Portopulmonary hypertension

Portopulmonary hypertension (PPHT) is a respiratory complication of portal hypertension, defined as an increase in mean pulmonary artery pressure (PAP) of > 25 mmHg with an increase in pulmonary vascular resistance of > 240 dyn.s/cm(-5) and a normal pulmonary capillary wedge pressure ( < 15 mmHg), which often occurs in subjects with liver cirrhosis. Histopathological features of PPHT are endothelial and smooth-muscle cell proliferation and fibrosis leading to luminal obstruction in the resistance arteries. The pathogenesis of PPHT may result from an imbalance between vasoconstrictor and vasodilating factors. The most common pulmonary symptom is exertional dyspnea; fatigue, chest pain and syncope occur more often at an advanced stage. Edema, ascites and prominent jugular veins are signs of both decompensated hepatic cirrhosis and right ventricular failure. Right heart catheterisation is the gold standard for the diagnosis and defines PPHT in mild disease with PAP less than 35 mmHg, moderate disease with PAP between 35 and 45 mmHg, and severe disease with PAP of 45 mmHg or higher. The medical treatment of portopulmonary hypertension is based on the treatment of other forms of pulmonary arterial hypertension, including vasomodulating pharmacologic agents. Liver transplantation is accompanied by high risk of mortality, generally due to acute right ventricular failure and cardiovascular collapse. The prognosis of PPHT is poor with mean survival of 15 months.     

超声心动图在窒患儿和早产儿肺动脉高压治疗中的价值

目的 探讨超声心动图在窒息儿和早产儿肺动脉高压治疗中的诊断价值.方法 选取超声心动图首诊为肺动脉高压的窒息儿和早产儿175例,轻度肺动脉高压组60例,中度组97例,重度组18例,排除先天性心脏病诊断,治疗后复查超声心电图,对比分析治疗前后的肺动脉压力及右心系统参数变化.结果 各组肺动脉高压患儿治疗后肺动脉压力均低于治疗前（P〈0.01）,其中重度肺动脉高压组下降明显,治疗前后对比为（72.89±2.61） mmHg vs （35.2±2.98） mmHg,各组肺动脉收缩压均降至正常范围（〈40 mmHg）,降压效果显著,主肺动脉内径及右心室前后径较治疗前减小（P〈0.01）,其中中度肺动脉高压组减小明显,主肺动脉内径治疗前后的对比为（8.57±0.52） mm vs （6.86±0.60） mm,右心室前后径治疗前后对比为（9.38±0.57） mm vs （7.40±0.50） mm,临床治疗效果满意,各组间差异有统计学意义.结论 超声心动图能够对窒息儿和早产儿治疗前后的肺动脉压力进行客观评价,为临床早期治疗、防止肺动脉高压的进一步发展及改善预后提供指导.     

上腔静脉频谱对大鼠肺动脉高压的评价作用

目的探讨上腔静脉频谱对野百合碱诱导的大鼠肺动脉高压的评价作用。 方法健康成年雄性SD大鼠168只,体重180~220 g,随机选取10只为正常对照组。大鼠腹腔注射2%野百合碱50 mg/kg造模,以肺动脉收缩压大于30 mmHg（1 mmHg=0.133 kPa）为模型成功的标准。第28天造模成功103只,随机选取8只进行模型检测,其余存活大鼠随机分为贝前列素组、西地那非组、波生坦组,每组24只,余23只为安慰剂组。灌胃治疗2周后进行上腔静脉超声检测及右心导管测量右心室压及肺动脉收缩压。 结果造模成功并测得肺动脉压力、进行上腔静脉超声检测的大鼠55只。大鼠模型体重减轻,肺动脉压增高,其中波生坦组肺动脉压力最高,与上腔静脉AR/S比值、上腔静脉S波相关性好。超声心动图检测上腔静脉血流频谱提示肺动脉高压大鼠AR/S增高,S波减低,与对照组比较差异有统计学意义（P<0.01）。Pearson相关示肺动脉收缩压与上腔静脉血流频谱参数AR/S明显相关（右侧AR/S：Y=50.07X＋24.62,R²=0.302,P<0.01;左侧AR/S：r=0.491,P<0.01）。从用药后的自然死亡率分析,每组死亡的大鼠出现不同程度胸腹腔积液和心包积液,以安慰剂和波生坦组较重,波生坦组在3种治疗药物中死亡率最高,但差异无统计学意义。肺组织光镜下显示：模型组、安慰剂组及各治疗组大鼠肺小动脉均出现不同程度中膜增厚,管腔变小,平滑肌增生。正常组肺小动脉未见明确异常。 结论右上腔静脉频谱AR/S与肺动脉收缩压相关性良好,可作为多普勒超声评价肺动脉高压的参数之一。     

