高碳酸血症预处理对肺缺血-再灌注损伤早期炎症反应的影响

目的观察不同程度高碳酸血症预处理对大鼠肺缺血-再灌注损伤(lung ischemia reperfusion injury,LIRI)的影响。方法雄性SD大鼠50只,2~3月龄,随机分为五组,每组10只。假手术组(S组):开胸后游离左侧肺门,不予其他处理;IR组:采用左肺原位缺血45min,再灌注180min建立大鼠左肺IR模型;L、M、H组:通过调节RR,使P_(ET)CO_2分别达到46~55mmHg(L组)、56~65mmHg(M组)、66~75mmHg(H组),预处理5 min,然后同IR组处理建立大鼠左肺IR模型。缺血-再灌注(ischemia-reperfusion,IR)180min后,采用ELISA法检测血清IL-8和IL-10浓度;处死大鼠,取肺组织标本,采用考马斯亮蓝染色法检测肺泡灌洗液(bronchial alveolar lavage fluid,BALF)中总蛋白(TP)含量,肺组织湿/干重比(W/D)、丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性,观察肺组织病理学变化及TNF-α蛋白阳性细胞面积。结果与S组比较,IR、L、M、H组血清IL-8浓度、肺组织病理学评分、肺组织W/D、MDA含量,以及TNF-α蛋白阳性细胞面积百分比明显升高(P0.05),SOD活性明显降低(P0.05)。与IR组比较,L、M、H组血清IL-8浓度、肺组织病理学评分、肺组织W/D、MDA含量,以及TNF-α蛋白阳性细胞面积百分比、SOD活性明显降低(P0.05)。与L组比较,H组以上各项指标均明显降低(P0.05)。IR组血清IL-10浓度明显高于S组(P0.05)。结论通过改变呼吸模式造成高碳酸血症预处理,可以抑制大鼠LIRI后氧自由基爆发和促炎细胞因子生成,降低早期炎症反应水平,减少炎性渗出,对减轻LIRI起到一定的作用,而且在P_(ET)CO_2 46~75mmHg内,随着P_(ET)CO_2升高,作用越强。     

Resting fluctuations in arterial carbon dioxide induce significant low frequency variations in BOLD signal

Carbon dioxide is a potent cerebral vasodilator. We have identified a significant source of low-frequency variation in blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) signal at 3 T arising from spontaneous fluctuations in arterial carbon dioxide level in volunteers at rest. Fluctuations in the partial pressure of end-tidal carbon dioxide (Pet(CO(2))) of +/-1.1 mm Hg in the frequency range 0-0.05 Hz were observed in a cohort of nine volunteers. Correlating with these fluctuations were significant generalized grey and white matter BOLD signal fluctuations. We observed a mean (+/-standard error) regression coefficient across the group of 0.110 +/- 0.033% BOLD signal change per mm Hg CO(2) for grey matter and 0.049 +/- 0.022% per mm Hg in white matter. Pet(CO(2))-related BOLD signal fluctuations showed regional differences across the grey matter, suggesting variability of the responsiveness to carbon dioxide at rest. Functional magnetic resonance imaging (fMRI) results were corroborated by transcranial Doppler (TCD) ultrasound measurements of the middle cerebral artery (MCA) blood velocity in a cohort of four volunteers. Significant Pet(CO(2))-correlated fluctuations in MCA blood velocity were observed with a lag of 6.3 +/- 1.2 s (mean +/- standard error) with respect to Pet(CO(2)) changes. This haemodynamic lag was adopted in the analysis of the BOLD signal. Doppler ultrasound suggests that a component of low-frequency BOLD signal fluctuations is mediated by CO(2)-induced changes in cerebral blood flow (CBF). These fluctuations are a source of physiological noise and a potentially important confounding factor in fMRI paradigms that modify breathing. However, they can also be used for mapping regional vascular responsiveness to CO(2).     

显著高碳酸血症58例次分析

目的　探讨慢性肺部疾病患者对显著高碳酸血症的耐受情况及临床意义。方法　选择 Pa CO2 显著增高 (>75 mm Hg) 5 8例次 ,以有脑部症状的 2 8例次作为观察组 ,无脑部症状的 30例次作为对照组。将两组对比分析。结果　有脑部症状的出现与 p H降低程度、Pa O2 下降程度、以及 Pa CO2 上升速度有关 ,而与 Pa CO2 数值的高低无直接关系。结论　患者可以较好地耐受缓慢上升的显著高碳酸血症     

Cough reflex is additively potentiated by inputs from the laryngeal and tracheobonchial receptors and enhanced by stimulation of the central respiratory neurons

