闭塞性肺动脉高压的血流动力学和急性药物试验

目的:研究闭寒性肺动脉高压,主要是慢性血栓栓塞性肺动脉高压(CTEPH)和原(特)发性肺动脉高压(PPH)的血流动力学特点和急性中西药物试验反应.方法:上世纪80年代对我院CTEPH患者46例(CTEPH组),PPH患者69例(PPH组)观察了右心导管术血流动力学变化,2组中对49例做了吸纯氧,21例舌下含服硝苯地平20 mg,18例中心静脉推注川芎嗪80 mg等急性药物试验.结果:82.60%(95/115)的患者诊断时已有中、重度[肺动脉平均压＞40 mmHg(1 mmHg=0.133 kPa)]肺动脉高压,56.52%(65/115)合并右心功能不全.PPH组肺动脉压(收缩压、舒张压及平均压)、心脏指数均高于CTEPH组,差异有统计学意义(P＜0.05～0.001).而体动脉收缩压CTEPH组高于PPH组,差异有统计学意义(P＜0.05).76%(37/49)吸氧患者肺动脉压下降,7例出现矛盾性升高,CTEPH组尤为明显(5例).硝苯地平仅19%(4/21)有选择性扩张肺循环作用,部分患者副作用较明显.川芎嗪对肺循环降压作用轻微,副作用也较少.结论:我院就诊的闭塞性肺动脉高压患者绝大多数已属中、晚期,不可避免地会影响其治疗与预后.硝苯地平作为急性药物试验药物副反应较大,不宜应用,川芎嗪未显示对肺循环有良好的降压作用,副作用也较少.     

Nonresponse to Acute Vasodilator Challenge and Prognosis in Heart Failure With Pulmonary Hypertension

BackgroundAn acute vasodilator challenge is recommended in patients with heart failure and pulmonary hypertension during heart transplant evaluation. The aim of the study was to assess which hemodynamic parameters are associated with nonresponsiveness to the challenge.Methods and ResultsThis study is a retrospective analysis of 402 patients with heart failure with pulmonary hypertension who underwent right heart catheterization and a pulmonary vasodilator challenge. Among the 140 who fulfilled the transplant guidelines eligibility criteria for the vasodilator challenge, 38 were responders and 102 nonresponders. At multivariable analysis, a diastolic blood pressure of <70 mm Hg, pulmonary vascular resistance of >5 Woods units, and pulmonary artery compliance of <1.2 mL/mm Hg were independently associated with poor response to vasodilator challenge (all P < .001). The presence of any 2 of these 3 conditions was associated with a 90% probability of being a nonresponder. The covariate-adjusted hemodynamic predictors of death in the entire population were a low baseline systolic blood pressure (P = .0017) and a low baseline right ventricular stroke work index (P = .0395).ConclusionsIn patients with heart failure and pulmonary hypertension, low pulmonary arterial compliance, high pulmonary vascular resistance, and low diastolic blood pressure predict the nonresponsiveness to acute vasodilator challenge whilst a poor right ventricular function predicts a dismal prognosis.     

Heterogeneous Vasomotor Responses of Coronary Conduit and Resistance Vessels in Hypertension