肝移植过程中肺动脉高压的处理(英文)

背景:严重肝功能损害时可出现肺动脉压升高,而肝移植过程中特别是新肝开放时的血流动力学波动也会直接导致肺动脉压力的改变。目的:观察肝移植过程中肺动脉压力的变化,以及出现肺动脉高压时的处理。设计、时间及地点:选择2004-06/2006-06解放军第一八一医院进行肝移植手术的患者为观察对象进行前后对照观察。对象:择期行同种异体肝移植的终末肝病患者13例,均为男性,年龄19～53岁。方法:全身麻醉后应用有创技术及漂浮导管连续监测患者术中平均动脉压、中心静脉压、肺动脉压、肺动脉楔压,通过有效的呼吸管理和持续泵注小剂量硝酸甘油0.1～5.0μg/(kg·min),间断给予前列腺素E11.0～2.0μg/次,以降低术中门静脉开放时升高的肺动脉压及肺动脉楔压。主要观察指标:平均动脉压和肺动脉压变化。结果:13例肝移植患者移植过程中门静脉开放时均发生不同程度平均动脉压下降,肺动脉压、肺动脉楔压在门静脉开放后5,15min明显高于开放前(P<0.05)。运用硝酸甘油及前列腺素E1后肺动脉压、肺动脉楔压30min左右恢复到开放前水平。结论:肝移植过程中合理应用硝酸甘油、前列腺素E1能明显缓解门静脉开放时的肺动脉高压。     

Splanchnic and systemic haemodynamic response to volume changes in patients with cirrhosis and portal hypertension

We investigated the haemodynamic response to volume depletion and subsequent repletion in patients with cirrhosis and portal hypertension. Twelve patients with compensated cirrhosis and portal hypertension were included in the study. The haemodynamic changes occurring after removal of approx. 15% of the blood volume, and subsequently after isovolume repletion with colloid, were assessed. Baseline haemodynamic measurements showed increased cardiac output and a systemic vascular resistance at the lower limit of normal. The hepatic venous pressure gradient (HVPG) was increased, at 18 mmHg. After depletion, arterial pressure, cardiac output and all right-heart-sided pressures decreased, and systemic vascular resistance increased. HVPG decreased to 16.0 mmHg. All the above changes were statistically significant. After blood volume restitution, the haemodynamic values returned to baseline. In particular, an increase in HVPG was shown in four out of the twelve patients (two with ascites and two without), which was small in three of them. However, HVPG remained the same as or lower than the baseline in the other eight patients. Patients with cirrhosis and portal hypertension exhibit an abnormal haemodynamic response to blood volume depletion. After volume repletion, no increase in the portal pressure was noted in this group of patients as a whole, although four out of the twelve patients did show an increase, possibly due to extensive collateral circulation.     

