Switching of the great vessels (arterial switch surgery) in transpositio vasorum

Since April 1992 the arterial switch operation (ASO) has been the treatment of neonates with transposition of the great arteries (TGA) at Rigshospitalet, Copenhagen. Thirteen mature neonates with TGA underwent ASO. Ten patients had simple TGA, two had TGA associated with a ventricular septal defect (VSD), and one had TGA with VSD and in addition moderate right ventricular hypoplasia. All patients survived the operation and are still alive. Perioperative bleeding was a problem in three cases. Eleven patients had an uncomplicated postoperative course. One patient had peri- and postoperative left ventricular failure and was reoperated after three months for a residual VSD. One child developed renal failure and needed peritoneal dialysis. The patients have been followed for 5.5 (range 0-12) months, they are all in good condition and thriving well. The presented early results after ASO justify continued recommendation of ASO as the operation of choice for TGA in neonates at Rigshospitalet.     

Heparin inhibits mesenteric vascular hypertrophy in angiotensin II-infusion hypertension in rats

OBJECTIVE: Chronic infusion with angiotensin II increases blood pressure and activates growth mechanisms to produce hypertrophy of the heart and vessels. In order to better understand mechanisms of angiotensin II induced vascular hypertrophy, this study aimed to determine whether heparin, a potent inhibitor of smooth muscle proliferation mechanisms, was able to inhibit vascular hypertrophy. METHODS: Angiotensin II (100, 200 or 300 ng/min/kg s.c.) or a saline vehicle control were infused into rats for 14 days. A separate group of animals were co-infused with heparin (0.3 mg/h/kg i.v.) and angiotensin II (200 ng/min/kg s.c.) to test whether hypertension or hypertrophy were antagonized. Blood pressure was measured by tail cuff method and vessel media cross sectional area was measured by morphometry in aorta and mesenteric arteries. RESULTS: Blood pressure elevation and cardiovascular hypertrophy produced by angiotensin II were strongly dose-dependent. Hypertrophy responses at 14 days of treatment also appeared to be influenced partly by local factors as medial cross sectional area was increased more in mesenteric arteries than in thoracic aorta, and left ventricle weight was least affected. Heparin treatment did not influence the increase of blood pressure in angiotensin II infused animals, but the mesenteric vascular hypertrophy response due to angiotensin II was inhibited by approximately 50%. Inhibition of a modest cardiac hypertrophy and aortic medial hypertrophy did not reach significance. CONCLUSIONS: Angiotensin II infusion produced vascular medial hypertrophy and increased blood pressure, however the inhibitory effect of heparin on hypertrophy in mesenteric arteries was not mediated through angiotensin II induced vasoconstriction or blood pressure elevation. These data suggest that heparin interferes directly with the hypertrophy mechanism in mesenteric arteries, and that heparin-sensitive growth mechanisms are important in mediating angiotensin induced mesenteric vascular hypertrophy.     

Inoperable pulmonary vascular disease in infants with congenital heart disease

BACKGROUND: Among 120 infants less than 12 months of age who had lung biopsy and autopsy, 20 were inoperable because of severe irreversible pulmonary vascular disease. METHODS: The infants were classified into three groups. Group 1 comprised 6 patients who showed complete obstruction of the small pulmonary arterial lumen and atrophy of the peripheral arterial media and who were considered to have absolute operative contraindications. Group 2 comprised 6 patients who had no pathologic findings of absolute operative contraindication and had an index of pulmonary vascular disease of more than 2.2. They were isolated as having advanced plexogenic pulmonary arteriopathy. Group 3 comprised 8 patients who had extremely thickened media of small pulmonary arteries, with abnormally thickened media extending into the small peripheral arteries characterized by extremely narrow lumina and medial thickness exceeding luminal diameter. RESULTS: Six of the 9 patients in whom operative repair was abandoned on the basis of preoperative or intraoperative lung biopsy are still alive. Of the 11 patients who underwent operation without biopsy, none survived. CONCLUSIONS: Preoperative or intraoperative lung biopsy and assessment of arteriopathy based on the above criteria are recommended in all patients in whom fatal pulmonary vascular disease is suspected.     

