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.     

葛根素对慢性低氧高二氧化碳大鼠肺动脉高压形成的预防作用

目的探讨葛根素对慢性低氧（O2）高二氧化碳（CO2）大鼠肺高压形成的预防作用。方法图像分析、氯胺T法、免疫组化、组织原位杂交技术等方法观察葛根素对慢性低O2高CO2大鼠肺组织羟脯氨酸含量、肺小血管显微结构、肺动脉管壁MMP-2、MMP-9、TIMP-2及其基因的影响。结果①光镜下葛根素组内弹力板扭曲、中膜平滑肌细胞增生及管腔狭窄程度均明显轻于低O2高CO2组。②血浆NO含量低O2高CO2组低于正常对照组（P〈0．01），葛根素组高于低O2高CO2组（P〈0．01）。③氯胺T法发现肺组织羟脯氨酸含量低O2高CO2组高于正常对照组（P〈0．01），葛根素组低于低O2高CO2组（P〈0．01）。④肺组织匀浆MMP-2、MMP-9H和TIMP-2含量低O2高CO2组高于正常对照组（P〈0．01）。葛根素组肺组织匀浆MMP-2、MMP-9和TIMP-2含量皆低于低O2高CO2组（P〈0．01）。⑤免疫组化、原位杂交法发现肺细小动脉MMP-2、MMP-9、TIMP-2和MMP-2mRNA、MMP-9mRNA、TIMP-2mRNA平均吸光度值（A）低O2高CO2组均高于正常对照组（P〈0．01），葛根素组均低于低O2高c0I组（P〈0．01）。结论葛根素预防慢性低氧高二氧化碳大鼠肺血管重建，降低肺动脉高压与其调节MMPs／TIMPs体系表达、抑制肺动脉管壁胶原的沉积有关。     

Cat carotid body chemosensory discharge (in vitro) is insensitive to charybdotoxin

Charybdotoxin (ChTX), a venom protein, suppresses Ca²⁺-activated K⁺ (K_Ca⁺) currents in the glomus cell of neonatal rat carotid body. If it works similarly for cat carotid body chemoreceptors, charybdotoxin is expected to stimulate the chemosensory discharge during normoxia, and particularly hypoxia and hypercapnia. We studied the effects of charybdotoxin (20–40 nM) in vitro (perfused/superfused) on the cat carotid chemosensory discharge, and simultaneously tissue PO₂ (PtiO₂), as a measure of positive control. ChTX (20 nM) only increased PtiO₂ and decreased carotid chemosensory discharge during hypoxia, indicating vasodilation. We conclude that K_Ca⁺ channels do not appear to play a significant role in chemotransduction in the cat carotid body.     

Effects of experimental hypercapnia on hippocampal long-term potentiation in anesthetized rats

The effects of hypercapnia, which has been reported to impair consciousness, on the long-term potentiation of the population spike in the CA1 pyramidal cell of the hippocampus in anesthetized rats were studied. Experimental hypercapnemia was induced by inspired 13% CO₂ with 21% O₂. Arterial blood gas analysis after 80 min inspired 13% CO₂ showed pH 7.08±0.05, PCO₂=104.09±12.86 mmHg, PO₂=90.71±18.89 mmHg, BE −4.64±2.97 (mean±SD, n=18). Inspired 13% CO₂ reduced the amplitude of the population spike to 50% of the baseline. After delivery of tetanic stimulation (400 Hz, five bursts of eight pulses, inter-burst interval 1 s) population spike height was enhanced to pre-tetanic levels. Withdrawal of inspired CO₂ unmasked an increase in population spike amplitude. These findings suggest that acute retention of carbon dioxide, which is designated as pure hypercapnemia without hypoxemia, may suppress hippocampal synaptic transmission but not its plasticity.     

肺动脉高压大鼠模型的复制

采用直接吸入常压低氧和低氧伴高二氧化碳混合气体的方法制备肺动脉高压大鼠模型。观察实验大鼠的平均肺动脉压，平均右尽室压，右心室重量及心脏和肺脏的病理学改变，并作血气分析。结果表明，实验大鼠可在较短时间内出现典型的肺动脉高压和右心室肥厚。     

The pathophysiology of the blood-brain barrier dysfunction induced by severe hypercapnia and by epileptic brain activity

Summary The cerebrovascular permeability to protein was studied in hypercapnic rats and in rats with epileptic seizures induced by bicuculline and homocysteine. Despite the differences of the basic pathophysiological mechanisms involved in these models, the blood-brain barrier (BBB) dysfunction was clearly related to the combined effects of high blood pressure and cerebral vasodilatation, thus indicating mechanical factors to be predominantly involved. The BBB changes were most frequent in central and basal regions in contrast to those induced by acute hypertension, which are most common in cortical areas.     