Pulmonary hypertension in aortic regurgitation: early surgical outcome

A review of the haemodynamic data of 139 patients with isolated, severe, chronic aortic regurgitation revealed severe pulmonary hypertension (pulmonary artery systolic pressure of greater than or equal to 60 mmHg) in 34 (24 per cent). The left ventricular end-diastolic pressure was high in all patients, suggesting that pulmonary hypertension was a consequence of severe long-standing regurgitation with ventricular dysfunction. Aortic valve replacement was performed in 69 patients, 33 of whom had normal or mildly elevated pulmonary artery systolic pressure (less than 39 mmHg; group I) and 36 of whom had moderate or markedly elevated pulmonary artery systolic pressures (less than 40 mmHg; group II). There was no difference in mortality or prevalence of post-operative complications between these two groups of patients. Furthermore, New York Heart Association (NYHA) functional class and cardiothoracic ratio were similar in both groups at the six-month assessment. The pulmonary vascular resistance fell from 4.7 +/- 3.5 to 1.5 +/- 0.8 units x m2 in 13 of 17 patients who had repeat catheterization after surgery. Pulmonary artery systolic pressure reverted to normal in 10 of these 13 patients. It is concluded that pulmonary hypertension consequent upon raised left ventricular end-diastolic pressure is common in severe aortic regurgitation, is largely reversible, and does not influence the early outcome after aortic valve replacement.     

Pharmacokinetics,safety, and efficacy of bosentan in pediatric patients with pulmonary arterial hypertension

BACKGROUND: Bosentan, a dual endothelin-receptor antagonist, is registered for the treatment of pulmonary arterial hypertension. Little is known about the effects of bosentan in children. This study was conducted to investigate the pharmacokinetics, safety, and efficacy of bosentan in pediatric patients with pulmonary arterial hypertension. METHODS: In this 2-center, open-label study, 19 pediatric patients with pulmonary arterial hypertension were enrolled and stratified for body weight and epoprostenol use. Patients weighing between 10 and 20 kg, between 20 and 40 kg, or greater than 40 kg received a single dose of 31.25, 62.5, or 125 mg, respectively, on day 1, followed by 4 weeks of treatment with the initial dose. The dose was then up-titrated to the target dose (31.25, 62.5, or 125 mg twice daily). Pharmacokinetic and hemodynamic parameters were obtained at baseline and after 12 weeks of treatment. Six-minute walk distance and cardiopulmonary exercise testing results were measured at baseline and at week 12 in children aged 8 years or older. RESULTS: The variability in exposure among the 3 groups was less than 2-fold after single- and multiple-dose administration. The exposure to bosentan decreased over time in all groups. The covariates body weight, gender, age, and the use of epoprostenol had no significant effect on the pharmacokinetics of bosentan. Bosentan produced hemodynamic improvement and was well tolerated. The mean change from baseline in mean pulmonary artery pressure was -8.0 mm Hg (95% confidence interval, -12.2 to -3.7 mm Hg), and that in pulmonary vascular resistance index was -300 dyne x s x m(2)/cm(5) (95% confidence interval, -576 to -24 dyne x s x m(2)/cm(5)). CONCLUSIONS: The pharmacokinetics of bosentan in pediatric patients with pulmonary arterial hypertension and healthy adults are similar, and treatment with bosentan resulted in hemodynamic improvement. These results suggest that the applied dosing regimens may be appropriate to treat pediatric patients.     

超声心动图对肺动脉高压和肺静脉高压的非侵入性鉴别诊断研究

目的 确定超声心动图是否能非侵入性鉴别诊断肺动脉高压(PAH)和肺静脉高压(PVH).方法 随机选择56例经超声心动图确定的肺动脉收缩压(PASP)≥40 mmHg的患者,并在7 d内进行心导管检查.依据左室舒张末压或肺毛细血管契压(PCWP)将患者分为PAH组30例,PVH组26例.两组患者应用常规和组织多普勒超声技术分别测定跨二尖瓣舒张早期峰值血流速度E峰,晚期A峰,E/A比值,二尖瓣血流减速时间(DT),舒张早期二尖瓣环运动速度(E')和E/E'值.结果 与PVH组比较,PAH组A峰、DT、PASP及E,增大,而E峰、E/A值和E/E'值却降低.E/E'值和E/A值是PAH和PVH鉴别诊断的最佳指标,其E/E'值和E/A值的ROC曲线下面积分别为97%和91%,而诊断PVH的最佳界值点是E/E'>9.2(敏感性为95%,特异性为97%),E/A>1.7(敏感性为75%,特异性为92%).结论 采用常规和组织多普勒超声技术可正确鉴别PAH和PVH.     

