一种针刺补泻法对小型猪皮下组织液压的影响

目的研究《灵枢》卷首《九针十二原》针刺补泻法对小型猪皮下组织液压(interstitial fluid pressure,IFP)的作用,探讨其调节组织液的生物力学机制。方法在9只健康实验用小型猪腹部随机取点行补法(提/按法)和泻法(摇大针孔),观察正常状态(normal state,NS)、抽取组织液的低组织液量(low volume,LV)状态和注入生理盐水的高组织液量(high volume,HV)状态下针刺前后IFP。结果 NS下提/按法可极显著升高IFP;泻法可极显著降低IFP,针后5 min泻法组IFP降低较快。LV状态提/按法均能升高IFP,针后10 min二者IFP下降较慢。HV状态下泻法可极显著降低IFP,针后5 min与对照组变化趋势不同。结论该补泻法可升高或降低IFP,证明其对IFP有相反方向的调节作用。研究结果为针灸临床使用补泻手法提供新的科学依据。     

A biophysical basis of enhanced interstitial fluid pressure in tumors

It is widely accepted that enhanced interstitial fluid pressure (IFP) in tumors is a major obstacle against delivery of therapeutic agents. On the other hand, the origin of enhanced IFP remains controversial. Here, the Van't Hoff equation is applied to examine how glucose breakdown to CO2 and lactate in tumor cells may affect intracellular osmotic pressure. According to the equation, it is found that production of CO2 from glucose lowers osmotic pressure inside cells, while glycolytic production of lactate generates significant increases. Crucial to a net enhancement of pressure in cells is the Warburg ratio, the ratio of the fraction of glucose transformed to lactate divided by the fraction of glucose metabolized to CO2: if (and only if) the ratio is higher than 1.0, there is a resulting increase in intracellular osmotic pressure. Under fully anaerobic glycolysis, the enhancement of intracellular pressure is maximal, namely 19.3 mmHg per mM of glucose metabolized to lactate (Van't Hoff equation). Cells are then biological pressure pumps driven by glycolytic production of lactate, causing IFP to raise. It is proposed that a regulatory feedback loop prevents IFP to raise above microvascular pressure (MVP). Accordingly, enhanced IFP in tumors is the result of high rates of tumor glycolysis, and enhancement of IFP is limited by MVP. It is thus concluded that a high rate of glycolytic production of lactate in tumor cells ultimately prevents both access of therapeutic agents to the malignant cells and immunological surveillance, and that it indirectly drives outward currents of interstitial fluid, thereby propelling both the process of tumor infiltration of surrounding structures and metastatic spread, depending on deformability and proteolytic capacity of the malignant cells.     

The discrepancy between thermometry and calorimetry during exercise

Summary During prolonged exercise in a hot and dry environment one may observe that a man seems to maintain a caloric equilibrium for about one hour. When the man dehydrates, however, a continuous rise in rectal temperature may be observed simultaneously. This discrepancy between calorimetry and thermometry was investigated by measuring calorimetrically the body heat storage during exercise. In a series of experiments work and heat load were kept constant throughout (M=7.5 kcal/min; 35°C; RH 15%), but the exposure time was increased in steps of 18 min up to 144 min. The heat storage did not alter between the 54th and the 108th min. In the same period the rectal temperature rose steadily.This article was prepared while holding a research fellowship from the Anglo-American Corporation of South Africa.     

Quantification and localisation of damage in rat muscles after controlled loading; a new approach to study the aetiology of pressure sores.

To obtain more insight in the aetiology of deep pressure sores, an animal model was developed to relate controlled external loading to local muscle damage. The tibialis anterior muscle (TA) and overlying skin of a rat were compressed between indentor and tibia. Loads of 10, 70 and 250kPa at skin surface were applied for 2 or 6h. During half of the 10 and 250kPa experiments interstitial fluid pressure (IFP) in the TA was measured. The TAs were excised 24h after load application. Both amount and location of damage were assessed by histological examination using a semi-automated image-processing program. In six of eleven loaded muscles damage was found. The damage was located from superficial to deep muscle tissue in a zone never exceeding the diameter of the indentor. The IFP measurements interfered with the occurrence of damage; application of 10 and 70kPa loads only caused damage when combined with IFP measurements, whereas IFP measurements increased damage at 250kPa loads. The results showed that the developed animal model can be used to provoke local damage by applying a controlled load and that the amount and location of damage can be assessed using the newly developed techniques.     