Objectives. The purpose of our study was to investigate the relation between conductance and resistance coronary vasomotor responsiveness in hypertensive patients without atherosclerosis.Background. Although similar in morphology, conduit and resistance coronary vessels differ importantly in size, function and local environment and appear to be differentially affected in certain disease processes, such as atherosclerosis and hypertension. However, little is known about the effect of hypertension on contiguous coronary conduit and resistance vessels in humans.Methods. Changes in coronary blood flow (a measure of resistance vessel reactivity) and coronary artery diameter (a measure of conduit vessel reactivity) were investigated in response to graded infusion of the endothelium-dependent agonist acetylcholine (ACh) in 98 patients with normal coronary arteries.Results. In 31 normotensive, euglycemic patients, conduit and resistance coronary artery responses to intracoronary infusion of ACh were significantly correlated (r = 0.73, p = 1 × 10⁻⁶), although eight patients (26%) had constriction of conduit but dilation of resistance arteries at peak effect. In 28 hypertensive patients without left ventricular hypertrophy (LVH), conduit and resistance artery responses to ACh remained significantly correlated (r = 0.5, p = 0.006), although 12 patients (43%) had discordant findings. Finally, in 39 hypertensive patients with LVH, conduit and resistance artery responses to ACh displayed the lowest correlation (r = 0.38, p = 0.02), with 22 patients (56%) demonstrating conduit artery constriction and resistance artery dilation.Conclusions. Despite angiographically normal coronary arteries, heterogeneous vasomotor responses (dilation and constriction) were demonstrated in contiguous conduit and resistance arteries in normotensive and hypertensive patients referred for cardiac catheterization because of chest pain. In addition to more severe endothelial dysfunction among conduit and resistance arteries, a greater frequency of discordant conduit and resistance artery responses and resistance vessel constriction was found with increasing severity of hypertension. Our study suggests differing mechanisms of endothelium responsiveness to ACh among conduit and resistance coronary arteries.     

Clinical Evaluation of Endralazine (BQ22708), A New Vasodilator,in Essential Hypertension

In the treatment of severe hypertension the choice of vasodilator is limited by side-effects, of which the lupus erythematosus syndrome induced by hydralazine is potentially the most serious, particularly in patients with the slow acetylator phenotype. This study describes the clinical evaluation of a new vasodilator, endralazine, which is related to hydralazine but which is not metabolised to any great extent by acetylation.

In 6 essential hypertensives not adequately controlled by combined β-blocker and diuretic therapy the additional administration of the first dose of 10 mg endralazine resulted in a significant reduction in blood pressure, without orthostatic symptoms, but associated with significant increases in heart rate and plasma noradrenaline concentration. These 6 patients and a further 9 similar hypertensive patients were then prescribed twice daily endralazien for 4 weeks with significant improvement in blood pressure control. During this short period of maintenance treatment with endralazine the single dose observations were repeated and no significant changes in heart rate or plasma noradrenaline concentration were observed.

In summary, endralazine is an effective vasodilator/antihypertensive which was well tolerated in a triple therapy regimen in this study.     

高血压合并急性脑血管病患者血压个体化治疗分析

目的探讨高血压合并急性脑血管病(ACVD)血压个体化治疗效果。方法将232例确诊为高血压合并ACVD的住院患者分成治疗组和对照组,两组均予降颅压、降纤、抗凝等常规治疗,治疗组除上述措施外,根据血压高低予以个体化治疗,观察两组ACVD在治疗20天的疗效,并进行统计学分析。结果治疗组治愈率和总有效率分别为27.19%和81.58%。对照组则为15.25%和61.02%。两组间比较有显著性差异。结论确定目标血压行个体化治疗是抢救ACVD的重要环节。     

Quinaprilat-Induced Vasodilatation in Forearm Vasculature of Patients with Essential Hypertension: Comparison with Enalaprilat

The aim of the present study was to assess the possible differences in hemodynamic and neurohumoral responses to local ACE inhibition in the human forearm of patients with essential hypertension with either quinaprilat or enalaprilat. Forearm vascular responses to infusion of quinaprilat or enalaprilat (0.5 g/dL/min) into the brachial artery were studied in 12 male patients with essential hypertension. The experiments were performed in a randomized, double-blind, crossover fashion. Before and during ACE inhibition, the vasoconstrictor response to four cumulative doses of angiotensin I (Ang I) was studied. Forearm blood flow was assessed using venous occlusion plethysmography. Local quinaprilat infusion induced a more rapid (even after 15 minutes; median vasodilation quinaprilat 29% vs. enalaprilat –1%, P > 0.02) and longer lasting forearm vaso-dilation as compared with enalaprilat. After 15 minutes of local ACE inhibition, the vasoconstrictor response to Ang I was completely blocked by both ACE inhibitors. We conclude that in patients with essential hypertension quinaprilat induces a more rapid and longer lasting vasodilatation than enalaprilat. These effects of quinaprilat are possibly related to its higher affinity for vascular ACE. On the other hand, the fact that these effects of quinaprilat were observed despite a similar degree of ACE inhibition as during enalaprilat may suggest that quinaprilat directly stimulates another vasodilatating mechanism.     