The role of cardiac catheterization for diagnosis and treatment of pulmonary hypertension]

The role of the cardiac catheterization for diagnosis and treatment of pulmonary hypertension (PH) is very important. When mean pulmonary artery pressure increased more than 25 mmHg, then PH is defined. But this is measured accurately only by the catheterization. And we can discriminate the etiology of PH clearly by pulmonary capillary wedge pressure (Ppcw) or intra-cardiac shunt (L to R) by blood oxygen saturation step-up, and both parameters are obtained by this method. The etiology of PH is diagnosed as left sided heart failure, if Ppcw is increased more than 13 mmHg. PH is produced by congenital heart disease (ASD, VSD, PDA etc.), when the oxygen saturation step-up is recognized. And PH is induced by any pulmonary disease or pulmonary thrombo-embolism or collagen disease or liver cirrhosis or PPH, if Ppcw is normal and no oxygen step-up is recognized.     

Overweight and obesity in hypertension

Many studies have shown body weight to correlate with blood pressure and the prevalence of hypertension, but few have examined whether the correlation between overweight and hypertension holds at higher levels of blood pressure. This study evaluated the degree of overweight and hypertension among 1795 adult men and women with hypertension (diastolic pressure greater than or equal to 90 mmHg) who were referred to a community-based hypertension clinic in Milwaukee during a five-year period. Using a nomogram for body mass index (BMI), we found that more than one-third of the subjects were overweight and over one-third were obese, with black and white females showing slightly higher indices than males. There was a trend for BMI to decline with age in both ethnic groups. Among the group not on antihypertensive medication (1344 patients), there was no correlation between BMI and blood pressure. Blood pressure correlated positively with age but BMI showed an opposite trend. After BMI was corrected for age, the correlation was the same and tended to be in the negative direction. A striking trend observed is that the higher the BMI, the greater the percentage of subjects with diastolic pressures between 90-104 mmHg. These results do not necessarily contradict a possible role of obesity in hypertension. Rather, they confirm the high prevalence of overweight among hypertensives and suggest that a large proportion of obese hypertensives tend to have a relatively mild pressure elevation. In view of the known hypotensive effect of weight reduction, the likelihood of reducing blood pressure to normotensive levels in this group by diet is stressed.     

Atrial natriuretic factor in chronic obstructive lung disease with pulmonary hypertension. Physiological correlates and response to peptide infusion.

To investigate the physiological role of atrial natriuretic factor (ANF) in patients with hypoxic pulmonary hypertension secondary to chronic obstructive lung disease (COLD), we infused synthetic alpha-human ANF in seven such patients, and investigated the physiological correlates to circulating peptide levels in 24 patients with COLD. ANF infusion, at incremental rates of 0.01, 0.03, and 0.1 micrograms/kg.min, increased basal plasma immunoreactive (ir) ANF (136 +/- 38 pg/ml) by 3-, 10-, and 26-fold, respectively, and reduced pulmonary artery pressure (from 33 +/- 3 to 25 +/- 2 mmHg, P less than 0.001) and systemic arterial pressure (from 88 +/- 4 to 79 +/- 4 mmHg, P less than 0.001) in a dose-related fashion. Cardiac index increased by 13.5% (P less than 0.01) while heart rate was unchanged. Cardiac filling pressures decreased at 0.1 micrograms/kg.min ANF. Pulmonary and systemic vascular resistance fell by 37% (P less than 0.001) and 19% (P less than 0.001), respectively. Arterial oxygenation was impaired during ANF infusion, suggesting partial reversal of hypoxic pulmonary vasoconstriction. Plasma renin activity remained unchanged but aldosterone fell by 44% (P less than 0.01). The levels of plasma irANF in 24 patients correlated directly with the degree of hemoconcentration (r = 0.67, P less than 0.001), respiratory acidosis (r = -0.65, P less than 0.001), and pulmonary hypertension (r = 0.52, P less than 0.01). The results suggest that ANF may serve as a potent pulmonary vasodilator involved in the circulatory homeostasis of patients with COLD.     