Rastelli's procedure

In 1969, Rastelli conceived a new technique to repair of transposition of the great arteries in the presence of ventricular septal defect and severe pulmonary stenosis (TGA III), based on the redirection of ventricular outflows. An intracardiac tunnel connected the left ventricle to the aorta and an external valved conduit established continuity between the right ventricle and the pulmonary artery. TGA III and truncus arteriosus are underwent a Rastelli operation. The present report is an analysis of indication, operative technique, early and late results with this procedure. Early deaths were related to unfavourable anatomy, conduit compression and sepsis. Residual VSD and postoperative infection were the main factors contributing to the late deaths. A current Re-Rastelli operation for the problems of extracardiac valved conduit is a good result.     

De subitaneis mortibus. XIX. On the cause of sudden death in pheochromocytoma, with special reference to the pulmonary arteries, the cardiac conduction system, and the aggregation of platelets

Pheochromocytoma may cause sudden and unexpected death. In this study of three fatal cases of pheochromocytoma the small pulmonary arteries were narrowed by a variety of chronic and acute processes which included medial hypertrophy and fibrosis, endothelial proliferation and fibrosis, and endothelial cellular edema; within the sinus node, atrioventricular (A-V) node and His bundle of all three cases there was focal degeneration and fibrosis similar to that also observed throughout the ventricular myocardium; and in addition to the focal narrowing of many small coronary arteries produced by medial hypertrophy, intimal fibrosis, and fibromuscular dysplasia, there were also focal aggregations of platelets clogging the lumen and occasionally mixed with a varying amount of fibrin. In patients known to have pheochromocytoma it may be necessary to direct new attention to the possibility of abnormal pulmonary vascular resistance, instability of normal cardiac rhythm, and perhaps difficulty in restoring it when disordered and to the effects of platelet aggregations, both causing acute obstruction and possibly contributing to the pathogenesis of chronic vascular disease.     

Characteristics of a human cell line transformed by DNA from human adenovirus type 5

One hundred and fifty lungs from the cases below 15 years of age with various congenital heart diseases and 80 controls were used for histometrical and histological studies. Cases with congenital heart disease were divided into two groups of the increased and the decreased pulmonary blood flow. In the former group, the thickness of the pulmonary arterial media was the same as that of controls in the neonatal period, and through the wall thickness gradually decreased in a pattern seen in controls, the thickness was constantly larger than that of controls. In some cases, the media increased gradually within 6 months after birth. Pneumonia and massive pulmonary hemorrhage were seen in a higher incidence in autopsy cases. Pneumonia in younger infants was histologically characteristic and possibly more correlated to their death. In the latter group, most of the cases were with the thinner medias of the pulmonary arteries. Massive pulmonary hemorrhage was not common in the latter group.     

Pathophysiological response of the blood coagulation system in acute glomerulonephritis

1. The effects of clonidine on blood pressure, cerebral norepinephrine content and vascular structures of the kidneys were investigated in 21 SHR. Although the body weight was not affected by long term clonidine treatment up to 36 weeks, the syatolic blood pressure was significantly reduced. The reduction of the blood pressure was already obvious after 1 week administration of clonidine but the effect was more prominent after long term treatment of 30 weeks or longer. 2. The cerebral norepinephrine content was significantly lower in SHR, regardless of with or without clonidine treatment, than in the control Wistar rats. Although the cerebral norepinephrine content was slightly increased following clonidine treatment SHR, the increase was not statistically significant. 3. Angiographic study of the kidneys revealed a poor opacification of the blood vessels and glomeruli in SHR compared with the control Wistar rats. There was no difference in the sizes of the arcuate and interlobular arteries in SHR and the control Wistar rats, although the medial muscular hypertrophy of the arteries was slightly more prominent in the SHR histologically. The more prominent in the SHR histologically. The angiographic and histologic findings of the renal arteries were not altered following long term clonidine treatment. A possibility was considered that the renal arterioles are mainly functionally affected in SHR.     

Evaluation of contrast echocardiography and lung perfusion scan in detecting intrapulmonary vascular dilatation in normoxemic patients with early liver cirrhosis

