高原低氧对CNP、ET和CGRP血浆含量的影响

目的:探索高原低氧对C型利钠肽、内皮素和降钙素基因相关肽血浆含量的影响。方法:采用放射免疫分析测定40名世居海拔1100m(对照组)的健康青年男性志愿者进入海拔2260m 3个月, 3780m 1d、5d和15d时血浆C型利钠肽(CNP)、内皮素(ET)和降钙素基因相关肽(CGRP)含量。结果: 1 方差分析结果:CNP血浆含量随海拔升高明显增加(海拔3780m15d组与前4组相比P<0 01)。ET进入海拔3780m5d时血浆ET含量显著减少(与海拔2260m相比P<0 01);随着在海拔3780m停留时间延长,ET含量显著增加(3780m 15d与前4组相比P<0 01),CGRP当志愿者进入海拔2260m3月时CGRP含量达峰值(与对照组相比P<0. 01),进入海拔3780m后其浓度持续下降, 15d时降至最低点(与海拔2260m相比P<0 01)。2 相关性分析:CGRP含量与ET呈负相关(r=-0 425,P<0 05);CNP含量与ET正相关(r=0.470,P<0. 01)。结论:ET、CGRP和CNP参与了人体肺循环对低氧的生理性调节,CGRP作用于缺氧初期肺循环的扩血管调节反应、ET和CNP含量则随缺氧时间延长和海拔升高增加。     

高原低氧大鼠肺组织超微结构及其低氧诱导因子1α的表达

背景：低氧诱导因子1α可介导哺乳动物细胞适应低氧环境。 目的：观察高原低氧对大鼠肺组织超微结构的影响及其低氧诱导因子1α表达变化。 方法：将SD大鼠分别为进行高原低氧干预1,2,3和30 d,并设置对照组。4个高原低氧组由海拔5 m的西安地区途中耗时1 d带到海拔2 700 m的青海格尔木地区、途中耗时2 d带到海拔5 000 m的唐古拉地区,途中耗时3,30 d分别带到海拔4 500 m的西藏那曲地区。 结果与结论：光镜及电镜观察显示,急性高原低氧2 d组肺组织出现明显的高原肺水肿,急性高原低氧30 d组低氧诱导因子1α mRNA的表达明显增高(P < 0.01),高原肺水肿现象则明显减轻。结果证实,低氧习服后肺组织低氧诱导因子1α mRNA表达的提高有利于减轻高原肺水肿。     

高原低氧对大鼠心肺组织超微结构的影响

背景：研究表明快速进入高原地区时,机体不可避免地会受到不同程度的损伤,以心肺损伤较显著。 目的：观察低氧习服对高原低氧大鼠心肺组织的超微结构影响。 方法：将SD大鼠分别为进行高原低氧干预1,3和30 d,并设置对照组。3个高原低氧组由海拔5 m的西安途中耗时1 d带到海拔2 700 m的青海格尔木地区、途中耗时3,30 d分别带到海拔4 500 m的西藏那曲地区,观察各时间点心肺标本的组织学变化。 结果与结论：急性高原低氧1,3 d组肺组织显微和超微结构出现明显的间质性肺水肿和肺泡性肺水肿,其心脏组织光镜下大鼠各室壁心肌细胞均可见不同程度的浊肿、空泡变性、溶解坏死及间质水肿等,电镜下可见心肌细胞线粒体肿胀,肌浆网扩张,肌原纤维溶解,细胞内外水肿等,急性高原低氧3 d上述改变右室壁较左室壁明显,而低氧习服后高原低氧30 d组间质性水肿和则肺水肿明显减轻。结果证实,高原急性缺氧可造成大鼠间质性肺水肿和肺泡型肺水肿,并引起以右心室为主的全心性损伤,经过高原低氧习服后心肺组织病变明显减轻。     

