Comparative scintigraphy in oleic acid pulmonary microvascular injury

Computerized gamma scintigraphy revealed a significant (p less than 0.001) rising lung:heart radioactivity ratio, which has been called "slope of injury" or "slope index", with both 99mTechnetium-tagged human serum albumin (99mTc-HSA) and 99mTechnetium-tagged red blood cells (99Tc-RBC) after 0.05 or 0.2 ml/kg iv oleic acid administration to dogs. This slope index was significantly greater with 99mTc-HSA than 99mTc-RBC (p less than 0.001). These findings verify that the scintigraphic 99mTc-HSA slope of injury is a result of a pulmonary capillary protein leak and not oleic acid induced changes in pulmonary blood or air volume. The leak of red blood cells noted with scintigraphy was confirmed by light microscopy and examination of the tracheal edema fluid. The leak of albumin, however, was much greater than the leak of red blood cells by microscopy and tracheal fluid examination, confirming the scintigraphic data. This study provides further evidence that computerized gamma scintigraphy will be of value for the diagnosis of permeability pulmonary edema and its response to treatment.     

Abnormal pulmonary vascular tone in canine oleic acid lung injury

OBJECTIVE: To characterize the endothelium-dependent and endothelium-independent components of abnormal pulmonary vascular tone in canine oleic acid lung injury. DESIGN: Prospective, interventional study. SETTING: University laboratory. SUBJECTS: Twenty anesthetized mongrel dogs. INTERVENTIONS: Right heart catheterization was performed to measure pulmonary vascular resistance before and after induction of oleic acid lung injury in ten anesthetized and ventilated dogs. Pulmonary and internal mammary artery rings were sampled in these ten dogs with oleic acid injury and in ten anesthetized healthy control dogs. We also studied the responses to acetylcholine, to phenylephrine, and to hypoxia of the intact or endothelium-denuded rings mounted in organ baths. MEASUREMENTS AND MAIN RESULTS: Oleic acid lung injury was associated with an increase in pulmonary vascular resistance from 118 +/- 11 to 245 +/- 47 dyne.sec.cm-5.m-2 and a decrease in the Pao2/Fio2 ratio from 451 +/- 42 to 139 +/- 26 mm Hg (mean +/- se, p <.05 and p <.01, respectively). Acetylcholine-induced relaxation was decreased in the oleic acid pulmonary artery rings compared with the controls (85 +/- 3% vs. 99 +/- 6% of precontraction level, p <.05). Phenylephrine-induced contraction was decreased in denuded oleic acid pulmonary artery rings compared with the controls (81 +/- 8% vs. 102 +/- 10% of contraction to KCl 120 mM, p <.05). In vitro hypoxia induced a small endothelium-dependent contraction followed by an endothelium-independent relaxation. These responses were not different in oleic acid lung artery rings and in controls, except for a decrease in hypoxic contraction in the oleic acid pulmonary artery rings. In vitro hypoxic pulmonary vasoconstriction and relaxation were, respectively, directly (r =.48) and inversely (r = -.67) correlated with oleic acid-induced increase in pulmonary vascular resistance. There was no correlation between in vitro internal mammary artery reactivity and oleic acid-induced increase in pulmonary vascular resistance. CONCLUSIONS: Oleic acid-induced lung injury slightly impairs pulmonary arterial endothelium-dependent relaxation and endothelium-independent contraction. In vitro hypoxic pulmonary vasoreactivity is related to in vivo oleic acid-induced increase in pulmonary vascular resistance.     

