急性肺损伤的药物治疗进展

急性肺损伤（ALI）是指机体遭受严重感染、创伤、辐射、休克等打击后,出现的以弥漫性肺泡毛细血管膜损伤导致的肺水肿和微肺不张为病理特征的一种肺部炎症和肺通透性增加综合征,是ARDS的早期阶段,病理生理改变以肺顺应性降低,肺内分流增加及通气／血流比例失调为主。临床表现为顽固性低氧血症、呼吸频数和呼吸窘迫。     

补体活化血浆导致山羊肺动脉高压发生机制的研究

补体活化的血浆在导致动物急性肺损伤的同时,常伴有肺血流动力学严重紊乱的征象。后者可严重影响肺血管内外液体与蛋白质的交换,加速肺损伤的发展,促进肺水肿的发生。本实验用山羊慢性肺淋巴瘘模型研究了补体活化血浆导致山羊肺动脉高压的机制,为急性肺损伤的防治提供理论基础。     

流感病毒导致肺水肿的相关机制

流感是一种非常严重的呼吸系统疾病,肺水肿是流感病毒造成的急性肺损伤的特征之一。有关流感导致肺水肿的机制并不完全清楚。本文将流感病毒感染后体内信号转导系统的转导过程和肺部离子转运通道的功能变化联系起来;主要从肺上皮钠离子通道、囊性纤维化跨膜电导调节因子、钾离子通道、钠钾泵这四种转运通道的功能变化介绍病毒造成肺水肿的机制,着力从分子水平阐述流感病毒对肺水肿的影响,此综述结果将对预防和治疗肺水肿提供新的作用靶点。     

有创-无创序贯机械通气对急性心源性肺水肿患者低氧血症和血流动力学的影响

目的:探讨有创-无创序贯机械通气对急性心源性肺水肿患者低氧血症及血流动力学的影响。方法:按照随机数字表法将2013年3月至2015年3月我院收治的49例急性心源性肺水肿患者分为两组,对照组行常规抗心衰治疗联合有创机械通气,观察组接受对照组治疗方案后,再给予无创鼻面罩双水平气道正压通气。比较两组患者治疗前后的动脉血气分析指标及血流动力学指标,以及有创机械通气时间、机械通气总时间、呼吸机相关肺炎(VAP)发生率、再发心衰率及死亡例数。结果:两组患者治疗过程中未出现死亡病例,治疗后,两组患者动脉血气分析指标、血流动力学指标较治疗前不同程度的改善,差异有统计学意义(P0.05),两组患者治疗后的动脉血气分析指标、血流动力学指标比较,差异无统计学意义(P0.05)。观察组患者有创通气时间、通气总时间少于对照组,VAP发生率低于对照组,差异有统计学意义(P0.05),两组患者再发心衰率差异无统计学意义(P0.05)。结论:有创-无创序贯机械通气能有效改善急性心源性肺水肿患者的低氧血症和血流动力学指标,安全有效,作为抢救急性心源性肺水肿的措施具有重要临床价值。     

急性神经源性肺水肿型手足口病患儿1例救治报告

本文报道急性神经源性肺水肿型手足口病1例。该患儿发热伴特征性手、足、臀部皮疹和口腔疱疹,继发呼吸困难、严重高血压、肺水肿、颅内高压,伴外周循环衰竭等症状。经过气管插管,正压机械通气,大剂量丙种球蛋白封闭,大剂量肾上腺皮质激素冲击,甘露醇、甘油果糖控制肺水肿和颅内高压,磷酸肌酸营养心肌,利巴韦林抗病毒等治疗,转危为安。     

抗氧化治疗与急性肺损伤

急性肺损伤（acute lung injury,ALI）是指心源性以外的各种肺内外致病因素导致的急性、进行性呼吸衰竭,其主要的病理特征是肺微血管通透性增高而导致的肺泡渗出液中富含蛋白质的肺水肿及透明膜形成,可伴有肺间质纤维化。病理生理改变以肺顺应性降低、     

