Hypobaric erythraemia: pathology and coagulation studies

Summary . Rhesus monkeys were made hypoxaemic and erythraemic by caging them in a hypobaric environment simulating an exposure to 17,500 feet above sea level for 28 days. Post-mortem examination of animals dying during the experiment showed both haemorrhage and thrombosis in the brain and lungs and patchy demyelination in the spinal cord. Coagulation studies showed evidence of accelerated intravascular coagulation which was manifested by marked decreases in blood levels of Factors VIII and IX with less pronounced diminution of Factors V and XI. Platelet counts and the plasma fibrinogen concentration remained normal, but fibrinogen degradation products were found in serum specimens from hypobaric monkeys. Coagulation abnormalities improved following heparin therapy. The coagulopathy seemed more proximately related to erythrocytosis than exposure to the hypobaric atmosphere because coagulation abnormalities were not observed during the first week in an altitude chamber, and they persisted for 2 weeks after removal of the animals from a hypobaric environment. We postulated that the coagulation abnormalities were a manifestation of the hypercoagulable state resulting from increased blood viscosity in the microcirculation.     

Biphasic Thrombopoietic Response to Severe Hypobaric Hypoxia

Thrombopoiesis has been studied during and after an 11 d exposure to discontinuous hypobaric hypoxia. Exposure of rats to 0.4 atmospheres for 16-17 h daily initially caused an increase in platelet count which reached a peak of 1.5 times baseline on days 4 and 5. This thrombocytosis was followed by a decrease in platelets to a nadir of 50-60% of baseline on days 12 and 13. That thrombocytosis results from increased platelet production is supported by increased [³⁵ S]sulphate incorporation into platelets and increased megakaryocyte size and turnover. The thrombocytopenia with continued hypoxia seems to result from decreased platelet production since ⁵¹Cr-platelet survival was normal while megakaryocyte concentration was decreased to one-half that of untreated controls. These observations suggest that differentiation of precursors into megakaryocytes was decreased during the thrombocytopenic period, although the fewer remaining megakaryocytes appeared stimulated because of their larger size and increased [³H]thymidine labelling. Thus, hypobaric hypoxia had a biphasic effect on thrombopoiesis with increased platelet production in the first few days of exposure followed by subnormal production.     

P130cas在低压低氧肺动脉高压大鼠中的表达

目的探究P130cas(Crk associated substrate)在低压低氧肺动脉高压大鼠血清及组织中的表达。方法将20只大鼠随机分为正常对照组和低压低氧组。正常对照组在正常环境下饲养28天,低压低氧组在低压低氧舱(低压低氧舱模拟海拔5000米高度)饲养28天。右心导管方法测定各组大鼠肺动脉压力,ELISA方法测定每组大鼠血清中P130cas表达,免疫组化检测肺动脉中P130cas的表达,应用Western blot测定大鼠肺组织中P130cas蛋白表达量。结果低压低氧组大鼠平均肺动脉压力较正常对照组明显升高,且达到肺动脉高压诊断标准;低压低氧组P130cas在大鼠血清及肺组织中的表达较对照组明显升高。结论P130cas可能参与了低压低氧肺动脉高压的形成。     

间歇性低压低氧促进载脂蛋白E基因敲除小鼠血管重构

目的　探讨高海拔间歇性低压低氧（IHH）环境对载脂蛋白E基因敲除（ApoE^－/－）小鼠血管重构的影响。方法　将14只8周龄雌性ApoE^－/－小鼠随机分为对照组和IHH组,IHH组每天在低压舱模拟的4000　m海拔低压低氧环境中放置8　h,持续60天。干预完成后采用Masson染色测定胸主动脉管壁胶原含量,采用免疫组织化学法检测基质金属蛋白酶（MMP）及其组织型基质金属蛋白酶抑制剂（TIMP）的表达情况。结果　与对照组比较,间歇性低压低氧组小鼠主动脉管壁胶原含量显著降低,MMP-9的表达显著增高,而TIMP-2的表达显著降低（P＜0.01）,而MMP-2、MMP-14在两组间没有显著差异（P＞0.05）。结论　IHH可能通过加重ApoE^－/－小鼠血管壁MMP-9和TIMP-2的表达失衡减少血管壁胶原含量,从而促进血管重构。     

