Control of air-breathing in fishes: Central and peripheral receptors

This review considers the environmental and systemic factors that can stimulate air-breathing responses in fishes with bimodal respiration, and how these may be controlled by peripheral and central chemoreceptors. The systemic factors that stimulate air-breathing in fishes are usually related to conditions that increase the O₂ demand of these animals (e.g. physical exercise, digestion and increased temperature), while the environmental factors are usually related to conditions that impair their capacity to meet this demand (e.g. aquatic/aerial hypoxia, aquatic/aerial hypercarbia, reduced aquatic hidrogenionic potential and environmental pollution). It is now well-established that peripheral chemoreceptors, innervated by cranial nerves, drive increased air-breathing in response to environmental hypoxia and/or hypercarbia. These receptors are, in general, sensitive to O₂ and/or CO₂/H⁺ levels in the blood and/or the environment. Increased air-breathing in response to elevated O₂ demand may also be driven by the peripheral chemoreceptors that monitor O₂ levels in the blood. Very little is known about central chemoreception in air-breathing fishes, the data suggest that central chemosensitivity to CO₂/H⁺ is more prominent in sarcopterygians than in actinopterygians. A great deal remains to be understood about control of air-breathing in fishes, in particular to what extent control systems may show commonalities (or not) among species or groups that have evolved air-breathing independently, and how information from the multiple peripheral (and possibly central) chemoreceptors is integrated to control the balance of aerial and aquatic respiration in these animals.     

无创正压通气治疗AECOPD合并呼吸衰竭高碳酸血症意识障碍临床分析

【目的】探讨呼吸重症监护病房的慢性阻塞性肺病（COPD）急性加重期（AECOPD）合并高碳酸血症意识障碍疗效观察。【方法】回顾性分析对39例AECOPD合并呼吸衰竭高碳酸血症意识障碍患者8≤GCS评分〈15在急性发作期入住呼吸重症监护病房,予无创正压通气治疗,观察机械通气前与机械通气后2h、d。、d2、ds的PH值、动脉二氧化碳分压（PaCO2）、碳酸氢根离子（HCO3-）、氧合指数指标的变化情况。根据无创通气治疗前GCS评分分为两组,A组为（10≤GCS评分〈15）,B组为（8分≤GCS评分〈10分）,对两组指标进行比较。【结果】无创呼吸治疗39例AECOPD意识障碍患者,平均住院时间为（17±10）d,住ICU的时间为（9土5）d,APACHE-Ⅱ评分平均（15．4±2．2）分。上呼吸机2h后GCS评分较机械通气前升高且有显著差异（P〈0．01）,动脉血气指标的PaCO2值明显低于机械通气前（P〈0．01）,治疗后pH高于机械通气前（P〈0．05）。对NIPPV治疗前GCS评分A组（10≤GCS评分〈15）同B组（8≤GCS评分〈10）相比,在APACHE-Ⅱ评分（P〈0．05）、pH值（P〈0．01）、PaCO：有显著差异（P〈0．01）。【结论】NIPPV对于AE-COPD合并呼吸衰竭高碳酸血症意识障碍有效,临床上能减少AECOPD及高碳酸血症呼吸衰竭患者的插管率及住院病死率。     