Compliance of the interstitial space in rats I. Studies on hindlimb skeletal muscle

Interstitial compliance, defined as the ratio between changes in interstitial fluid volume (ΔIFV) and interstitial fluid pressure (ΔIFP), was determined for rat skeletal muscle. IFV was measured as the extravascular distribution space for ⁵¹Cr-EDTA, while sharpened micropipettes connected to a servo-controlled counterpressure system were used to measure IFP. The experimental protocol was designed to bring about acute (2–4 h) and chronic (24–28h) tissue over- and dehydration. During dehydration, the average compliance was 0.056 ml/g dry weight · mmHg, corresponding to 1.40 ml/100 g wet tissue mmHg, and was not significantly different in acute and chronic experiments. In hydration (acute and chronic), compliance increased several-fold when IFV increased. Even at greatly increased IFV, IFP did not rise more than 1 to 1.5 mmHg above control level. Since control IFV amounts to 10 ml/100 g wet tissue, IFV will decrease by 14% when IFP falls by 1 mmHg from this control level. Provided unchanged interstitial protein mass the dehydration will cause interstitial fluid colloid osmotic pressure to increase by somewhat more than 1 mmHg—from a control level of 9 mmHg. Furthermore, since IFP was not increased by more than 1 to 1.5 mmHg during hydration, an increase in IFP plays a minor role in edema-prevention compared to dilution and/or washout of interstitial proteins.     

Extracellular fluid volume and central circulation after long lasting exercise and dehydration in conscious dogs

Summary Two aspects of the recovery period after endurance exercise were investigated: a) the fluid distribution between the intra- and extravascular parts of the extracellular fluid volume (ECFV) induced by exercise dehydration, b) the cardiovascular response pattern [blood pressure (BP), heart rate (HR), cardiac output (CO), total peripheral resistance (TPR), and central venous pressure (CVP)] to the heat load which results from the preceding exercise.Seven conscious dogs performed endurance exercise in a cool environment (16°C) on a horizontal treadmill till 4% of the body weight was lost. It was found that about 70% of the total fluid loss of the body came from intracellular water. During exercise sodium and chloride concentrations rose by 6 mMol and 7 mMol respectively (P<0.005) and remained elevated throughout the early recovery period indicating a fluid loss of about 100–200 ml out of the ECFV. Direct measurements of the ECFV as sulfate space confirmed these values. Since the plasma volume remained unchanged, this fluid loss was carried totally by the interstitial fluid volume.Immediately after exercise body temperature was elevated by 1.5°C and returned towards control within 90 min. Cardiac output was above control level for 2 h after the end of exercise, at first due to an increased HR and thereafter to an elevated stroke volume (SV) (P<0.02). CVP and TPR were below control levels for at least 2 h (P<0.01). A linear correlation was found between CVP and TPR.A close correlation existed between the body temperature and the cardiovascular parameters. It can be concluded that even long after exercise the cardiovascular system has to serve thermoregulatory needs.This study was supported by the Bundesinstitut für Sportwissenschaften Köln andthe Deutsche Forschungsgemeinschaft     

Differential acclimatisation as a function of duration of exposure

Summary The length of time required to achieve the highest degree of acclimatisation was studied in two groups of men who were acclimatised at either one of two temperature conditions, namely 32.2 °/33.9 ° C W.B./D.B. or 33.9 °/35.5 ° C W.B./ D.B. The acclimatisation procedure consisted of 4 hours work daily at a metabolic rate of 5 kcal/min for the duration of 12 days. Changes in rectal temperature and heart rate followed immediately upon the first exposure to, and work in, heat. Judged by the rectal temperature reactions, the process of acclimatisation was completed within 8 days. An extension of the period of acclimatisation to between 9 and 12 days was without effect on the state of acclimatisation acquired by the subjects after an 8-day procedure. With an acclimatisation procedure shorter than 8 days the men were not fully acclimatised. Acclimatisation procedures of either 4, 5, or 6 days duration (at 32.2 ° C W.B.) induced a degree of acclimatisation in the subjects which proved to be adequate to enable them to work with body temperatures similar to those of fully acclimatised men, for periods of either 1, 2 or 3 hours respectively in the test environment.     

