Coronary arterial ectasia, a predominant type of coronary sclerosis in aged captive rhesus monkeys (Macaca mulatta).

In hearts from aged rhesus monkeys, ranging from 20 to over 30 years, marked coronary arterial ectasia, dilatation, and tortuosity of the entire vessel were observed in 18 animals. Another 7 animals showed a moderate degree of ectatic changes. Dilated arteries showed remarkable thinness of the tunica media with atrophy and attenuation of the muscle cells and increased fibrous tissue. Diffuse or focal intimal fibrous thickening was present in the ectatic arterial wall, but cholesterol deposit, calcification, or the presence of lipid-laden foam cells in the intimal and medial wall was not observed. A focal degeneration and fibrosis of the myocardium were seen in the hearts of 11 cases. Clinically, 2 cases had either spontaneous diabetes mellitus or cardiac decompensation with mitral insufficiency, but the others had no abnormal metabolic or cardiovascular histories. Coronary arterial ectasia accompanied with medial fibrosis appears to be a predominant type of coronary arterial lesion in aged rhesus monkeys under long-term captivity.     

Pulmonary vasculitis with hypereosinophilia and episodic pulmonary hypertension: Report of three siblings

Three siblings with eosinophilia who developed pulmonary hypertension are reported. They consisted of a 3 year old boy (case I), a 9 year old boy (case 2) and a 13 year old girl (case 31, all of whom died within an 18 month period of severe episodic attacks of pulmonary hypertension and the resultant low cardiac output. Marked peripheral eosinophilia was found in cases 1 and 2, and mild eosinophilia in case 3. Open lung biopsy of case 1 revealed pulmonary arteritis with massive eosinophilic infiltration and intimal thickening of muscular arteries of 300–1500μm in diameter. At autopsy, caws 2 and 3 showed almost similar findings, comprising widespread obliteration of the pulmonary arteries by concentric intimal thickening, medial hypertrophy and recanalized thrombi of arterioles. Rarely, there were foci of granulomas in the thickened intima surrounding birefringent foreign bodies. There were small areas of infarction in the lungs and heart due to arterial thrombi. Vascular lesions other than those in the lungs were mild and almost limited to the branches of the coronary arteries. Therefore, the present cases appear to be a single disease of pulmonary hypertension secondary to endothelial injury and the resultant intimal fibrosis probably evoked by toxic substances, although such agents were not confirmed.     

Circumferential wall tension due to hypertension plays a pivotal role in aorta remodelling

The present study was carried out to investigate the role of hypertension in the genesis and localization of intimal lesions and medial remodelling found in the prestenotic segment in relation to a severe stenosis of the abdominal aorta just below the diaphragm. Male young rats were divided randomly into operated group, animals submitted to surgical abdominal aorta stenosis, and sham-operated group, a control group of animals submitted to sham operation to simulate abdominal aorta stenosis. Aortas in the hypertensive prestenotic segment with increased circumferential wall tension associated with normal tensile stress, laminar flow/normal wall shear stress were characterized by enlarged heterogeneous endothelial cells elongated in the direction of the blood flow, diffusely distributed conspicuous neointimal plaques and medial thickening. The immunohistochemical analysis revealed an increased expression of eNOS, iNOS, nitrotyrosine and transforming growth factor-beta (TGF-beta) in endothelial cells and/or smooth muscle cells in this segment. Our findings suggest that increased circumferential wall tension due to hypertension plays a pivotal role in the remodelling of the prestenotic segment through biomechanical effects on oxidative stress and increased TGF-beta expression. Further studies are needed to clarify the intrinsic pathogenetic mechanism of focal distribution of the neointimal plaques in the hypertensive segment.     

