高碳酸血症在器官损伤中的作用

传统观点认为“允许性高碳酸血症”时升高的PaCO2 对机体无保护性作用 ,甚至认为其对机体有害。而最近的一些动物实验表明 ,高碳酸血症在器官损伤中具有保护性作用。在心肌缺血 -再灌注损伤中 ,高碳酸血症能促进心肌功能的恢复 ;在缺血性脑损伤中 ,通过神经病理检查 ,发现高碳酸血症有保护作用 ;在肺损伤中 ,高碳酸血症可减轻肺损伤的程度 ,其机制考虑与改善氧合、抑制炎症反应及防止细胞内Ca2 +超负荷有关     

阻塞性睡眠呼吸暂停低通气综合征患者的日间高碳酸血症

部分阻塞性睡眠呼吸暂停低通气综合征患者伴有日间高碳酸血症,甚至出现Ⅱ型呼吸衰竭,病死率明显高于不伴有日间高碳酸血症者.本文综述了阻塞性睡眠呼吸暂停低通气综合征患者日间高碳酸血症的发生情况、机制、影响因素及治疗策略.     

高碳酸血症在器官损伤中的作用

传统观点认为“允许性高碳酸血症”时升高的PaC02对机体无保护性作用，甚至认为其对机体有害。而最近的一些动物实验表明，高碳酸血症在器官损伤中具有保护性作用。在心肌缺血一再灌注损伤中，高碳酸血症能促进心肌功能的恢复；在缺血性脑损伤中，通过神经病理检查，发现高碳酸血症有保护作用；在肺损伤中，高碳酸血症可减轻肺损伤的程度，其机制考虑与改善氧合、抑制炎症反应及防止细胞内Ca^2 超负荷有关。     

氧疗后单纯高碳酸血症50例临床分析

对慢性阻塞性肺病氧疗后出现单纯高碳酸血症５０例患者的临床及血气资料进行分析，发现其中３４例氧疗后低氧血症改善但持续存在高碳酸血症，ＰａＣＯ２≥６．６７ｋＰａ，另１６例则高碳酸血症很快被纠正；顽固性高碳酸血症组中有１５例分别在持续低流量吸氧（１￣２升／分）和停止吸氧３０分钟后进行血气对比分析，结果提示顽固性高碳酸血症可能系严重的气道阻塞所至。持续低流量吸氧可明显改善低氧血症，而对ＰａＣＯ２影响小。     

吸入一氧化氮可逆转ARDS患者因高碳酸血症所致的肺血管阻力增加

该前瞻性研究的目的在于确定吸入一氧化氮(NO)是否可以逆转急性呼吸窘迫综合征(ARDS)患者因高碳酸血症(代偿期)所致的肺动脉压力和肺血管阻力的增加。 对11例ARDS的危重患者进行研究,其中有9例男性,2例女性;3例为外伤后发生ARDS,8例为外科术后引起;平均年龄在59±22岁。Murray评分≥2.5。对上述患者持续静脉给予镇静镇痛药物,并进行连续正压机械通气。调整每分通气量使PaCO_2在4.7～6kPa以造成常碳酸血症,使通气量减少一半而造成代偿性高碳酸血症。分别于常碳酸血症期和高碳酸血症期采用含NO(浓度为2ppm)的气体进行机械性肺通气,并进行四个时相的研究:①常碳酸血症期(PaCO_25.1±0.8kPa,潮气量65±132ml)。此期为1小时。②常碳酸血症期+NO(2ppm)吸入,为时30分钟。⑧高碳酸血症期(PaCO_2 8.7±2kPa,潮气量330±93ml),为时60～     

AECOPD合并高碳酸血症患者T淋巴细胞亚群的相关研究

目的观察和分析慢性阻塞性肺疾病急性加重期(AECOPD)合并高碳酸血症患者外周血T淋巴细胞亚群的变化和临床意义。方法根据AECOPD患者的血气分析结果分为高碳酸血症组和非高碳酸血症组,检测两组患者外周血T淋巴细胞亚群的变化,并与健康体检人员对照。结果 AECOPD合并高碳酸血症组和非合并高碳酸血症组的CD_3~+、CD_4~+、CD_4~+/CD_8~+比值均明显低于正常人(P0.01),高碳酸血症组较非高碳酸血症的CD_3~+、CD_4~+、CD_4~+/CD_8~+比值降低更为明显(P0.05)。高碳酸血症得到纠正后上述指标均有不同程度恢复,但和健康对照组对比仍有差异(P0.01)。结论 AECOPD的患者存在原发性免疫功能障碍,其中合并高碳酸血症患者的免疫功能障碍尤为严重,临床上监测外周血T淋巴细胞亚群对评估此类患者的免疫功能、指导临床治疗、判断病情进展、评估预后具有重要意义。     

