Double outlet right ventricle in a calf

Double outlet right ventricle is a conotruncal malformation where both great arteries (aorta and pulmonary trunk) arise from the right ventricle. A 2-month-old Holstein calf was slaughtered due to severe respiratory distress. At necropsy, the heart was enlarged, globose, and had ventricular and atrial septal defects. The only outlet for the left ventricle was a large ventricular septal defect located at 6 cm distance from the heart apex and involved atrial septum too. The right ventricle was enlarged and markedly thickened with a left to right free wall ratio of 2.5:2 and prominent papillary muscles. The aorta arose from the right ventricular infundibulum adjacent to pulmonary trunk. Two valvular hematomas were observed on the edge of the right atrioventricular valve. The lungs were rubbery with ecchymotic and petechial hemorrhages and did not collapse after removing from thoracic cavity. Enhanced lobular pattern was evident on both the capsular and cut surfaces of the liver. Histopathological examination of the lungs revealed thickening of alveolar septa, hemorrhages, and infiltration of hemosiderophages within alveoli. Periportal hepatocellular fatty changes, substitution of centrilobular and midzonal hepatocytes by red blood cells, and dilation of midzonal and periportal sinusoids were seen in the liver. To our knowledge, this particular combination of cardiac defects has not been previously described in domestic animals and the pathological lesions observed in the calf may be resulted as a sequel to left–right blood shunting and heart failure.     

Double-outlet right ventricle without ventricular septal defect. A challenge to the embryologist? microscopic investigation

Summary A male infant died at the age of four weeks with the following clinical diagnosis: ventricular septal defect, patent ductus arteriosus, total heart block. Postmortem X-ray investigation of the heart-lung-specimen (in which the aorta and the pulmonary trunk had a normal interrelationship, with an approximately normal caliber) and succeeding dissection of the heart chambers, revealed that both great arteries took their origin from the right ventricle; there was no ventricular septal defect and consequently the non-functioning left ventricle was rudimentary; ductus arteriosus and foramen ovale were patent.The lack of a ventricular septal defect, from embryologic viewpoint an almost obligatory part of the well-known entity of double-outlet right ventricle, compelled an extensive microscopic serial investigation of the central part of the heart septum (with the adjacent parts of tricuspid and mitral valves) and the outflow tract of the right ventricle, including the arterial orifices and a paraseptal flap of the ventral right ventricular wall.In the ventricular septum, underneath the lower left aortic semilunar cusp, at the usual site of the pars membranacea, a large mass of chondroïd tissue was found, coherent with a vast area filled with inflammatory cells, calcification, necrosis and another, smaller-sized piece of chondroid tissue in the left ventricular septal wall. Furthermore, there was pronounced endocardial fibro-elastosis of the left ventricle, demarcated by a ring of numerous thick-walled arteries with narrowed or even occluded lumina, and with several conspicuous communicating channels toward the left ventricular cavity (arterio-luminal vessels).Most likely this malformation was the result of an embryonic inflammatory process, started before the 16 mm stage and involving the region of the foramen interventriculare so violently as to occlude it before the aorta had reached its left ventricle.The endocardial fibro-elastosis, the large arterio-ventricular communications and the coronary arterial lesions are attributed to the exceeding pressure in the blind left ventricular cavity and the associated ischemia in the left ventricular wall. The ischemia might also have contributed to the aberrant cartilage formation.The significance of the findings for the functional, embryological and anatomical distinction from the usual type of double-outlet ventricle is emphasized.     