Human VIP-alpha: an emerging biologic response modifier to treat primary pulmonary hypertension

Primary pulmonary hypertension (PPH) is a rare life-threatening disorder of unknown etiology manifested by chronic elevation of pulmonary arterial pressure. Given that pulmonary vasoconstriction, endothelial and vascular smooth muscle cell proliferation and in situ thrombosis contribute appreciably to the evolution of PPH, treatment with vasodilators, antiproliferative drugs and anticoagulants, alone or in combination, constitute the pharmacologic standard of care. To this end, long-term administration of oral calcium channel blockers, prostacyclin analogs by various routes and oral endothelin-1 receptor antagonists, alone or in combination, is efficacious in treating patients with PPH. Unfortunately, efficacy is hampered by poor stability, delivery and bioavailability, and by systemic toxicity. Hence, there is an ongoing need to develop and test new drugs to treat patients with PPH. To address this issue, a novel, targeted, long-acting, biocompatible and safe sterically stabilized liposomal and micellar formulation of human vasoactive intestinal peptide (VIP) was developed and tested for human use: the 28-amino acid pleiotropic biologic response modifier, human VIP-alpha. The long-lasting salutary effects of phospholipid-associated VIP on vasomotor tone and arterial pressure were expressed at low concentrations solely in diseased animals and were independent of its route of administration. Thus, the author proposes that human VIP-alpha could be developed as a safe long-acting drug to treat patients with PPH.     

Effects of the angiotensin II antagonist 1-sar-8-ala-angiotensin II in hypertension in man

The angiotensin II antagonist 1-sar-8-ala-angiotensin II (saralasin) was infused in forty-six patients with hypertension of various aetiology (essential, renal arterial or parenchymal disease, primary hyperaldosteronism), before and/or during sodium volume depletion obtained by chlorthalidone and low sodium diet. When saralasin was infused in twenty-five patients ingesting 130 mmol of sodium per day, including patients with proven renovascular hypertension, the changes in mean arterial pressure and ranged from +10 to -7 mmHg (mean: +0.20 mmHg) and were not related to the plasma renin concentration (PRC) (r = -0.11). During sodium volume depletion, saralasin induced changes in mean arterial pressure, ranging from +21 to -76 mmHg, which were closely related to log PRC (n = 32; r = -0.87). Combined sodium depletion and antagonism of angiotensin II 'normalized' mean arterial pressure (less than or equal to 100 mmHg) in twenty-one of the thirty-two patients, while pressure remained between 106 and 147 mmHg in eleven 'poor' responders, so that pressor mechanisms other than sodium volume and angiotensin must be responsible for the remaining elevation of pressure in these patients. The study indicates that arterial pressure is not dependent on the immediate pressor effects of angiotensin II in sodium replete patients, and in sodium deplete subjects whose PRC remains low, while it is at least partly angiotensin II dependent during sodium volume depletion in the others. The results cast doubts on the clinical usefulness of saralasin in the investigation of patients with hypertension, when studied in the conditions of the present study.     