肠道病毒71型致神经源性肺水肿发病机制研究进展

肠道病毒71型(EV71)是人类肠道病毒的一种,近30年来,EV71感染在亚太地区广泛流行,是手足口病重症病例的主要病原体之一.EV71感染最严重的并发症为中枢神经系统和呼吸系统受累,其中神经源性肺水肿病程进展迅速、治疗困难、病死率高,近年来受到人们的广泛关注,但其发病机制目前尚不十分清楚.本研究对EV71感染导致的神经源性肺水肿的发病机制从脑干脑炎、全身炎症反应及免疫等方面的研究进展作一综述.     

急性肺损伤的生物标记物

急性呼吸窘迫综合征(ARDS)和急性肺损伤(ALI)多由低氧性呼吸衰竭引起,导致高通透性肺水肿,临床上有较高的发病率与死亡率。近十年来,针对血浆和支气管肺泡灌洗液中相关生物标记物的研究为探索急性肺损伤的病理生理机制指明了新的方向。个别生物标记物已在一些大型、多中心ARDS试验中得到证实。但迄今仍没有一个或一组生物标记物常规应用于临床。随着人类对ALI发病机制理解的进一步深入,或许不久的将来,生物标记物会真正应用于评估疾病的严重程度和预后。本文将概述近年来ALI相关生物标记物的研究进展。     

猪心脏移植中供体急性脑死亡模型的初步研究

目的建立猪心脏移植供体的急性脑死亡模型,观察急性脑死亡前及后1、5、10 min时的血流动力学和血浆中儿茶酚胺释放的变化并进行初步探讨。方法采用30~40 kg的猪8只,急性脑死亡前为对照组,急性脑死亡后为实验组。测定脑死亡前基础水平及脑死亡后1、5、10 min时血流动力学改变和血浆中儿茶酚胺释放的变化,并对二者的变化进行初步探讨。结果急性脑死亡后1 min时血流动力学及儿茶酚胺水平改变最明显,心率增加了88%,收缩压升高了132%,心排量增加了80%,肾上腺素(E)和去甲肾上腺素(NE)分别升高240%和241%,多巴胺(DA)没有明显增加。随后二者均持续下降,至10 min时已降至基础水平以下。血流动力学改变的程度及时间分布与儿茶酚胺中的肾上腺素和去甲肾上腺素一致。结论急性脑死亡可造成机体血流动力学及血浆儿茶酚胺水平的剧烈改变,血中儿茶酚胺含量升高是造成急性脑死亡后血流动力学改变的原因,其中E和NE与血流动力学改变直接相关。     

急性心肌梗死的急诊诊疗体会

急性心肌梗死（AMI）是指在冠状动脉粥样硬化伴有粥样斑块出血、血栓形成或冠状动脉痉挛导致管腔急性闭塞和血流中断,使血栓血管供应的心肌出现严重而持久的急性缺血,从而导致心肌细胞坏死。是急诊科常见的急危重症,须紧急救治。现将2001-2006年本院急诊科院前急救后送人心内科治疗的AMI43例,结合有关文献资料报告如下。     

Influence of lung volume and left atrial pressure on reverse pulmonary venous blood flow

Infarction of the lung is uncommon even when both the pulmonary and the bronchial blood supplies are interrupted. We studied the possibility that a tidal reverse pulmonary venous flow is driven by the alternating distension and compression of alveolar and extra-alveolar vessels with the lung volume changes of breathing and also that a pulsatile reverse flow is caused by left atrial pressure transients. We infused SF6, a relatively insoluble inert gas, into the left atrium of anesthetized goats in which we had interrupted the left pulmonary artery and the bronchial circulation. SF6 was measured in the left lung exhalate as a reflection of the reverse pulmonary venous flow. No SF6 was exhaled when the pulmonary veins were occluded. SF6 was exhaled in increasing amounts as left atrial pressure, tidal volume, and ventilatory rates rose during mechanical ventilation. SF6 was not excreted when we increased left atrial pressure transients by causing mitral insufficiency in the absence of lung volume changes (continuous flow ventilation). Markers injected into the left atrial blood reached the alveolar capillaries. We conclude that reverse pulmonary venous flow is driven by tidal ventilation but not by left atrial pressure transients. It reaches the alveoli and could nourish the alveolar tissues when there is no inflow of arterial blood.     