Effect of nifedipine on oxygen delivery in canine asymmetric oleic acid lung injury

Increasing the ratio of tissue oxygen delivery (DO2) to oxygen consumption can improve the survival of critically ill patients, including those with acute respiratory failure. However, under conditions of ventilation/perfusion mismatch, the use of inotropic or vasodilator drugs to augment cardiac output could, in turn, worsen venous admixture. In a canine model of asymmetric oleic acid-induced pulmonary edema, we examined this possibility by studying the effect of 20 and 40-micrograms/kg doses of parenteral nifedipine on oxygenation variables, venous admixture, and intrapulmonary blood flow distribution. After oleic acid injury, nifedipine caused significant increases in cardiac index by 70% as systemic vascular resistance decreased proportionately by 61%. Stroke volume index (SI) and mean pulmonary arterial pressure increased, while venous admixture and the distribution of intrapulmonary blood flow did not change with nifedipine. However, nifedipine significantly improved the tissue DO2 index so that the coefficient of DO2 increased. Thus, nifedipine significantly increased SI in a dose-dependent manner, thereby improving the tissue oxygen supply-demand balance.     

肺表面活性物质在急性油酸性肺损伤时的变化

目的：探讨肺表面活性物质（ＰＳ）系统在急性油酸（ＯＡ）性肺损伤时变化的作用机制。方法：３６只新西兰白兔经麻醉、气管切开插管后给予机械通气。动物随机分成２组（每组１８只）,即油酸致急性肺损伤组（ＯＡ组）和生理盐水对照组（ＮＳ组）。观察１、２和４小时（各时间点动物均为６只）,监测静态胸肺总顺应性（ＴＲＣ）、肺功能残气量（ＦＲＣ）、动脉血氧分压（ＰａＯ２）和血清肺表面活性物质蛋白Ａ（ＳＰ－Ａ）浓度,测定     

不同剂量猪肺表面活性物质对大鼠油酸型急性肺损伤疗效的影响

目的 探讨不同剂量猪肺表面活性物质（PPS）混悬液对油酸致大鼠急性肺损伤（ALI）的治疗作用及量-效关系。方法56只SD大鼠按随机数字表法分为假手术组、油酸模型组和5个不同剂量PPS治疗组。静脉注入油酸诱发大鼠ALI，30min后治疗组和模型组经气管分别滴入50、80、100、150和200mg／kg PPS和等量生理盐水。实验过程中计数大鼠呼吸频率，测定动脉血气。4h后处死，计算大鼠存活率，观察肺组织形态学改变，并检测肺系数、支气管肺泡灌洗液（BALF）中总蛋白含量和血浆肿瘤坏死因子-α（TNF-α）的浓度。结果与模型组比较，PPS50mg／kg组有减慢呼吸频率、短时间内提高动脉血氧分压（PaO2）的作用，但是并不能明显改善肺损伤；PPS80～200mg／kg组除改善呼吸功能外，大鼠肺毛细血管通透性、肺出血、肺水肿、血浆TNF-α浓度以及大鼠死亡率也均明显降低（P均〈0．05）。显示高剂量PPS（150～200mg／kg）在减轻炎症反应和肺损伤方面具有更好的效果。结论单独应用PPS能明显改善早期油酸型ALI大鼠的呼吸功能，≥80mg／kg的PPS有明显减轻肺损伤的作用，而各剂量之间无量-效关系。     

Atrial natriuretic peptide blocks the renal vasoconstrictor response to hypertonic saline in the dog

The role of atrial natriuretic peptide to modulate the renal tubuloglomerular feedback response was examined in the dehydrated anesthetized dog using an infusion of hypertonic sodium chloride to increase renal plasma sodium concentration by 30 mEq/l as the stimulus to activate the tubuloglomerular feedback. Two sequential infusions of hypertonic sodium chloride into the renal artery for 10 min were separated by 90 min, and various interventions were introduced before the second hypertonic saline infusion. In the first group of dogs, the first infusion of hypertonic saline resulted in a significant decrease in renal blood flow from 234 +/- 36 to 199 +/- 31 ml/min, but when atriopeptin III (APIII) was infused into the renal artery at 3 x 10(-10) mol/min, the repeat infusion of hypertonic saline resulted in a significant increase in blood flow from 221 +/- 28 to 269 +/- 35 ml/min that was maintained throughout the 10 min of hypertonic saline. In the second group of dogs only the vehicle for APIII was infused during the second hypertonic saline infusion. In these dogs, renal blood flow decreased significantly the first time from 201 +/- 17 to 170 +/- 16 ml/min, and the second time from 232 +/- 22 to 177 +/- 20 ml/min. In a third group of dogs, the vasodilator sodium nitroprusside, a stimulator of smooth muscle soluble guanylate cyclase, was infused into the renal artery during the second hypertonic saline infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical syndromes with vasoconstrictor response