脑出血患者血浆胶质纤维酸性蛋白浓度的变化

目的:揭示脑出血患者血浆胶质纤维酸性蛋白浓度的变化,探讨并评价其与疾病预后的相关性。方法:收集脑出血患者和同期健康体检合格者各86例。患者静脉血在脑出血后第1、2、3、5和7d获得,健康体检合格者静脉血在体检时获得,ELISA检测血浆胶质纤维酸性蛋白浓度。结果:脑出血患者血浆胶质纤维酸性蛋白浓度在脑出血后第1d升高,第2d到达高峰,后逐渐下降,均显著高于正常对照组(均P<0.01);与入院时美国国立卫生院神经功能缺损评分呈显著正相关(均P<0.01)。死亡组血浆胶质纤维酸性蛋白浓度均显著高于生存组(均P<0.01)。R0C曲线分析显示,脑出血后第1、2、3、5和7d血浆胶质纤维酸性蛋白浓度预测脑出血1月内死亡均有显著价值(均P<0.01),相比之下,第2d的血浆胶质纤维酸性蛋白浓度对脑出血1月内死亡的预测价值最高。结论:血浆胶质纤维酸性蛋白浓度脑出血后显著升高,与疾病预后显著相关。     

高原低氧对女性孕酮、雌二醇的影响

目的:了解高原低氧环境对女性孕酮(P)、雌二醇(E2)的影响。探讨性激素与高原低氧的关系。方法:采用放射免疫分析对在平原及从平原进驻拉萨(海拔3658m)地区一个月及一年后的284名某部女性新兵分别进行P、E2的测定。结果:进驻海拔3658m第一个月后,P为(7.41±1.72)ng/m l,E2为(38.01±3.04)pg/m l,较平原对照组的P(17.21±2.10)ng/m l,E2(87.26±21.64)pg/m l降低非常显著(P<0.01);一年后,P(11.40±4.56)ng/m l,E2(50.21±5.56)pg/m l,略有回升,但仍显著低于对照组(P<0.01)。结论:短期内缺氧可能是导致孕酮、雌二醇水平下降的主要原因。     

复方丹参滴丸对高原习服期心血管反应的影响

目的：研究复方丹参滴丸（DSP）对高原习服期心血管生理效应和心脏低氧病理损害的影响。方法:平原医学体检正常者进入海拔5 000 m高原的施工群体617人，随机分为DSP服药组（186人）和对照组（431人）,观察6个月期间，进行心电图、血压、血氧饱和度（SpO₂）595人次和1 029人次检测。另设雄性Wistar大鼠DSP干预组和对照组各7只，在同一海拔饲养20 d后处死做病理常规形态学及Hitachi-500电镜下观察摄片。结果:与对照组比较：DSP组心电图心肌缺血患病率明显下降（5.55% vs 18.76%，P<0.01）；减少右房高电压与过渡区左移发生率、QRS电轴右倾程度、QT_C时限、T-QRS夹角等（均P<0.05或P<0.01）；左室高电压与过渡区右移发生率则高于对照组（P<0.01）；明显降低血压、心率及二者乘积、SpO₂的异常率(均P<0.05或P<0.01)；DSP能预防、改善大鼠心肌细胞的低氧性水肿、变性、坏死、组织淤血、出血及超微结构的损害。结论:DSP显著改善对低氧的心血管生理习服水平和具有抗低氧病理损伤作用，是理想的抗低氧与低氧习服药物。     

NALP3在低氧肺损伤大鼠肺组织中的表达及意义

目的:探讨SD大鼠在急性低氧肺损伤形成过程中NALP3炎性体的表达变化及其意义.方法:将40只SD大鼠随机分为4组:正常对照组、模拟海拔5 000 m 1 d组、3 d组、7 d组.分别在进入模拟海拔5 000 m后1、3、7 d取肺组织.血气分析仪检测动脉血气;电子天平称量肺组织湿干重并计算湿/干比值;显微镜下观察肺组织形态结构变化和超微结构变化;免疫组化法检测肺组织NALP3、caspase-1、IL-1β蛋白表达水平;ELISA法检测血清IL-1β水平.结果:肺组织病理炎症评分的等级实验各组均高于对照组(P<0.05),3 d组高于1 d、7 d组(P<0.05);电镜结果显示:实验组肺泡II型上皮细胞内有空泡,肺泡腔内较多巨噬细胞;免疫组化结果显示:NALP3、caspase-1、IL-1β的表达1 d开始增加,3 d达到高峰,7 d下降(P<0.05),与肺损伤程度呈正相关(r=0.81, P=0.01;r=0.76,P=0.03;r=0.84,P=0.01).实验各组血清IL-1β水平高于对照组(P<0.05),3 d组高于1 d、7 d组(P<0.05).结论:低氧急性肺损伤早期,NALP3炎性体被激活,通过caspase-1的活化,下游信号IL-1β成熟释放增加,引发肺损伤,提示NALP3炎性体可能在高原低氧急性肺损伤的发生发展中发挥作用.     