A severe vicious cycle in uncontrolled subarachnoid hemorrhage: the effects on cerebral blood flow and hemodynamic responses upon intracranial hypertension

In subarachnoid hemorrhage (SAH), Cushing postulated that the increase in systemic arterial pressure (SAP) in response to elevation of intracranial pressure (ICP) was beneficial to cerebral perfusion. However, in uncontrolled SAH, the increased SAP may cause more bleeding into the subarachnoid space and further increase the ICP. We created an animal model to simulate SAH by connecting a femoral arterial catheter to the subarachnoid space. The global cerebral blood flow (CBF) was measured with a venous outflow method. The purposes were to observe the CBF change under the simulated SAH, and to evaluate the effects of an adrenergic blocker and a vasodilator. In addition, spectral analysis of the aortic pressure and flow was employed for the analysis of hemodynamic changes at various ICP levels. When the femoral arterial blood was allowed to flow into the subarachnoid space, the ICP was elevated. The Cushing response to increased ICP caused an increase in SAP. A vicious cycle was generated between ICP and SAP. The CBF under the vicious cycle was greatly depressed. The dog developed pulmonary edema (PE) within 5 mins. An alpha-adrenergic blocker (phentolamine) and a vasodilator (nitroprusside) were beneficial to the reduction of SAP and ICP, improvement of CBF, and prevention of PE. Hemodynamic analysis revealed that graded increases in ICP caused increases in SAP, total peripheral resistance, arterial impedance, and pulse reflection with decreases in stroke volume, cardiac output and arterial compliance. The hemodynamic changes may contribute to acute left ventricular failure that leads to pressure and volume loading in the lung circulation, and finally acute PE.     

Oleic acid lung injury in sheep

Intravenous infusion of oleic acid into experimental animals causes acute lung injury resulting in pulmonary edema. We investigated the mechanism of oleic acid lung injury in sheep. In experiments with anesthetized and unanesthetized sheep with lung lymph fistulas, we measured pulmonary arterial and left atrial pressures, cardiac output, lung lymph flow, and lymph and plasma protein concentrations. We injured the lungs with intravenous infusions of oleic acid at doses ranging from 0.015 to 0.120 ml/kg. We found that oleic acid caused reproducible dose-related increases in pulmonary arterial pressure and pulmonary vascular resistance, arterial hypoxemia, and increased protein-rich lung lymph flow and extravascular lung water. The lung fluid balance changes were characteristic of increased permeability pulmonary edema. Infusion of the esterified fat triolein had no hemodynamic or lung fluid balance effects. Depletion of leukocytes with a nitrogen mustard or platelets with an antiplatelet serum had no effect on oleic acid lung injury. Treatment of sheep before injury with methylprednisolone 30 mg/kg or ibuprofen 12.5-15.0 mg/kg also had no effects. Unlike other well-characterized sheep lung injuries, injury caused by oleic acid does not require participation of leukocytes.     

Effects of lung inflation on pulmonary arterial blood volume in intact dogs.

