不同压力呼气末正压对单肺通气时肺内分流及氧合的影响

目的观察单肺通气(OLV)期间通气侧肺实施不同大小的呼气末正压通气(PEEP)对肺内分流及氧合的影响。方法45例ASAⅠ～Ⅱ级择期在全麻下行肺叶切除手术病人,随机分为3组,每组15例。A组为不采用PEEP的OLV对照组;B组为OLV PEEP(5cmH2O)组;C组为OLV PEEP(8cmH2O)组。各组病例于OLV前、OLV后30min、OVL结束、恢复双肺通气后30min进行动脉血气分析,根据公式计算肺内分流率(QS/QT)。结果OVL30min及OVL结束时,B、C两组的PaO2较A组高,QS/QT较A组低(P<0.05);B、C两组各时点参数比较差异无统计学意义(P>0.05)。结论OVL期间通气侧肺实施5cmH2O及8cmH2O的PEEP可明显提高PaO2,减少肺内分流;5cmH2O的PEEP有利于手术操作,临床实用价值更高。     

Postnatal Outcomes In Term And Preterm Lambs Following Fetal Growth Restriction

1. Epidemiological evidence indicates that low birthweight increases the risk of a number of adult-onset diseases. It is now apparent that many babies with a low birthweight may have been subjected to a combination of reduced growth rates in utero as well as preterm birth. However, the long-term effects of preterm birth following intra-uterine growth restriction (IUGR) are unknown. Thus, our objectives were: (i) to identify prenatal factors associated with preterm birth in IUGR fetuses; and (ii) to characterize postnatal effects of preterm birth following IUGR. 2. We studied pregnant sheep and their offspring, in which fetal growth was restricted by umbilico-placental embolization during late gestation. Some of these animals were born at term (146 +/- 1 days) and some were born prematurely (139 +/- 1 days). In both groups, we have conducted longitudinal studies of postnatal respiratory function, cardiovascular function and learning ability up to 6-8 weeks of age. 3. Before birth, IUGR fetuses born prematurely (P-IUGR) were more hypoxaemic and acidaemic and had higher haemoglobin concentrations than both control fetuses and IUGR fetuses born at term (T-IUGR). In P-IUGR fetuses, plasma cortisol concentrations increased earlier than in the two other groups. The P-IUGR lambs had lower birthweights than T-IUGR lambs and both groups of IUGR lambs remained lighter than controls for 8 weeks. 4. After birth, P-IUGR lambs were hypoxaemic compared with T-IUGR and control lambs. Pulmonary diffusing capacity (adjusted for lung volume) was significantly lower in both groups of IUGR lambs than in controls, with P-IUGR lambs having lower values than T-IUGR lambs. Lung compliance (adjusted for lung volume), was not different between P-IUGR and control lambs, but values were higher in T-IUGR lambs than in control and P-IUGR lambs. Chest wall compliance (adjusted for lung volume) was higher in both groups of IUGR lambs than in controls. 5. During the 8 week postnatal study period, both groups of IUGR lambs had lower mean arterial pressures than control lambs; this relative hypotension was greatest in P-IUGR lambs. 6. In tests of learning ability, P-IUGR lambs took longer to complete a simple maze task at all ages and, in the second postnatal week, made a greater number of errors compared with controls. In an obstacle course, P-IUGR lambs recorded longer trial durations; they also made more errors than control lambs. 7. We conclude that preterm birth in the presence of late- gestational placental insufficiency and IUGR can result in specific effects on respiratory and cardiovascular development after birth, in addition to the effects of IUGR alone.     