BACKGROUND/AIMS: Intrapulmonary vascular dilatations (IPVD) are extrahepatic complications occurring in liver transplant candidates, that can result in severe hypoxemia. The aim of this study was to compare the use of two diagnostic modalities, contrast echocardiography and lung perfusion scan, in detecting IPVD in normoxemic patients with early liver cirrhosis. METHODOLOGY: Fifty-six consecutive outpatients with biopsy-proven cirrhosis had contrast-echocardiography, a lung perfusion scan, pulmonary function tests, and arterial blood gas estimations. All patients were grade A or B according to the Child-Pugh classification. Patients with chronic intrinsic lung disease, heart failure or malignancy were excluded from the study. RESULTS: All patients had normal arterial blood-gas analyses. Eight out of 56 patients (14.3%) had a positive contrast echocardiogram, all with a decreased diffusion capacity (DLCO < 75% of the predicted value). An isolated DLCO impairment was observed in 40% of the patients with normal spirometry. None of the patients with echocardiography-proven IPVD had a positive lung perfusion scan (p<0.005). CONCLUSIONS: In normoxemic cirrhotic patients, subclinical pulmonary vasodilatation and gas-exchange abnormalities can occur. Contrast-enhanced echocardiography is the most valuable screening test in detecting IPVD in the early stages of hepatic insufficiency.     

Differentiation between selected pairs of tripeptide diastereomers by tandem mass spectrometry on a hybrid tandem mass spectrometer

Two cases of transposition of the great arteries (TGA) with posterior aorta are reported. The first was submitted to the Senning procedure with good outcome; the other had the diagnosis of double outlet right ventricle with severe pulmonary stenosis, and a Blalock-Taussig shunt was accomplished for hypoxic crisis. The patient died 11 days after surgery and the necropsy demonstrated TGA with posterior aorta. In both cases there was a sub-pulmonary infundibulum. The presence of ventricular septal defects allowed aortic-mitral fibrous continuity, a finding previously described in anatomical reports. Clinical and angiographic aspects are discussed.     

Intramural coronary artery dysplasia of the ventricular septum and sudden death

We report four cases of sudden unexpected death in three males and one female aged 12 to 31 years. Death occurred during exercise in three of four cases, and there was no history of sudden death or previous cardiac history in any patient. At autopsy, there was marked intramural coronary artery dysplasia of the ventricular septum, accompanied in three of the four cases by myocardial fibrosis. The arterial dysplasia was characterized by severe medial thickening with smooth muscle cell disorganization and marked luminal narrowing. There was no evidence of myofiber disarray or asymmetric septal hypertrophy to suggest hypertrophic cardiomyopathy. Other than an ostium secundum type atrial septal defect in one case, there were no associated cardiac or extracardiac lesions found at complete autopsy of these individuals. We conclude that small vessel disease of intramural coronary arteries of the ventricular septum may be an isolated finding leading to sudden cardiac death in young adults.     

Sturge-Weber syndrome: experience with 14 cases

We report a first documented case in Senegal with simple transposition of the great arteries diagnosed in a 2 months old girl treated by Rashkind atrioseptostomy. Our patient benefited from clinical examination, ECG (15 derivations), chest X ray and standard laboratory tests. Pulsed-Doppler, two dimensional and TM echocardiography have been performed with an ATL MK 600 echocardiograph. Cardiac catheterism, angiocardiography and Rashkind procedure have been realized in our Department. These data are discussed and compared to the literature. At admission this patient presents with major cyanosis and polypnea. At examination, there is a 3/6 murmur at the left sternal border and a subclavicular continuous murmur. Laboratory tests showed metabolic acidosis and severe hypoxemia. Chest x-ray showed a cardio-thoracic ratio at 0.64 with increased pulmonary vascular markings. ECG showed right ventricular hypertrophy. Echocardiography-Doppler revealed ventriculo-arterial discordance with restrictive atrial septal defect and persistent ductus arteriosus. Rashkind procedure was followed by an increased aortic saturation. After 6 weeks there was an improvement of cyanosis and cardiac failure. Diagnosis of transposition of the great arteries is actually easier with development of ultrasonography which is useful when performed by experienced cardiologist. Spontaneous prognosis of this malformation is very poor. Rashkind atrioseptostomy is an important step for the initial treatment of transposition of the great arteries in terms of survival before open heart surgery.     

