Histologic changes of pulmonary arteries in congenital heart disease with left-to-right shunt (part 2): emphasis on the significance of pulmonary arterial concentration in the correlation with pulmonary hemodynamics after repair Ed-- the above is an alternative title for your consideration

We performed this study to assess the correlation of residual pulmonary hypertension in the immediate postoperative period with that in the late follow-up period, to assess the histologic changes of pulmonary arteries (PA) at the time of repair for patients with congenital heart disease consisting of left-to-right shunt, and to clarify the role of lung biopsy in determining the operability and reversibility of pulmonary vascular changes. Lung biopsy was performed during repair in 38 patients, with a wide range of age, who had congenital left to right shunt and pulmonary hypertension. All were Heath-Edward grade III or less. Morphometric study included measurement of medial wall thickness (MWT) and decrease rate of pulmonary arterial concentration (PAC). Mean PA pressure in the immediate postoperative period was measured in all 38 patients. Follow-up cardiac catheterization was performed in 15 patients (average 3.8 years after repair). At operation, 5 patients of this late follow-up group were under 2 years of age and the other 10 were 2 or more. During catheterization, pulmonary hemodynamic reaction was observed both under room air inhalation and after inhalation of hypoxic gas FiO2 0.15. Mean PA pressure and pulmonary vascular resistance (PVR) in the immediate postoperative period had a significant correlation with PA pressure and PVR values before the operation, but not with morphometry, Heath-Edward grade, or with pulmonary hemodynamics in late follow-up. During the late follow-up study, 5 of the 15 patients had pulmonary hypertension (defined as mean PA pressure > or = 15 mmHg) under room air inhalation, and PA hypertension was induced in 4 additional patients after hypoxic gas inhalation. There was no incidence of PA pressure or PVR values registering above the preoperative level. The degree of PA hypertension showed a correlation with the rate of PAC decrease and also with patients' age-at-operation. Multiple regression analysis showed that both the rate of PAC decrease and the age-at-operation contributed significantly to the degree of PA hypertension. Some of the patients over age 2 had a decreased rate of PAC above the regression line, which none of the patients under age 2 experienced. In patients with Heath-Edward grade III or less, residual pulmonary hypertension in the immediate postoperative period was not correlated with histology, but in late follow-up, it was with PAC and the age-at-operation. Therefore, a decrease of PAC is assumed to be a totally or partially irreversible pulmonary vascular change depending on the patient's age-at-operation, while medial hypertrophy is thought to be a reversible pulmonary vascular change. Lung biopsy could play an important role in determining the reversibility of pulmonary vascular obstruction, particularly in patients older than 2 years. Ed- re highlights above: such hyphenation is optional, but if used then it should be applied consistently throughout the paper. As 3 of the 4 entries in the abstract use it, I have maintained it consistently below.     

MR imaging of non-visualized pulmonary arteries at angiography in patients with congenital heart disease.

The aim of this study was to evaluate whether MR could depict pulmonary arterial anatomy in more detail than routine angiography in patients with congenital interruption or acquired occlusion of the left pulmonary artery or pulmonary atresia. This study included 10 patients with tetralogy of Fallot (n=6) or pulmonary atresia with ventricular septal defect (n=3) or aorticopulmonary window (n=1) diagnosed by cardiac angiography and MR. Surgical confirmation was made in seven patients. Interruption of the proximal left pulmonary artery, diagnosed at the time of evaluation, was found in seven patients and acquired obstruction of the hilar pulmonary artery (PA) was found in two at cardiac angiography. In the remaining one patient with pulmonary atresia and an occluded palliative shunt, the central PA was not visualized at angiography. MR showed 3-6 mm-sized hilar PAs in five and a central PA in a patient with pulmonary atresia. In 4 of 6 (67%) surgically-proven patients with congenital or acquired left PA obstruction, the status of the PA distal to the obstruction was correctly diagnosed with MR. In conclusion, MR is an effective modality in depicting sizable PAs when routine angiography fails to visualize the PA anatomy.     

Heart failure in congenital heart disease: the role of genes and hemodynamics

Heart failure can be a consequence of insufficient palliation of structural malformations in patients with congenital heart disease (CHD) or genetic perturbations resulting in cardiomyopathies. Although CHD is traditionally considered a pediatric clinical problem, there is a rapidly increasing population of patients surviving into adulthood with CHD and a corresponding increase in the rate of hospital admissions for adult CHD patients with heart failure. Therefore, there is recognition of the clinical importance in translating conventional heart failure pharmacotherapies to patients with CHD, improving management of heart failure in the context of structural consequences of CHD, and understanding the underlying genetic abnormalities which impact myocardial performance. Heart failure in CHD typically involves complex interactions between primary structural defects, the consequences of interventions (i.e., residual lesions), and the heart’s response to enhanced myocardial mechanical stress which depends on many other genetic factors (i.e., gene modifiers). In this review, we will examine how altered genes and hemodynamic loading contribute to heart failure seen in congenital heart patients. Understanding mechanisms of myocardial response and remodeling within the congenital population can provide insight into physiological principles and improve our understanding of heart failure.     