急性呼吸衰竭的预后与高碳酸血症、血小板聚集现象的关系

通过对１０８例小儿急性呼吸衰竭血气分析和血液分析资料的观察，发现ＰａＣＯ２越高、血小板聚集现象越明显，且红细胞压积也升高（贫血者例外），小儿预后越差；反之，预后较好。提示：有高碳酸血症，血液“浓度”、“聚”现象时，除了及早机械通气，排除ＣＯ２外，还需要扩容，保证有效循环血量，同时边补边脱，也可用降低血液粘稠度、改善脑循环药物治疗（但慎用血管扩张药物），这才能有效地降低小儿呼吸衰竭死亡率，增加脑复苏率     

Effect of sinus denervation and vagotomy on c-fos expression in the nucleus tractus solitarius after exposure to C02

Exposure to hypercapnia and electrical stimulation of the carotid sinus nerve (CSN) has been shown to induce c-fos expression in several brain stem regions including the nucleus tractus solitarius (NTS). To test whether the labeled neurons were activated directly by hypercapnia or secondarily via the carotid bodies (sinus nerve), adult rats were exposed to either air or 14–16% CO₂ for 1 h. Experiments were done on eight groups: (1) exposure to air, (2) exposure to CO₂, (3) chronic CSN denervation/CO₂, (4) chronic unilateral CSN denervation/CO₂, (5) chronic sham CSN denervation/CO₂, (6) anesthetized/CO₂, (7) anesthetized and acute vagotomy/CO₂, and (8) premedicated with morphine, 10 mg s.c., 20 min before exposure to CO₂. After exposure to CO₂ or air the rats were anesthetized, perfused with 4% paraformaldehyde and the brains processed for immunohistochemical staining for c-fos protein using the PAP (i.e. peroxidase anti-peroxidase) technique. Labeled neurons in the area of the NTS in every second 50-μm section were counted and their position plotted using a microscope and camera lucida attachment. Rats exposed to CO₂ had a significantly greater number of labeled neurons in the NTS than those exposed to air. Other interventions, such as CSN denervation, surgery, anesthesia, vagotomy or injection of morphine did not significantly affect the level of c-fos expression in rats exposed to hypercapnia, indicative of central stimulation rather than secondary peripheral input. These responsive neurons may be part of a widespread central chemoreceptive complex. Received: 27 March 1995/Received after revision and accepted: 21 November 1995     

Vascular responses to hypercapnia in anesthetized dogs

To evaluate the vascular responses to systemic acute mild hypercapnia (Pa_{CO 2} = 65mmHg), we determined the vascular compliance with the relation between the change in circulating blood volume and the change in central venous pressure during and after fluid infusion in dogs anesthetized with halothane in normocapnia and hypercapnia. Circulating blood volume was measured continuously by ⁵¹Cr-labeled erythrocyte dilution method together with hemodynamic variables. Small reduction in vascular compliance (8.1 ± 1.0ml·mmHg^–1·kg^–1 in normocapnia, 5.8 ± 0.5ml·mmHg^–1·kg^–1 in hypercapnia), large reduction in delayed compliance, which were quantitated by computer simulation using Maxwells viscoelastic model, and significant increase in blood volume in central circulation were observed in hypercapnia. The essential change in hypercapnia was concluded as the vasoconstriction in capacitance vessels. Simultaneously, the reduction of total peripheral resistance (1.09 ± 0.08mmHg·min·kg·ml^–1 in normocapnia, 0.98 ± 0.07mmHg·min·kg·ml^–1 in hypercapnia) with no change in transvascular filtration coefficient (0.14 ± 0.02ml·mmHg^–1·min^–1·kg^–1) suggests the increase in shunt flow in peripheral circulation.(Shigemi K: Vascular responses to hypercapnia in anesthetized dogs. J Anesth 2: 1–7, 1988)     

Hypoxic and hypercapnic responses of [Ca]0 and [K]0 in the cat carotid body in vitro

Measurements of extracellular Ca2+ and K+ activities [( Ca2+]o, [K+]o) in the superfused cat carotid body in vitro with triple-barrelled ion-selective electrodes have shown that hypoxia induced a decrease in [Ca2+]o of 0.035 +/- 0.17 mM (mean +/- S.D.; n = 17) and a biphasic change in [K+]o which consisted of an increase of 2.3 +/- 1.8 mM followed by an undershoot of -0.52 +/- 0.34 mM (mean +/- S.D.; n = 17). Hypercapnia induced a monophasic upward deflection increase of both [Ca2+]o and [K+]o of about 0.037 +/- 0.013 mM and 0.33 +/- 0.15 mM, respectively (n = 17). During hypoxia, lowering [Ca2+] in the medium to 0.1 mM resulted in a reversed [Ca2+]o response, attenuated [K+]o increase and absence of chemosensory nerve discharges. TTX generally did not affect the hypoxic and hypercapnic induced ionic changes, although the [K+]o undershoot was reduced by 30%. Co2+ competitively blocked the changes in [Ca2+]o and the increase in the sensory nerve discharge elicited by hypoxia and, not competitively, the changes of [K+]o. The ionic changes to hypercapnia were less affected by Co2+. Ouabain inhibited the [K+]o undershoot induced by hypoxia, as did the removal of Na+ from medium. It is concluded that changes in extracellular free Ca2+ and K+ ions concentration induced by hypoxia and hypercapnia represent ionic fluxes related to the transduction process of carotid body cells (glomus and/or sustentacular).