Vasospasm implies reversible vasoconstriction that may diminish blood flow to the perfused tissues followed by an ischaemia of varying severity. The exact pathophysiology of the condition remains unknown to this day. Vasospasms are not only present in Raynaud's disease, migraine, Prinzmetal's variant angina, visual field defects and partially in low-tension glaucoma, but may also be involved in the pathogenesis of Crohn's disease. Vasospastic diseases may result from more than one mechanism. It is difficult to determine which of the underlying abnormalities is the most important in vasospastic syndromes of different vascular beds.     

不同时间给予猪肺表面活性物质对大鼠油酸型急性肺损伤疗效的影响

目的 探讨不同时间给予猪肺表面活性物质(PPS)混悬液对油酸致大鼠急性肺损伤(ALI)的治疗作用.方法 将48只SD大鼠随机分为假手术组、模型组、0.5 h PPS治疗组和2 h PPS治疗组.假手术组仅行气管和颈动脉插管手术操作,其余各组大鼠静脉注入油酸诱发ALI;0.5 h PPS治疗组和2 h PPS治疗组分别于油酸注入后0.5 h和2 h经气道均滴入100 mg/kg和150 mg/kg两个剂量的PPS,实验过程中计数大鼠呼吸频率,测定动脉血气指标;于实验4 h计算大鼠存活率后处死动物,观察肺组织病理学改变,并检测肺系数及支气管肺泡灌洗液(BALF)中总蛋白(TP)含量和血浆中肿瘤坏死因子-α(TNF-α)浓度.结果 与模型组比较,0.5 h给予PPS 100 mg/kg和150 mg/kg以及2 h给予PPS 150 mg/kg治疗都能显著降低大鼠的呼吸频率,提高动脉血氧分压(PaO2)及大鼠存活率,降低肺毛细血管通透性及肺出血、肺水肿发生率,降低血浆中TNF-α和BALF中TP含量(P均＜0.05).而2 h给予100 mg/kg PPS的治疗作用不明显.结论 早期气道内滴入≥100 mg/kg的PPS,能明显改善油酸型ALI大鼠的呼吸功能、减轻肺损伤;晚期较大剂量的PPS(150 mg/kg)才有治疗作用.     

山莨菪碱雾化吸入对油酸诱导大鼠急性肺损伤的保护作用及其机制

急性肺损伤/急性呼吸窘迫综合征(ALI/ARDS) 是指由心源性以外的各种肺内外致病因素导致的急性、进行性、缺氧性呼吸衰竭.ARDS晚期多诱发或合并多器官功能障碍综合征(MODS),甚至多系统器官功能衰竭(MSOF),是外科危重患者常见的致命并发症之一.     