Kabuki make-up syndrome (Niikawa-Kuroki syndrome) associated with congenital heart disease.

Kabuki make-up syndrome has been reported mainly among Japanese, so far occurring in more than 20 cases. Among these, however, only one case associated with congenital heart defect has been reported. We have treated three patients with this syndrome and of these two had congenital heart disease. We suggest the possibility that the association of congenital heart disease with Kabuki make-up syndrome may not be fortuitous.     

左向右分流型先天性心脏病患儿血清MMP-2和MMP-9变化

目的探讨左向右分流先天性心脏病（CHD）患儿血清基质金属蛋白酶（MMPs）-2、9水平的变化及意义。方法采用ELISA方法检测并比较40例CHD患儿（其中无肺动脉高压组22例、肺动脉高压组18例）和20例健康患儿的血清MMP-2、MMP～9。结果CHD无肺动脉高压组及肺动脉高压组患儿MMP-2（分别为206．14±20．62及258．83±31．44,pg／ml）、MMP-9（分别为207．68±20．77及240．00±31．10pg／m1）与正常对照组相比均有显著性（P均小于0．05）;而肺动脉高压组MMP-2及MMP-9水平明显高于无肺动脉高压组,差异有显著性（P均小于0．01）。CHD患儿血清MMP-2、MMP-9与LVEF、LVFs均无明显相关性（P〉0．05）;CHD患儿血清MMP-2及MMP-9浓度与肺动脉收缩压呈正相关（r分别为0．783及0．635,n=40,P〈0．05）。结论CHD肺动脉高压患儿血清MMP-2、MMP-9浓度升高并与肺动脉收缩压成正相关,提示MMP-2、MMP-9与肺动脉高压的病理生理有关。     

The index of pulmonary vascular disease in children with congenital heart disease: relationship to clinical and haemodynamic findings

OBJECTIVE: We asked whether a scoring system [index of pulmonary vascular disease (IPVD)] that quantifies the individual pulmonary vascular pathology would relate to postoperative survival in patients with congenital heart disease and pulmonary hypertension (PH). METHODS: Lung biopsy specimens from 28 patients at a median age of 6 months (1 month to 21 years) were analysed qualitatively and morphometrically. The IPVD and other morphometric parameters were related to haemodynamic findings and survival. RESULTS: Mean pulmonary artery pressure (PAP) was 44 mmHg (15-72 mmHg), and the resistance to pulmonary perfusion was 5 U x m(2) (0.9-14 U x m(2)). There were three early (in-hospital) and three late deaths during the follow-up period of 2.5 years (6 months to 7 years). Incipient plexiform lesions were observed in one infant with trisomy 21 and complete atrioventricular septal defect (cAVSD). An IPVD score above the upper critical limit (>2.2) was not observed during the first year of life. On discriminant analysis, morphometric parameters could not predict mortality ( P=0.08). CONCLUSIONS: The IPVD is not helpful to predict surgical mortality during the first year of life. Patients with trisomy 21 and cAVSD may show advanced pulmonary vascular disease in infancy.     

Effects of mildronate (quaterin) on hemodynamics in spontaneous and artificial heart rhythm in patients with ischemic heart disease

Central hemodynamic parameters under the effect of mildronate were examined in 62 patients suffering from coronary heart disease, 35 of these with acute myocardial infarction complicated by acute left-ventricular insufficiency and 20 with atherosclerotic cardiosclerosis with chronic cardiac insufficiency. The drug effect was assessed in two groups of patients after a single intravenous injection of 0.5-3 g. In group 1 (n = 53) mildronate effect on central hemodynamic parameters was assessed in spontaneous cardiac rhythm. Variously directed statistically unreliable hemodynamic shifts were revealed, related to heart rhythm changes. In group 2 (n = 9) the drug effect on heart rhythm was eliminated with the use of two-chamber electrocardiostimulation, and various hemodynamic regimens with hypo-, eu-, and hyperkinetic circulation types were artificially created by changing the A-V interval. Mildronate had no effect on the hemodynamics during two-chamber electrocardiostimulation.     