DOES MODERATE PRETERM BIRTH LEAD TO ALTERED ARTERIAL PRESSURE? STUDIES IN SHEEP

1. Low birth weight (LBW) is associated with an increased risk of cardiovascular disease. Preterm birth is a major determinant of LBW and has been shown to result in elevated arterial pressure (AP) in humans, but few studies have investigated the effects of preterm birth in the absence of potentially confounding factors. Our aim was to determine whether moderately preterm birth per se alters the postnatal development of AP in lambs. 2. Preterm lambs were delivered approximately 14 days before term (i.e. approximately 133 days of gestation); controls were born at term (approximately 147 days). Mean arterial pressure (MAP), heart rate (HR), blood composition and indices of growth were measured at 4 and 8 weeks post term-equivalent age (PTEA). We also studied a separate cohort of preterm and term sheep as young adults (approximately 1.1 years). 3. Preterm lambs had significantly lower birth weights than term lambs, but bodyweights were not significantly different by Day 12 PTEA. In addition, MAP, HR and most blood variables did not differ between term and preterm lambs at 4 or 8 weeks PTEA. Preterm birth per se did not alter MAP or HR in young adult sheep. 4. Low birth weight due to preterm birth does not result in an altered AP during early postnatal life or at maturity. Moderate intrauterine growth restriction (IUGR) due to twinning, which further reduces birth weight, does not affect MAP in preterm lambs. Other factors, such as the degree of prematurity or IUGR, exposure to corticosteroids or postnatal nutrition, may be important in the later development of elevated AP.     

Dose-response comparisons of five lung surfactant factor (LSF) preparations in an animal model of adult respiratory distress syndrome (ARDS).

1. We have examined the effects of five different lung surfactant factor (LSF) preparations in the rat lung lavage model. In this model repetitive lung lavage leads to lung injury with some similarities to adult respiratory distress syndrome with poor gas exchange and protein leakage into the alveolar spaces. These pathological sequelae can be reversed by LSF instillation soon after lavage. 2. The tested LSF preparations were: two bovine: Survanta and Alveofact: two synthetic: Exosurf and a protein-free phospholipid based LSF (PL-LSF) and one Recombinant LSF at doses of 25, 50 and 100 mg kg-1 body weight and an untreated control group. 3. Tracheotomized rats (10-12 per dose) were pressure-controlled ventilated (Siemens Servo Ventilator 900C) with 100% oxygen at a respiratory rate of 30 breaths min-1, inspiration expiration ratio of 1:2, peak inspiratory pressure (PIP) of 28 cmH2O at positive end-expiratory pressure (PEEP) of 8 cmH2O. Two hours after LSF administration, PEEP and in parallel PIP was reduced from 8 to 6 (1st reduction), from 6 to 3 (2nd reduction) and from 3 to 0 cmH2O (3rd reduction). 4. Partial arterial oxygen pressure (PaO2, mmHg) at 5 min and 120 min after LSF administration and during the 2nd PEEP reduction (PaO2(PEEP23/3)) were used for statistical comparison. All LSF preparations caused a dose-dependent increase for the PaO2(120'), whereas during the 2nd PEEP reduction only bovine and recombinant LSF exhibited dose-dependency. Exosurf did not increase PaO2 after administration of the highest dose. At the highest dose Exosurf exerted no further improvement but rather a tendency to relapse.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of low-dose milrinone on weaning from cardiopulmonary bypass and after in patients with mitral stenosis and pulmonary hypertension

