气管内吹气对急性高碳酸血症家兔血气及呼吸力学的影响

目的　探讨气管内吹气（ Ｔ Ｇ Ｉ） 对急性高碳酸血症（ Ｈ Ｃ） 家兔二氧化碳清除的效果及其对通气效率的改善作用。方法　用自行设计的 Ｔ Ｇ Ｉ装置对常规正常机械通气（ Ｃ Ｍ Ｖ） 和低通气致 Ｈ Ｃ 家兔行 Ｔ Ｇ Ｉ,分别观察两组动物在不同吹气流量（０２ Ｌ·ｍｉｎ１ 和０４ Ｌ·ｍｉｎ１） 时呼气末二氧化碳分压（ Ｐｅｔ Ｃ Ｏ２） 、血气与呼吸力学等指标的变化。结果　（１） Ｔ Ｇ Ｉ可明显降低两组动物的动脉血二氧化碳分压（ Ｐａ Ｃ Ｏ２） 水平,并能在潮气量（ Ｖ Ｔ） 降低３０ ％ 的情况下维持 Ｐａ Ｃ Ｏ２ 在正常范围, Ｔ Ｇ Ｉ降低 Ｐａ Ｃ Ｏ２ 的作用呈流量依赖性;（２） Ｔ Ｇ Ｉ使两组动物的气道压力明显增高,但 Ｈ Ｃ 组气道峰压（ Ｐｐｅａｋ） 、平台压（ Ｐｐａｕｓｅ） 水平均显著低于 Ｃ Ｍ Ｖ 组;（３） Ｔ Ｇ Ｉ使 Ｐｅｔ Ｃ Ｏ２ 明显降低,呼气阻力（ Ｒｅ） 及呼气潮气量（ Ｖ Ｅ） 显著增高,而对肺顺应性（ Ｃｓｔ） 无明显影响;（４） Ｔ Ｇ Ｉ对平均动脉压及心率无显著影响。结论　 Ｔ Ｇ Ｉ是一种简便实用的机械通气的辅助手段,它能有效地降低 Ｐａ Ｃ Ｏ２ ,并使气道压力维持在低水平。     

成比例辅助机械通气治疗慢阻肺合并高碳酸血症的研究

目的探讨成比例辅助机械通气（PAV）对慢性阻塞性肺疾病（COPD）合并高碳酸血症患者呼吸力学的影响。方法在常规药物治疗的基础上,应用无创成比例辅助机械通气（PAV）治疗COPD合并高碳酸血症患者40例,观察并比较不同模式下动脉血气分析指标（Pa02、PaC02）及呼吸力学变化,包括潮气量（VT）、每分通气量（MV）、呼吸频率（RR）、气道峰压（PUP））和吸气／呼吸周期时间比（Ti/Ttot）,并计算平均吸气流速（VT/Ti）。结果COPD合并高碳酸血症患者PAV通气时的RR、PIP和VT/Ti与BiPAP（S/T）相比有显著降低（P〈0．05）,Ti/Ttotal明显增加（P〈0．05）,MV有所增加,夜间连续通气时间显著延长。结论与BiPAP相比,无创成比例辅助机械通气（PAV）应用于慢性阻塞性肺病并高碳酸血症患者时气道峰压低、吸气,呼吸周期时间比明显增加,通气依存性好。PAV适宜的辅助比例在40％-60％。     