先天性心脏病伴肺动脉高压肺组织中腺泡内动脉转化生长因子-β1 mRNA和内皮素-1 mRNA的表达及意义

目的探讨转化生长因子-β1(TGF-β1)和内皮素-1(ET-1)在先天性心脏病(先心病)伴肺动脉高压(PH)的肺组织腺泡内肺动脉中的表达及意义.方法收集51例肺组织,其中41例为左向右分流型先心病患儿[伴PH 25例(A组),无PH 16例(B组)],对照组10例(C组),应用原位杂交、图像分析检测51例腺泡内肺动脉(IAPA)TGF-β1 mRNA和ET-1 mRNA的表达及平均吸光度值(A值);透射电镜观察肺组织超微结构;弹力纤维(VG)染色显示腺泡内肺动脉并计算其数量的变化.结果 (1)肺腺泡内部分肌型及环肌型动脉的数量,A、B两组分别与C组比较, F值分别为149.96、142.01,P<0.01;(2)电镜观察,有的肺小动脉内皮细胞增生;中膜平滑肌增厚,平滑肌细胞面积增大;外膜胶原纤维密集;毛细血管基膜增厚;(3)原位杂交发现,TGF-β1 mRNA在A、B两组腺泡内肺动脉均有阳性表达,A值分别为(0.1988±0.0498)、(0.1098±0.0428),C组表达微弱(A值=0.0578±0.0096),A、B、C三组间比较差异有统计学意义(P<0.05);ET-1 mRNA 在A、B两组肺腺泡内肺动脉内皮细胞表达明显增强,A值分别为(0.1692±0.0205)、(0.1004±0.0140),C组仅有微弱表达(A值=0.0746±0.0119),A、B、C三组间比较差异有统计学意义(P<0.01).结论左向右分流型先心病患儿肺组织腺泡内部分肌型及肌型动脉数量明显增加,肺血管结构重组,TGF-β1 mRNA、ET-1 mRNA表达增高与先心病伴PH的发生有关系.     

Open lung biopsies in congenital heart disease for evaluation of pulmonary vascular disease. Predictive value with regard to corrective operability

For evaluation of pulmonary vascular disease 140 open lung biopsies were performed in 137 patients with congenital heart disease in order to decide whether the state of the lung vessels would allow corrective surgery. As far as possible follow-up was obtained in patients who underwent a cardiac repair. From the study of these biopsy specimens it appeared that medial hypertrophy of pulmonary arteries and changes in pulmonary veins should not be considered an impediment for a corrective operation as long as more advanced changes are absent. The same is true for intimal thickening due to longitudinal smooth muscle, post-thrombotic changes or cellular proliferation. Concentric-laminar intimal fibrosis forms no contra-indication as long as it is mild but, if severe, it is likely that hypertensive pulmonary vascular disease will progress in spite of cardiac repair. In the presence of fibrinoid necrosis or plexiform lesions correction of a cardiac anomaly should not be attempted. The presence of dilatation lesions is more disputable but probably, as long as they are scarce and not accompanied by fibrinoid necrosis or plexiform lesions, corrective surgery may be attempted. This becomes very dubious when they are more numerous.     

先天性心脏病家系心室肌球蛋白轻链1基因的RFLP分析

本研究利用人心室肌球蛋白轻链1cDNA探针对先天性心脏病家系心室肌球蛋白轻链1基固进行了RFLP分析．从患有四种不同先天性心脏病的9个家系40名成员和13名无血缘关系患者的RFLP分析结果发现，有两个家系呈现限制酶切片段多态性，但这种限制性酶切片段多态性似与先天性心脏病的发生没有联系．     

Effects of nocturnal desaturation on pulmonary hemodynamics in patients with overlap syndrome (chronic obstructive pulmonary disease and obstructive sleep apnea)