Right Ventricular Function Predicts Clinical Response to Specific Vasodilator Therapy in Patients with Pulmonary Hypertension

Introduction: We followed patients with pulmonary arterial hypertension (PAH) receiving specific vasodilator therapy and tested for predictors of clinical outcome. Methods: Thirty‐two patients (mean age 39 ± 15 years, 22 women, diagnosed with pulmonary hypertension; PH): 29 with PAH and 3 patients with inoperable chronic thromboembolic PH received therapy with either bosentan, sildenafil, or both and were evaluated with clinical parameters, biomarkers (B‐type natriuretic peptide values), and echocardiography before receiving specific medication and every 3 months thereafter. A right heart catheterization was performed at baseline. A composite endpoint of death, worsening of functional class, or the need of a second vasodilator agent was used to define the clinical nonresponders. Results: Patients were followed for 14 months (7.5–21). The endpoint was reached by 15 patients: four patients died (two idiopathic PAH and two PAH in context of Eisenmenger syndrome), seven patients showed 1 functional class worsening, and four patients needed to be switched to combination therapy. Patients who remained clinically stable or improved had at baseline a better cardiac output with a less remodeled right ventricle (RV) and better functioning RV (all P < 0.05). A RV fractional area change (RVFAC) lower than 25.7% and a RV global strain value higher than ?13.4% predict with 87% sensitivity and 83% specificity (AUC 87.3%, P = 0.001) and 73% sensitivity and 91% specificity (AUC 84.2%, P = 0.003), respectively, patients who will deteriorate clinically under specific vasodilator therapy. A multivariate model showed RVFAC to be the only independent predictor of the endpoint with a HR of 0.87 (0.8–0.96), P = 0.007. Conclusions: Over an average period of 1 year, almost half of patients showed signs of clinical deterioration despite specific vasodilator therapy. Parameters of right ventricular morphology and function had prognostic value in these patients.     

高血压病患者舌下络脉的对照观察

观察高血压病患者舌下络脉的变化。对92例高血压病患者舌下络脉进行观察，并与86例正常者进行对照比较。结果发现，高血压病患者舌下络脉变化明显增加，且随着年龄的增长或高血压的病程增长，舌下络脉增粗、延长、迂曲、扩张、侧枝多以及色泽深紫等变化程度益甚。结果提示，观察舌下络脉的变化，对高血压的中医辨证、治疗效果及判断病情转归有重要参考价值。     

高血压病患者大血管顺应性变化及其对降压的反应

应用颈动脉搏动图(CPT)反应高血压(EH)病人大血管的顺应性及功能变化。结果显示:EH病人大血管阻力指数增加、顺应性下降。顺应性的改变与细胞内Na~+浓度(Na~+_1)异常有关,降压治疗可通过降低Na~+_1,改善EH的血管顺应性     

Exercise Capacity Affects Quality of Life in Patients with Pulmonary Hypertension

Background

The objective of this prospective study was to evaluate the impact of exercise capacity, mental disorders, and hemodynamics on quality-of-life (QoL) parameters in patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH).

Methods

Sixty-three patients with invasively diagnosed PAH (n = 48) or CTEPH (n = 15) underwent a broad panel of assessments, including cardiopulmonary exercise testing (CPET), 6-minute walking distance (6-MWD), World Health Organization functional class (WHO-FC), and assessment of hemodynamics. QoL was evaluated by the 36-item Medical Outcome Study Short Form Health Survey Questionnaire (SF-36). Exercise capacity, hemodynamics, age, gender, and mental disorders (anxiety and depression) were assessed for association with QoL subscores by uni- and multivariate regression analyses.