Renal and vascular effects of chronic endothelin receptor antagonism in malignant hypertensive rats

The effect of the combined ETA/ETB endothelin receptor antagonist bosentan on blood pressure, vascular hypertrophy, and pathologic renal changes was investigated in a model of malignant hypertension, severe vascular hypertrophy, and enhanced vascular expression of endothelin-1, the deoxycorticosterone acetate (DOCA), and salt-treated spontaneously hypertensive rat (SHR). DOCA-salt treated SHR received 100 mg bosentan per kilogram weight per day mixed with their food. Systolic blood pressure of untreated DOCA-salt SHR rose to 241 +/- 1.5 mm Hg, whereas that of bosentan-treated rats rose to 221 +/- 5.1 mm Hg (P < .01). Cardiac and conduit artery mass were not affected by treatment. Small arteries from the coronary, renal, and mesenteric circulations showed a smaller media width and cross-sectional area of the media in rats treated with bosentan than in untreated rats. The kidneys showed the presence of fibrinoid necrosis in a high percentage of afferent arterioles and glomeruli of untreated DOCA-SHR. Some kidneys of treated rats exhibited less severe vascular hypertrophy and lesser extent of vascular or glomerular fibrinoid necrosis, but the renal injury score of bosentan-treated DOCA-SHR was only at the limit of significance from that of untreated rats (P = .06). These results suggest a role for endothelin-1 in blood pressure elevation and the severe vascular hypertrophy of small arteries of the coronary, renal, and mesenteric vasculature, but not of the heart or larger conduit vessels in the malignant hypertension that SHR develop after treatment with DOCA and salt. Although some bosentan-treated rats showed fewer renal lesions, a significant effect on renal pathology could not be unambiguously demonstrated. Further studies will be necessary to determine whether endothelin antagonists may indeed offer some degree of renal protection and have therapeutic potential in severe or malignant hypertension.     

The genetics of black larva, an autosomal recessive lethal mutation located on chromosome 3 in the mosquito Anopheles albimanus

Lung tissue from 14 normal residents of high altitude regions, 10 patients with chronic bronchitis and emphysema, and 1 patient with Pickwickian syndrome was studied with regard to the occurrence of pulmonary vascular changes. In addition to the well-known pulmonary arterial alterations, lesions in small pulmonary veins were found in the great majority of the cases. These changes, consisting of medial hypertrophy and arterialization and of bundles of smooth muscle cells within the venous intima, have not been described before in man. These findings suggest that alveolar hypoxia acts not only on small pulmonary arteries and arterioles but also on veins of small caliber, probably by inducing venoconstriction.     

Congenitally corrected transposition of the great arteries: morphologic study of 32 cases

The detailed anatomy of the heart is described in 32 autopsy cases of congenitally corrected transposition of the great arteries.Tis condition is defined as the combination of atrioventricular (A-V) discordance and transposition of the great arteries. Examples of primitive (single) ventricle with "inverted" (that is, left-sided in situs solitus) outlet chamber are excluded. Six hearts with A-V discordance and pulmonary atresia are described in an appendix. In 29 cases of corrected transposition the heart was in situs solitus; in 3 it was in situs inversus totalis. Only 5 of these 32 hearts had no potential for intracardiac shunting. Anomalies of the tricuspid valve (91 percent of cases), ventricular septal defect (78 percent) and pulmonary outflow tract obstruction (44 percent) occurred with sufficient frequency to be considered part of the basic malformation and are described in detail. The precise anatomy and disposition of the A-V valve tension apparatus, the coronary arteries and the conducting tissues are described with special reference to possible surgical approaches for repair of the anomalies. In two hearts with situs solitus the aortic valve was right-sided with respect to the pulmonary valve. This finding is important for both diagnosis and nomenclature.     

An autopsy case of urinary bladder carcinoma with pulmonary infarction and subacute cor pulmonale caused by tumor embolization

Pulmonary tumor embolism is a common finding at autopsy but is difficult to diagnose clinically antemortem. We report an autopsy case of urinary bladder carcinoma associated with tumor emboli of the pulmonary arteries and subsequent pulmonary infarctions. An eighty-six-year-old man with bloody sputum showed multiple infiltrates on chest X-ray and multiple pleural based parenchymal lesions with truncated apex on computed tomography. The patient had a history of radiation therapy against urinary bladder carcinoma two years earlier. Transitional type carcinoma cells were identified from a urine sample obtained on admission. Three weeks later, the patient developed subacute cor pulmonale and died in severe respiratory distress. Postmortem examination revealed primary carcinoma of the urinary bladder. Multiple tumor emboli of pulmonary arteries and subsequent pulmonary infarctions were visible microscopically. There was a large amount of effusion in both the pleural and the abdominal space. The heart contained focal scarring and mild right ventricular hypertrophy and there was congestion of the lungs, liver, kidneys and spleen. Pulmonary tumor embolization may present at any stage of the patient's illness but rarely causes subsequent pulmonary infarctions. Cytologic examination of blood samples obtained from Swan-Ganz catheters may be useful in the diagnosis of tumor embolization.     

