高原红细胞增多症动物模型的建立及其生理功能反应

背景：国内外关于高原红细胞增多症的动物研究主要以模拟海拔进行,少数情况下进行现场研究,但在现场究竟多长时间可以使平原大鼠发生高原红细胞增多症还需要进一步研究。目的：建立高原红细胞增多症动物模型并对相关生理功能反应进行初步观察。设计、时间及地点：随机对照动物实验,于2007-08／09在青海大学医学院高原医学研究中心教育部和青海省重点实验室完成。材料：SPF级Wistar大鼠50只,体质量160-200g,雌雄各半。10只高原鼠兔（Pika）于青海玛多县4300m现场捕获,体质量100-180g。促红细胞生成素试剂盒由美国R＆D Systems公司提供。方法：将30只Wistar大鼠随机分成高原15和30d两组（雌雄分开）,每组各15只,运至海拔4300m青海省果洛州玛多县饲养。余20只大鼠为对照组在西宁海拔2260m饲养。另10只高原鼠兔作为高海拔对照组。分别在第15天和第30天进行血红蛋白、红细胞压积、促红细胞生成素测定。主要观察指标：①高原15d组和高原30d组中出现高原红细胞增多症阳性数。②高原红细胞增多症组与各正常对照组血红蛋白等指标的比较。③高原红细胞增多症组与各正常组促红细胞生成素水平的变化。④高原红细胞增多症组血红蛋白水平与血氧饱和度和促红细胞生成素相关性分析。结果：高原15,30d组大鼠血红蛋白,红细胞压积水平明显升高,与高海拔和低海拔对照组相比差异有显著性意义（P〈0．01）;高原15d对照组中血红蛋白,207g／L,红细胞压积〉65％的高原红细胞增多症大鼠模型占75％,高原30d组中占93％。高原组促红细胞生成素值显著高于高海拔和低海拔对照组（P〈0．01）。结论：通过对Wistar大鼠各项生理指标的测定认为在海拔4300m地区饲养30d才可完全建立高原红细胞增多症的动物模型,并进一步说明低海拔动物在不同海拔具有不同的生理反应机制。     

Renal and hormonal responses to acute hypoxia in normal individuals

We studied, in normal volunteers, the effects of 1 hour of hypoxia on the concentration of angiotensin-converting enzyme and bradykinins, along with previously measured parameters of renal and endocrine function. Ten men, 18 to 42 years of age, undergoing water diuresis, breathed a low-oxygen mixture (five breathed 10.5% O2 and five 12% O2); all breathed 21% O2 on a control day. Measurements included mean blood pressure and heart rate every 2 to 3 minutes; plasma levels of renin activity, aldosterone, arginine vasopressin, norepinephrine, and bradykinin, and angiotensin-converting enzyme activity, before and at the end of gas breathing; and urine volume (UV), creatinine, Na+, and bradykinin concentration. Arterial blood gases and effective renal plasma flow were determined at the end of gas breathing only. Mean values +/- SEM for arterial blood gases with low O2 were pH 7.39 +/- 0.02, PO2 46 +/- 2 torr, PCO2 39 +/- 2 torr (12% O2) and 7.48 +/- 0.01, 35 +/- 1 torr, 33 +/- 1 torr (10.5% O2). Responses were otherwise identical in both groups, and data were combined for analysis. With hypoxia, heart rate and effective renal plasma flow increased significantly, P less than 0.005; no changes occurred in Uv, urine Na+ concentration, glomerular filtration rate, plasma or urine bradykinin concentration, serum angiotensin-converting enzyme activity, plasma renin activity, plasma aldosterone concentration, plasma arginine vasopressin concentration, or plasma norepinephrine concentration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Human responses to colonoscopy.

Registered nurses must not only anticipate the usual responses that a patient may experience during colonoscopy but also must be able to predict and prevent atypical responses. Normal healthy compensation (physiologic) and decompensation (pathophysiologic) responses as well as observable and measurable patient behaviors are included in a comprehensive assessment. In developing a plan of care, nurses must also consider the patient's past experiences, knowledge, and usual coping mechanisms. Professional nurses are responsible and accountable for diagnosing and treating human responses to actual or potential health problems. A human response framework emphasizes the multiple perspectives in which humans adapt to health and illness. This framework provides a model to clarify what constitutes a human response.     