血液病与缺氧

大气中的氧气随呼吸进入肺泡 ,并弥散入肺泡周围毛细血管 ,与血红蛋白 (Ｈｂ)结合后随血液循环输送到全身 ,最后被组织细胞摄取利用。上述任何环节发生障碍都可引起缺氧 ,其中Ｈｂ数量的减少或性质的改变可使血氧含量[Ｃａ(Ｏ2 ) ]降低或Ｈｂ与氧分子 (Ｏ2 )结合力异常 ,导致组织缺氧 ,称为血液性缺氧 (ｈｅｍｉｃｈｙｐｏｘｉｎ) [1] 。血液性缺氧时 ,由于肺的呼吸功能正常 ,动脉血氧分压 [Ｐａ(Ｏ2 ) ]和饱和度[Ｓａ(Ｏ2 ) ]也相应正常 ,但因Ｈｂ数量或性质的改变 ,出现Ｃａ(Ｏ2 )下降 ,动静脉氧含量差 (Ｃａ -ｖＯ2 )小于正常 ;在少部分…     

Hyperventilation-induced cerebral hypoxia

Acute respiratory alkalosis decreases cerebral blood flow, increases the affinity of hemoglobin for oxygen, and can result in cerebral hypoxia. This experiment was designed to study this phenomenon in dogs, and to demonstrate the effect of an increased concentration of inspired oxygen. Seven mongrel dogs were anesthetized with pentobarbital and ventilated with a constant volume respirator. A Telfon-coated stainless steel catheter was placed through a craniotomy into the parietal lobe and advanced through the corona radiata to monitor cerebral PO2 and PCO2 with a mass spectrometer. Steady state cerebral and arterial gas tensions were recorded during eucapnic ventilation with air, eucapnic ventilation with 100% oxygen, hypocapnic ventilation with air, and hypocapnic ventilation with 100% oxygen. Decreased cerebral tissue oxygen tension was demonstrated in hypocapnic dogs ventilated with air. When the concentration of inspired oxygen was increased, the relatively small increase in artrial oxygen content was associated with a marked increase in PO2 at the cerebral tissue level. This may be of clinical importance in therapeutic or centrally mediated hyperventilation.     

慢性间歇性低压低氧抑制内质网应激改善大鼠血管钙化

目的证实慢性间歇性低压低氧(CIHH)通过抑制内质网应激(ERS)改善大鼠血管钙化。方法使用维生素D3肌注和尼古丁灌胃(VDN)制备的大鼠在体血管钙化模型,检测主动脉组织Ca2+含量和碱性磷酸酶(ALP)活性以及血浆ALP活性,Western blot检测相关蛋白的表达水平。结果与对照组大鼠相比,VDN大鼠主动脉组织Ca2+含量和ALP活性以及血浆ALP活性均显著升高(P0.05),同时主动脉组织平滑肌细胞收缩表型标志蛋白calponin和SM22α的表达水平显著下调(P0.05),成骨样细胞表型标志蛋白骨形态发生蛋白2(BMP2)和RUNX2的表达水平显著上调(P0.05)。而CIHH能够显著改善VDN大鼠的上述改变。此外,VDN大鼠主动脉组织ERS标志蛋白葡萄糖调节蛋白78(GRP78)、CHOP(C/EBP homologous protein)和active-caspase12的表达水平较对照组大鼠显著升高(P0.05),而CIHH能够显著抑制上述蛋白表达水平的升高(P0.05)。结论 CIHH可能通过抑制ERS,发挥改善血管钙化和平滑肌细胞表型转化的作用。     