Chronic thromboembolic pulmonary hypertension

Acute pulmonary hypertension has a high mortality at the onset. Patients surviving the first phase will usually recanalize the pulmonary arteries through intrinsic thrombolytic mechanisms and medical treatment. However, in some cases there is insufficient resolution of the emboli with subsequent thrombotic and fibrotic reorganization, leading to a worsening of the pulmonary obstruction. In the open pulmonary arteries the disease may lead to hypertrophy of the media and intimal proliferation, thus leading to a further increase in the pulmonary vascular resistance. This again leads to hypertrophy of the right ventricle and ultimately to right-sided heart failure. Untreated, chronic thromboembolic pulmonary hypertension has a five-year mortality approaching 100%, but extensive pulmonary thrombendarterectomy using extracorporeal circulation and deep hypothermia has been shown to lower the pulmonary vascular resistance and thereby improve the prognosis significantly. Operative treatment can now be offered in Denmark, and the purpose of this review is to draw attention to the disease, its symptoms, diagnosis and the surgical treatment.     

Is angiographic spasm real spasm?

Systematic morphological study of the cerebral arteries was made in six autopsy cases of ruptured aneurysms. The time course of the arterial luminal narrowing was observed by repeated angiograms, and segments of the narrowed arteries were studied histologically. Various histological changes were found consistent with the angiographic findings. We have devided these into three stages according to the duration of the disease. In the acute stage (less than one day) the contraction of the medial smooth muscle cells may be the main cause of the luminal narrowing. In the subacute stage, arteries showed a reduction in lumen size with medial thickening, marked corrugation of the internal elastic lamina, and thrombus formation attached to the endothelial surface. If vasoconstriction remained localized to the same segment for several days, the intimal or medial thickening and thrombus might produce the luminal narrowing consistent with the angiographic narrowing. In the chronic stage (more than two weeks), most cases showed dilatation of the arterial lumen on angiography. These arteries showed frank necrosis of the smooth muscle cells histologically. In a case which demonstrated progressive luminal narrowing on angiograms over 2 weeks, the arterial wall showed luminal narrowing with cellulofibrous thickening of the intima and organization of the thrombus. The presence of these structural changes in the narrowed arteries seen at angiography seems to be very important for proper understanding and treatment of vasospasm.     

Clinical primary pulmonary hypertension: three pathologic types

Clinically, there is a group of patients with elevated pulmonary arterial pressure in whom the underlying cause is not apparent. The pulmonary arterial wedge pressure is not elevated. For such cases, the designation of primary pulmonary hypertension may be made clinically. From the clinical categorization of primary pulmonary hypertension, three distinct pathologic entities emerge, namely 1) plexogenic pulmonary arteriopathy, 2) recurrent pulmonary thromboembolism, and 3) pulmonary veno-occlusive disease. The plexogenic type is characterized initially by pulmonary arterial vasoconstriction with medial hypertrophy. Secondary proliferative intimal lesions, including the plexiform lesion, develop. Recurrent pulmonary thromboembolism is characterized by the presence of arterial thrombi of varying ages involving the microscopic-sized pulmonary arteries. Thrombi may be embolic in nature or may develop in situ. Pulmonary veno-occlusive disease is characterized by obstructive lesions of pulmonary veins and venules. The clinical presentation of the three pathologic types may be so similar that definitive diagnosis depends upon histologic examination of the lung from tissue obtained either by biopsy or at necropsy.     

Pulmonary intralobar sequestration in a patient with cystic fibrosis

We report a case in which pulmonary Intralobar Sequestration (ILS) was an incidental finding at autopsy in an adult with Cystic Fibrosis. Two aberrant arteries from the descending thoracic aorta supplied a bronchial cystic lesion in the right lower lobe. Termination of the segmental bronchus and scar formation proximal to the cyst suggested prior bronchial obliteration. The elastic configuration of the aberrant aortic-derived vessels of the sequestration contrasted sharply with massively hypertrophied, muscular, bronchial arteries which supplied the bronchiectatic upper lobe. Sections of inferior pulmonary ligament were studied in five additional patients with CF but without ILS. Small muscular arteries were consistently noted within the inferior pulmonary ligament. These histologic findings support the concept that the vascular portion of ILS is congenital, whereas the bronchocystic component, in some cases, may be acquired.