The cough is an essential airway defense reflex. In this study we investigated the coordination of inputs from the laryngeal and tracheobronchial receptors in the cough reflex. In 15 beagle dogs (7–9 kg) lightly anesthetized with intravenous profobol (20–30 mg/kg/h), the cough response was elicited with mechanical stimulation of either the vocal chord or tracheal bifurcation. Simultaneous stimulation of both sites increased all the parameters of cough strength, that is, mean pleural pressure (P _pl), mean expiratory flow, number of cough bouts, and cough duration, in comparison with stimulation of the sites individually. The increases in mean P _pl and cough duration reached statistical significance (13.3 vs. 18.4 cmH₂O and 13.3 vs. 18.2 s, respectively). When the anesthetic level became deeper, the prolongation of cough duration almost disappeared, but the augmentation of mean P _pl was much less affected. During stimulation of the central respiratory neurons by intravenous dimorphoramine or acute hyperoxic hypercapnia, the cough strength increased significantly. We concluded that inputs from the laryngeal and tracheobonchial cough receptors acted in concert and potentiated the cough reflex. Furthermore, stimulation of the central respiratory neurons may increase the intensity of a cough response.     

允许性高碳酸血症对行腹腔镜下胃癌根治术患者外周血炎性因子的影响

目的 探讨允许性高碳酸血症的通气策略在腹腔镜下胃癌根治术麻醉中的应用价值,观察其对患者外周血炎性因子的影响.方法 选择行腹腔镜下胃癌根治术患者36例,随机分为两组:对照组和试验组,每组各18例.对照组行传统的通气策略:呼气末二氧化碳分压(P<,ErCO2)为34.5～45.0miHg(1 mm Hg=0.133 kPa),pH值为7.35～7.45;试验组行允许性高碳酸血症的通气策略:P<,ErCO2为49.5～60.0mmHg,pH>7.20.分别于麻醉前(T0)、手术1 h(T1)、手术3 h(T2)、术毕(T3)四个时间点检测两组患者外周血炎性因子的变化.结果 T2、T3时间点对照组白细胞介素(IL)-8、IL-6、肿瘤坏死因子(TNF)-α[(96.732±3.173)μg/L和(107.767±3.654)μg/L、(0.273±0.009)ng/L和(0.287±0.008)ng/L、(1.443±0.086)μg/L和(1.614±0.107)μg/L]与试验组[(91.771±4.332)μg/L和(97.682±4.998)μg/L、(0.231±0.008)ng/L和(0.241±0.006)ng/L、(1.268±0.066)μg/L和(1.428±0.058)μg/L]比较均明显增高(P<0.05或<0.01),平均动脉压、动脉血氧分压、心率都保持相对稳定.结论 腹腔镜下胃癌根治术麻醉中,允许性高碳酸血症的通气策略能减少炎性因子的释放,可能是一种较好的通气策略.     

Regional differences in the coupling of cerebral blood flow and oxygen metabolism changes in response to activation: implications for BOLD-fMRI

Functional magnetic resonance imaging (fMRI) based on blood oxygenation level dependent (BOLD) signal changes is a sensitive tool for mapping brain activation, but quantitative interpretation of the BOLD response is problematic. The BOLD response is primarily driven by cerebral blood flow (CBF) changes, but is moderated by M, a scaling parameter reflecting baseline deoxyhemoglobin, and n, the ratio of fractional changes in CBF to cerebral metabolic rate of oxygen consumption (CMRO(2)). We compared M and n between cortical (visual cortex, VC) and subcortical (lentiform nuclei, LN) regions using a quantitative approach based on calibrating the BOLD response with a hypercapnia experiment. Although M was similar in both regions (~5.8%), differences in n (2.21+/-0.03 in VC and 1.58+/-0.03 in LN; Cohen d=1.71) produced substantially weaker (~3.7x) subcortical than cortical BOLD responses relative to CMRO(2) changes. Because of this strong sensitivity to n, BOLD response amplitudes cannot be interpreted as a quantitative reflection of underlying metabolic changes, particularly when comparing cortical and subcortical regions.     

In vitro responses of neurons in the periaqueductal gray to hypoxia and hypercapnia

Hypoxia-sensitive neurons in the caudal hypothalamus (CH) have been shown to project to the periaqueductal gray (PAG) which, in turn, sends descending projections to an area of the ventrolateral medulla (VLM) containing neurons inherently excited by hypoxia. The purpose of this study was to determine if neurons in the PAG are excited by hypoxia or hypercapnia in an in vitro environment. Extracellular responses to hypoxia and hypercapnia of neurons located throughout the PAG were recorded in a rat brain slice (400–500 μm thick) preparation. Hypoxic (10% O₂/5% CO₂/85% N₂) and hypercapnic (7% CO₂/93% O₂) stimuli were delivered to the tissue through gas bubbled into the brain slice chamber. A majority (39 of 53) of the neurons tested responded to hypoxia. Of these neurons, 92% responded to hypoxia with an increase in firing rate. Neurons in the dorsolateral/lateral regions increased firing rates to a greater extent than neurons located in ventrolateral regions. All neurons tested (n=6) also responded to hypoxia after perfusion of the tissue with a low Ca²⁺/high Mg²⁺ solution to block classic synaptic transmission. Only a small proportion (7/33) of neurons tested responded to hypercapnia. These findings indicate that neurons in the periaqueductal gray region of the brain have an inherent responsiveness to hypoxia and, thus, may contribute to the overall coordination of cardiorespiratory responses to systemic hypoxia.     