允许性高碳酸血症的临床应用

允许性高碳酸血症（PHC）在急性肺损伤，严重气流阻塞的困难撤机时得到了临床应用，初步的证据提示PHC策略可明显改善预后和有利于撤机，且临床可采取一些措施减少限制性通气后产生的高碳酸血症。     

营养和代谢疾病

,71728低血钾性周期性麻痹32例临床分析/郭书英…//临床医学一1996,16(9)一8一9 男18女14例,女性并非少见。21~40岁者23例。发病快,进展快,恢复快,65.6%病人只持续1一5天。14例误诊格林一巴利综合征,须注意鉴别。经补钾后症状迅速缓解,但1/2病人反复发作。参3(杨直),71729叙疗后单纯高碳酸血症50例临床分析/洪新…刀临床内科杂志一1996,13(5)一21一22 慢阻肺氧疗后边出现单纯高碳酸血症50例,有34例氧疗后低氧血症改善而持续存在高碳酸血症,PaCO:李6.67kPa,另16例高碳酸血症很快纠正。15例在停止吸氧30分钟后,Pa02显著下降.而PaC02无显著…     

容许性高碳酸血症对急性肺损伤动物心肺影响的观察

观察不同水平的容许性高碳酸血症对油酸型急性肺损伤模型的心肺功能影响。复制猪ＡＬＩ模型，四腔热稀释漂浮导管监测血液动力学不同潮气量致不同程度的ＰＨＣ。     

容许性高碳酸血症通气治疗在危重哮喘中的应用

容许性高碳酸血症通气治疗在危重哮喘中的应用黄建安马家用王光杰陶岳多史美芬机械通气救治危重哮喘在国内逐步增多，方法各异。我们使用小潮气量、低频率、低通气量致容许性高碳酸血症这一通气方式抢救危重哮喘２例，报告如下。例１患者男性，４５岁，体重６５公斤。既往...     

Effects of hypoxia and hypercapnia on aerobic metabolic processes in northern elephant seals.

An hypoxia-induced metabolic down-regulation has been implicated as an important protective mechanism against tissue deoxygenation in mammals. Whether the same response to hypoxia occurs in northern elephant seals was studied. The effects of hypercapnia were also examined to determine whether the reduced ventilatory response of seals to CO2 is associated with an analogous protective metabolic down-regulation. Thirty three seals (7-300-days-old) were studied using open-flow respirometry with simultaneous monitoring of apnea frequencies and heart rates. Hypoxia (11% O2) and hypercapnia (7% CO2) caused increases in metabolism of up to 38% with corresponding decreases in the percent time spent apneic (%AP) and increases in heart rate. The metabolic, breathing and heart rate responses to altered inspired gases were independent of age. Metabolism was strongly negatively correlated with %AP suggesting that elevated metabolism during hypoxia and hypercapnia exposure is attributable to decreases in %AP. In young elephant seals metabolic down-regulation is not an automatic protective response to experimentally-imposed hypoxia or hypercapnia.     

Buffering hypercapnic acidosis worsens acute lung injury

Hypoventilation, associated with hypercapnic acidosis (HCA), may improve outcome in acute lung injury (ALI). We have recently reported that HCA per se protects against ALI. The current study explored whether the mechanisms of protection with HCA were related to acidosis versus hypercapnia. Because CO(2) equilibrates rapidly across cell membranes, we hypothesized that (1) HCA would afford greater protection than metabolic acidosis. We further hypothesized that (2) buffering HCA would attenuate its protection. Forty isolated perfused rabbit lung preparations were randomized to: control (normal pH, PCO(2)); HCA; metabolic acidosis; or buffered hypercapnia. After ischemia-reperfusion (IR) injury wet:dry ratio was greatest with control and buffered hypercapnia, and rank order of capillary filtration coefficient was: control approximately buffered hypercapnia > metabolic acidosis > HCA. Isogravimetric pressure reduction was greatest with buffered hypercapnia. Despite comparable injury, pulmonary artery pressure elevation was less with buffered hypercapnia versus control. In vitro xanthine oxidase (XO) activity depended on pH, not PCO(2). We conclude that: (1) HCA and metabolic acidosis are protective, but HCA is the most protective; (2) buffering HCA attenuates its protection; (3) buffering HCA causes pulmonary vasodilation; (4) because metabolic acidosis and HCA similarly inhibit in vitro XO activity, the differential effects cannot be explained solely on the basis of extracellular XO activity.     