Human intracranially-recorded cortical responses evoked by painful electrical stimulation of the sural nerve

Intracranial recordings were obtained from 5 epilepsy patients to help identify the generators of the scalp somatosensory evoked potential (SEP) components that appear to be involved in orienting attention towards a potentially threatening, painful sural nerve electrical stimulus. The intracranial recording data support, for the most part, the generators suggested by our scalp SEP studies. The generators of the central negativity at 70-110 ms post-stimulus and the contralateral temporal negativity at 100-180 ms are located in the somatosensory association areas in the medial wall of the parietal cortex and in the parietal operculum and insula, respectively. The negative potential at 130-200 ms recorded from over the fronto-central scalp appears to be generated in the medial prefrontal cortex and primary somatosensory cortex foot area. The intracranial recording data suggest that the positive scalp potential at 280-320 ms, which corresponds to the pain-related P2, has multiple generators, including the anterior cingulate cortex, inferior parietal cortex, and possibly the somatosensory association areas in the medial wall of the parietal cortex. Finally, the positive scalp potential at 320-400 ms has generators in brain areas that others have shown to generate the P3a, including the dorsolateral and medial prefrontal cortices, temporal parietal junction, and the posterior hippocampus, which supports our hypothesis that this potential is a pain-evoked P3a. The putative functional roles of the brain areas generating these components and the response properties of the intracranial peaks recorded from these brain areas are in most cases consistent with the attention- and pain-related properties of their corresponding scalp SEP components. The intracranial recordings also demonstrate that the source configuration underlying the SEP components are often more complex than was suggested from the scalp studies. This complexity implies that the dipole source localization analysis of these components will at best provide only a very crude estimate of source location and activity, and that caution must be used when interpreting a change in the scalp component amplitude.     

Sympathoadrenal responses to acute and chronic hypoxia in the rat.

The sympathoadrenal responses to acute and chronic hypoxic exposure at 10.5 and 7.5% oxygen were determined in the rat. Cardiac norepinephrine (NE) turnover was used to assess sympathetic nervous system (SNS) activity, and urinary excretion of epinephrine (E) was measured as an index of adrenal medullary activity. The responses of the adrenal medulla and SNS were distinct and dependent upon the degree and duration of hypoxic exposure. Chronic hypoxia at 10.5% oxygen increased cardiac NE turnover by 130% after 3, 7, and 14 d of hypoxic exposure. Urinary excretion of NE was similarly increased over this time interval, while urinary E excretion was marginally elevated. In contrast, acute exposure to moderate hypoxia at 10.5% oxygen was not associated with an increase in SNS activity; in fact, decreased SNS activity was suggested by diminished cardiac NE turnover and urinary NE excretion over the first 12 h of hypoxic exposure, and by a rebound increase in NE turnover after reexposure to normal oxygen tension. Adrenal medullary activity, on the other hand, increased substantially during acute exposure to moderate hypoxia (2-fold increase in urinary E excretion) and severe hypoxia (greater than 10-fold). In distinction to the lack of effect of acute hypoxic exposure (10.5% oxygen), the SNS was markedly stimulated during the first day of hypoxia exposure at 7.5% oxygen, an increase that was sustained throughout at least 7 d at 7.5% oxygen. These results demonstrate that chronic exposure to moderate and severe hypoxia increases the activity of the SNS and adrenal medulla, the effect being greater in severe hypoxic exposure. The response to acute hypoxic exposure is more complicated; during the first 12 h of exposure at 10.5% oxygen, the SNS is not stimulated and appears to be restrained, while adrenal medullary activity is enhanced. Acute exposure to a more severe degree of hypoxia (7.5% oxygen), however, is associated with stimulation of both the SNS and adrenal medulla.     

Cardiorespiratory, tissue oxygen and hepatic NADH responses to graded hypoxia

Objective: To assess cardiorespiratory, tissue oxygen and hepatic nicotine adenine dinucleotide hydride (NADH) responses to graded hypoxia. Design: Prospective, controlled, randomized study. Setting: University laboratory. Animals and interventions: 18 anaesthetised Sprague-Dawley rats spontaneously breathing either 21 % (controls), 12.5 % or 10 % inspired oxygen concentrations (6 rats per group). Measurements and results: All animals in the 21 and 12.5 % O₂ groups survived the 3-h study period, compared to only 1 in the 10 % O₂ group. In this latter group, mean arterial pressure and renal blood flow fell immediately with hypoxaemia, whereas aortic blood flow was maintained until the preterminal stages. Critical cellular hypoxia was suggested by an increasingly severe base deficit, an initial rise then a preterminal fall in hepatic NADH intensity and premature death in all but 1 animal. Hepatic NADH fluorescence intensity was unchanged in control animals but showed a progressive rise in the 12.5 % O₂ group, accompanied by a small though static increase in arterial base deficit. No significant differences were seen in arterial and tissue partial pressure of oxygen between the 12.5 and 10 % O₂ groups. Conclusions: This study demonstrates major differences in cardiorespiratory, hepatic NADH and outcome responses to small variations in the degree of hypoxic hypoxia. The fall in NADH fluorescence intensity presages impending death and is likely to reflect failure of cellular metabolic processes. Received: 2 April 1998 Accepted: 26 August 1998     