Pathomorphology of myocardial circulation: Comparative study in increased left or right ventricle afterload

Comparative study of pathomorphology of myocardial circulation under conditions of increased afterload of the left or right ventricles showed similar changes. All compartments of the coronary bed were plethoric, capillary blood stasis and perivascular edema, more pronounced in arterial vessels, were detected in both cases. These changes equally involved both ventricles and the ventricular septum. Significant differences consisted in local increase in the density of functioning capillaries. The increase was the maximum in hemodynamically overloaded ventricle and ventricular septum, presumably due to increase of their contractile activity. The density of functioning capillaries in the intact (vs. pressure overloaded) ventricle also increased, but to a lesser degree, which could be due to systemic neurohumoral effects. If increased afterload was complicated by the development of heart failure, circulatory disorders in the myocardium progressed. Significant increase in the density of functioning capillaries in all cardiac compartments indicated decreased vascular tone and exhaustion of coronary reserve. This was paralleled by a sharp arterial plethora in case of increased afterload of the left ventricle and sharp blood stasis in the microcirculatory bed in case of increased right ventricle afterload. Reduction of effective perfusion pressure in the presence of coronary dystonia can cause coronary insufficiency and myocardial ischemia in case of increased right ventricle afterload. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 3, pp. 352–356, March, 2008     

Spectrum of looping disturbances in stage 34 chicken hearts after retinoic acid treatment

Background: In a recently developed chick model the teratogen retinoic acid has appeared to induce a spectrum of double outlet right ventricle, which needs further detailed evaluation. It is known that retionic acid is able to induce cardiac malformations. Although the exact mechanism is not known, an interaction with neural crest cell function is thought to exist. Methods: After treatment with 1 μg all-trans retinoic acid at Hamburger and Hamilton stage 15 and reincubation until stage 34 of development 41 chicken embryos were evaluated macroscopically and microscopically, supported by graphic reconstructions. These retinoic acid treated embryos were compared with a control group (n = 8). Results: The retinoic acid treated embryos could be divided in three groups. Group 1 (23/41) had an intact septum, group 2 (11/41) had an isolated ventricular septal defect (VSD), and group 3 (7/41) had a double outlet right ventricle (DORV). Besides, in the group with an intact septum 11 hearts showed an abnormal course of the subaortic outflow tract. In the group with DORV a straddling tricuspid orifice (7/8) and a double inlet left ventricle (1/8) could be distinguished. Considering the external contour, the hearts in the DORV group all showed a dextroposed arterial pole. Malformed pharyngeal arch arteries were found in all three groups (11/41) and with a great diversity. Conclusions: The present cardiac malformations in the chicken as a result of retinoic acid treatment are part of a continuous spectrum, varying from hearts with an intact ventricular septum and a normal course of the subaortic outflow tract to a double outlet right ventricle with a straddling tricuspid orifice or even a double inlet left ventricle. A remarkable observation in this spectrum concerns the correlation of malformations of the inflow and outflow tracts, which is explained as a cardiac looping disturbance. The disturbance of the looping process seems to lead to malalignment of septal components, although, in the chick, retinoic acid does not in general interfere with the formation of these septal components themselves. © 1995 Wiley-Liss, Inc.     

Specific function and morphology of the right ventricle of the heart during ischemic injury of the left ventricle

Focal ischemia of the left ventricular myocardium was modeled by surgical ligation of the descending branch of the left coronary artery at the junction of the lower and middle thirds of this artery in anesthetized rabbits. Contractility and morphological characteristics of the right ventricular myocardium were evaluated 24, 72, and 120 h after treatment. Significant morphofunctional changes in the right ventricle manifested in the development of severe extracellular edema and increase in the area of damaged and destroyed myofibrils. However, the actual and maximum intraventricular pressure remained unchanged under these conditions. The degree of cardiomyocyte apoptosis increased on day 1, but returned to normal in the follow-up period. Our study demonstrated high sensitivity of the right ventricle to left ventricular dysfunction and early activation of compensatory mechanisms. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 4, pp. 392–394, April, 2008     