Percutaneous transluminal coronary angioplasty - Histopathological analysis of nine necropsy cases

Summary From 1982 to 1984 nine of 300 patients undergoing transluminal coronary angioplasty died. The nine coronary arteries and one saphenous aorto-coronary by-pass graft affected by angioplasty were studied by light microscopy. The following types of lesions were found, frequently in association: rupture of the plaque, circumscribed or reaching to the intimal layer or extending beyond it, dissections (fissures) between arterial layers, intra-plaque haemorrhage, plaque emboli and thrombosis. In two cases the therapeutic approach was considered to be clinically and pathologically successful; the patients survived 24 h (case 6) and forty days (case 4). Case 6 which presented recent lesions indicative of success showed, in contrast with the other non-successful cases, rupture affecting not only the initimal layer but also deeper structures of the arterial wall. There were also more extensive fissures. Case 4 which presented late alterations indicative of success showed a plaque fracture whose borders were kept apart by fibrous tissue. In conclusion, we believe that angioplasty allows the re-establishment of arterial blood flow by provoking deep intimal and medial rupture producing a small fissure between the arterial layers and a widening of the lumen; in cases with good late results these alterations cicatrize leaving a wider arterial lumen.     

Pulmonary hypertension associated with portal hypertension in childhood. Case report of a 6-year-old child and review of the literature

Pulmonary hypertension is a rare complication of portal hypertension. Reports of childhood cases especially rare. This report describes an autopsy case of a 6-year-old boy with congenital biliary atresia followed by liver cirrhosis in whom severe hypertensive pulmonary arterial changes, including medial hypertrophy, intimal fibrosis and plexiform lesions were demonstrated. Fresh and organizing fibrin-platelet thrombi as well as probable organized thrombi with recanalization were occasionally found in the pulmonary vasculature, but it was thought that they had probably been formed locally as a late complication rather than being of thromboembolic origin. Retrospectively, the chest roentgenograms had revealed abnormalities suggestive of pulmonary hypertension since infancy, but the patient showed no apparent symptoms of it during life. Previously reported childhood cases of pulmonary hypertension associated with portal hypertension were briefly reviewed. Although the mechanism is presently not known, it is suggested that patients with portal hypertension, even in early childhood, are at risk of developing this unusual complication.     

PULMONARY HYPERTENSION ASSOCIATED WITH PORTAL HYPERTENSION IN CHILDHOOD. Case Report of a 6-Year-Old Child and Review of the Literature

Pulmonary hypertension is a rare complication of portal hypertension. Reports of childhood cases are especially rare. This report describes an autopsy case of a 6-year-old boy with congenital biliary atresia followed by liver cirrhosis in whom severe hypertensive pulmonary arterial changes, including medial hypertrophy, intimal fibrosis and plexiform lesions were demonstrated. Fresh and organizing fibrin-platelet thrombi as well as probable organized thrombi with recanalization were occasionally found in the pulmonary vasculature, but it was thought that they had probably been formed locally as a late complication rather than being of thromboembolic origin. Retrospectively, the chest roentgenograms had revealed abnormalities suggestive of pulmonary hypertension since infancy, but the patient showed no apparent symptoms of it during life. Previously reported childhood cases of pulmonary hypertension associated with portal hypertension were briefly reviewed. Although the mechanism is presently not known, it is suggested that patients with portal hypertension, even in early childhood, are at risk of developing this unusual complication. ACTA PATHOL JPN 38: 897∼907, 1988.     

Eliminating Arterial Pulsatile Strain by External Banding Induces Medial but Not Neointimal Atrophy and Apoptosis in the Rabbit

We have examined the role of vessel pulsation and wall tension on remodeling and intimal proliferation in the rabbit infrarenal abdominal aorta. A rigid perivascular polyethylene cuff was used to reduce vessel systolic diameter by 25%, producing a region of reduced circumferential strain. At 6 weeks postoperatively, reduced circumferential strain caused medial atrophy, with 45% reduction of medial area and 30% loss of medial smooth muscle cells. Apoptotic cell death was indicated by DNA fragmentation, propidium iodide staining, and cell morphology. Cuffing the aorta after balloon denudation produced medial atrophy but did not inhibit neointimal growth. At 1 week postoperatively, intimal thickness was slightly decreased in regions with reduced strain; however, intimal thickening in regions of reduced strain was not different from control segments at 3 weeks postoperatively (intimal area was 0.37 ± 0.05 mm² with reduced strain and 0.50 ± 0.08 for controls, mean ± SEM). We conclude that circumferential strain is a major factor controlling medial structure and cell number, whereas growth of the neointima after injury is not significantly affected by either reduced strain or extensive medial cell death. Vessel cuffing represents a new model of blood vessel remodeling in vivo that involves extensive smooth muscle cell apoptosis.     

