selection (+6.0 Gz) and one G-LOC was observed during tertiary selection (+7 Gz). G-LOC is the only "endpoint" in the centrifuge selection which disqualifies the candidate at once and forever for planned flying duties. The other "endpoints" (loss of peripheral vision, heart rate above 180 b.p.m., arrhythmias) allow one more testing, not less than seven days later.     

Central venous pressure in humans during short periods of weightlessness

Central venous pressure (CVP) was measured in 14 males during 23.3 +/- 0.6 s (mean +/- SE) of weightlessness (0.00 +/- 0.05 G) achieved in a Gulfstream-3 jet aircraft performing parabolic flight maneuvers and during either 60 or 120 s of +2 Gz (2.0 +/- 0.1 Gz). CVP was obtained using central venous catheters and strain-gauge pressure transducers. Heart rate (HR) was measured simultaneously in seven of the subjects. Measurements were compared with values obtained inflight at 1 G with the subjects in the supine (+1 Gx) and upright sitting (+1 Gz) positions, respectively. CVP was 2.6 +/- 1.5 mmHg during upright sitting and 5.0 +/- 0.7 mmHg in the supine position. During weightlessness, CVP increased significantly to 6.8 +/- 0.8 mmHg (P less than 0.005 compared with both upright sitting and supine inflight). During +2 Gz, CVP was 2.8 +/- 1.4 mmHg and only significantly lower than CVP during weightlessness (P less than 0.05). HR increased from 65 +/- 7 beats/min at supine and 70 +/- 5 beats/min during upright sitting to 79 +/- 7 beats/min (P less than 0.01 compared with supine) during weightlessness and to 80 +/- 6 beats/min (P less than 0.01 compared with upright sitting and P less than 0.001 compared with supine) during +2 Gz. We conclude that the immediate onset of weightlessness induces a significant increase in CVP, not only compared with the upright sitting position but also compared with the supine position at 1 G.     

Effect of changing the gravity vector on respiratory output and control.

We studied the respiratory output in five subjects exposed to parabolic flights [gravity vector 1, 1.8 and 0 gravity vector in the craniocaudal direction (Gz)] and when switching from sitting to supine (legs bent at the knees). Despite differences in total respiratory compliance (highest at 0 Gz and in supine and minimum at 1.8 Gz), no significant changes in elastic inspiratory work were observed in the various conditions, except when comparing 1.8 Gz with 1 Gz (subjects were in the seated position in all circumstances), although the elastic work had an inverse relationship with total respiratory compliance that was highest at 0 Gz and in supine posture and minimum at 1.8 Gz. Relative to 1 Gz, lung resistance (airways plus lung tissue) increased significantly by 52% in the supine but slightly decreased at 0 Gz. We calculated, for each condition, the tidal volume changes based on the energy available in the preceding phase and concluded that an increase in inspiratory muscle output occurs when respiratory load increases (e.g., going from 0 to 1.8 Gz), whereas a decrease occurs in the opposite case (e.g., from 1.8 to 0 Gz). Despite these immediate changes, ventilation increased, going to 1.8 and 0 Gz (up to approximately 23%), reflecting an increase in mean inspiratory flow rate, tidal volume, and respiratory frequency, while ventilation decreased (approximately -14%), shifting to supine posture (transition time approximately 15 s). These data suggest a remarkable feature in the mechanical arrangement of the respiratory system such that it can maintain the ventilatory output with small changes in inspiratory muscle work in face of considerable changes in configuration and mechanical properties.     

大鼠正加速度高耐力相关基因的分离

 为从基因水平上揭示正加速度 (+Gz)高耐力产生机理及寻找 +Gz高耐力相关功能性蛋白 ,利用抑制消减杂交技术分离 +Gz高耐力相关基因 .雄性SD大鼠在离心机上处理后 ,选取耐受终点在高、低两个极端的动物 ,立即取全脑 ,分离mRNA .以高耐力者为Tester ,低耐力者为Driver,利用抑制消减杂交技术进行 +Gz耐力处于高、低两个极端动物脑组织间基因表达差异显示 ,获得 +Gz高耐力大鼠脑组织相关cDNA .以高、低耐力大鼠脑组织mRNA来源的cDNA为探针 ,对获得的cDNA克隆进行斑点杂交 .分别以杂交筛选出的阳性克隆为探针 ,对高、低耐力大鼠脑组织总RNA进行Northern杂交分析 .两次杂交结果均选择高耐力组杂交信号是低耐力组 3倍以上的cDNA克隆 .经过斑点杂交筛选 ,从大鼠脑组织中获得了 6 7个在 +Gz高耐力大鼠脑组织中上调表达的cDNA克隆 .Northern杂交分析发现 ,钙离子 钙调蛋白依赖性蛋白激酶Ⅱβ亚基 (Camk2b)和一未知基因在 +Gz高耐力大鼠脑组织中的表达量增加 .结果提示 ,+Gz耐力处于高、低两个极端的大鼠脑组织基因表达有明显差异 ,这些差异表达的基因很可能与 +Gz高耐力的产生有关 ,且钙离子 钙调蛋白依赖性蛋白激酶Ⅱβ亚基和一未知基因是初步获得的与 +Gz高耐力的产生特异相关的基因     

Feasibility of real-time 3D echocardiography in weightlessness during parabolic flight

Aim of the study was to test the feasibility of transthoracic real-time 3D (Philips) echocardiography (RT3D) during parabolic flight, to allow direct measurement of heart chambers volumes modifications during the parabola. One RT3D dataset corresponding to one cardiac cycle was acquired at each gravity phase (1 Gz, 1.8 Gz, 0 Gz, 1.8 Gz) during breath-hold in 8 unmedicated normal subjects (41 +/- 8 years old) in standing upright position. Preliminary results, obtained by semi-automatically tracing left ventricular (LV) and left atrial (LA) endocardial contours in multiple views (Tomtec), showed a significant (p<0.05) reduction, compared to 1 Gz, of LV and LA volumes with 1.8 Gz, and a significant increase with 0 Gz. Further analysis will focus on the right heart.