藏羚羊和藏系绵羊左心室收缩功能的比较研究

目的:探讨藏羚羊适应高原低氧环境的左心功能特点。方法:捕捉海拔4 300 m藏羚羊9只、藏系绵羊10只运至格尔木(海拔2 800 m)实验基地。测定二者的心脏/体重比(HW/BW)、右心室/(左心室+室间隔)重量比[RV/(LV+IVS)];应用心导管技术测定心率(HR)、收缩压(SBP)、舒张压(DBP)、左室等容收缩期心室内压力上升最大速率和左室等容舒张期心室内压力下降最大速率(±dp/dt)。以格尔木市的氧浓度(21.1%)为基线,分别给予更低浓度氧14.6%、12.5%(分别相当于海拔5 300 m、6 300 m)的低氧吸入15 min后重复测定以上指标。应用透射电镜观察心肌超微结构。结果:藏羚羊HW/BW显著高于藏系绵羊(P0.01),基础状态下藏羚羊SBP低于藏系绵羊(P0.05),+dp/dt与藏系绵羊比无显著差异,吸入14.6%和12.5%的低氧气体后藏羚羊+dp/dt分别升高至145.1%和148.1%,而藏系绵羊分别降低至68.4%和70.5%(P0.05);电镜下观察藏羚羊心肌超微结构与藏系绵羊比较,其心肌细胞线粒体较为丰富。结论:藏羚羊心脏对高海拔低氧环境的适应,是通过增加心脏器官的重量及心肌细胞线粒体的含量来实现,其心肌收缩功能的适应性特征为:在静息状态下以较低的左心室心肌收缩力来降低氧耗量以此适应高原低氧环境,而以海拔更高的较低氧浓度为应激条件下,左心室心肌收缩力明显升高。提示:藏羚羊作为高原适应性动物,经过漫长的自然选择其心脏对高原低氧环境的适应不同于藏系绵羊。     

不同低氧水平暴露对大鼠空间学习记忆、探究能力的影响

目的:观察不同低氧水平暴露对大鼠空间学习记忆、自主探究行为和焦虑情绪的影响。方法:将80只健康雄性SD大鼠随机分为11%和15%氧浓度组,每组均包括对照组(C11、C15)、4 h组(4H11、4H15)、8 h组(8H11、8H15)和12 h组(12H11、12H15),每组10只。C11和C15组大鼠在常氧条件下饲养7 d,其余各组大鼠接受低氧暴露,持续7 d,结束后分别检测大鼠的空间学习记忆、自主探究行为和焦虑情绪的行为学表现。结果:(1)低氧对大鼠空间学习记忆的影响,与C15相比,8H15大鼠第1 d逃避潜伏期显著延长(P0.05),其第1 d与第2 d、第1 d与第3 d逃避潜伏期的差值显著增加(P0.05)。(2)低氧对大鼠自主探究行为和焦虑情绪的影响,与C15相比,4H15大鼠在总运动距离、跨格数、站立次数和进入开放区域次数方面明显减少(P0.05),12H15大鼠在跨格数、进入开放区域次数和开放区域时间方面均显著降低(P0.05,P0.01)。结论:11%和15%氧浓度每天分别暴露8 h、4 h、12 h均会减少大鼠的自主探究行为,增加焦虑情绪。     