Results

Exercise capacity, WHO-FC, oxygen therapy, symptoms of right heart failure, right atrial pressure, and mental disorders were significantly associated with QoL (p < 0.05). In the stepwise backward selection multivariate analysis, depression remained an independent parameter in seven of eight subscales of the SF-36. Furthermore, peak oxygen uptake (peakVO₂) during CPET, 6-MWD, anxiety, long-term oxygen therapy, right heart failure, and age remained independent factors for QoL. Hemodynamic parameters at rest did not independently correlate with any domain of the SF-36 QoL subscores.

Conclusions

Mental disorders, exercise capacity, long-term oxygen therapy, right heart failure, and age play important role in the quality of life in patients with PAH and CTEPH.     

抗氧化剂对脂质过氧化内皮细胞表达细胞粘附分子的影响

为研究一氧化氮合酶抑制剂左旋硝基精氨酸诱导的肺动脉高压大鼠各部位离体血管环对多巴胺－ １ 受体反应性的影响，采用大鼠肺动脉、肠系膜动脉和肾动脉离体血管标本，在去甲肾上腺素收缩血管后，用多巴胺－ １ 受体选择性激动剂非诺多泮使血管舒张，所有实验在吲哚美辛（１０ μｍｏｌＬ） 和普萘洛尔（３ μｍｏｌＬ） 存在下进行。左旋硝基精氨酸组大鼠各动脉对非诺多泮的反应性均有不同程度的降低，以肺动脉最明显，最大舒张占预收缩的百分比为４５．５％ ±４．１％ ，低于对照组的９７．３ ％ ±１０ ．６ ％（ Ｐ＜ ０．０１）；亲合常数为２０４２ ±２２１，低于对照组的４２７４ ．２±５１２（Ｐ＜ ０．０１） ，接近对照组的去内皮水平。肠系膜动脉和肾动脉对非诺多泮的反应性亦有下降，但下降程度明显低于肺动脉。结果提示，内皮依赖性受体介导多巴胺－ １ 的舒张效应降低是左旋硝基精氨酸形成肺动脉高压的因素之一。     

The Roles of Integrins in Mediating the Effects of Mechanical Force and Growth Factors on Blood Vessels in Hypertension

Hypertension is characterized by a sustained increase in vasoconstriction and attenuated vasodilation in the face of elevated mechanical stress in the blood vessel wall. To adapt to the increased stress, the vascular smooth muscle cell and its surrounding environment undergo structural and functional changes known as vascular remodeling. Multiple mechanisms underlie the remodeling process, including increased expression of humoral factors and their receptors as well as adhesion molecules and their receptors, all of which appear to collaborate and interact in the response to pressure elevation. In this review, we focus on the interactions between integrin signaling pathways and the activation of growth factor receptors in the response to the increased mechanical stress experienced by blood vessels in hypertension.     

Vasodilator therapy in chronic congestive heart failure

Benefits from vasodilator therapy in patients with chronic heart failure are partly related to the severity of functional derangements. Agents with an arteriolar-dilating effect are more likely to be effective in patients with higher left ventricular outflow resistance. Vasodilators with primary venodilating properties are more likely to be effective in the presence of an increased ventricular preload. The mechanisms by which preload and left ventricular outflow resistance increase in patients with cardiac insufficiency are not well understood and may not be similar in all patients. Vasodilators also have the capacity to ameliorate myocardial metabolic functional abnormalities by influencing myocardial energetics, but the effects of different agents on coronary hemodynamics may not be uniform. Effects on renal hemodynamics may also vary, as may neurohumoral changes after therapy. Angiotensin-converting enzyme inhibitors have been shown to exert beneficial effects on both coronary and renal hemodynamics in patients with chronic heart failure, while producing favorable neurohumoral changes. These agents provide some advantages over direct-acting vasodilators in that myocardial oxygen consumption is decreased, myocardial metabolic function is improved, and norepinephrine and aldosterone levels are reduced. Further controlled studies are needed to assess the efficacy of angiotensin-converting enzyme inhibitors in relation to other vasodilators for the long-term management of these patients.