NKX2.5 mutation identification on exome sequencing in a patient with heterotaxy

Exome sequencing enables us to screen most of the protein coding genes in an unbiased way, this technique represents an ideal tool to identify previously under- or unappreciated phenotypes associated with known disease genes and genetic disorders. Here we present an illustrative case that required exome sequencing to identify a genetic alteration associated with the clinical features. The phenotype of the proband included heterotaxy, double outlet right ventricle, common atrioventricular canal, total anomalous pulmonary venous connection, asplenia, failure to thrive and short stature. Exome sequencing demonstrated a frameshift mutation c.397_400del (p.P133GfsTer 42) in NKX2.5. Although a single previous case of heterotaxy was reported in a large familial case of NKX2.5, heterotaxy is not clinically appreciated to be a part of the phenotypic spectrum associated with NKX2.5 mutations. This case report demonstrates the utility of exome sequencing in expanding a phenotypic spectrum of a known Mendelian disorder. We predict that this type of unexpected identification of mutations in known-disease associated genes in patients with atypical or expanded phenotypes will occur with increasing frequency as the use of exome and genome sequencing become more common tools in diagnosing patients with syndromic and non-syndromic foms of structural birth defects.     

Double outlet right ventricle in a human embryo

Summary A human embryo of 14 mm crown-rump length is described to exemplify the anomaly of double outlet right ventricle with subaortic defect. The configuration of endocardial swellings in the outflow portion of the heart are compatible with the general architecture of full-grown examples of the anomaly. This configuration differs considerably from normal embryonic anatomy, but is still supported by the architecture of the myoepicardial mantle. It is concluded that endocardial swellings play a secondary role in the determination of fullgrown cardiac anatomy.     

Fat in the right ventricle of the normal heart

AIMS: Fibrofatty replacement of the right ventricle wall, often with associated inflammation, is the hallmark of arrhythmogenic right ventricular cardiomyopathy (ARVC), a rare but established cause of sudden cardiac death in young adults. Fatty infiltration of the right ventricle alone without fibrosis may also occur but its relation to sudden death is not well established. In this study we assessed the amount of epicardial and intramyocardial fat in the right ventricle of 'normal' hearts from subjects who had died of non-cardiac causes. METHODS AND RESULTS: Hearts (n = 148) were examined from 81 males and 67 females, with an age range of 6 months to 68 years, who had died of non-cardiac causes. The extent and distribution of right ventricular epicardial and intramyocardial fat was assessed macro- and microscopically, respectively. The majority of hearts (85%) contained at least some intramyocardial fat with significantly more fat replacement noted in the right ventricles of older subjects and in females than in males. There was no significant fibrosis or inflammation in any of the 148 cases. CONCLUSION: Variable amounts of intramyocardial fat may be seen in the right ventricle of subjects dying of non-cardiac related causes. Care should be taken not to confuse this relatively common simple fatty infiltration with ARVC.     

自制可调节肺动脉环缩装置对右心室作用实验研究

目的通过对动物右心室作用实验的研究,验证自制可调节肺动脉环缩装置的有效性。方法 12只健康雄性小尾寒羊,5～6个月龄,体质量26～37kg。随机分为实验组和对照组,每组各6只,体质量分别为（29.00±2.78）kg和（28.36±4.24）kg,差异无统计学意义（P=0.722）,从左侧第二肋间进胸,游离肺动脉主干,置入自制可调节肺动脉环缩装置,向球囊内注入0.9%NaCl溶液,逐渐增加右心室压力,进行心室训练,达到训练标准所需时间为9～18d。观察超声下右心室形态、血流动力学及心肌组织病理学变化。结果超声下右心室形态、室间隔位置、游离壁厚度均较训练前发生明显改变;血流动力学结果表明右心室/左心室收缩压力比值大于0.6,达到临床上心室训练的标准;右心室的收缩功能（P〈0.05）和舒张功能（P〈0.001）均得到了增强;病理检查结果右心室游离壁厚度及质量、右心室肥大指数、心肌细胞横径与对照组比较差异存在显著统计学意义（P〈0.001）。结论该装置能够达到肺动脉环缩、训练心室的目的 ,并且可双向调节,使用方便,效果可靠。     

Primary cardiac fibroma of the right ventricle in an adult: report of one case

Cardiac fibroma is a rare primary benign cardiac tumor, especially in adults. It often occurs in the interventricular septum and free wall of the left ventricle and is solitary and space-occupying with clear boundaries. Here we report a 27-year-old male with a cardiac fibroma in the right ventricle, with extensive infiltrative growth. He was admitted to hospital with the complaint of exertional chest tightness, shortness of breath, hemoptysis, and edema of lower extremities. Ultrasound showed a large right ventricular mass blocking the outflow tract. The patient underwent palliative resection. Pathologic examination and Masson staining showed that collagen tissue proliferated and infiltrated myocardial fibers. The final diagnosis was cardiac fibroma.     