Vascular component analysis of hyperoxic and hypercapnic BOLD contrast

Hyperoxia or hypercapnia provides a useful experimental tool to systematically alter the blood oxygenation level dependent (BOLD) contrast. Typical applications include calibrated functional magnetic resonance imaging (fMRI), BOLD sensitivity mapping, vessel size imaging or cerebrovascular reactivity mapping. This article describes a novel biophysical model of hyperoxic and hypercapnic BOLD contrast, which accounts for the magnetic susceptibility effects of molecular oxygen that is dissolved in blood and tissue, in addition to the well-established effects caused by the paramagnetic properties of deoxyhaemoglobin. Furthermore, the concept of vascular component analysis (VCA) is introduced and is shown to provide a computationally efficient tool for investigating the vascular specificity of hyperoxic and hypercapnic BOLD contrast. A theoretical investigation of gradient and spin echo BOLD contrast based on computer simulations was performed to compare three different conditions (hypercapnia induced by breathing 6% CO₂, hyperoxia induced by breathing 100% O₂, and simultaneous hypercapnia and hyperoxia induced by breathing carbogen, i.e. 5% CO₂ in 95% CO₂) with baseline (breathing air). Simulations were carried out for different levels of metabolic oxygen extraction fraction (OEF) ranging from 0 to 0.5. The key findings can be summarised as follows: (i) for hyperoxia the susceptibility of dissolved O₂ may lead to a significant arterial BOLD contrast; (ii) under normoxic conditions the susceptibility of dissolved O₂ is negligible; (iii) an almost complete loss of BOLD sensitivity may occur at lower OEF values in all parts of the vascular tree, whereas hyperoxic BOLD sensitivity is largely maintained; (iv) under hyperoxic conditions, a transition from positive to negative BOLD contrast occurs with decreasing OEF values. These findings have important implications for experimental applications of hyperoxic and hypercapnic BOLD contrast and may enable new clinical applications in ischemic stroke and other forms of acquired brain injury.     

高频振荡通气治疗新生儿肺出血疗效观察

目的观察高频振荡通气(HFOV)治疗新生儿肺出血(NPH)的临床疗效。方法对30例NPH患儿进行HFOV治疗,对上机前及上机后2,6,12,24 h吸入氧浓度(FiO2)、氧合指数(OI)、二氧化碳分压(PaCO2)进行比较。结果 30例NPH治愈23例(76.7%),包括4例常频机械通气无效及1例常频机械通气发生气漏改为HFOV治疗治愈者,死亡5例(16.7%),自动出院2例。肺出血时间(14.4±7.6)h,机械通气时间(77.4±21.2)h,无发生气漏,发生脑室内出血4例(17.4%)。存活患儿HFOV后2,6,12,24 h FiO2、OI、PaCO2均显著下降(P<0.01)。结论 HFOV治疗可以明显改善NPH患儿氧合功能,迅速改善高碳酸血症。HFOV治疗NPH安全、有效,具有较好的临床应用价值。     

线粒体途径在慢性低氧高二氧化碳小鼠骨骼肌凋亡中的作用

目的探讨线粒体途径在慢性低氧高二氧化碳小鼠骨骼肌凋亡中的作用。方法成年storage protect feature(SPF)级雄性C57BL/6小鼠16只随机分成两组:正常对照组(n=8)和实验组(n=8),将实验组小鼠置于常压低氧高二氧化碳舱内,通过氮气调节舱内氧浓度,使其维持在9%～11%,通入二氧化碳使其浓度维持在5%～6%,每天8h,共4周。用酶联免疫吸附测定法(ELISA)检测骨骼肌细胞胞质内半胱氨酸天冬氨酸特异性蛋白酶3(caspase-3)的含量,荧光实时定量PCR法检测胞浆内细胞色素C(Cyt-C)及细胞凋亡因子Bax、Bcl-2基因的表达情况。结果与正常对照组相比,实验组骨骼肌细胞内的caspase-3含量增加(P<0.05),Cyt-C mRNA表达增多,Bax mRNA表达增多,而Bcl-2 mRNA表达减少,Bcl-2/Bax比值下降。结论线粒体途径可能参与了慢性低氧高二氧化碳小鼠骨骼肌细胞的凋亡,Bcl-2/Bax比值下降可能是促进骨骼肌线粒体途径凋亡的重要因素。     

Novel methodology to comprehensively assess retinal arteriolar vascular reactivity to hypercapnia