Vascular changes in radiation bowel disease

A series of 20 cases of radiation bowel disease (RBD) was studied qualitatively and the arterial changes were studied quantitatively. A control series of 45 cases was studied. In the control cases there were positive correlations between the medial thickness of all vessels studied and the diastolic blood pressure as well as the incidence of intimal fibrosis in both intramural and extramural arteries. The medial thickness in all the arteries in cases of RBD was significantly higher than in the controls. This was probably due to the large number of fibrin thrombi which increased the vascular resistance. The degree of intimal fibrosis of the intramural arteries and arterioles was significantly greater than in the controls. Similarly the incidence of intimal fibrosis in all arterioles and intramural arteries was greater than the control group. The degree of intimal fibrosis was related to the dose of radiation received. The effect of radiation was an on-going process since the percentage of arterioles with intimal fibrosis increased with the time after radiotherapy. Blood pressure and age played no part in these correlations in RBD. The most consistently observed qualitative changes in RBD were in the arteries, arterioles and to a lesser extent the veins. These showed fibrin thrombi, fibrinoid necrosis, subendothelial oedema and fibrin. Various stages of healing were seen in the vessels. We believe that the blood vessels are the main site of injury in RBD and that the endothelial cell is the initial target for radiation damage.     

Surgical pathology of chronic ascending aortic dissections

AIMS: A majority of aortic dissections affect the ascending aorta and are acute in nature. Chronic dissections in this region are uncommon. This report characterises the clinicopathological features of 15 non-iatrogenic chronic ascending aortic dissections. METHODS: Among 65 patients who had surgery for ascending aortic dissection over a period of 6 years, 15 showed morphological evidence of chronic dissection. Clinical data and morphological features of these were analysed. RESULTS: Twelve patients (80%) were over the age of 50 years, with a male predominance (11 patients, 73.33%). Exertional dyspnoea was the most common presenting symptom, while chest pain was noted in three cases. An echocardiographic diagnosis of dissection was made in six patients. The disease was restricted to the ascending aorta in nine (60%) and all had aortic regurgitation of varying severity. Areas of recent dissection were also noted in three specimens. The risk factors or pathogenetic mechanisms noted were hypertension in four and Marfan's syndrome, penetrating atherosclerotic ulcer, patent ductus arteriosus, and vehicular accident, in one patient each. The aortic segment of the latter patient had shown intimal flaps to be associated with multiple saucer-shaped depressions with thin walls. These features were also noted in two of the seven patients without risk factors and in two hypertensives. This raises the possibility of subclinical intimal injury sustained during sudden deceleration with blunt chest trauma. Significant aortopathy was seen in 10 cases. CONCLUSIONS: Chronic dissections as a cause of aortic regurgitation and aneurysmal dilatation, especially in the elderly, should be kept in mind. This may follow sudden deceleration intimal injuries, superimposed on aged-related medial degeneration.     

Sequence of cellular responses in rabbit aortas following one and two injuries with a balloon catheter

In order to further elucidate the pathogenesis of intimal proliferation and increased thrombogenesis following repeated arterial injuries we studied the sequence of the cellular changes following two injuries of rabbit aortas with a balloon catheter. Following the first injury, the de-endothelialized surface was covered by a platelet monolayer. Polymorphonuclear leucocytes adhered to the inner surface of this monolayer and did not appear to penetrate the vessel wall. By 4 to 7 days, areas of neointima had formed. Within seconds after the reinjury at 7 days after the de-endothelialization small platelet aggregates formed on injured neointimal smooth muscle cells. Within I min platelet thrombi and fibrin strands formed. At 30 min most of the platelet thrombi had become fibrin-rich. Polymorphonuclear leucocytes had accumulated and many had begun to penetrate into the neointimal tissue. The number and extent of penetration of leucocytes into the inner parts of the arterial wall increased with time. Four days after the injury the neointimal cushions were restored and thickened. Both following the first and second injury the formation of neointimal cushions was accompanied by a change in the polarity of the inner layers of medial smooth muscle cells, some of which appeared to have migrated into the neointima.     

Sequence of cellular responses in rabbit aortas following one and two injuries with a balloon catheter.