Spectrum of pathological changes in both ventricles of patients dying suddenly with arrhythmogenic right ventricular dysplasia. Relation of changes to age

AIMS: To quantify the variation in fibrosis, fat and muscle within the walls of both ventricles and within the different regions of the heart from six patients dying suddenly of arrhythmogenic right ventricular dysplasia (ARVD) aged 20-60 years. METHODS: Seven heart regions were examined both macroscopically and histologically using the Picro-Sirius red stain. Quantification of fibrosis, fat and muscle was performed in each region and transmural layer using grid counting. RESULTS: There were macroscopic changes in all examined hearts. A higher percentage of fat with less fibrosis and muscle was observed within the right ventricle of the older patients. The left ventricle had more pathology in the older age group. Statistical differences in pathology in the heart were found. Fat predominated in the epicardial layer in the right and left ventricles of all patients, while the interventricular septum was the least affected. CONCLUSIONS: In ARVD, the pathology varies with age in both ventricles, fibrosis being the earliest hallmark of disease, with fatty infiltration evolving later. It should be labelled arrhythmogenic ventricular dysplasia because of biventricular involvement. Histopathologists should therefore sample from whole slices of the heart, so that all the changes can be observed.     

176例右心室双出口的手术治疗分析

目的观察并探讨右心室双出口（DORV）手术矫治的疗效和治疗方法。方法分析1998年1月至2010年1月间176例DORV病人手术治疗的疗效。其中男105例,女71例,124例室缺（VSD）位于主动脉口下,12例室缺位于肺动脉口下,32例室缺位于两大动脉开口下,8例室缺远离两大动脉开口。114例建立室缺到主动脉口心内隧道,或者同时行右室流出道加宽,21例行内隧道外管道手术（Rastelli）,18例行改良G lenn分流术,11例行Fontan纠治术,7例行大动脉调转术（Sw itch）。结果住院期间死亡18例;出院后116例获随访,时间为6个月至8年,临床效果满意。结论 DORV解剖类型复杂多样,心室内隧道或补片要简洁,以确保左心室流出道顺畅。室缺位置及左室发育状况决定手术方案及疗效。     

伴异常冠状动脉法乐四联症右室双出口的外科治疗

目的：总结法乐四联症和右室双出口合并冠状动脉畸形手术治疗经验，探讨冠状动脉畸形对右室流出道重建的影响。方法：自1989年4月至2004年5月治疗合并冠状动脉畸形的法乐四联症和右室双出口20例，其中单支冠状动脉畸形11例，左前降支起自右冠状动脉6例，右冠状动脉-肺动脉瘘2例，左右冠状动脉交通支形成蔓状血管丛1例。行姑息手术1例，根治术19例。结果：根治术早期死亡1例，18例随访10个月至8年，残余漏2例，残余梗阻3例，余结果满意。结论：根据畸形冠状动脉走行特点，选择手术切口，避免损伤异常冠状动脉。     

Ventricular hypertrophy In sleep apnoea

SUMMARY  Ventricular hypertrophy is associated with an increased risk of cardiovascular death and cardiac events. In response to a haemodynamic load, ventricular hypertrophy may either be eccentric (dilation in response to volume overload) or concentric (increase in wall thickness in response to pressure overload). Ventricular hypertrophy increases with age, weight, blood pressure, and the presence of cardiovascular disease. It is greater in men than in women when adjusting for other variables. Echocardiography is the best method for accurate quantification of left ventricular mass and for detecting right ventricular hypertrophy. In obstructive sleep apnoea there are reports of both eccentric and concentric hypertrophy of the left ventricle. However, many of these reports have failed to control for patient weight or age. More recent reports indicate that much of the hypertrophy of the left ventricle reported in obstructive sleep apnoea can be related to patients' age, blood pressure, or size. However, right ventricular hypertrophy appears to be distinctly associated with the presence and severity of obstructive sleep apnoea. Right ventricular hypertrophy secondary to obstructive sleep apnoea may be the substrate for the eventual development of cor pulmonale and right heart failure. Its pathophysiological significance and potential use as a marker of severe OSA requires further investigation. Further investigation into left ventricular hypertrophy and sleep apnoea must control for the potentially confounding variables listed above and will require population-based and/or carefully matched case control studies.     