Body heat balance in man subjected to endogenous and exogenous heat load

Summary The body heat balance, measured by a thermometric method, was investigated in humans subjected to endogenous and exogenous heat load. The purpose of the present study was to test the concept of heat exchange by a servomechanism in human thermoregulation. Two series of experiments were performed on male volunteers. In series I 15 subjects performed physical exercise (50% max) for 60 min at a constant ambient temperature of 25‡ C. In series II 16 subjects rested in a climatic chamber where the ambient temperature was elevated over 30 min from 22 to 42‡ C and kept stable at this level during the subsequent 60 min. It was found that in both series of experiments the sweating rate followed an exponential curve exhibiting an inertial course. Heat was stored in the body mainly at the beginning of experiment. In series I the net body heat load of 125 W/m² was equalized by sweat evaporation, beginning after 40 min of the exercise. In series II the net body heat load of 80 W/m² was equalized in the same way, starting after 35 min of the constant high ambient temperature. In both series of experiments the amount of heat stored in the body calculated from the body heat balance was quite close to the amount of heat calculated from the calorimetric equation. It is concluded, that under the present experimental conditions, heat loss from the body by sweat evaporation seems to be a regulated variable in the human thermoregulatory System. The observed increase in rectal temperature may resuit from an inertial course of the sweating reaction. Supported by the Polish Academy of Sciences within the project 10.4     

Interstitial Stress and Fluid Pressure Within a Growing Tumor

A solid tumor is composed of a population of cells that is expanding as a result of cell division. With dense cell packing, the solid matrix of the interstitial tissue is subject to residual stress. In addition, elevated interstitial fluid pressure (IFP) has been reported by researchers for a number of solid tumors. These features were incorporated into a mathematical model that predicts the mechanical response of a solid tumor within its host environment. A theoretical framework accounting for volumetric expansion, transvascular exchange and extravascular transport of fluids was developed using poroelastic theory, and applied to a spherical, vascularized, alymphatic tumor undergoing small growth increments. Simulations of tumor IFP were similar to those predicted by Jain and Baxter (Ref. 23), showing elevated IFP that is driven by microvascular fluid pressure. Tumor growth, tissue stiffness, and IFP contribute to the compressive stresses predicted in the solid tumor interior. Tensile and compressive stresses were predicted in adjacent host tissues corresponding to radial and circumferential directions, respectively. An application of this model includes a solid stress-based framework for predicting regions of vascular collapse within the tumor interior. © 2003 Biomedical Engineering Society. PAC2003: 8717Ee, 8710+e, 8719Rr, 8719Xx     

Interstitial compliance and transcapillary fluid balance in renal hypertensive rats

Local interstitial fluid volume (IFV) and pressure (IFP) were used to estimate interstitial compliance (= delta IFV/delta IFP) in skin and skeletal muscle of normotensive (NT) and renal hypertensive rats (HT). The IFV was measured as the extravascular 51Cr-EDTA space, and IFP with micropipettes (tip diameter 2-4 microns) connected to a servocontrolled counter-pressure system. After control measurements, overhydration was induced by infusion of saline, 10% of body weight i.v. with or without venous stasis. Alternatively, dehydration was induced by peritoneal dialysis with 20% glucose or by furosemide infusion with or without 24 h fluid deprivation. Control ECV averaged 24.94 and 24.73 ml per 100 g in NT and HT, respectively (P greater than 0.05). Control PV averaged 2.81 and 3.28 ml per 100 g in NT and HT, respectively (P = 0.061), and control IFP was more positive in HT than in NT: 0.4 mmHg in skin (P less than 0.05) and 0.2 mmHg in skeletal muscle (P greater than 0.05). Dehydration changed PV significantly more in HT than in NT (P less than 0.05). The interstitial volume-pressure curve was linear in dehydration and the initial part of overhydration but gradually levelled off, and the maximal rise in IFP was 1-1.5 mmHg in skin and muscle. Interstitial compliance was calculated from the dehydration part of the volume-pressure curve and was in NT 14% per mmHg both in skin and skeletal muscle. In HT, compliance during dehydration was 10.2 and 20.7% reduction in IFV per mmHg fall in IFP in skin and muscle, respectively, not significantly different from corresponding values in NT (P greater than 0.05). We conclude that HT had unaltered ECV and a tendency to higher PV, and that interstitial compliance was not significantly different in normotensive and hypertensive rats.     