Human amygdala responses to fearful eyes

Fearful facial expressions evoke increased neural responses in human amygdala. We used event-related fMRI to investigate whether eye or mouth components of a fearful face are critical in evoking this increased amygdala activity. In addition to prototypical fearful (FF) and neutral (NN) faces, subjects viewed two types of chimerical face: fearful eyes combined with a neutral mouth (FN), and neutral eyes combined with a fearful mouth (NF). FE faces evoked specific responses in left anterior amygdala. FN faces evoked responses in bilateral posterior amygdala and superior colliculus. Responses in right amygdala, superior colliculus, and pulvinar exhibited significant time x condition interactions with respect to faces with fearful eyes (FF, FN) vs neutral eyes (NF, NN). These data indicate that fearful eyes alone are sufficient to evoke increased amygdala activity. In addition, however, left amygdala displayed discriminatory responses to fearful eyes in different configural contexts (i.e., in FF and FN faces). These results suggest, therefore, that human amygdala responds to both feature-specific and configural aspects of fearful facial expressions.     

Human responses to traumatic brain injury.

A traumatic brain injury can have devastating effects on the patient and the family. The patient with TBI faces deficits that influence life after hospitalization. With the use of specific nursing therapies, human responses to TBI can be treated and a patient can return to a satisfactory lifestyle.     

Blood glucose concentration dependent ACTH and cortisol responses to prolonged exercise

Summary. The purpose of this study is to investigate responses of serum ACTH and cortisol concentration to low intensity prolonged exercise. In experiment 1, 10 subjects fasted for 12 h and performed bicycle exercise at 49·3%V?O₂max (±4·3%) until exhaustion or up to 3 h. During the early part of the exercise, serum ACTH and cortisol concentrations did not increase from the pre-exercise values (ACTH: 44±5 μg/1, cortisol: 139±52 μg/1). Whilst the time to serum ACTH concentration increasing varied among the subjects (60·180 min), the increases of this hormone occurred for all subjects (175±85 ng/1, P<0·05) when blood glucose concentration decreased to a critical level of 3·3 mmol/1. At the end of the exercise, blood glucose concentration decreased to 2·60±0·21 mmol/1, and serum ACTH and cortisol concentrations increased to 313±159 μg/1 and 371±151 μg/1, respectively. In experiment 2, four subjects performed the same intensity exercise until exhaustion, and were then given 600 ml of 20 g glucose solution, and immediately afterwards, they were asked to repeat the same exercise. The subjects continued the exercise for between 30 to 90 min until again reaching exhaustion. During the second exercise, blood glucose concentration increased to the pre-exercise value (2·72±0·58 to 4·00±0·22 mmol/1, P<0·05) and simultaneously, serum ACTH concentration decreased considerably (354±22 to 119±54 ng/1, P<0·05). The results of the present study suggest that serum ACTH and cortisol concentration during low intensity prolonged exercise may be dependent on blood glucose concentration.     

Hepatic oxygen and glucose metabolism in the fetal lamb. Response to hypoxia.

Although the fetal liver is an active metabolic organ, its oxygen and glucose requirements have not previously been described. We measured hepatic blood flows and the oxygen and glucose differences across the liver in 12 late gestation fetal lambs in utero. Four animals were studied at least 1 wk postsurgically and again 2-5 d later to assess daily variations in hepatic blood flow and metabolism (group I). A second group of eight animals was studied 3-5 d postsurgically during a control period and during acute fetal hypoxia (group II). Under control conditions total hepatic blood flow averaged 400 ml/min per 100 g in both groups, and 75-80% was of umbilical origin. Liver blood flow and oxygen consumption were usually similar during repeated measurements, but in one animal varied considerably. During periods of normoxia, oxygen consumption for both the right and left lobes of liver was 4 ml/min per 100 g. Oxygen consumption of the whole liver accounted for 20% of total fetal oxygen consumption. This was achieved with oxygen extraction of 10-15%, so that hepatic venous blood was well oxygenated and provided an important source of oxygen for other fetal tissues. Under control conditions we could demonstrate no net hepatic uptake or release of glucose suggesting that the liver ultimately utilizes another carbon source to support its oxidative metabolism. During acute hypoxia total liver blood flow and its umbilical venous contribution both fell by 20%. Blood flow to the right lobe of the liver fell twice as much as that to the left lobe. Hepatic oxygen consumption was linearly related to oxygen delivery during the control and hypoxic periods. Consequently, right hepatic oxygen uptake fell by 45% whereas left hepatic oxygen uptake was unchanged, suggesting a functional difference between the lobes. During hypoxia glucose was released from both liver lobes; 6 mg/min per 100 g for the right lobe and 9 mg/min per 100 g for the left lobe. Total hepatic release of glucose was estimated to nearly equal umbilical uptake, so that 45% of the glucose available to fetal tissues was of hepatic origin. We conclude that the fetal liver responds to acute hypoxia by reducing its own oxygen consumption and releasing glucose to facilitate anaerobic metabolism.     