牛右心室节制索及右束支的解剖观测

目的了解牛右心室节制索及右束支的形态特点及分布规律,为比较解剖学和兽医学积累解剖学资料。方法24例新鲜市售牛心,用大体解剖和墨汁灌注方法显示牛右心室传导系。肉眼观察右心室内各结构的形态和分布,用游标卡尺测量数据,SPSS统计软件处理相关数据。结果节制索多为扁圆柱状(90.5%),长(45.48±1.32)mm,长直径(3.78±1.54)mm,短直径(2.55±1.26)mm,右束支长(65.52±20.78)mm,直径(1.45±0.56)mm。发现1例双节制索。Purkinje纤维的分布第Ⅰ、Ⅱ象限最密集,第Ⅲ三象限较少分布,第Ⅳ象限分布最少。结论牛心节制索的形态与其他哺乳动物相似,其中有右束支穿行,其表面有分布不均的Purkinje纤维。     

Crista Supraventricularis Purkinje Network and Its Relation to Intraseptal Purkinje Network

Using transparent specimens with a dual color injection, microscopy, and computer tomography, this report shows that the right and left ventricular subendocardial Purkinje networks are connected by an extensive septal network in the bovine heart. The septal network is present along the entire septum except at a free zone below ventricular valves. Being the only communication of the basal right septum with the right free wall, the supraventricular crest is an enigmatic but not, by any means, hidden muscular structure. It is one of the last structures to be activated in human heart. It is shown here that the supraventricular crest Purkinje network connects the anterosuperior right ventricular basal free wall Purkinje network to anterior right ventricular basal septal Purkinje network. It is suggested that the stimulus initiated at middle left ventricular endocardium will activate the supraventricular crest. The intraseptal connection found between the basal left ventricular subendocardial septal Purkinje network and the right ventricular basal septal Purkinje network is, probably, the pathway for the stimulus. An anatomic basis is provided to explain why the inflow tract contracts earlier than the outflow tract in the right ventricle systole. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 300:1793–1801, 2017. © 2017 Wiley Periodicals, Inc.     

Chronic right ventricular pressure overload results in a hyperplastic rather than a hypertrophic myocardial response

Myocardial hyperplasia is generally considered to occur only during fetal development. However, recent evidence suggests that this type of response may also be triggered by cardiac overload after birth. In congenital heart disease, loading conditions are frequently abnormal, thereby affecting ventricular function. We hypothesized that chronic right ventricular pressure overload imposed on neonatal hearts initiates a hyperplastic response in the right ventricular myocardium. To test this, young lambs (aged 2-3 weeks) underwent adjustable pulmonary artery banding to obtain peak right ventricular pressures equal to left ventricular pressures for 8 weeks. Transmural cardiac tissue samples from the right and left ventricles of five banded and five age-matched control animals were studied. We found that chronic right ventricular pressure overload resulted in a twofold increase in right-to-left ventricle wall thickness ratio. Morphometric right ventricular myocardial tissue analysis revealed no changes in tissue composition between the two groups; nor were right ventricular myocyte dimensions, relative number of binucleated myocytes, or myocardial DNA concentration significantly different from control values. In chronic pressure overloaded right ventricular myocardium, significantly (P < 0.01) more myocyte nuclei were positive for the proliferation marker proliferating cellular nuclear antigen than in control right ventricular myocardium. Chronic right ventricular pressure overload applied in neonatal sheep hearts results in a significant increase in right ventricular free wall thickness which is primarily the result of a hyperplastic myocardial response.     