低压低氧对SD大鼠肺动脉压及肺组织骨桥蛋白表达的影响

目的观察不同时间低压低氧刺激下SD大鼠肺动脉压及肺组织骨桥蛋白(OPN)表达的变化,探讨OPN在肺动脉高压发病机制中的作用。方法将30只SD大鼠随机分成5组:对照组(海拔2 260 m)、低压低氧(低压氧舱模拟5 000 m海拔)1天组、7天组、14天组、21天组,每组动物均测定平均肺动脉压(m PAP)和右心室肥厚指数[RV/(LV+S)];并分别采用RT-PCR法检测各组大鼠肺组织中OPN m RNA的水平,Western blot技术检测各组大鼠肺组织中OPN蛋白表达水平。结果低压低氧1天、7天、14天、21天组动物m PAP均高于对照组(P0.05),1天、7天、14天组呈逐渐增高趋势、21天组m PAP下降,差异有显著性(P0.05);低压低氧7天组、14天组、21天组动物呈现随低氧时间延长RV/(LV+S)逐渐增高的趋势、均高于对照组和1天组(P0.05),但1天组、7天组和对照组间差异无显著性(P0.05);RT-PCR法和Western blot法结果显示低压低氧1天、7天、14天、21天组动物肺组织中OPNm RNA、OPN蛋白表达水平与对照组比较均增高(P0.05)。结论低压低氧刺激可使m PAP和RV/(LV+S)增高并促进大鼠肺组织OPN的表达增高,因此OPN可能参与高原性心脏病形成中肺动脉压的增高和右心室重塑。     

Intermittent high altitude hypoxia

The effect of intermittent high altitude (IHA) hypoxia on the myocardium and lesser circulation was investigated in adult male Wistar rats. IHA can induce intermittent pulmonary hypertension and right ventricular hypertrophy in a relatively short time. Even marked pulmonary hypertension, right ventricular hypertrophy, and pulmonary vascular changes can be normalized when rats are removed from the hypoxic atmosphere. At the beginning of the exposure to IHA acute myocardial necrotic changes were found; prolongation of IHA did not lead to further acute lesions. Experimentally induced CO polycythemia leads to mild pulmonary hypertension; IHA-induced pulmonary hypertension may, thus, be partly due to polycythemia. Beta blocking agents are able to decrease chronic hypoxic pulmonary hypertension, hypertensive changes in the pulmonary circulation, the degree of right ventricular hypertrophy, and necrotic myocardial changes.     

一氧化碳中毒与缺氧

一氧化碳 (ＣａｒｂｏｎｍｏｎｏｘｉｄｅＣＯ)为无色、无味、无刺激性的气体。大气中ＣＯ含量甚微 ,仅有 0 0 4× 10 6。空气混合爆炸极限为 12 5 %～ 74%。当吸入气中ＣＯ含量超过 5× 10 -4 (即 0 0 5 % )或 30ｍｇ/ｍ3 时 ,就可使人中毒 ;当空气中含量超过 12 5× 10 -3 (12 5 % )时 ,有爆炸的危险。ＣＯ在红外线波段区吸收电磁辐射 ,主要吸收带为 4 6 μｍ ,利用这个性质可测定空气中的ＣＯ浓度。1　中毒原因环境中ＣＯ主要来源有职业性和生活性两大类 ,也偶有意外情况。凡含碳的物质燃烧不完全时 ,都可产生ＣＯ气体。在工业生产中…     

慢性间断缺氧小鼠缺氧诱导因子1α的研究

目的　探索睡眠呼吸暂停综合征(SAS)的慢性间断性缺氧(CIH)对心血管损害的可能机制。方法　制作CIH小鼠模型。将30只ICR小鼠均分为实验组、空气模拟对照组及空白对照组。免疫组织化学方法检测实验小鼠心肌细胞缺氧诱导因子1α(HIF1α)及诱导型一氧化氮合成酶(NOS2)的表达。酶联免疫吸附测定(ELISA)方法检测小鼠血浆血管内皮生长因子(VEGF)及内皮素1(ET1)的浓度。结果　实验组心肌细胞HIF1α表达高于空白对照组(t=354,P<005)及空气模拟对照组(t=292,P<005);空白对照组HIF1α表达与空气模拟对照组比较差异无统计学意义(P>005)。实验组血浆VEGF浓度[(957±141)ng/ml]高于空白对照组[(810±062)ng/ml,q=427,P<005]及空气模拟对照组[(832±099)ng/ml,q=364,P<005];空白对照组血浆VEGF浓度与空气模拟对照组比较差异无统计学意义(P>005)。实验组血浆ET1浓度[(331±081)ng/ml]高于空白对照组[(250±072)ng/ml,q=364,P<005];空气模拟对照组血浆ET1浓度[(269±043)ng/ml]与实验组及空白对照组[(331±081)、(250±072)ng/ml]比较差异均无统计学意义(P均>005)。小鼠心肌细胞NOS2表达在各组间比较差异均无统计学意义(P均>005)。结论　CIH可引起小鼠HIF1α表达增加,并可促进HIF1α目的基因产物VEGF、ET1的表达。这可能