We studied pulmonary haemodynamics and nocturnal desaturation in 17 patients with an overlap syndrome (OS), all males, mean age 51.4 +/- 8.3 years, mean BMI 37 +/- 4.2 kg/m2. Diagnosis of COPD was based on pts history, clinical examination, lung function tests and chest radiography. Spirometry showed: FVC 2.7 +/- 0.7 L (59 +/- 16% N), FEV1 1.5 +/- 0.7 L (43 +/- 16% N), FEV1% FVC 54 +/- 13%, Raw 0.58 +/- 0.4 kP.s/L, RV 3.3 +/- 1.2 L (144 +/- 51% N), TLC 6.6 +/- 1.3 L (100 +/- 14% N) and RV% TLC (49.5 +/- 12.1%. Arterial blood gas values were: PaO2 56.9 +/- 9.5 mmHg, PaCO2 46.9 +/- 9.8 mmHg, pH 7.37 +/- 0.05. Mean apnoea/hypopnoea index (AHI) was 63.9 +/- 18.9. Pulmonary haemodynamics at rest (Swan Ganz thermodilution catheter) were: mean pulmonary artery pressure (PAP-SP) 24.2 +/- 7.4 mmHg, mean pulmonary wedge pressure (PW-SP) was 9.1 +/- 7.3 mmHg, cardiac output (CO-SP) was 5.6 +/- 2.3 L/min. and pulmonary vascular resistance (PVR) was 229 +/- 97 dyn.sec.cm-5. During exercise (40 Watts, 7 mins, in 8 pts) PAP rose from 19 +/- 6 mmHg to 41.2 +/- 15.1 mmHg, PW rose from 7.4 +/- 7.2 mmHg to 11 +/- 10.2 mmHg, CO rose from 5.8 +/- 2.7 L/min to 12.7 +/- 2.4 L/min. Overnight pulse oximetry showed: mean oxygen saturation (SaO2 mean) 80.2 +/- 8.5%, minimal saturation (SaO2 min) was 50.7 +/- 19.7%. Time spent in desaturation SaO2 < 90% (T 90) was 76.9 +/- 25.7%. We conclude that pts with OS have resting pulmonary hypertension and elevated PVR. During low grade exercise the rise in PAP was highly abnormal. Statistical analysis showed no correlations between nocturnal SaO2 and diurnal pulmonary haemodynamics data.     

The site of origin of nonconfluent pulmonary arteries from a common arterial trunk or from the ascending aorta: its morphological significance

There are three possible embryological derivatives for nonconfluent pulmonary arteries which arise from a common arterial trunk or from the ascending aorta. We considered the feasibility of identifying these derivatives on the basis of the site of origin. We examined 15 specimens, in which both pulmonary arteries arose by separate orifices from a common arterial trunk (persistent truncus arteriosus), and 3 specimens, in which one pulmonary artery arose from the ascending aorta, the other being connected to the morphologically right ventricle (hemitruncus). Measurements were made for both the upper and lower margins of the orifices of the pulmonary arteries and then expressed as a percentage of the length of the ascending common trunk or aorta. The position of origin ranged from 39 to 100% for the upper margin and from 17 to 90% for the lower margin, without significant difference between left and right arteries. Since the range varied so widely, we contend that it is not possible to make a morphological identification of the pulmonary artery under consideration simply on the basis of the location of the site of origin.     

Thromboangiitis obliterans with eosinophilia (Buerger's disease) of the temporal arteries

Thromboangiitis obliterans (Buerger's disease) is a nonatherosclerotic, inflammatory, occlusive vascular disease occurring almost exclusively in young male smokers. It involves principally medium sized and small arteries and veins of the lower and upper extremities, and only rarely the visceral and cerebral blood vessels. Buerger's disease of the temporal arteries, unassociated with the involvement of blood vessels of either the upper or lower extremities has not been previously reported. Three such cases, clinically mimicking the classic (giant cell) temporal arteritis of the elderly, are described. This unusual arterial lesion also bears some resemblance to subcutaneous angiolymphoid hyperplasia with eosinophilia (Kimura's disease).     

乌司他汀对先天性心脏病肺动脉高压患者围术期黏附分子的抑制作用

中性粒细胞表达的黏附分子CD11／CD18家族和内皮细胞表达的细胞间黏附分子-1(intercellular adhesion molecule-1，ICAM-1)在与体外循环有关的炎症反应过程中起重要作用。本研究通过观察乌司他汀(Ulinastatin，UT)对先天性心脏病合并肺动脉高压患者CD11b／CD18和ICAM-1的影响作用，探讨先天性心脏病合并肺动脉高压患者围术期黏附分子的变化，为体外循环导致的全身炎症反应寻求一种有效的防治措施。     

慢性肺心病患者PAC-1、CD62p的变化及临床意义

目的：探讨慢性肺心病患者血小板膜糖蛋白PAC-1、CD62p的变化及其临床意义。方法：用三色全血流式细胞术测定加例慢性肺心病患者外周血中血小板PAC-1、CD62p的表达水平，并与30例健康对照者比较。用超声心动图检测慢性肺心病患者肺动脉收缩压。结果：慢性肺心病组PAC-1、CD62p的表达均明显高于正常对照组（均P〈0．001），并与肺动脉收缩压呈正相关。慢性肺心病患者PAC-1的变化与CD62p之间有显著的正相关（r=0．73；P〈0．001）。结论：慢性肺心病患者血小板明显活化，其活化程度与肺动脉高压关系密切。