允许性高碳酸血症治疗ARDS对肺力学的影响

目的探讨允许性高碳酸血症(PHC)对重度急性呼吸窘迫综合征(ARDS)肺力学及血流动力学的影响。方法观察不同潮气量(VT)时,30例重度ARDS患者肺气体交换、肺力学的改变。结果当VT从15ml/kg降至6ml/kg时,病人均出现PHC,动脉血氧分压、氧饱和度和混合静脉血氧饱和度显著降低(P<0.05)。PHC时,气道压力显著降低,气道阻力明显增高(P<0.05)。静态肺压力-容积曲线高位转折点对应的压力为(22.2±1.9)cmH2O,容积为10ml/kg。结论在实施PHC时,只有当气道平台压<20~25cmH2O时才有可能避免肺泡过度膨胀,减少呼吸机相关性肺损伤。     

Obesity hypoventilation syndrome: prevalence and predictors in patients with obstructive sleep apnea

Patients with obesity hypoventilation syndrome (OHS) have a lower quality of life, more healthcare expenses, a greater risk of pulmonary hypertension, and a higher mortality compared to eucapnic patients with obstructive sleep apnea (OSA). Despite significant morbidity and mortality associated with OHS, it is often unrecognized and treatment is frequently delayed. The objective of this observational study was to determine the prevalence of OHS in patients with OSA seen at the sleep disorders clinic of a large public urban hospital serving predominantly minority population and to identify clinical—not mechanistic—predictors that should prompt clinicians to measure arterial blood gases. In the first stage, we randomly selected 180 patients referred to our sleep disorders clinic between 2000 and 2004 for suspicion of OSA. From this retrospective random sample we calculated the prevalence of OHS in patients with OSA and identified independent clinical predictors using logistic regression. In the second stage, we prospectively validated these predictors in a sample of 410 consecutive patients referred to the sleep disorders clinic for suspicion of OSA between 2005 and 2006. The prevalence of OHS in patients with OSA was 30% in the retrospective random sample and 20% in the prospective sample. Three variables independently predicted OHS in both samples: serum bicarbonate level (p < 0.001), apnea–hypopnea index (p = 0.006), and lowest oxygen saturation during sleep (p < 0.001). Due to the serious morbidity associated with OHS, we selected a highly sensitive threshold of serum bicarbonate level. A threshold of 27 mEq/l had a sensitivity of 92% and a specificity of 50%. Only 3% of patients with a serum bicarbonate level <27 mEq/l had hypercapnia compared to 50% with a serum bicarbonate ≥27 mEq/l. In conclusion, OHS is common in severe OSA. A normal serum bicarbonate level excludes hypercapnia and an elevated serum bicarbonate level should prompt clinicians to measure arterial blood gases.     

阻塞性睡眠呼吸暂停低通气综合征发生慢性高碳酸血症相关因素探讨

目的探讨阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者发生慢性高碳酸血症的相关因素。方法对苏州大学附属第二医院2004-02～2005-04收治的56例OSAHS患者进行血气分析和肺功能测定。分为高碳酸血症组和正常碳酸组、肥胖组和非肥胖组。记录患者的体重指数(BMI)、多导睡眠图(PSG)指标、肺功能测定值和血气分析值。分别比较高碳酸血症组和正常碳酸组、肥胖组和非肥胖组上述指标的差异程度。通过直线相关分析获得动脉血二氧化碳分压(PaCO2)与其他变量的相关性;有相关性的变量再通过多元线性回归分析比较各自对PaCO2变化所起的作用。结果多元回归分析显示,在高碳酸血症组,肺活量占预计值的百分比(%VC)和夜间平均脉搏血氧饱和度(SpO2)是影响日间PaCO2的两个主要变量。二者组成的模型解释了总变异的约74%(R2=0.738,P<0.001)。在肥胖组,%VC和平均SpO2也是影响PaCO2水平的两个主要变量,模型解释了总变异的79%(R2=0.792,P<0.001)。结论限制性通气功能障碍和夜间血氧饱和度降低在OSAHS患者发生慢性高碳酸血症中起主要的作用。