三七总皂苷对急性肺损伤犬血管外肺水及呼吸力学的影响

目的 探讨三七总皂苷(PNS)对急性肺损伤(ALI)犬血管外肺水(EVLW)与呼吸力学参数的影响.方法 18只犬被随机均分为正常对照组、模型组,PNS治疗组.均给予犬气管插管建立人工气道并实施机械通气支持[潮气量(VT)10 ml/kg,呼气末正压(PEEP)0,吸人氧浓度(FiO2)1.00].静脉注射油酸建立ALI犬模型.成模后PNS组静脉给予PNS 10 mg/kg(溶于葡萄糖注射液中,2.5 ml/min),正常对照组和模型组给予等量葡萄糖注射液.连续监测各组犬的呼吸力学参数及动脉血气.成模后4 h处死动物,采用重力法测定EVLW,计算血管外肺水指数(EVLWI).结果 PNS能显著降低ALI犬的EVLWI[(14.10±1.45)ml/kg比(17.97±0.85)ml/kg,P<0.05],但仍显著高于正常对照组[(8.82±0.54)ml/kg,P<0.01].制模成功后,氧合指数(PaO2/FiO2)及静态肺顺应性(Cst total)显著下降;静脉注射PNS 2 h后PaO2/FiO2和Cst total较模型组显著升高(P<0.05或P<0.01);而气道阻力(Raw)、动脉血二氧化碳分压(PaCO2)则无明显变化,3组间比较差异亦无统计学意义(P均>0.05).结论 PNS对ALI犬具有一定的保护作用,使EVLW降低、肺顺应性增高,有助于改善低氧血症.     

Inhibition of angiotensin-converting enzyme by perindopril diacid in canine oleic acid pulmonary edema

To test the hypothesis that angiotensin II could be a mediator of acute lung injury, we studied the effects of perindopril diacid, a new angiotensin-converting enzyme inhibitor, on hemodynamics, blood gases, lung mechanics, and extravascular lung water (EVLW). Twenty-four dogs were anesthetized, paralyzed and ventilated with a fraction of inspired oxygen of 0.4 in which pulmonary edema was induced by 0.1 ml/kg iv oleic acid. Perindopril diacid (1 mg/kg) was administered iv either before (eight dogs) or 100 min after (eight dogs) oleic acid injection. In the control group (eight dogs) not treated with perindopril diacid, 150 min after oleic acid injection, PaO2 changed from 193 +/- 7 (mean +/- SEM) to 55 +/- 4 torr, venous admixture from 3 +/- 1% to 52 +/- 5%, cardiac index from 4.1 +/- 0.3 to 3.1 +/- 0.3 L/min X m2, mean pulmonary artery pressure from 13 +/- 1 to 17 +/- 1 mm Hg, dynamic compliance from 90 +/- 8 to 46 +/- 7 ml/cm H2O, and EVLW from 165 +/- 25 to 750 +/- 92 ml/m2. Administration of perindopril diacid reduced systemic BP by 20% but did not affect other hemodynamic variables, blood gases, or dynamic compliance. Maximum increases in EVLW were from 169 +/- 16 to 615 +/- 54 ml/m2 in the pretreated group and from 188 +/- 23 to 675 +/- 56 ml/m2 in the treated group (no significant difference from the control group). However, pretreatment with perindopril diacid significantly (p less than .05) slowed the rise in EVLW, which was lower 60 and 90 min after oleic acid injection compared to untreated dogs. Plasma renin activity and angiotensin I concentration increased after oleic acid injection.(ABSTRACT TRUNCATED AT 250 WORDS)     

Breathing patterns in lambs after oleic acid lung injury utilizing respiratory inductive plethysmography

We measured breathing patterns utilizing a respiratory inductive plethysmograph (RIP) in seven healthy nonsedated lambs after an iv infusion of oleic acid (50 mg/kg) to induce acute pulmonary edema. Our single position graphic (SPG) calibration technique was employed for gain factor calculation. Accuracy was validated by the simultaneous volume measurement of RIP and integrated pneumotachography (PNT). Of a total 840 validation breaths, 467 (56%) were within 5% of PNT, 734 (87%) were within 10%, and 834 (99.9%) were within 20%. In each study baseline physiologic and breathing pattern data were collected and also at 15, 30, 60, 90, 150, and 210 min postoleic acid infusion. Validation of RIP accuracy before each data collection revealed 29% required new gain factor calculation. Recalibration was done within 5 min. Excluding respiratory frequency, which remained at 30% above baseline, variables were not significantly different than baseline measurements at the 210-min interval. Results suggest that calibration of RIP using our SPG technique is a time-efficient method and that RIP can accurately measure breathing patterns, providing an additional tool for assessment of experimental lung injury in lambs.     