一氧化碳饱和血红蛋白通过抑制TREM-1/TLR4通路发挥对高原低氧心脏损伤的保护作用

目的：探究一氧化碳饱和血红蛋白（CO-HBOC）能否通过抑制TREM-1/TLR4通路调节免疫,减轻炎症反应,发挥对高原低氧心脏损伤的保护作用。方法：30只雄性C57/BL6小鼠随机分为常氧生理盐水（NS）组、高原低氧生理盐水（HS）组和高原低氧CO-HBOC(HC)组。低氧组置于低压低氧动物实验舱模拟海拔5 500 m高原环境。实验舱运行时间为24 h/d,控制昼夜比约12 h∶12 h,连续低氧处理7 d;NS组置于相同条件的常压常氧环境下饲养。在建模过程中,HC组给予0.3 g Hb/kg/d CO-HBOC连续处理3 d,NS组和HS组给予等量生理盐水。采用心肌酶和心肌组织HE染色分析评估心肌组织损伤程度,qPCR和ELISA分别检测心肌组织和血浆中IL-1β、TNF-α表达,Western blot检测心肌组织髓源细胞表面触发受体1(TREM-1)、Toll样受体4(TLR4)表达。结果：(1)HS组小鼠CK-MB、LDH较NS组明显升高,但CO-HBOC处理后小鼠心肌损伤减轻;(2)HE染色显示HS组小鼠较NS组出现明显心肌细胞水肿、核坏死、灶状变性并伴有炎症细胞浸润,而H...     

Changes in plasma lipids and lipoprotein cholesterol during a high altitude mountaineering expedition (4800 m)

Summary Effects of high altitude exposure on plasma lipids and lipoprotein cholesterol were studied in 8 mountaineers who spent 3 weeks at the Annapurna IV base camp (4800 m) after a 12 day trek. In spite of the moderate physical exertion at the camp, the loss of body weight was more pronounced during the stay at high altitude than during the trekking period. Compared with baseline values observed at sea level, marked reductions in plasma cholesterol (–27%) and phospholipids (–19%) were found 3 days after arrival at the camp and persisted during the next 17 days. A less marked fall in plasma triglycerides occurred, weakly significant at the end of the stay. Because there were no relevant changes in very low density lipoproteins or in high density lipoprotein (HDL)-cholesterol, the low plasma cholesterol levels at the high altitude resulted mainly from the reduction in low density lipoprotein (LDL)-cholesterol: the mean HDL/LDL cholesterol ratio changed from 0.39 at sea level to 0.63 at the end of the stay at 4800 m. Fluctuations in LDL-cholesterol were not concomitant with those in body weight and were independent of the exercise training during the expedition. This study shows moreover that the early drop in LDL-cholesterol was associated with an opposite change in plasma levels of catecholamines and thyroid hormones. Taking into account that such hormonal responses are classically observed at high altitude, the concomitant decrease in LDL-cholesterol might be interpreted as being a relevant adaptative response to hypoxic conditions at high altitude.Abbreviations VLDL very low density lipoproteins - LDL low density lipoproteins - HDL high density lipoproteins     

急进不同海拔健康人微循环变化特点──对阿尼玛卿山中日医学考察队的微循环监测

在高原自然环境下，１７名健康男性中日二国科研人员，年龄２５～５４岁，由２２６１ｍ急进３７００ｍ、４６００ｍ，５天内急进阿尼玛卿山５１００ｍ，分别对上述海拔平段动态观察球结膜微循环变化。结果表明：①球结膜微循环随海拔高度上升变化显著，加权总积分值呈递增变化（Ｐ＜０．０１）；②球结膜微血管数目与海拔升高无相关性（Ｐ＞０．０５）；③微动脉管径随海拔升高逐渐变细，尤以到达４６００ｍ和５１００ｍ时更明显（Ｐ＜０．０１），微静脉管径随海拔升高而增宽，达到５１００ｍ时，其管径不再扩张而逐渐回缩；④微动脉囊状扩张也随海拔升高而增多，血流速度减慢，红细胞重度聚集，白色微栓形成，致使微血管管壁通透性改变，局部出血、渗出、水肿。     