The phosphodiesterase inhibitor milrinone is usually preferred in patients with pulmonary hypertension and myocardial dysfunction after cardiopulmonary bypass. We investigated the effects of low-dose milrinone on pulmonary hypertension in the immediate pre- and postoperative period. Forty-seven patients were randomized to the control and milrinone groups. All patients had mean pulmonary artery pressure greater than 30 mmHg and pulmonary capillary wedge pressure greater than 20 mmHg and were candidates for mitral valve replacement for rheumatic mitral stenosis. Twenty-four patients received a loading dose of milrinone 25 microg/kg(-1) during weaning from cardiopulmonary bypass, followed by a maintenance dose of 0.25 microg/kg(-1)/min(-1) to the end of the surgery. Cardiac output and other hemodynamic variables were noted at induction, weaning from bypass, and postoperative 1 h. Pulmonary artery pressure, capillary wedge pressure, and central venous pressure were significantly lower in the milrinone group during weaning after cardiopulmonary bypass, while other variables were roughly similar. However, patients in the control group required higher doses of vasodilators, inotropes, and antiarrhythmic agents. Mean arterial pressure in the milrinone group was significantly lower at 1 h postoperatively than in the control group; however, the patients did not need many more vasopressors. Fluid restriction and diuretic agent use were more significant in the control group. Systemic arterial hypotension and vasopressor requirements with milrinone use at inotropic doses were not observed at the doses used for the study. A total of 21.7% of the patients in the control group required vasopressors in the perioperative period. Both groups demonstrated similar hematologic variables except that the hemoglobin level in the control group was significantly lower during postoperative days 1 and 7. Low-dose milrinone for a short-term during weaning from cardiopulmonary bypass may be used in patients with mitral stenosis and pulmonary hypertension for its effects on pulmonary artery pressures, less inotropic and vasopressor requirements, and fluid balance.     

术中不同时期呼气末正压通气对全身麻醉老年患者血气指标和肺顺应性的影响

目的 探讨术中低潮气量复合不同时期呼气末正压通气(PEEP)的保护性肺通气策略对开腹手术全身麻醉老年患者动脉血气分析指标和肺顺应性的影响. 方法 选择接受开放性腹部手术的老年全身麻醉患者60例,随机分为常规通气组、中期PEEP组和后期PEEP组.常规通气组未复合PEEP,中期PEEP组在手术开始后1 h 复合PEEP,后期PEEP组在拔管前1h复合PEEP,各组PEEP设定为10cmH2O,持续1h.3组均采用间歇性正压通气(IPPV)模式,潮气量为6mL/kg,吸呼比为1∶1.5~2,调节呼吸频率,维持呼气末二氧化碳分压(PETCO2) 在35~45mmHg(1mmHg=0.133kPa).分别于术前、术后1h、术后24h抽取动脉血行血气分析,并记录气管插管后30min、术中90min和拔管前30min的潮气量、PEEP值、气道峰压(Ppeak),计算肺顺应性(CL). 结果 与术前比较,术后1h各组PaCO2明显升高(P<0.05),常规通气组和后期PEEP组氧合指数(OI)明显降低(P<0.05),常规通气组和中期PEEP组肺泡-动脉氧分压差(A-aDO2)明显升高(P<0.05);与术后1h比较,术后24h中期PEEP组PaCO2明显降低(P<0.05),常规通气组OI明显升高(P<0.05),常规通气组和中期PEEP组A-aDO2明显下降(P<0.05),其余差异无统计学意义(P>0.05). 结论 低潮气量复合术中1h PEEP或拔除气管导管前1h复合PEEP均能改善术后血气指标,前者可以改善术后1h和术后24h的氧合功能.     

面罩与鼻导管在极早产儿稳定期辅助通气中的应用效果比较

目的 比较面罩和鼻导管在极早产儿稳定期辅助通气中的应用效果.方法 接受辅助通气治疗的极早产儿80例,采用序贯入组的方法分为鼻导管组与面罩组,各40例.鼻导管组患儿出生后使用单侧鼻导管进行辅助通气,面罩组患儿出生后使用面罩进行辅助通气,采用呼吸监测仪对患儿的辅助通气压力峰值(PIP)、呼气末正压(PEEP)通气、潮气量、辅助通气呼吸次数、漏气量、大量漏气次数、气道阻塞次数进行测量,并记录出生后第1、5 分钟Apgar 评分、气管插管患儿数、住院期间死亡患儿数,出生第5 分钟心率和氧饱和度.结果 鼻导管组与面罩组患儿呼吸指标比较,PIP,PEEP,平均辅助通气呼吸次数,出生后第1、5 分钟Apgar评分,气管插管患儿数,住院期间患儿死亡率,出生后第1、5 分钟的心率与氧饱和度差异均无统计学意义(P>0.05);鼻导管组患儿平均大量漏气次数为425.11±20.92显著高于面罩组的321.67±17.26,平均漏气量百分比(30.58±9.26)%显著高于面罩组的(14.15±6.76)%,平均气道阻塞次数112.53±13.91显著高于面罩组的46.62±13.04,鼻导管组患儿的平均实际呼气潮气量为(4.62±2.40)mL·kg-1显著低于面罩组的(7.31±2.76)mL·kg-1,均差异有统计学意义(P<0.05).结论 采用面罩进行辅助通气比鼻导管能获得更好的辅助通气指标.其使用方法简单,易于掌握,值得在临床上推广.     