No difference in the skeletal muscle angiogenic response to aerobic exercise training between young and aged men

Ischaemia-induced skeletal muscle angiogenesis is impaired in aged compared with young mice. In humans, vascular endothelial growth factor (VEGF) mRNA and protein following an acute exercise bout are lower in aged compared with young untrained men. We hypothesized that exercise-induced skeletal muscle angiogenesis would be attenuated in aged compared with young men. In eight aged (mean age: 64 years) and six young (mean age: 25 years) sedentary men, muscle biopsies were obtained from the vastus lateralis prior to (Pre), after 1 week and after 8 weeks of an aerobic exercise training program for the measurement of capillarization and VEGF mRNA. Dialysate VEGF protein collected from the muscle interstitial space was measured at rest and during submaximal exercise at Pre, 1 week and 8 weeks. Exercise training increased capillary contacts (CC) and capillary-to-fibre perimeter exchange index (CFPE) of type I and IIA fibres similarly in young and aged. The CC of type IIA and IIB fibres was lower in aged compared with young independent of training status. Exercise-induced interstitial VEGF protein was lower in aged compared with young independent of training status. In untrained, greater exercise-induced interstitial VEGF protein during exercise was associated with greater type I, IIA and IIB CC. Exercise training increased VEGF mRNA similarly in young and aged. These results demonstrate that the angiogenic response to aerobic exercise training is not altered during the ageing process in humans. In addition, muscular activity-associated increases in interstitial VEGF protein may play an important role in the maintenance of skeletal muscle capillarization across the life span.     

Cell Proliferation of Cultured Human Cancer Cells are Affected by the Elevated Tumor Pressures that Exist In Vivo

Elevated interstitial fluid pressure (IFP) is observed in most solid tumors. However, the study of the cellular processes of tumors and the development of chemotherapy are routinely studied using in vitro culture systems at atmospheric pressure. Using a new pressurized cell culture system, we investigated the influence of hydrostatic pressure on population dynamics of three primary osteosarcoma (HOS, U2OS, SaOS2) and two metastatic tumor cell lines (MCF7 breast, H1299 lung) that invade bone. Values of IFP in normal human bone and muscle, and in osteosarcoma tumors obtained during their surgical biopsy established the hydrostatic pressure range for the in vitro cell studies. The IFP values were obtained from a retrospective review of patient records. IFP from confirmed osteosarcoma was 35.9± 16.2 mmHg. Tumor IFP was significantly higher than muscle IFP (p < 0.001) and bone IFP (p < 0.003).The in vitro study measured the cell-line proliferation using hydrostatic pressures of 0, 20, 50 and 100 mmHg. The findings suggest that hydrostatic pressure either increases or decreases tumor proliferation rates depending on cell type. Furthermore, cell death was not associated with apoptosis.     

组织液压波在大白鼠胃经皮下组织传送规律的研究

注射０．９％的生理盐水到麻醉的大白鼠胃经的皮下，形成一个水泡，然后给予一个机械压力，由此产生一个组织液压波，测量组织液压在胃经上和胃经外的变化，发现了五种基本的组织液型及亚型，这些波型基于组织不同的粘弹性特性，组织液压波在经线上与经线外幅度差异与距离的线性回归方程为Ｙ＝－０．３５Ｘ＋１．９６，具有统计学显著性（Ｐ＜０．０１）。表明经脉线组织可能具有较好的渗透性和柔性。     