Austrian Moderate Altitude Study (AMAS 2000) - fluid shifts,erythropoiesis, and angiogenesis in patients with metabolic syndrome at moderate altitude (congruent with 1700 m)

It was hypothesized that subjects with metabolic syndrome (hypertension, obesity, hyperlipidemia, diabetes mellitus): (1) develop measurable peripheral edema at moderate altitude and (2) might show differences on erythropoiesis, iron status and vascular endothelial growth factor (VEGF) in comparison to healthy subjects during and after a long-term stay (3-week exposure) at moderate altitude (≅1700 m). Twenty-two male subjects with metabolic syndrome were selected. Baseline investigations (t1) were performed in Innsbruck (500 m). All participants were transferred by bus to 1700 m (Alps) and remained there for 3 weeks with examinations on day 1 (after the first night at altitude, t2), day 4 (t3), day 9 (t4) and day 19 (t5). After returning to Innsbruck, post-altitude examinations were conducted after 7–10 days (t6) and 6–7 weeks (t7), respectively. Body mass was decreased from t1 to t7 (P<0.01). Total body water was decreased at t2 (P<0.01), returned to control level (t3, t4), and was found elevated at t7 (P<0.01). Lean body mass did not change, but body fat decreased during the study (P<0.01). Tissue thickness at the forehead decreased during and after altitude exposure (P<0.01), whereas tissue thickness at the tibia did not alter. Erythropoietin (EPO) was elevated as early as t2 and remained increased until t5. Reticulocyte count was increased at t3 and remained above pre-altitude values. VEGF levels were unchanged. After a 3-week exposure to moderate altitude, patients with metabolic syndrome had reduced their body mass, mainly because of a reduction in body fat. The moderate altitude was found to stimulate erythropoiesis in these patients but this was not sufficient to increase serum VEGF concentration. Electronic Publication     

不同延迟时间后修复大鼠坐骨神经缺损对CGRP表达的影响

目的：观察大鼠坐骨神经缺损不同延迟时间后修复对降钙素基因相关肽（CGRP）表达的影响.方法：大鼠右侧坐骨神经切断分别预变性0、3、7、14和21 d后（n=6）以左侧自体新鲜神经桥接,神经再生6周后用免疫组化方法检测CGRP在脊髓和背根节（DRG）的表达变化.结果：术侧DRG CGRP表达均明显增强,其中21 d组明显强于0 d组（P＜0.05）;术侧脊髓后角CGRP免疫阳性面积明显增大,21 d组明显大于0 d组（P＜0.05）,其CGRP表达在0 d、3 d和21 d组均强于对侧（P＜0.05）,而3 d和21 d组又明显强于0 d组（P＜0.05）;3d组脊髓前角的CGRP表达在明显强于0 d组和对侧（P＜0.05）.结论：预变性处理可以影响CGRP的表达从而影响神经再生过程.     

Differential expression of calcitonin gene-related peptide (CGRP) and choline acetyltransferase (ChAT) in the axotomized motoneurons of normoxic and hypoxic rats

We employed a double injury model (axotomy along with hypoxia) to determine how nerve injury and hypoxic insult would affect the expression of calcitonin gene-related peptide (CGRP) and choline acetyltransferase (ChAT) in the hypoglossal nucleus (HN) and nucleus ambiguus (NA). Adult rats were subjected to unilateral vagus and hypoglossal nerve transection, following which half of the animals were kept in an altitude chamber (PO₂ = 380 Torr). The immunoexpression of CGRP and ChAT (CGRP-IR/ChAT-IR) were examined by quantitative immunohistochemistry at 3, 7, 14, 30 and 60 days post-axotomy. The results revealed that CGRP-IR in the HN was increased at 3 days but decreased to basal levels at 7 days following nerve injury. The decline was followed by a second rise in CGRP-IR at 30 days post-axotomy, followed again by a return to basal levels at 60 days. In the NA, CGRP-IR was up-regulated at 3 days and remained increased for up to 60 days after nerve injury. Animals treated with a double injury showed a greater CGRP-IR than normoxic group in both nuclei at all post-axtomized periods. In contrast to CGRP, ChAT-IR was markedly reduced in the HN and NA at 3 days reaching its nadir at 14 days following nerve injury. Hypoxic animals showed a stronger reduction of ChAT-IR in both nuclei at all post-axtomized periods. Results of cell counting showed that neuronal loss was somewhat obvious in hypoxic HN than that of normoxic ones. The present results suggest that up-regulation of CGRP-IR may exert its trophic effects while down-regulation of ChAT-IR may correlate with the poor neurotransmission within the injured neurons. It is speculated that the enhanced expression of CGRP-IR and the pronounced reduction of ChAT-IR in hypoxic rats may result from a drastic shift of intracellular metabolic pathways, which in turn could lead to more metabolic loading to the severely damaged neurons following the double insult.     