Effect of beta-adrenergic receptor antagonism on chloralose-induced hemodynamic changes in newborn lambs.

alpha-Chloralose is an anesthetic commonly used in cardiovascular research. Using a chronically instrumented neonatal lamb model, we previously determined that chloralose has important effects on basal hemodynamics and arterial oxygen tension as compared with those of paired conscious control lambs. We wished to determine whether beta-adrenergic receptor stimulation accounted for chloralose-induced hemodynamic effects and to investigate the influence of chloralose and beta-adrenergic receptor antagonism on oxygen metabolism. In paired studies, five lambs were given chloralose intravenously (30 mg/kg i.v.) after propranolol (1 mg/kg i.v.) or saline control. The group pretreated with propranolol had reduced heart rate (HR 206 +/- 12 vs. 244 +/- 10 beats/min, p = 0.04) and cardiac output (CO 253 +/- 29 vs. 302 +/- 40 ml/min/kg, p = 0.005) 30 min after chloralose as compared with control; pretreatment with propranolol also attenuated the systemic hypertensive response to chloralose (77 +/- 8 vs. 89 +/- 5 mm Hg, p = 0.055). No difference in the response of stroke volume (SV), atrial or pulmonary arterial pressures, or pulmonary and systemic vascular resistances (PVR, SVR) were observed between treatment groups. No differences between propranolol and saline treatment groups were observed in arterial and mixed venous oxygen contents, arteriovenous (A-V) oxygen difference, oxygen extraction, or oxygen consumption; a reduction in oxygen delivery observed after propranolol as compared with saline was not altered by chloralose. We conclude that tachycardia and increase in CO induced by chloralose in lambs probably are mediated by beta-adrenergic receptor stimulation, which may be direct or indirect.(ABSTRACT TRUNCATED AT 250 WORDS)     

Resuscitation with Na+/H+ exchanger inhibitor in traumatic haemorrhagic shock: Cardiopulmonary performance,oxygen transport and tissue inflammation

1. The aim of the present study was to examine the effects of inhibition of the Na⁺/H⁺ exchanger (NHE‐1) on cardiopulmonary performance, oxygen carrying capacity and tissue inflammation in a pig model of traumatic haemorrhage–resuscitation. 2. In 12 instrumented anaesthetized pigs, traumatic haemorrhage was modelled by producing tibia fractures, followed by haemorrhage of 25 mL/kg for 20 min, and then a 4 mm hepatic arterial tear with surgical repair after 20 min. Animals then underwent low‐volume fluid resuscitation with either Hextend (vehicle; n = 6; Hospira, Lake Forest, IL, USA) or 3 mg/kg BIIB513 (an NHE‐1 inhibitor) + Hextend (n = 6). The experiment was terminated 6 h after the beginning of resuscitation. 3. Compared with vehicle‐treated controls, the addition of NHE‐1 inhibition with BIIB513 significantly improved the left ventricle stroke work index and attenuated increases in pulmonary arterial pressure and pulmonary vascular resistance. Furthermore, BIIB513 treatment significantly increased the oxygenated haemoglobin ratio, blood oxygen content and mixed venous blood oxygen saturation and improved blood oxygen delivery. In addition, BIIB513 treatment reduced lung tissue levels of interleukin‐6 by 80%, tumour necrosis factor‐α by 37% and myeloperoxidase activity by 38%. Nuclear factor‐κB DNA binding activity in the lung was also slightly and significantly attenuated following BIIB513 treatment. 4. In conclusion, the present study shows that NHE‐1 inhibition facilitates the response to fluid resuscitation after traumatic haemorrhage by improving cardiac function, pulmonary vascular function and oxygen carrying capacity, which results in reduced tissue inflammatory injury.     