肺动脉高压大鼠一氧化氮及过氧化氢依赖的可溶性鸟苷酸环化酶通路的变化

目的：观察低O2高CO2对血浆一氧化氮（NO）、肺组织超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、可溶性鸟苷酸环化酶(sGC)活性以及cGMP含量的变化，探讨NO-sGC和H2O2-sGC通路于肺动脉高压中的作用。 方法： 复制低O2高CO2 1、2、4周组及对照组大鼠模型。测定平均肺动脉压（mPAP）。比色法测定血浆一氧化氮（NO）、肺组织超氧化物歧化酶（SOD）、过氧化氢酶（CAT）活性，酶动力学分析基础及过氧化氢（H2O2）及硝普钠（SNP）激活的肺组织sGC酶活性，［125I］-放射免疫法检测肺组织cGMP含量。 结果： 低O2高CO2 1、2、4周组mPAP均明显高于对照组（均P<0.01）；血浆NO、肺组织SOD、CAT活性、基础sGC活性、过氧化氢（H2O2）及硝普钠（SNP）激活的sGC活性和肺组织cGMP含量均显著低于对照组（分别P<0.05, P<0.01）。 结论： 低O2高CO2抑制NO-sGC和H2O2-sGC通路参与肺动脉高压的形成与发展。     

低氧和高二氧化碳作用下肺动脉高压形成过程中骨桥蛋白表达与分布的实验研究

目的： 观察慢性低O2高CO2大鼠肺动脉骨桥蛋白（OPN）及其基因的表达与分布情况，探讨OPN在肺动脉高压发病机制中的作用。方法： 48只雄性SD大鼠随机分为4组：即正常对照组（NC组），低O2高CO2 1周、2周和4周组（1HH、2HH和4HH）。采用RT-PCR法测定不同低O2高CO2 组大鼠离体肺动脉和肺组织骨桥蛋白（OPN）mRNA，免疫组织化学染色法测定肺细小动脉骨桥蛋白分布表达情况，ELISA 法定量测定肺组织匀浆OPN水平，Western blotting 法测定离体肺动脉OPN表达水平。结果： ①低O2高CO2各组大鼠mPAP和RV/LV+S均明显高于NC组（P<0.01），4组大鼠间mCAP比较无显著差异（P>0.05）；②低O2高CO2 各组大鼠肺组织和离体肺主动脉OPN mRNA表达水平显著高于对照组（均P<0.01）；③免疫组化法显示NC组大鼠肺组织OPN表达主要见于支气管、肺泡上皮细胞内，1HH组大鼠肺细小动脉内皮细胞、平滑肌细胞以及周围巨噬细胞均见有OPN的表达，其中以中膜平滑肌细胞最为明显，而2HH和4HH组大鼠OPN表达更加明显, 低O2高CO2 各组肺细小动脉OPN相对含量与对照组比较有显著差异（均P<0.01），且随缺氧时间的延长，骨桥蛋白表达也呈增高趋势；④ 低O2高CO2 各组大鼠肺组织匀浆OPN含量分别为正常对照组的1.69倍、2.28倍和2.87倍（均P<0.01）；⑤ Western blotting 分析1HH、2HH和4HH各组大鼠离体肺动脉OPN表达明显增强，与NC组比较有显著差异（均P<0.01）。结论： 慢性低O2高CO2能够刺激大鼠肺组织和肺动脉OPN及其基因表达增强，OPN可能在慢性低O2高CO2性肺动脉高压发病的病理和病理生理过程中起着重要的作用。     

Central drive and ventilatory failure in late-onset Pompe disease: At the gates of a new phenotype

Subjects with late-onset Pompe disease (LOPD) typically present as slowly progressive proximal muscle weakness. Respiratory muscle weakness and diaphragmatic paralysis are common features, and may be the initial manifestation of the disease. There is often a poor correlation between the severity of limb and respiratory muscle weakness. Early clinical observations about disproportionate hypercapnia to the respiratory muscular weakness in late-onset Pompe disease were recognized and will be discussed with special reference to blunted respiratory drive, and the connections between early clinical observations, respiratory functional studies and anatomical findings. According to new evidence about blunted respiratory drive in Pompe disease, it is necessary to rethink what is meant by “asymptomatic Pompe disease” and propose a new phenotype with its therapeutic implications. The conceptual model of the mechanisms leading to respiratory failure in this disease could be considered according to these new findings. It may broaden the diagnostic spectrum of the adult forms and warrants a closer interaction between neurologists and pulmonologists. The recognition of this new phenotype of predominant central alveolar hypoventilation in Pompe disease will improve the understanding of the underlying mechanisms of ventilatory failure and could lead to improved future therapeutic strategies.     