Reversal of experimental pulmonary hypertension by PDGF inhibition

Progression of pulmonary hypertension is associated with increased proliferation and migration of pulmonary vascular smooth muscle cells. PDGF is a potent mitogen and involved in this process. We now report that the PDGF receptor antagonist STI571 (imatinib) reversed advanced pulmonary vascular disease in 2 animal models of pulmonary hypertension. In rats with monocrotaline-induced pulmonary hypertension, therapy with daily administration of STI571 was started 28 days after induction of the disease. A 2-week treatment resulted in 100% survival, compared with only 50% in sham-treated rats. The changes in RV pressure, measured continuously by telemetry, and right heart hypertrophy were reversed to near-normal levels. STI571 prevented phosphorylation of the PDGF receptor and suppressed activation of downstream signaling pathways. Similar results were obtained in chronically hypoxic mice, which were treated with STI571 after full establishment of pulmonary hypertension. Moreover, expression of the PDGF receptor was found to be significantly increased in lung tissue from pulmonary arterial hypertension patients compared with healthy donor lung tissue. We conclude that STI571 reverses vascular remodeling and cor pulmonale in severe experimental pulmonary hypertension regardless of the initiating stimulus. This regimen offers a unique novel approach for antire-modeling therapy in progressed pulmonary hypertension.     

Increased blood pressure in diabetes: essential hypertension or diabetic nephropathy?

This study was performed to evaluate whether it is possible to distinguish between diabetics with essential hypertension and diabetics with elevated blood pressure due to diabetic nephropathy. We investigated 46 young diabetics, 21 having incipient nephropathy defined as urinary albumin excretion (UAE) persistently above 15 micrograms/min and total urinary protein less than 0.5 g per 24 h, and 25 patients having overt nephropathy with total protein excretion equal to or above 0.5 g per 24 h. Twenty-three patients with essential hypertension were also studied as well as 24 healthy controls. Only males and females between the age of 25 years and 40 years were included. We found a positive correlation between UAE and blood pressure (BP) but a considerable overlap in BP and UAE values between diabetics and patients with essential hypertension. However, plotting urinary albumin excretion against BP, diabetics and non-diabetics with essential hypertension could be nearly totally separated. Comparison at a similar blood pressure level, for example, mean arterial blood pressure of 125 mmHg, shows that diabetics have UAE 100 times higher than non-diabetic essential hypertensives. Conversely, UAE of 100 micrograms/min would imply that mean arterial blood pressure is about 70 mmHg higher in the non-diabetic essential hypertensives than in the diabetics. Five diabetics with normal UAE and elevated blood pressure higher or equal to 160/95 mmHg were clearly within the area of the essential hypertensive patients. Our observations indicate that it seems possible to distinguish diabetic patients with essential hypertension from diabetics with elevated blood pressure due to early or advanced nephropathy.     

大动脉调转术治疗年龄6个月以上重度肺动脉高压患者疗效分析

目的评价大动脉调转术治疗年龄6个月以上重度肺动脉高压伴室间隔缺损、大动脉转位和Taussig-Bing畸形患者的中期疗效。方法对86例年龄6个月以上的重度肺动脉高压伴室间隔缺损、大动脉转位和Taussig-Bing畸形患者行大动脉调转手术,观察术后病死率、并发症发生率、术后肺动脉压力等,分析手术死亡、术后持续性肺动脉高压的影响因素。结果本组住院死亡6例（6.98%）,72例完成随访,死亡2例;存活者心功能NYHAⅡ级2例（2.86%）,心功能NYHAⅠ级68例（97.14%）;术后肺动脉压（30.5±13.0）mm Hg明显低于术前（64.9±13.0）mm Hg,经皮血氧饱和度（99.7±0.7）%明显高于术前（72.0±15.0）%（P〈0.05）;多因素回归分析显示,术后肺动脉高压、一氧化氮吸入、血浆胶体渗透压监测是手术死亡的独立预测因子（OR=1.236,95%CI：1.080-1.415,P=0.002;OR=0.016,95%CI：0.001-0.345,P=0.008;OR=0.070,95%CI：0.006-0.829,P=0.035）,手术年龄与持续性肺动脉高压独立相关（OR=1.283,95%CI：1.073~1.536,P=0.006）。结论大动脉调转术治疗大龄重度肺动脉高压伴室间隔缺损、大动脉转位和Taussig-Bing畸形患者中期效果良好。     