呼气末正压对不同肺部病变重症患者腹内压的影响

目的 探讨呼气末正压(PEEP)对不同肺部病变重症患者腹内压(IAP)的影响.方法 选择2012年1月至2016年12月本院重症医学科进行机械通气的重症患者72例,按照肺部病变分为慢性阻塞性肺疾病(COPD)组、急性呼吸窘迫综合征(ARDS)组及无胸肺部疾患组各24例,观察患者在平卧位时PEEP分别为0、3、6、9、12和15 cmH2O(1 cmH2O=0.098 kPa)条件下的IAP、肺顺应性(CL)、总顺应性(CT)及胸廓顺应性(CTH)的变化,并分析IAP与PEEP、CL、CT、CTH的关系.结果 PEEP对不同肺部病变重症患者IAP的影响:ARDS组＜无胸肺部疾患组＜COPD组(P＜0.05);各组患者肺顺应性:ARDS组＜无胸肺部疾患组＜ COPD组(P＜0.05).相关分析显示,IAP与PEEP存在明显的线性相关(r=0.92,P＜0.01),IAP与CL、CT、CTH存在明显的线性相关(r=0.83、0.64、-0.56,P均＜0.05).结论 不同肺部病变状态下PEEP对IAP的影响不同,其中COPD患者影响较大,而ARDS患者影响较小;影响的大小与肺顺应性大小一致.     

伊洛前列素雾化吸入治疗全腔肺动脉连接术后肺动脉高压效果观察

目的评估吸入性伊洛前列素治疗全腔肺动脉连接术（total cavopulmonary connection,TCPC）后肺动脉高压（pulmongary arterial hypertension,PAH）临床疗效。方法选择2011年1月—2013年12月行TCPC术后合并PAH患儿12例,在停体外循环（cardiopulmonary bypass,CPB）后超声雾化吸入伊洛前列素,观察吸入前、吸入结束、吸入结束后30 min血流动力学、呼吸及血气分析参数。结果肺动脉收缩压、肺动脉压/体动脉压及中心静脉压吸入结束、吸入结束后30 min均低于吸入前,氧和指数高于吸入前（P〈0.05）。结论 TCPC术后吸入伊洛前列素可选择性舒张肺血管,降低肺循环阻力,改善肺部血流动力学。     

Acute inhalation of ozone induces DNA methylation of apelin in lungs of Long-Evans rats

Apelin has cardiopulmonary protective properties that promote vasodilation and maintenance of the endothelial barrier. While reductions in apelin have been identified as a contributor to various lung diseases, including pulmonary edema, its role in the effect of air pollutants has not been examined. Thus, in the current study, we sought to investigate if apelin is a downstream target of inhaled ozone and if such change in expression is related to altered DNA methylation in the lung. Male, Long-Evans rats were exposed to filtered air or 1.0?ppm ozone for 4?h. Ventilation changes were assessed using whole-body plethysmography immediately following exposure, and markers of pulmonary edema and inflammation were assessed in the bronchoaveolar lavage (BAL) fluid. The enzymatic regulators of DNA methylation were measured in the lung, along with methylation and hydroxymethylation of the apelin promoter. Data showed that ozone exposure was associated with increased enhanced pause and protein leakage in the BAL fluid. Ozone exposure reduced DNA cytosine-5-methyltransferase (DNMT) activity and Dnmt3a/b gene expression. Exposure-induced upregulation of proliferating cell nuclear antigen, indicative of DNA damage, repair, and maintenance methylation. Increased methylation and reduced hydroxymethylation were measured on the apelin promoter. These epigenetic modifications accompanied ozone-induced reduction of apelin expression and development of pulmonary edema. In conclusion, epigenetic regulation, specifically increased methylation of the apelin promoter downstream of DNA damage, may lead to reductions in protective signaling of the apelinergic system, contributing to the pulmonary edema observed following the exposure to oxidant air pollution.     