低氧大鼠血清和肺小动脉壁胰岛素样生长因子-I的变化

目的:探讨低氧对大鼠血清胰岛素样生长因子-I(IGF-I)水平、肺小动脉壁IGF-I多肽的影响及其与低氧性肺动脉高压之间的关系。方法:用图像分析技术检测肺小动脉的形态改变;RIA法检测血清IGF-I浓度;免疫组织化学染色法检测肺小动脉壁IGF-I多肽表达并进行定量分析。结果:经3周低氧后大鼠平均肺动脉压(mPAP)明显增高(P<0.01);反映管壁增厚的两个指标MT%和MA%均显著高于正常对照组(P<0.05)。灰度扫描示低氧大鼠肺小动脉壁的灰度值显著强于正常对照组(P<0.01)。低氧大鼠血清IGF-I水平明显高于正常对照组(P<0.05);大鼠血清IGF-I水平与mPAP呈显著正相关(r=0.745,P<0.01)。结论:在低氧情况下,肺小动脉壁IGF-I多肽产生显著增加;并且IGF-I不仅以自分泌和旁分泌的方式刺激血管平滑肌细胞增生肥厚,而且可能还存在内分泌机制。     

Differential and cell-specific expression of calcitonin receptor-like receptor and receptor activity modifying proteins in the human uterus.

The calcitonin receptor-like receptor (CRLR) can function as a receptor for either calcitonin gene-related peptide (CGRP) or adrenomedullin (AM), depending upon co-expression with members of a novel family of receptor activity-modifying proteins (RAMP). RAMP1 presents the CRLR at the cell surface as a CGRP/AM receptor. RAMP2- and RAMP3-transported CRLR receptors act as AM-specific receptors. However, it is still unknown if this signalling system operates in vivo. Of particular interest is the uterus, where both peptides and their binding sites are known to be present and where both mitogenic and vasodilatory responses to AM and CGRP have been demonstrated. In this study, we examined whether CRLR and RAMP are co-expressed in the same populations of cells in human uterine tissue. Analysis by in-situ hybridization and immunocytochemistry revealed a heterogeneous and cell type-specific distribution of components of this AM/CGRP signalling system. Adrenomedullin mRNA was expressed and evenly distributed across all cell types. CRLR mRNA was predominantly found in blood vessels. RAMP1 expression was specific to myometrial myocytes and vascular smooth muscle cells in uterine arteries. RAMP2 and RAMP3 mRNA were not detectable by in-situ hybridization. The pattern of differential and cell-specific expression of CRLR and RAMP suggests the involvement of CRLR/RAMP1 in the processes of vasodilation, smooth muscle relaxation and angiogenesis in response to AM and CGRP in the human uterus, but also indicates that other receptors may be implicated.     

