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.     

Recent research on extracorporeal carbon dioxide removal北大核心CSCD

体外二氧化碳去除技术是基于肺外气体交换的人工肺辅助技术,可有效清除二氧化碳,并提供有限的氧合,是近年来继机械通气、体外膜肺氧合等技术之后发展起来的治疗高碳酸血症的有效技术之一,具有广泛的应用前景。该文具体阐述体外二氧化碳去除技术的发展、工作原理及优势、分类、并发症及临床应用等,旨在为临床上进行体外二氧化碳去除提供一种新选择。     

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