The isolated effects of alterations of lung inflation and transmural pulmonary arterial pressure (pressure difference between intravascular and pleural pressure) on pulmonary arterial blood volume (Vpa) were investigated in anesthetized intact dogs. Using transvenous phrenic nerve stimulation, changes in transmural pulmonary arterial pressure (Ptm) at a fixed transpulmonary pressure (Ptp) were produced by the Mueller maneuver, and increases in Ptp at relatively constant Ptm by a quasi-Valsalva maneuver. Also, both Ptm and Ptp were allowed to change during open airway lung inflation. Vpa was determined during these three maneuvers by multiplying pulmonary blood flow by pulmonary arterial mean transit time obtained by an ether plethysmographic method. During open airway lung inflation, mean (plus or minus SD) Ptp increased by 7.2 (plus or minus 3.7) cmH2O and Ptm by 4.3 (plus or minus 3.4) cmH2O for a mean increase in Vpa by 26.2 (plus or minus 10.7) ml. A pulmonary arterial compliance term (Delta Vpa/Delta Ptm) calculated from the Mueller maneuver was 3.9 ml/cmH2O and an interdependence term (Delta Vpa/Delta Ptp) calculated from the quasi-Valsalva maneuver was 2.5 ml/cmH2O for a 19% increase in lung volume, and 1.2 ml/cmH2O for an increase in lung volume from 19% to 35%. These findings indicate that in normal anesthetized dogs near FRC for a given change in Ptp and Ptm the latter results in a greater increase of Vpa.     

Pulmonary vascular resistance in the fluorocarbon-filled lung

Pulmonary vascular resistance was investigated in the fluorocarbon-filled lung in an in situ isolated lung preparation. Lungs were perfused at constant flow (100 ml X min-1 X kg-1) with whole blood from a donor cat. left atrial pressure was held constant at zero pressure. Measurements of pulmonary arterial pressure enabled calculation of pulmonary vascular resistance. Regional changes in pulmonary blood flow were determined by the microsphere technique. During quasi-static deflation over a range of 0-30 mmHg, dependent alveolar pressure was consistently greater for a volume of fluorocarbon than for gas, with each pressure-volume curve for the fluorocarbon-filled lung shifted to the right of the curve for the gas-filled lung. In turn, pulmonary vascular resistance was found to increase linearly as a function of increasing alveolar pressure, independent of the medium in the lung. Thus, for a given volume, pulmonary vascular resistance was consistently greater in the fluorocarbon-filled lung compared with the gas-filled lung. This increase in pulmonary vascular resistance was accompanied by a redistribution of pulmonary blood flow in which blood flow to the dependent region was decreased in the fluorocarbon-filled lung compared with the gas-filled lung. Conversely, the less-dependent regions of the lung received a relatively greater percentage of blood flow when filled with fluorocarbon compared with gas. These findings suggest that pulmonary vascular resistance is increased during liquid ventilation, largely as the result of mechanical interaction at the alveolar-vascular interface.     

Fasudil inhibits the myogenic response in the fetal pulmonary circulation

In addition to high pulmonary vascular resistance (PVR) and low pulmonary blood flow, the fetal pulmonary circulation is characterized by mechanisms that oppose vasodilation. Past work suggests that high myogenic tone contributes to high PVR and may contribute to autoregulation of blood flow in the fetal lung. Rho-kinase (ROCK) can mediate the myogenic response in the adult systemic circulation, but whether high ROCK activity contributes to the myogenic response and modulates time-dependent vasodilation in the developing lung circulation are unknown. We studied the effects of fasudil, a ROCK inhibitor, on the hemodynamic response during acute compression of the ductus arteriosus (DA) in chronically prepared, late-gestation fetal sheep. Acute DA compression simultaneously induces two opposing responses: 1) blood flow-induced vasodilation through increased shear stress that is mediated by NO release and 2) stretch-induced vasoconstriction (i.e., the myogenic response). The myogenic response was assessed during acute DA compression after treatment with N(omega)-nitro-L-arginine, an inhibitor of nitric oxide synthase, to block flow-induced vasodilation and unmask the myogenic response. Intrapulmonary fasudil infusion (100 microg over 10 min) did not enhance flow-induced vasodilation during brief DA compression but reduced the myogenic response by 90% (P<0.05). During prolonged DA compression, fasudil prevented the time-dependent decline in left pulmonary artery blood flow at 2 h (183+/-29 vs. 110+/-11 ml/min with and without fasudil, respectively; P<0.001). We conclude that high ROCK activity opposes pulmonary vasodilation in utero and that the myogenic response maintains high PVR in the normal fetal lung through ROCK activation.     