超声心动图对诊断双腔右心室的价值

目的 探讨超声心动图对诊断双腔右心室（DCRV）的价值；方法 总结1995年1月-2001年5月间经手术证实为双腔右心室的12例住院病例资料，分析其超声心动图特点，并与手术结果进行对照；结果 超声心动图上右心室腔内室上嵴至右心室游离壁见粗大肌束横跨，中央孔狭窄，将右心室分成高压腔及低压腔，彩色多普勒血流显像（CDFI）在中央孔示五色镶嵌的湍流，CW估测中央孔狭窄压差来判断病变程度；12例患，超声心动图诊断DCRV与手术符合10例，符合率为83.3%；DCRV以合并室间隔畸形最为常见；结论 超声心动图在诊断DCRV及其合并心脏畸形等方面具可靠价值，已成为临床上术前正确诊断及术后疗效评价重要手段。     

致心律失常性右室心肌病心力衰竭期的病理特点分析

目的 通过分析致心律失常性右室心肌病(ARVC)心力衰竭期的病理改变,以进一步了解其临床分期与病理表型的关系.方法 从2004-2007 年在阜外心血管病医院接受心脏移植的心力衰竭病例中,收集病理诊断为ARVC的受体心脏8例,测量心脏重量,评价左右心室心腔扩张、心肌细胞肥大、脂肪浸润、纤维化、附壁血栓和伴发心肌炎等指标,注意左心室受累情况,并进行病理分型.结果 8例中的7例为经典型(即右心室改变为主),1例为左优势型(左心室改变为主),未见双室型病例.组织学均为纤维脂肪型,未见单纯脂肪型病例.经典型病例的右心室中、重度扩张,少数有室壁瘤形成,其中6例伴左心室受累,受累左心室轻、中度扩张,心肌广泛间质纤维化,部分病例伴替代性疤痕,而脂肪浸润量小,多局限于心外膜下.左心室心肌细胞肥大普遍.而左优势型的左心室重度扩张,弥漫间质纤维化和局部透壁性脂肪浸润.8例中3例左心室明显肥厚,3例查见双室附壁血栓,1例伴局灶性心肌炎.结论 ARVC心力衰竭期的左心室受累多见而严重,左心室间质纤维化突出,心肌细胞肥大明显,但脂肪替代少见和局限.左、右心室多扩张,可见附壁血栓,应注意与扩张型心肌病等鉴别.     

Hypertension-induced changes in the rat myocardium during the development of cardiac hypertrophy – a comparison between the left and the right ventricle

The hypertrophy of the cardiac muscle is one of the most significant maladaptive mechanisms activated in response to increased workload. It is associated with histological and ultrastructural alterations, changes in the quantitative parameters and the expression of different enzymes. While the structural and functional consequences of systemic hypertension on the left ventricle have been well evaluated, the right ventricle has received less attention. The aim of the present study was to analyse and compare the changes in the left and right ventricle during the development of cardiac hypertrophy initiated by systemic hypertension in different age groups of spontaneously hypertensive rats. Therefore, we studied the histology and ultrastructure of the cells of the myocardium, evaluated the immunohistochemical expression of the enzyme neuronal nitric oxide synthase and conducted a quantitative analysis of several morphometric parameters. We used three groups of spontaneously hypertensive rats. For the quantitative analysis we also used three age groups of age- and weight-matched control animals (normotensive Wistar rats). In both ventricles, we described cardiomyocytic hypertrophy, focal myocytolysis and increased collagen deposition in the interstitial space. Our observations on the ultrastructural level were associated with changes in the cardiomyocytic nuclei, the arrangement, maturity and organisation of the myofibrils, the localisation and ultrastructure of the mitochondria, the development and maturity of the intercalated discs, as well as changes in the components of the interstitium. The immunohistochemical expression of neuronal nitric oxide synthase in the left ventricle was stronger than that in the right ventricle across all age groups. The comparative quantitative analysis revealed that changes in the studied morphometric parameters in the two ventricles occurred disproportionately. In conclusion, the present study characterised the development of cardiac hypertrophy in response to systemic hypertension in both ventricles and demonstrated the involvement of the right ventricle.