Hipercapnia permisiva o no permisiva: mecanismos de acción y consecuencias de altos niveles de dióxido de carbono

Acute lung injury is a disease with high incidence of mortality and its treatment is still controversial. Increasing the levels of CO₂ beyond the physiological range has been proposed as a potential protective strategy for patients on mechanical ventilation, as it could moderate the inflammatory response. In this article we review the published evidence on the role of CO₂ during acute lung injury. We conclude that although there are reports suggesting benefits from hypercapnia, more recent evidence suggests that hypercapnia could be deleterious, contributing to worsening of the lung injury     

Is permissive hypercapnia a beneficial strategy for pediatric acute lung injury?

It is clear that mechanical ventilation strategies influence the course of lung disease, and the choice of a ventilation strategy that avoids volutrauma and atelectrauma is firmly based on experimental literature and clinical experience. The application of a lung-protective strategy with reduced tidal volumes, effective lung recruitment, adequate PEEP to minimize alveolar collapse during expiration, and permissive hypercapnia has been shown to be advantageous in adult patients who have ARDS, although it has not been systematically studied in children. A significant body of literature confirms the beneficial effects of hypercapnic acidemia in the setting of acute lung injury. As a corollary, experimental evidence indicates that buffering hypercapnic acidosis abrogates its protective effects. The use of permissive hypercapnia as part of a lung-protective strategy in children should be accepted and perhaps even desired, provided it does not result in significant hemodynamic instability. This acceptance should be tempered with the recognition that a low-stretch, reduced-tidal volume strategy without hypercapnia has also been shown to improve outcomes in adults who have ARDS and that HFOV can generally provide lung-protective ventilation without necessarily inducing hypercapnia. Thus, a synthesis of the available clinical and research data strongly supports a graded approach to managing patients who have acute lung injury requiring intubation. The highest priority should be a mechanical ventilation strategy that limits the tidal volume, with the allowance of hypercapnia to a degree that does not compromise hemodynamic status.     

Chronotropic effects of progressive hypoxia and hypercapnia

The effects of acute, progressive isocapnic hypoxia and hyperoxic hypercapnia on heart rate (HR) were determined in 13 normal individuals. In all subjects there was an inverse linear relationship between hemoglobin oxygen saturation and HR. For the group, the HR (mean +/- SE) increased from 72 +/- 2 to 89.5 +/- 3 beats/min representing a 25% increase. During progressive hypercapnia, the HR increased from 72 +/- 2 to 75 +/- 2 beats/min, representing only a 4% increase. In contrast to the HR response to hypoxia, there was a heterogeneous HR response to hypercapnia, with most subjects having a mild increase in HR, but some showing no response and a few exhibiting a decrease in HR. We conclude that although there is a significant tachycardic response to isocapnic hypoxia, the tachycardic response to hyperoxic hypercapnia is small and clinically insignificant. In addition, while there is uniformly a tachycardic response to isocapnic hypoxia, there is a considerable interindividual variability of the HR response to hyperoxic hypercapnia.     

Randomized controlled trial of fluticasone in preschool children with intermittent wheeze

Previous studies have suggested that during non-rapid eye movement (NREM) sleep, neither large short-duration resistive loads nor sustained normoxic hypercapnia alone leads to increased genioglossus muscle activation. However, in normal individuals during stable NREM sleep, genioglossus activity rises above baseline as PCO2 rises and airway resistance increases. We therefore hypothesized that combinations of chemical (PCO2, PO2) and mechanical stimuli during NREM sleep would lead to increased genioglossal activation. We studied 15 normal subjects (9 males, 6 females) during stable NREM sleep, measuring genioglossus electromyogram, epiglottic/choanal pressure, and airflow under six conditions: (1) baseline, (2) inspiratory resistive loading (-5 to -15 cm H2O/ L/second), (3) increased PCO2 (5-10 mm Hg above baseline), (4) combined resistive loading and increased PCO2, (5 ) hypoxia (SaO2 80-85%), and (6 ) combined hypoxia/inspiratory resistive loading. Only the combined condition of hypercapnia and resistive loading led to significantly increased genioglossal activation, 3.91 +/- 0.77% to 9.64 +/- 1.96% of maximum. These data suggest that the genioglossus muscle is less responsive to either chemical stimuli (hypercapnia, hypoxia) or inspiratory resistive loading alone during NREM sleep at the degrees tested. When hypercapnia is combined with resistive loading, the muscle does respond. However, the possibility that higher levels of PCO2 or greater resistive loading alone could activate the muscle cannot be excluded.     