The dopamine congener, ibopamine, in congestive heart failure

The hemodynamic effects of the dopamine congener, ibopamine, were investigated in nine patients with chronic congestive heart failure. A placebo-controlled design was utilized. Placebo and ibopamine in doses of 100, 200, and 300 mg were given orally as a single dose to each patient on 4 successive days. Dopamine at 1, 2, 4, and 6 micrograms/kg/min intravenously, was used as an internal standard. Ibopamine did not significantly change heart rate, systemic and pulmonary arterial pressures, pulmonary capillary wedge pressure, or mean right atrial pressure. Significant decreases of systemic arterial resistance (19%) and total pulmonary arterial resistance (21%), and significant increases of cardiac index (20%) and stroke volume index (16%) were elicited by ibopamine at doses of 200 and 300 mg. Peak effects occurred at 1 to 2 h with a duration of action of less than 4 h. The 2 changes were comparable with those obtained by dopamine 2-4 micrograms/kg/min. Except for mild changes at 30 min postdosing, the inotropic indices of the systolic time intervals were not altered significantly by ibopamine. Ibopamine elicits significant hemodynamic effects in patients with chronic congestive heart failure; in large part, these effects appear to be mediated through vasodilatory properties rather than direct positive inotropy.     

双侧肺同期手术中保护性单肺通气策略定容和定压通气的比较

目的探讨双侧肺同期手术单肺通气（OLV）期间采用定容（VCV）和定压（PCV）不同通气模式对呼吸力学及动脉血气的影响,并评价其临床效果。方法9例双侧肺同期手术患者,双肺通气（TLV）期间均采用VCV模式（TLV—VCV）,OLV后通气侧肺先采用传统方法大潮气量（10ml／kg）通气（OLV—VCV1）,30min后改为单肺保护通气：小潮气量（6～8ml／kg）＋PEEP的通气模式（OLV—VCV2）;或PCV＋PEEP的通气模式（OLV—PCV）。用旁气流通气监测法（SSS）监测呼吸力学参数：气道峰压（Ppeak）、气道平台压（Pplat）、气道阻力（Raw）、动态胸肺顺应性（Cdyn）、分钟通气量（MV）等。同时抽动脉血做血气分析。结果单肺保护通气时,Ppeak、Pplat、Raw较低,Cdyn相对较好（P均〈0．05）。PaO2及PaCO2显著升高（P〈0．05）,但PaCO2的升高在临床允许范围内。结论双侧肺同期手术在实行单肺保护通气策略时,OLV—PCV和OLV—VCV2通气模式均可改善肺泡氧舍,预防和减轻单肺通气造成的低氧血症,还可以有效地降低气道压力、气道阻力,但PCV模式控制气道压更有效,更有利于减少气道损伤。     

The effect of epinephrine following practolol on the pulmonary circulation of dogs

Epinephrine (1 and 2 μg/kg/min) was infused in 10 urethane-anesthetized dogs following administration of practolol. Practolo. was administered to block the cardiac β-adrenoceptors and thereby permit a better assessment of the direct action of epinephrine on the pulmonary circulation.Following practolol, both infusion rates of epinephrine were associated with an increase in cardiac output, stroke volume, mean pulmonary arterial and venous pressures and no change in heart rate and pulmonary blood volume. It is concluded that epinephrine, in the doses used, produces a mild increase in ‘tone’ of the pulmonary arterial and venouse system.     