高压氧对油酸诱导大鼠急性肺损伤作用的实验研究

目的 探讨高压氧(HBO)对油酸(OA)诱导大鼠急性肺损伤(ALI)的干预作用.方法 80只SD大鼠按随机数字表法分为4组.OA组30只,经鼠尾静脉注射OA 0.15 ml/kg制备ALI模型,分别于制模后4 h、3 d、7 d各随机活杀10只;OA+HBO组20只,在HBO治疗箱给予2.5 atm(1 atm=101.325 kPa)下单次治疗90 min,分别于HBO治疗后3 d、7 d各随机活杀10只;单纯HBO干预组20只,分别于HBO治疗后3 d、7 d各随机活杀10只;另设正常对照组10只.取腹主动脉血进行血气分析,测定血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、IL-6;取左肺标本,观察大体形态改变及镜下病理学改变;取右肺,测定湿/干重(W/D)比值.结果 OA组4 h后动脉血氧分压(PaO2,mm Hg,1 mm Hg=0.133 kPa)由107.70±5.37降至57.40±2.63;肉眼可见肺脏明显淤血、水肿;光镜下肺泡正常结构消失,间质水肿增宽,大量炎性细胞浸润,毛细血管明显扩张、透明膜形成;W/D比值较正常对照组明显增加(6.94±0.44比4.59±0.44,P<0.05),血清TNF-α、IL-1β、IL-6水平升高[TNF-α(μg/L):18.52±1.20比5.27±0.61,IL-1β(μg/L):13.73±1.37比6.13±1.51,IL-6(μg/L):14.51±1.21比11.14±0.89].经HBO治疗3 d、7 d时PaO2(mm Hg,3 d:79.20±1.68比59.00±2.70,7 d:94.30±3.77比74.00±3.85)、肺W/D比值(3 d:7.43±0.73比9.82±0.99,7 d:6.75±1.14比8.77±1.60)均较OA组同期有不同程度改善(P<0.05或P<0.01).治疗3 d后HBO有降低血清中IL-1β(μg/L)的作用(6.46±1.99比9.09±1.09,P<0.05).结论 HBO治疗有改善ALI大鼠氧合,促进肺水吸收、抑制部分炎症介质产生的作用.     

Effects of mannitol on the acute lung injury induced by oleic acid in rats.

Our purpose was to evaluate the pulmonary effects of mannitol infusion in a rat model of acute lung injury induced by oleic acid (OA) to compare the effects of mannitol to those of another diuretic, furosemide (FUR), and to assess if mannitol effects remained after correction of the volume depletion induced by this agent. Acute lung injury was induced in Wistar rats by intravenous administration of 100 mg/kg of OA. Mannitol (1 mL of a 20% solution) was infused either 15 min before or 2 h after OA infusion. FUR was infused intravenously in a dose (1 mg/kg) that induced a similar amount of diuresis compared to mannitol. We also studied rats that received NaCl 0.9% infusion to correct for volume losses induced by mannitol. The severity of the acute lung injury was evaluated by morphometric studies of the lungs 4 h after OA infusion. The amount of intraalveolar fluid accumulation and the intensity of alveolar distention and collapse were evaluated. Mannitol infusion either 15 min before or 2 h after OA administration resulted in a significant decrease in the amount of intraalveolar edema and alveolar distention and collapse (P < 0.001). FUR administration before OA infusion had an effect similar to mannitol. We did not observe any significant effect of mannitol when the rats received saline infusion to correct for diuresis induced by mannitol. We conclude that mannitol decreases the severity of pulmonary injury induced by OA in rats. This effect is mainly due to its diuretic properties.     