PURPOSE: (1) Describe a new methodology that permits the comprehensive assessment of retinal arteriolar vascular reactivity in response to a sustained and stable hypercapnic stimulus. (2) Determine the magnitude of the vascular reactivity response of the retinal arterioles to hypercapnic provocation in healthy, young subjects. METHODOLOGY: Eleven healthy subjects of mean age 27 years (SD 3.43) participated in the study and one eye was randomly selected. A mask attached to a sequential rebreathing circuit, and connected to a gas delivery system, was fitted to the face. To establish baseline values, subjects breathed bottled air for 15 min and at least 6 blood flow measurements of the supero-temporal arteriole were acquired using the Canon Laser Blood Flowmeter (CLBF). Air flow was then decreased until a stable increase in fractional end-tidal CO(2) concentration (F(ET)CO(2)) of 10-15% was achieved. CLBF measurements were acquired every minute (minimum of 6 measurements) during the 20-minute period of elevated F(ET)CO(2). F(et)CO(2) was then reduced to baseline levels, and 6 further CLBF measurements were acquired. Respiratory rate, blood pressure, pulse rate and oxygen saturation were monitored continuously. RESULTS: Retinal arteriolar diameter, blood velocity and blood flow increased during hypercapnia relative to baseline (p=0.0045, p<0.0001 and p<0.0001, respectively). Group mean F(ET)CO(2) showed an increase of 12.0% (SD 3.6) relative to baseline (p<0.0001). CONCLUSIONS: This study describes a new methodology that permits the comprehensive assessment of retinal arteriolar vascular reactivity in response to a sustained and stable hypercapnic stimulus. Retinal arteriolar diameter, blood velocity and blood flow increased significantly in response to a hypercapnic provocation in young, healthy subjects.     

Hypercapnia in late-phase ALI/ARDS: providing spontaneous breathing using pumpless extracorporeal lung assist

Objective  The fibroproliferative phase of late ALI/ARDS as described by Hudson and Hough (Clin Chest Med 27:671–677, 2006) is associated with pronounced reductions in pulmonary compliance and an accompanying hypercapnia complicating low tidal volume mechanical ventilation. We report the effects of extracorporeal CO₂ removal by means of a novel pumpless extracorporeal lung assist (p-ECLA) on tidal volumes, airway pressures, breathing patterns and sedation management in pneumonia patients during late-phase ARDS. Design  Retrospective analysis. Setting  Fourteen-bed university hospital ICU. Patients  Ten consecutive late-phase ALI/ARDS patients with low pulmonary compliance, and severe hypercapnia. Intervention  Gas exchange, tidal volumes, airway pressures, breathing patterns and sedation requirements before (baseline) and after (2–4 days) initiation of treatment with p-ECLA were analysed. Patients were ventilated in a pressure-controlled mode with PEEP adjusted to pre-defined oxygenation goals. Measurements and main results  Median reduction in pCO₂ was 50% following institution of p-ECLA. Extracorporeal CO₂ removal enabled significant reduction in tidal volumes (to below 4 ml/kg predicted body weight) and inspiratory plateau pressures [30 (28.5/32.3) cmH₂O, median 25, 75% percentiles]. Normalization of pCO₂ levels permitted significant reduction in the dosages of analgesics and sedatives. The proportion of assisted spontaneous breathing increased within 24 h of instituting p-ECLA. Conclusion  Elimination of CO₂ by p-ECLA therapy allowed reduction of ventilator-induced shear stress through ventilation with tidal volumes below 4 ml/kg predicted body weight in pneumonia patients with severely impaired pulmonary compliance during late-phase ARDS. p-ECLA treatment supported control of breathing pattern while sedation requirements were reduced and facilitated the implementation of assisted spontaneous breathing.     