Hydroxyethyl starch 130/0.4 prevents the early pulmonary inflammatory response and oxidative stress after hemorrhagic shock and resuscitation in rats

BackgroundThis study was designed to determine the effects of various resuscitation fluids on pulmonary capillary leakage and pulmonary edema after HS and fluid resuscitation (HS/R) and to determine whether an antiinflammatory or antioxidative mechanism was involved.MethodsWe induced HS by bleeding male Sprague–Dawley rats to a blood pressure of 30 to 40 mm Hg for 60 min. 60 min later, the rats were killed (HS group) or immediately resuscitated with L-isomer lactated Ringer's solution (HS + LR group), shed blood (HS + BL group), or hydroxyethyl starch (HS + HES group) to maintain the blood pressure to the original value during the 60-min resuscitation period. 3 h after resuscitation, pulmonary capillary leakage and wet/dry weight ratio, levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, malondialdehyde (MDA), oxidized and reduced glutathione (GSH and GSSG), myeloperoxidase (MPO) activity, nuclear factor (NF)-κB, activator protein (AP)-1 activation, and lung microscopic and ultrastructural histological changes were measured.ResultsHES and BL treatment significantly improved pulmonary capillary leakage, wet/dry weight ratio and lung injuries after HS/R. In addition, both HES and BL could attenuate the increase in TNF-α, IL-6, MPO levels and NF-κB activation. However, HES but not BL could attenuate the increase in MDA level and GSSH/GSH ratio and AP-1 activation.ConclusionsHES might attenuate pulmonary injuries by modulating pulmonary inflammatory response and oxidative stress, whereas BL attenuates pulmonary injuries by modulating pulmonary inflammatory response but not oxidative stress.     

Reconciling paradigms of abnormal pulmonary blood flow and quasi-malignant cellular alterations in pulmonary arterial hypertension

In pulmonary arterial hypertension (PAH) structural and functional abnormalities of the small lung vessels interact and lead to a progressive increase in pulmonary vascular resistance and right heart failure. A current pathobiological concept characterizes PAH as a ‘quasi-malignant’ disease focusing on cancer-like alterations in endothelial cells (EC) and the importance of their acquired apoptosis-resistant, hyper-proliferative phenotype in the process of vascular remodeling. While changes in pulmonary blood flow (PBF) have been long-since recognized and linked to the development of PAH, little is known about a possible relationship between an altered PBF and the quasi-malignant cell phenotype in the pulmonary vascular wall. This review summarizes recognized and hypothetical effects of an abnormal PBF on the pulmonary vascular bed and links these to quasi-malignant changes found in the pulmonary endothelium. Here we describe that abnormal PBF does not only trigger a pulmonary vascular cell growth program, but may also maintain the cancer-like phenotype of the endothelium. Consequently, normalization of PBF and EC response to abnormal PBF may represent a treatment strategy in patients with established PAH.     

In-vivo blood-brain barrier transport of a novel adrenocorticotropic hormone analogue, ebiratide, demonstrated by brain microdialysis and capillary depletion methods.