油酸型肺损伤大鼠肺病理与磷脂组分的研究

目的：探讨肺损伤时磷脂（ＰＬ）及其组分变化规律与肺病理改变的关系。方法：应用大鼠油酸型肺损伤模型观察肺的病理变化，并与支气管肺泡灌洗液中ＰＬ及其组分进行对照比较。结果：根据肺损伤后病理学的改变，将其病程分为急性期、急性后期、恢复期及恢复后期。整个实验过程中ＰＬ总量趋于增加；急性期和急性后期磷脂酰甘油（ＰＧ）含量减少，ＰＧ与磷脂酰肌醇（ＰＩ）的比值（ＰＧ／ＰＩ）下降。结论：ＰＧ及ＰＧ／ＰＩ的减少可能是肺急性损伤的后果，ＰＬ组分的变化可作为肺损伤病理改变的一种标志。     

饱和氢气生理盐水对油酸致急性肺损伤大鼠肺的保护作用

目的 探讨饱和氢气生理盐水是否对油酸所致大鼠急性肺损伤具有保护作用.方法 将健康成年SD大鼠30只,随机分为对照组、油酸+生理盐水组和油酸+饱和氢气生理盐水组,每组10只.对照组(假手术组):予股动脉置管留取血气标本,待血流动力学稳定后经尾静脉注入生理盐水0.1 mL/kg;油酸+生理盐水组:注入高纯度油酸0.1 mL/kg,余同对照组;油酸+饱和氢气生理盐水组:注入高纯度油酸5 min后给予腹腔注射饱和氢气生理盐水5 mL/kg,余同油酸+生理盐水组;同时予前两组腹腔注射等量生理盐水,3 h后再次留取动脉血标本并处死大鼠.检测血气分析,肺组织髓过氧化物酶(MPO)活性、丙二醛(MDA)及肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和NF-κB p65水平;观察肺组织病理变化.结果 与注射油酸前比较,生理盐水治疗组和饱和氢气生理盐水治疗组在注射油酸3 h后PaO2显著降低(P<0.05),且显著低于对照组(P<0.05).此外,饱和氢气生理盐水治疗组PaO2显著高于生理盐水治疗组(P<0.05).与对照组比较,生理盐水治疗组和饱和生理氢气盐水治疗组肺组织MPO活性及MDA水平显著增加(P<0.01,P<0.05),且饱和氢气生理盐水治疗组显著低于生理盐水治疗组(P<0.05).生理盐水治疗组和饱和氢气生理盐水治疗组肺组织TNF-α、IL-1β和NF-κB p65水平显著高于对照组(P<0.05),且饱和氢气生理盐水治疗组显著低于生理盐水治疗组(P<0.05).结论 饱和氢气生理盐水能够降低大鼠油酸肺损伤模型中肺的损伤程度,其机制可能与氢分子在体内的选择性抗氧化作用有关.     

高氧液治疗油酸型肺损伤家兔的实验研究

目的:研究高氧液(hyperoxiasolution,HO)对油酸型急性肺损伤(acutelunginjury,ALI)家兔的治疗作用。方法:以林格氏液为基液制备HO。将18只家兔随机分为油酸组(A组),高氧液组(B组)和正常对照组(C组),每组6只。A、B各组均按文献方法经耳缘静脉注入油酸0.06mL/kg建立ALI模型,C组动物注入等量生理盐水。B组于注射油酸30min时经右侧颈外静脉给予HO20ml/Kg,A、C组给予等量林格氏液。各组分别在ALI模型制备前(0min)、注射油酸后30,60,120min时间点经右颈外动脉进行血气分析,并测定肺水含量,肺体比值及病检。结果:与C组相比A组PaO2、PaCO2显著降低(P<0.01),肺水含量及肺体比值显著增高(P<0.01),镜下见肺灶性出血,间质、肺泡水肿,大量炎细胞浸润。B组经HO治疗后迅速提升PaO2、PaCO2(P<0.05),减轻肺水肿(P<0.01),大部分肺组织无明显病理学改变。结论:HO对油酸型ALI家兔有治疗作用。