急、慢性低氧对大鼠脑线粒体蛋白翻译合成的影响

目的:探讨模拟高原低氧对大鼠脑线粒体蛋白合成功能的影响。方法:雄性wistar大鼠随机分为急性低氧组、慢性低氧组和平原对照组。急、慢性低氧组动物分别连续暴露于模拟4000m高原3d和40d, 分离脑线粒体, 用[³H]-亮氨酸掺入法测定线粒体体外翻译活性, [³⁵S]-蛋氨酸掺入并对翻译后产物经SDS-PAGE和放射自显影进行分子量鉴定。结果:急性低氧脑线粒体蛋白翻译活性明显低于对照组60%(P<0.01), 慢性低氧时线粒体翻译活性与对照组无显著差异(P>0.05), 但显著高于急性低氧组(P<0.05).急性与慢性低氧暴露均未发现线粒体蛋白体外翻译产物与平原对照组有质的差异。结论:低氧可影响线粒体DNA编码蛋白合成, 并且与低氧暴露时间有关。     

Austrian Moderate Altitude Study 2000 (AMAS 2000). The effects of moderate altitude (1,700 m) on cardiovascular and metabolic variables in patients with metabolic syndrome

We investigated the changes in the cardiovascular system [resting blood pressure (BP) and heart rate (HR), measured by means of a 24-h ambulatory BP and a holter-electrocardiogram (ECG)], glycemic parameters, and lipid metabolism of subjects suffering from metabolic syndrome during a 3-week sojourn at 1,700 m in the Austrian Alps. A total of 22 male subjects with metabolic syndrome were selected. Baseline investigations were performed at Innsbruck (500 m above sea level). During the 3-week altitude stay the participants simulated a holiday with moderate sports activities. Examinations were performed on days 1, 4, 9, and 19. After returning to Innsbruck, post-altitude examinations were conducted after 7–10 days and 6–7 weeks, respectively. The 24-h ambulatory BP and holter ECG revealed a decrease in average HR, BP, and rate pressure product (RPP: systolic blood pressure × HR) after 3 weeks of altitude exposure. In some patients, an increase in premature ventricular beats was observed at the end compared to the beginning of the exposure to moderate altitude. The ECG revealed no ischemic ST-segment changes. Maximal physical capacity as measured by symptom-limited maximal cycle ergometry tests remained unchanged during the study. Six weeks after the altitude exposure the blood pressure increased again and returned to pretest levels. The Homeostasis Model Assessment index, which is a measure of insulin resistance, decreased significantly and glucose concentrations obtained after an oral glucose tolerance test were significantly lower after the stay at altitude compared to the basal values. We conclude that after a 3-week exposure to moderate altitude, patients with metabolic syndrome (1) tolerated their sojourn without any physical problems, (2) exhibited short-term favorable effects on the cardiovascular system, and (3) had significant improvements in glycemic parameters that were paralleled by a significant increase in high-density-lipoprotein-cholesterol. Electronic Publication     

Effects of exercise stress on the endocannabinoid system in humans under field conditions

The effects of physical exercise stress on the endocannabinoid system in humans are almost unexplored. In this prospective study, we investigated in a crossover design and under field conditions at different altitudes the effects of physical exercise on the endocannabinoid system (ECS) in 12 trained healthy volunteers. For determination of alterations on the ECS three different protocols were analyzed: Protocol A (physical exercise at lower altitude) involved strenuous hiking below 2,100 m, whereas Protocol B (physical exercise by active ascent to high altitude) involved hiking up to 3,196 m, an accommodation at the cottage and a descent the next day. Protocol C (passive ascent) included a helicopter ascent to 3,196 m, an overnight stay at this altitude and a flight back to the base camp the following day. The cumulative hiked altitude in Protocol A and B was comparable (~1,650 m). The blood EC concentrations of anandamide increased significantly in Protocol A/B from baseline (T0) 0.12 ± 0.01/0.16 ± 0.02 (mean ± SEM) to 0.27 ± 0.02/0.42 ± 0.02 after exercise (T1) (p < 0.05). Anandamide levels in Protocol C remained stable at 0.20 ± 0.02. We conclude that the ECS is activated upon strenuous exercise whereas the combination with hypoxic stress further increases its activity. The reduced partial pressure of oxygen at high altitude alone did not affect this system. In summary, physical exercise activates the endocannabinoid system, whereas the combination with high altitude enhances this activation. This discloses new perspectives to adaptation mechanisms to physical exercise.