The transport of ebiratide, a novel adrenocorticotropic hormone (ACTH) analogue, [H-Met-(O2)-Glu-His-Phe-D-Lys-Phe-NH(CH2)8-NH2], through the blood-brain barrier was directly demonstrated in-vivo. [125I]Ebiratide (16.9 MBq mL-1) or [14C]sucrose (29.2 MBq mL-1) known to be restrictively transported through the blood-brain barrier was infused into the rat internal carotid artery at a flow rate of 50 microL min-1 for 10 min, and after 15 min infusion the distribution volume of each compound in the brain parenchyma was determined by the capillary depletion method. The distribution volume of [125I]ebiratide was 167.8 +/- 62.2 microL (g brain)-1, which was about seven times higher than that of [14C]sucrose (24.9 +/- 4.0 microL g brain)-1, indicating the uptake of ebiratide into brain parenchymal cells. During the infusion into the internal carotid artery, brain microdialysis was simultaneously performed to directly collect the brain interstitial fluid as the dialysate. Radioactivity was detected in the dialysate during the [125I]ebiratide infusion and HPLC analysis of the dialysate revealed that the intact ebiratide accounted for greater than or equal to 80% total radioactivity. The concentrations of [125I]ebiratide and [14C]sucrose in the brain interstitial fluid were estimated based on the relative recovery obtained in the in-vitro recovery study. The brain interstitial fluid/internal carotid arterial blood concentration ratio for [125I]ebiratide was determined to be 1.47 x 10(-2) +/- 0.17 x 10(-2) and was about eight times higher than that for [14C]sucrose (1.92 x 10(-3) +/- 0.36 x 10(-3)), indicating significant transport of ebiratide to the brain interstitial fluid.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vasodilator properties of prostacyclin after coronary artery bypass surgery

The vasodilatory properties of prostacyclin were studied in 12 intubated patients who underwent coronary artery bypass surgery. When infused in doses of 2.5, 5, 10, and 20 ng/kg/min, prostacyclin produced a dose-dependent decrease in systemic vascular resistance from 2,702 +/- 143 to 1,654 +/- 106 dynes/cm5/m2 (p less than 0.05). Heart rate, right atrial pressure, and pulmonary arterial and capillary wedge pressures did not change. Cardiac function was improved, since stroke volume index increased from 29.5 +/- 1.4 to 35.5 +/- 2.0 ml/min/m2 (p less than 0.05) and the rate pressure product decreased from 13.3 +/- 1.3 to 10.9 +/- 0.9 X 10(3) mm Hg/beats/min (p less than 0.05), while stroke work index remained unchanged. These hemodynamic changes were associated with a dose-dependent decrease in arterial oxygen tension which occurred from 278 +/- 25 to 133 +/- 22 mm Hg; however, oxygen transport increased as a result of the prostacyclin-induced increase in cardiac index. This study demonstrates that prostacyclin is a potent arterial vasodilator that may be of interest in the treatment of postoperative vasoconstriction occurring after coronary artery bypass surgery.     

Onset of cardiovascular action after oral ibopamine. Early hemodynamic effects of single and repeated doses in patients with idiopathic dilated myocardiopathy

The acute effects of ibopamine (active ingredient of Inopamil), an orally active dopaminergic agent, were invasively evaluated in 16 consecutive patients with idiopathic dilated cardiomyopathy (New York Heart Association Functional Class II and III) Single doses of 100 and 200 mg were administered to 7 and 9 patients, respectively, and two repeated doses of 100 mg were studied in 6 patients. In order to assess the onset of cardiovascular effect, control hemodynamic measurements were repeated 5, 10, 15, 20, 30, 60, 120, and 180 min after ibopamine 200 mg. Both the tested doses of ibopamine increased the mean pulmonary arterial pressure and the mean pulmonary wedge pressure, with a maximal effect 15 min after drug ingestion (+ 47.0 and + 65.4% in the 200 mg group, p less than 0.002). Pulmonary pressures returned to baseline or lower values beyond 60 min. Systemic arterial pressure showed a small transient increase (+ 7.9% in the 200 mg group at 15 min), but fell significantly below baseline after 120 min, a larger decrease occurring in the 100 mg group (p less than 0.05). Ibopamine had a slower but more prolonged effect on cardiac output (increase of up to 32.1% at 60 min) and systemic vascular resistances. Repeated doses (100 mg after an 8-h interval) elicited comparable cardiovascular effects. Oral ibopamine caused a significant increase in mean pulmonary arterial and capillary pressures as early as 5 min after drug ingestion, before cardiac output and peripheral vascular resistances were affected. A biphasic hemodynamic response was also observed after single and repeated low (100 mg) doses of ibopamine.