Effects of vasodilatation and acidosis on the blood-brain barrier

Hypercapnia protects the blood-brain barrier against disruption during acute hypertension. Our goal was to determine whether protection of the blood-brain barrier by hypercapnia may be related to an affect of acidosis on the barrier, vasodilatation produced during hypercapnia, or attenuation of increases in cerebral venous pressure by hypercapnia. Pial vessels were examined in rats by means of fluorescent microscopy. We examined disruption of the blood-brain barrier in response to acute hypertension during hypercapnia (vasodilatation with acidosis), during topical adenosine (vasodilatation without acidosis), and during passive increases in cerebral venous pressure produced by venous occlusion during hypercapnia. Acute hypertension in normocapnic rats increased venular pressure and disrupted the blood-brain barrier and often produced bleeding from cerebral venules. Hypercapnia alone increased venular pressure, and acute hypertension produced only a modest further increase in venular pressure, with minimal disruption of the blood-brain barrier. Venous occlusion in hypercapnic rats increased venular pressure and disrupted the blood-brain barrier. We conclude that vasodilatation and acidosis produced by hypercapnia do not protect the blood-brain barrier from disruption during acute hypertension. Protection by hypercapnia during acute hypertension appears to be related to attenuation of increases in cerebral venous pressure.     

Elevated CO2 suppresses specific Drosophila innate immune responses and resistance to bacterial infection

Elevated CO₂ levels (hypercapnia) frequently occur in patients with obstructive pulmonary diseases and are associated with increased mortality. However, the effects of hypercapnia on non-neuronal tissues and the mechanisms that mediate these effects are largely unknown. Here, we develop Drosophila as a genetically tractable model for defining non-neuronal CO₂ responses and response pathways. We show that hypercapnia significantly impairs embryonic morphogenesis, egg laying, and egg hatching even in mutants lacking the Gr63a neuronal CO₂ sensor. Consistent with previous reports that hypercapnic acidosis can suppress mammalian NF-κB-regulated innate immune genes, we find that in adult flies and the phagocytic immune-responsive S2* cell line, hypercapnia suppresses induction of specific antimicrobial peptides that are regulated by Relish, a conserved Rel/NF-κB family member. Correspondingly, modest hypercapnia (7–13%) increases mortality of flies inoculated with E. faecalis, A. tumefaciens, or S. aureus. During E. faecalis and A. tumefaciens infection, increased bacterial loads were observed, indicating that hypercapnia can decrease host resistance. Hypercapnic immune suppression is not mediated by acidosis, the olfactory CO₂ receptor Gr63a, or by nitric oxide signaling. Further, hypercapnia does not induce responses characteristic of hypoxia, oxidative stress, or heat shock. Finally, proteolysis of the Relish IκB-like domain is unaffected by hypercapnia, indicating that immunosuppression acts downstream of, or in parallel to, Relish proteolytic activation. Our results suggest that hypercapnic immune suppression is mediated by a conserved response pathway, and illustrate a mechanism by which hypercapnia could contribute to worse outcomes of patients with advanced lung disease, who frequently suffer from both hypercapnia and respiratory infections.     

Ventrolateral neurons of medullary organotypic cultures: intracellular pH regulation and bioelectric activity.

The hypothesized role of the intracellular pH (pH(i)) as a proximate stimulus for central chemosensitive neurons is reviewed on the basis of data obtained from organotypic cultures of the medulla oblongata (obex level) of new born rats (OMC). Within OMC a subset of neurons responds to hypercapnia as do neurons in the same (or similar) brain areas in vivo. Maneuvers altering intra- and/or extracellular pH (pH(o)) such as hypercapnia, bicarbonate-withdrawal, or ammonium pre-pulses, evoked well defined changes of the neuronal pH(i). During hypercapnia (pH(o) 7.0) or bicarbonate-withdrawal (pH(o) 7.4) most ventrolateral neurons adopted a pH(i) which was < or = 0.2 pH units below the steady state pH(i), while signs of pH(i)-regulation occurred only in a small fraction of neurons. During all treatments leading to intracellular acidosis, bioelectric activity of chemosensitive neurons increased and was often indistinguishable from the response to hypercapnia, regardless of whether pH(o) was unchanged, decreased or increased during the treatment. These data strongly suggest that the pH(i) acts as proximate stimulus. The mode of acid extrusion of chemosensitive neurons is, therefore, of major importance for the control of central chemosensitivity. Immunocytochemical data, pH(i) measurements and neuropharmacological studies with novel drugs pointed to the Na(+)/H(+) exchanger subtype 3 (NHE3) as a main acid extruder in ventrolateral chemosensitive neurons. Possible functions and neuropharmacological strategies arising from this very local NHE3 expression are discussed.     

Reversible respiratory muscle weakness in hypothyroidism

Physiological studies performed 1 week after initiation of thyroid replacement showed persistence of significant respiratory muscle weakness in a patient presenting with hypothyroidism and hypercapnia. Repeat studies 12 months later demonstrated return of respiratory muscle strength to normal. Earlier reports on respiratory failure in hypothyroidism had postulated a critical role for respiratory muscle weakness in the genesis of hypercapnia. Since hypercapnia was rapidly reversed despite the persistence of severe respiratory muscle weakness, this explanation may not be always correct. It appears than in our patient thyroid replacement had its primary effect on the respiratory control system.