各向异性传导系数对实体肿瘤间质流体流动影响的二维边界元模拟

目的研究实体肿瘤组织间质各向异性传导系数对流体流动的影响。方法用图像处理方法建立具有实体肿瘤微血管形态和分布特征的二维微血管网络模型, 应用边界元方法数值计算多连通区域内组织液的流动及水力传导系数变化的影响。结果横向与纵向间质水力传导系数的不同, 对整个肿瘤内组织间质压强的分布有明显的影响; 不同函数形式分布的水力传导系数, 影响肿瘤局部区域内间质流体压强的分布。结论各向异性水力传导系数对实体肿瘤组织间质压强有明显影响, 与传导系数变化的范围和肿瘤内微血管网络的形态有关。     

Circadian variations in psychophysiological responses to heat exposure and exercise

Summary Ten healthy men were tested at 0600, 1200, 1800 and 2400 hours on different days at rest in a laboratory at room temperature followed by 1 h of heat exposure in a climatic chamber at 42° C, 60% rh (50 min rest and 10 min exercise on a cycle ergometer at 50% ). Heart rate, blood pressure, rectal temperatureT _re, metabolic rate, number connection test, visual and auditory reaction time, flicker test and catecholamine excretion were measured. Heat exposure and exercise caused lower heart rate acceleration at 2400 hours than at 0600 and 1200 hours, the smallest increase ofT _re at 1800 hours, and an increase in metabolic rate greater at 1200 than at 1800 hours. In the afternoon, when, according to the circadian rhythm, the body temperature is highest, the additional heat load produced the smallest physiological effects. Performance efficiency, after heat exposure combined with physical exercise, improved slightly, but diurnal variations did not show significant circadian rhythm. The work was supported from Poland's Central Programme of Basic Research 06-02.III.2.2     

Measurement of interstitial fluid pressure: Comparison of methods

Interstitial fluid pressure (IFP), i.e., the pressure in a saline-filled tube brought into contact with the interstitium, has been measured in cats with two “acute” [micropipettes and wick-in-needle (WIN)] and two chronic (perforated and porous capsules) methods. In a control situation, similar pressures of −1.5 and −1.6 mm Hg were recorded in skin with micropipettes and both types of capsules, respectively, while WIN pressure in subcutis was −1.2 mm Hg. IFP in skeletal muscle was −0.5, −0.5, and −1.1 mm Hg as recorded with micropipettes, WIN, and porous capsules, respectively. During infusion of Ringer's solution, pressures in both types of capsules rose by 4 to 6 mm Hg, while pressure recorded with the acute methods increased by 1 to 1.5 mm Hg only. Two hours after infusion all techniques gave similar pressures. Peritoneal dialysis for 2 hours reduced micropipette and WIN pressures by 3 to 4 mm Hg. Pressure in perforated capsules fell by 10 mm Hg during dialysis and remained low for an additional 2 hours, while porous capsule pressure fell by 7 mm Hg during dialysis but thereafter increased and reached the pressure recorded with micropipettes and WIN 2 hours after ended dialysis. In both overhydration and dehydration, capsules probably react to changes in interstitial fluid colloid osmotic pressure; in overhydration the capsules react also to changes in capillary pressure, resulting in the discrepancy between chronic and acute methods during non-steady-state conditions. In conclusion, acute and chronic methods record similar pressures during steady-state conditions, but the chronic methods are sensitive to changes in vascular pressure and interstitial fluid colloid osmotic pressure and are therefore not suitable for measuring the changes that occur in IFP within a few hours.     

Time course of ventilatory acclimatisation to hypoxia in a model of anemic transgenic mice

We questioned the assumption that polycythemia is essential for adaptation to chronic hypoxia. Thus, the objective of our study was to determine if anemic Epo-TAg(h) mice could survive in hypoxia despite low oxygen carrying capacity. We explored the possibility that ventilatory acclimatisation is involved in the strategy used by anemic transgenic mice to adapt to chronic hypoxia. Epo-TAg(h) and Wild Type mice were exposed during 2 weeks at a barometric pressure of 450 Torr. After 1, 5 and 14 days of exposure, ventilation at different inspired oxygen fraction was measured in both groups. Ventilation during acclimatisation to hypoxia was significantly greater in Epo-TAg(h) than in Wild Type. The difference was mainly due to a higher tidal volume that could explain a higher arterial PO2 in Epo-TAg(h) mice. Epo-Tag(h) mice did not develop right ventricle hypertrophy after 2 weeks of exposure to hypoxia while Wild Type did. Hemoglobin concentration was 60% lower in anemic mice versus Wild Type after acclimatisation. In conclusion, ventilatory acclimatisation contributed to the adaptation of Epo-Tag(h) mice in chronic hypoxia despite low arterial oxygen carrying capacity.     