硫氮卓酮对慢性低O2高CO2大鼠肺动脉压力和结构型一氧化氮合酶及其基因表达的影响

目的：探讨硫氮卓酮对慢性低O₂高CO₂大鼠肺动脉压力的影响及其作用机制。方法：将Sprague-Dawley大鼠分为正常对照组（A组）、四周低O₂高CO₂组（B组）和四周低O₂高CO₂+硫氮卓酮组（C组），采用透射电镜、图像分析、免疫组化、原位杂交等方法，研究硫氮卓酮对慢性低O₂高CO₂大鼠肺动脉平均压（mPAP）、颈动脉平均压（mCAP）及肺动脉显微和超微结构、肺动脉结构型一氧化氮合酶（ceNOS）及其基因表达的影响。结果：①B组mPAP明显高于A组（P<0.01），C组mPAP明显低于B组（P<0.01），A组和B组mCAP无明显差异（P>0.05），C组mCAP低于B组（P<0.01）；②光镜下，肺细小动脉管壁面积/管总面积比值（WA/TA）C组明显低于B组（P<0.01）；电镜下，C组大鼠肺细小动脉内皮损伤、中膜平滑肌细胞和胶原纤维增生明显轻于B组；③免疫组化见C组肺细小动脉ceNOS的平均吸光度值明显高于B组（P<0.01）；原位杂交发现C组肺细小动脉ceNOS mRNA平均吸光度值明显高于B组（P<0.01）。结论：硫氮卓酮可抑制慢性低O₂高CO₂性肺动脉高压形成和肺血管结构重建，肺动脉ceNOS及其基因表达的增加为其重要作用机制，硫氮卓酮可能为治疗COPD、肺动脉高压伴高血压或室上性心律失常患者较为理想的药物。     

Ventilation during air breathing and in response to hypercapnia in 5 and 16 month-old <Emphasis Type="Italic">mdx</Emphasis> and C57 mice

Previous studies have shown a blunted ventilatory response to hypercapnia in mdx mice older than 7 months. We test the hypothesis that in the mdx mice ventilatory response changes with age, concomitantly with the increased functional impairment of the respiratory muscles. We thus studied the ventilatory response to CO₂ in 5 and 16 month-old mdx and C57BL10 mice (n = 8 for each group). Respiratory rate (RR), tidal volume (VT), and minute ventilation (VE) were measured, using whole-body plethysmography, during air breathing and in response to hypercapnia (3, 5 and 8% CO₂). The ventilatory protocol was completed by histological analysis of the diaphragm and intercostals muscles. During air breathing, the 16 month-old mdx mice showed higher RR and, during hypercapnia (at 8% CO₂ breathing), significantly lower RR (226 ± 26 vs. 270 ± 21 breaths/min) and VE (1.81 ± 0.35 vs. 3.96 ± 0.59 ml min⁻¹ g⁻¹) (P < 0.001) in comparison to C57BL10 controls. On the other hand, 5 month-old C57BL10 and mdx mice did not present any difference in their ventilatory response to air breathing and to hypercapnia. In conclusion, this study shows similar ventilation during air breathing and in response to hypercapnia in the 5 month-old mdx and control mice, in spite of significant pathological structural changes in the respiratory muscles of the mdx mice. However in the 16 month-old mdx mice we observed altered ventilation under air and blunted ventilation response to hypercapnia compared to age-matched control mice. Ventilatory response to hypercapnia thus changes with age in mdx mice, in line with the increased histological damage of their respiratory muscles. J. Gayraud and S. Matecki contributed equally to this work     

先天性中枢性低通气综合征一例报告并文献复习

目的报告1例先天性中枢性低通气综合征（congenital central hypoventilation syndrome,CCHS）,并复习文献,以提高对该病的认识和临床诊疗水平。方法对1例确诊为CCHS的患儿的临床资料和治疗情况进行总结。并结合文献资料进行分析。结果患儿男孩,生后当天以精神反应差起病,自主呼吸弱,反复撤机失败,基因检测证实存在Phox2b基因突变,确诊为CCHS。患儿熟睡时在呼吸机辅助呼吸（SIMV）下,基本无自主呼吸,DUOPAP辅助呼吸时,自主呼吸浅弱,胸壁活动弱,对CO：升高和血氧饱和度下降无呼吸增快及觉醒反应,家长要求终止治疗出院后13h死亡。结论对于持续存在的睡眠状态下通气不足、反复高碳酸血症、撤机失败,而无心、肺、神经肌肉功能障碍原发病,需考虑CCHS,Phox2b基因检测可作为CCHS的重要诊断手段。