Effect of a surgical aortocaval fistula on monocrotaline-induced pulmonary hypertension

OBJECTIVE: Increased pulmonary blood flow is believed to contribute to the development of pulmonary hypertension. We investigated the effect of overcirculation via an aortocaval fistula, on the development of monocrotaline-induced pulmonary hypertension in rats. Monocrotaline was administered 1 wk after the creation of an aortocaval fistula. DESIGN: Randomized, controlled study. SETTING: Research laboratory of an academic institution. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Overcirculation was induced by pneumonectomy and by surgical creation of aortocaval fistula. Pulmonary artery hypertension was induced by administration of monocrotaline. MEASUREMENTS AND MAIN RESULTS: Aortic blood flow, Pao(2), and pulmonary arterial pressure were measured 4 wks later. A blinded investigator quantified pulmonary arterial neointimal formation in small pulmonary arteries. Compared with animals that received monocrotaline and/or underwent pneumonectomy but did not undergo aortocaval fistula, the presence of a surgical aortocaval fistula was associated with increased aortic blood flow (p <.001), increased Pao(2) (p <.001), and lower mean pulmonary arterial pressure (p <.001). In addition, rats with aortocaval fistula had less pulmonary arterial neointimal formation than matched animals without an aortocaval fistula (p =.034). CONCLUSIONS: The presence of a surgical aortocaval fistula attenuates, rather than worsens, the development of monocrotaline-induced pulmonary hypertension in rats.     

Failure of postnatal adaptation of the pulmonary circulation after chronic intrauterine pulmonary hypertension in fetal lambs.

To determine the effects of chronic intrauterine pulmonary hypertension on the perinatal pulmonary circulation, we induced chronic elevations of pulmonary artery pressure in 24 late-gestation fetal lambs by maintaining partial compression of the ductus arteriosus with an inflatable vascular occluder. Pulmonary artery pressure was increased from 44 +/- 1 to 62 +/- 3 mmHg for 3-14 d. Although left pulmonary artery blood flow initially increased during acute partial ductus compression, the increase in flow was not sustained during chronic ductus compression despite persistent elevations of pulmonary artery pressure (P less than 0.01). Chronic hypertension decreased the slope of the pressure-flow relationship from 3.4 +/- 0.3 (initial) to 0.9 +/- 0.1 ml/min per mmHg, and blunted the fetal pulmonary vascular response to small increases in PO2 (P less than 0.0001). Pulmonary hypertension for greater than 8 d increased the wall thickness of small pulmonary arteries (P less than 0.001). Compared with controls, hypertensive animals had higher pulmonary artery pressure, lower pulmonary blood flow, and predominant right-to-left ductus shunting after cesarean-section delivery (P less than 0.0001). We conclude that chronic pulmonary hypertension in utero, in the absence of hypoxemia or sustained increases in blood flow, causes abnormal fetal pulmonary vasoreactivity, structural remodeling, and the failure to achieve the normal decline in pulmonary resistance at birth.     

Urapidil-induced increase of the intracranial pressure in head-trauma patients

This report deals with two patients suffering from a closed head injury who demonstrated a rise of intracranial pressure (ICP) after bolus injections of urapidil to control arterial hypertension. The rapid fall of the arterial pressure was accompanied by an increase of ICP that amounted to approximately 50% to 100% of the initial values (and thereby reaching ICP values between 32.5 and 40 mmHg); cerebral perfusion pressure decreased to less than 50 mmHg, and nearly reached control values at 15 min after administration of urapidil. The mechanism for this ICP rise is unknown and remains speculative. So far, no other clinical or experimental data are known to us reporting a urapidil induced increase of ICP in head trauma patients.