Novel method for measuring effects of gas compression on expiratory flow

During forced vital capacity maneuvers in subjects with expiratory flow limitation, lung volume decreases during expiration both by air flowing out of the lung (i.e., exhaled volume) and by compression of gas within the thorax. As a result, a flow-volume loop generated by using exhaled volume is not representative of the actual flow-volume relationship. We present a novel method to take into account the effects of gas compression on flow and volume in the first second of a forced expiratory maneuver (FEV(1)). In addition to oral and esophageal pressures, we measured flow and volume simultaneously using a volume-displacement plethysmograph and a pneumotachograph in normal subjects and patients with expiratory flow limitation. Expiratory flow vs. plethysmograph volume signals was used to generate a flow-volume loop. Specialized software was developed to estimate FEV(1) corrected for gas compression (NFEV(1)). We measured reproducibility of NFEV(1) in repeated maneuvers within the same session and over a 6-mo interval in patients with chronic obstructive pulmonary disease. Our results demonstrate that NFEV(1) significantly correlated with FEV(1), peak expiratory flow, lung expiratory resistance, and total lung capacity. During intrasession, maneuvers with the highest and lowest FEV(1) showed significant statistical difference in mean FEV(1) (P < 0.005), whereas NFEV(1) from the same maneuvers were not significantly different from each other (P > 0.05). Furthermore, variability of NFEV(1) measurements over 6 mo was <5%. We concluded that our method reliably measures the effect of gas compression on expiratory flow.     

Physiological factors in fetal lung growth

Adequate pulmonary function at birth depends upon a mature surfactant system and lungs of normal size. Surfactant is controlled primarily by hormonal factors, especially from the hypophysis, adrenal, and thyroid; but these have little influence on fetal lung growth. In contrast, current data indicate that lung growth is determined by the following physical factors that permit the lungs to express their inherent growth potential. (a) Adequate intrathoracic space: lesions that decrease intrathoracic space impede lung growth, apparently by physical compression. (b) Adequate amount of amniotic fluid: oligohydramnios retards lung growth, possibly by lung compression or by affecting fetal breathing movements or the volume of fluid within the potential airways and airspaces. (c) Fetal breathing movements of normal incidence and amplitude: fetal breathing movements stimulate lung growth, possibly by stretching the pulmonary tissue, and do not affect mean pulmonary blood flow but do induce small changes in phasic flow; these changes are probably too slight to influence lung growth. (d) Normal balance of volumes and pressures within the potential airways and airspaces: in the fetus, tracheal pressure greater than amniotic pressure greater than pleural pressure. This differential produces a distending pressure which may promote lung growth. Disturbing the normal pressure relationships alters the volume of fluid in the lungs and distorts lung growth, which is stimulated by distending the lungs and is impeded by decreasing lung fluid volume. The mechanisms by which these factors affect lung growth remain to be defined. Fetal lung growth also depends on at least a small amount of blood flow through the pulmonary arteries.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary circulation in embolic pulmonary edema

The ultrasonic method was used in acute experiments on cats with open chest under artificial lung ventilation to obtain blood flow in low-lobar pulmonary artery and vein, the blood pressure in pulmonary artery, as well as the left atrial pressure in fat (olive oil) and mechanical (Lycopodium spores) pulmonary embolism. It is shown that pulmonary embolism produces the decrease in the blood flow in pulmonary artery and vein, the increase of the pressure in pulmonary artery and left atria, the increase of lung vessels resistance. The decrease is observed of systemic arterial pressure, bradycardia, and extrasystole. After 5-10 min the restoration of arterial pressure and heart rhythm occur and partial restoration of blood flow in pulmonary artery and vein. In many experiments the blood flow in vein outdoes that in the artery--it allows to suppose the increase of the blood flow in bronchial artery. After 60-90 min there occur sudden decrease of systemic arterial pressure, the decrease of the blood flow in pulmonary artery and vein. The pressure in pulmonary artery and resistance of pulmonary vessels remain high. Pulmonary edema developed in all animals. The death occurs in 60-100 min after the beginning of embolism.