Rat brain interstitial fluid pressure measured with micropipettes

Interstitial fluid pressure (IFP) in the rat brain has been measured with micropipettes, 2-4 microns in diameter, after trepanation and incision of dura. IFP was compared with cerebrospinal fluid pressure (CSFP) measured by a 0.3-mm (OD) cannula in the lateral ventricle. Control IFP averaged 3.43 +/- 0.65 (SD) mmHg (n = 83) with a corresponding CSFP of 3.53 +/- 0.71 (n = 83). Pretreatment with indomethacin to reduce inflammation during preparation did not affect IFP and CSFP. Infusion of a 20% mannitol solution amounting to 5% of body weight resulted in an average IFP of -5.66 mmHg and CSFP of -4.56 mmHg 20 min after start of the infusion, after which a gradual rise in both pressures was observed. Similar results were obtained after infusion of hypertonic urea. Inflation of a cuff around the rat neck resulted in an immediate and similar rise in IFP and CSFP. Increasing the arterial CO2 partial pressure to 80 mmHg increased IFP to 12-14 mmHg and pial venular pressure to 13-15 mmHg, while CSFP rose to about 10 mmHg. The micropuncture technique for measurement of brain IFP is rapid and practically atraumatic and may be used in a variety of animals.     

循经低流阻通道组织液压的初步观察

目的 测量循经低流阻通道与周围的组织液压,观察其差异及变化情况。方法 在麻醉的小型猪上,使用连续流阻测量仪测出低流阻点和非低流阻点,然后采取针中芯方法测量组织液压。结果 统计结果表明,小型猪胃经、肾经和任脉的低流阻通道平均压力均显著低于旁开的高流阻区域,其压力差分别为1.06、0.70、3.69 mmHg（1 mmHg=0．133 kPa）,总压力差为1.44 mmHg,压力梯度为1.44~2.88 mmHg/cm。在一些低流阻点上发现了与呼吸频率一致的压力波。结论 外周皮下组织中存在着指向经脉低流阻通道的压力差,可能构成组织液向经脉流动的动力。     

Quantification of the decay and re-induction of heat acclimation in dry-heat following 12 and 26 days without exposure to heat stress

Compared with the induction of heat acclimation (HA), studies investigating the decay and re-induction of HA (RA) are relatively sparse and have yielded conflicting results. Therefore, 16 semi-nude men were acclimated to dry-heat by undertaking an exercise protocol in a hot chamber (dry-bulb temperature 46.1 ± 0.1°C; relative humidity 17.9 ± 0.1%) on 10 consecutive days (HA1–10) in winter UK. Thereafter, the subjects were divided into two groups and re-exposed to the work-in-heat tests after 12 and 26 days until RA was attained (RA₁₂, n = 8; RA₂₆, n = 8). The exercise protocol consisted of 60 min of treadmill walking (1.53 m s⁻¹) at an incline individually set to induce a rectal temperature (T _re) of ∼38.5°C during HA1 (equating to 45 ± 4% peak oxygen uptake), followed by 10 min of rest and 40 min of further treadmill exercise, the intensity of which was increased across HA to maintain T _re at ∼38.5°C. T _re, mean skin temperature, heart rate and rate of total water loss measured at 60 min did not change after HA7, and HA was taken as the mean of the responses during HA8–10. For both groups, there was no decay in T _re and for all measured variables RA was attained after 2 and 4 days in RA₁₂ and RA₂₆, respectively. It is concluded that once adaptation to heat has been attained, the time that individuals may spend in cooler conditions before returning to a hot environment could be as long as one month, without the need for extensive re-adaptation to heat.