Acute and steady-state insulin responses to glucose in nonobese diabetic subjects

Previous observations in normal subjects have suggested that when 5-g glucose pulses (P) were given in the following sequence: before (P1) and 45 min after beginning a 300 mg/min glucose infusion (P2); during the 20th hr (P3) and 1 hr after the infusion was stopped (P4); the insulin responses were consistent with a simple two-pool model. One pool is a readily available small storage pool which is refilled by a second, larger, more slowly responding pool that controls basal and steady-state insulin output. The identical protocol was employed to evaluate the insulin responses in 13 nonobese diabetic subjects.DIABETICS HAD BASAL INSULIN LEVELS INDISTINGUISHABLE FROM NORMALS (DIABETICS: 10.7+/-4; normals: 10.7+/-5, mean +/-SD, muU/ml), but had significantly elevated basal glucose levels (diabetics: 161+/-27; normals: 88+/-7, mg/100 ml, P < 0.05). The mean early insulin response (3-5 min Delta IRI) after a 5 g glucose pulse (P1) was significantly diminished in diabetics (diabetics 6.4+/-9; normals: 32.5+/-14, muU/ml, P < 0.01) consistent with a defective storage pool output. The glucose disappearance rate, K(G), decreased in parallel with the early insulin response and the slope of the regression line between these two variables was virtually identical with that calculated from 16 normal subjects. Similar to normal subjects, during the short glucose infusion, the acute insulin response to P2 was diminished in diabetics (P < 0.02). In normal subjects after 20 hr of infusion, the rapid insulin responses to P3 are restored to the preinfusion P1 values, and 1 hr after the infusion was stopped, the responses to P4 are increased twofold (P < 0.001). Diabetics, however, demonstrated decreased early responses to P3 (P < 0.001) and no increased response to P4.In contrast to the diminished acute insulin responses to glucose pulses, diabetics have steady-state insulin levels after 20 hr of glucose infusion similar to those of normal subjects (diabetics: 25.7+/-13; normals: 32.5+/-14, muU/ml). Thus both basal and steady-state insulin levels of diabetics were comparable with those of normal subjects, which suggest that although the rapid insulin response from the storage pool output is defective in diabetics, the more slowly responding pool is intact.     

Acute physiological and perceptual responses to high‐load resistance exercise in hypoxia

This study assessed whether hypoxia during high‐load resistance exercise could enhance the acute physiological responses related to muscular development. Twelve trained men performed exercise in three conditions: normoxia (fraction of inspired oxygen [F_IO₂] = 21%), moderate‐level hypoxia (F_IO₂ = 16%) and high‐level hypoxia (F_IO₂ = 13%). Exercise comprised high‐load squats and deadlifts (5 × 5 using 80% of 1‐repetition maximum with 180‐s rest). Muscle oxygenation and activation were monitored during exercise. Metabolic stress was estimated via capillary blood sampling. Perceived fatigue and soreness were also quantified following exercise. While the hypoxic conditions appeared to affect muscle oxygenation, significant differences between conditions were only noted for maximal deoxyhaemoglobin in the deadlift (P = 0·009). Blood lactate concentration increased from 1·1 to 1·2 mmol l^?1 at baseline to 9·5–9·8 mmol l^?1 after squats and 10·4–10·5 mmol l^?1 after deadlifts (P≤0·001), although there were no between‐condition differences. Perceived fatigue and muscle soreness were significantly elevated immediately and at 24 h following exercise, respectively, by similar magnitudes in all conditions (P≤0·001). Muscle activation did not differ between conditions. While metabolic stress is thought to moderate muscle activation and subsequent muscular development during hypoxic resistance training, it is not augmented during traditional high‐load exercise. This may be explained by the low number of repetitions performed and the long interset rest periods employed during this training. These findings suggest that high‐load resistance training might not benefit from additional hypoxia as has been shown for low‐ and moderate‐load training.