Impaired cerebrovascular reactivity after cortical spreading depression in rats: Restoration by nitric oxide or cGMP

We investigated the role of the NO/cGMP system in the vasodilatory response to hypercapnia after cortical spreading depression (CSD) in barbiturate anesthetized rats in vivo. Regional cerebral blood flow (rCBF) was measured by laser Doppler flowmetry (LDF). Hypercapnia (arterial pCO2 50-60 mm Hg) increased rCBF by 2.8+/-1.0%/mm Hg (n = 34). Fifteen minutes after CSD, resting rCBF was reduced to 87%, and rCBF response to hypercapnia was abolished (p < 0.001, n = 28). Within 1 h after CSD, only little restoration of vascular reactivity occurred. Topical application of the NO-donors S-nitroso-N-acetylpenicillamine (SNAP), 3-morpholinosydnonimine (SIN1), or spermine/NO complex (Sperm/NO), or of the cell permeable guanosine 3',5'-cyclic monophosphate (cGMP) analogue 8-Br-cGMP reestablished resting rCBF to values measured before CSD, and reversed CSD-induced attenuation of the cerebrovascular response to hypercapnia. Restoration of resting rCBF to pre-CSD level by the NO-independent vasodilator papaverine had no effect on the attenuated hypercapnic response. In conclusion, we have shown that the compromised vascular reactivity to hypercapnia after CSD can be reversed to normal reactivity by restoration of the basal NO or cGMP concentration in the cortex, suggesting a reduction of the cerebrovascular NO or cGMP concentration following CSD.     

Hypercapnic acidosis minimizes endotoxin-induced gut mucosal injury in rabbits

Objective  Recent evidence demonstrated that hypercapnic acidosis due to lung protective strategy was not only permissive but also even therapeutic for injured lung. Since the effects of hypercapnic acidosis on extra-pulmonary organs remain to be clarified, we tested the hypothesis that hypercapnic acidosis protects gut mucosal barrier function by modulating inflammation in a rabbit model of endotoxemia. Design  Prospective randomized animal study. Setting  University research laboratory. Subjects  Male New Zealand white rabbits. Interventions  Thirty-two animals were randomly allocated into two groups: normocapnia (n = 17) and hypercapnia (n = 15). The latter group received F_ICO₂ 5% under mechanical ventilation to achieve hypercapnia throughout the study periods, whereas the former with F_ICO₂ 0%. Measurements and results  Arterial blood gas, intramucosal pH (pHi) and portal blood flow were assessed at baseline, 2-h and 4-h infusion of lipopolysaccharide. At 4 h, ileal myeloperoxidase (MPO) activity and intestinal permeability were measured. The animals in the hypercapnia group showed apparent hypercapnic acidosis and progressive intramucosal acidosis at 4 h, accompanied by significantly lower intestinal permeability versus normocapnia group. Ileal MPO activity was comparable between the study groups. Conclusions  Hypercapnic acidosis attenuates endotoxin-induced gut barrier dysfunction possibly through neutrophil-independent mechanisms. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

低温海水淹溺濒死大鼠血气与酸碱失调的研究

目的 观察低温海水淹溺濒死大鼠不同时间血气与酸碱代谢的改变,分析形成原因和机制,为治疗提供理论依据。方法 置动物于16－17 C海水自由游动,直至沉入水底,呼吸暂停;取出后于不同时间测量肛温,心脏取血检测血气与酸碱,处死动物称取沛湿重计算肺脏／体重比值。结果 大鼠出海水后的肛温、PaO2、PaSO2(%)、pH、BE－EC、BE－B、SBC、HCO3^-及TCO2均明显降低,而肺脏／体重比值及PaCO2则显著升高;上述指标随时间延长均呈恢复趋势,但大多数指标至60min仍未回到正常对照水平。结论 低温海水淹溺濒死大鼠,主要受低温海水浸泡和低温海水吸入呼吸系统所致侵害;前者导致代谢性酸中毒,后者则引起低氧血症、高碳酸血症、呼吸性酸中毒及代谢性酸中毒。