In order to further elucidate the pathogenesis of intimal proliferation and increased thrombogenesis following repeated arterial injuries we studied the sequence of the cellular changes following two injuries of rabbit aortas with a balloon catheter. Following the first injury, the de-endothelialized surface was covered by a platelet monolayer. Polymorphonuclear leucocytes adhered to the inner surface of this monolayer and did not appear to penetrate the vessel wall. By 4 to 7 days, areas of neointima had formed. Within seconds after the reinjury at 7 days after the de-endothelialization small platelet aggregates formed on injured neointimal smooth muscle cells. Within I min platelet thrombi and fibrin strands formed. At 30 min most of the platelet thrombi had become fibrin-rich. Polymorphonuclear leucocytes had accumulated and many had begun to penetrate into the neointimal tissue. The number and extent of penetration of leucocytes into the inner parts of the arterial wall increased with time. Four days after the injury the neointimal cushions were restored and thickened. Both following the first and second injury the formation of neointimal cushions was accompanied by a change in the polarity of the inner layers of medial smooth muscle cells, some of which appeared to have migrated into the neointima.     

Pulmonary vascular disease in ventricular septal defect: structural and functional correlations in lung biopsies from 85 patients, with outcome of intracardiac repair

Pulmonary vascular structure was analysed using morphometric techniques, and arterial wall abnormalities in lung biopsy specimens taken from 85 cases of ventricular septal defect, aged 3 weeks to 30 years were described. The defect was closed in 53 patients, 12 died at operation and 11 survivors were recatheterized. Structural examination revealed a characteristic pathological picture which appeared to precede classical grade IV pulmonary vascular disease. This predilatation phase was identified by finding pre-acinar obstructive intimal proliferation or fibrosis, associated with only a slight increase in intra-acinar arterial muscularity, in the absence of stigmata of grade IV disease in patients with a pulmonary resistance greater than 6 units m2. Predilatation features occurred in 62 per cent of patients who either died at repair or who had post-operative pulmonary hypertension. These findings help identify a high risk group in whom resistance is higher than expected in the absence of classical grade IV changes. In addition, a marked increase in muscularity without intimal obstruction can also be associated with a pre-operative resistance of more than 6 units m2. The presence of medial hypertrophy only does not ensure either survival or a normal post-operative pulmonary arterial pressure. Early intra-cardiac repair is recommended before obstructive intimal fibrosis develops during the second year.     

Pathology of coronary narrowing after arterial switch operation: autopsy findings in two patients who died within 3 months of surgical treatment and review of the literature.

The arterial switch operation (ASO) has become the surgical treatment of choice for transposition of the great arteries (TGA). Myocardial ischemia owing to coronary complication remains the commonest cause of mortality and morbidity following ASO. The main clinical manifestations of coronary obstruction reported after a switch procedure are heart failure, arrhythmias, or sudden death. Coronary complications are responsible for about 50% of early death and for almost all late deaths. We describe pathologic and anatomic findings in two cases of late sudden death after an ASO. Critical intimal thickening and acute take-off of coronary trunks were the main pathological substrates of death. Histological examination revealed an obstructive coronary proliferation characterised by a concentric stratum of intimal smooth muscle cell hyperplasia with preserved tunica media. Pathogenetic assessment of intimal coronary lesions after an ASO should consider the role of endothelium and vascular parietal wall in the unavoidable response to injury caused by arterial reconstruction. Since a rapidly progressive proliferative disease is suspected, to explain coronary narrowing, understanding endothelial biology and improving surgical technique should help to prevent late coronary events.     

Segmental arterial mediolysis: course,sequelae, prognosis,and pathologic–radiologic correlation

BackgroundSegmental arterial mediolysis is a vascular disease of putative vasospastic origin that causes massive hemorrhages. Although once considered rare, awareness of this disease has resulted in increased reports in the pathology and radiology literature. Despite this, uncertainties concerning pathologic and radiologic correlations, the course of this disease, and aspects of its prognosis exist. This article addresses these issues.MethodsThirteen radiologic reports of segmental arterial mediolysis are analyzed, and slides of 25 cases of segmental arterial mediolysis are searched for lesions analogous to the radiologic findings.ResultsSix angiographic presentations are identified: (a) arterial dilatation, (b) single aneurysm, (c) multiple aneurysms, (d) dissecting hematomas, (e) arterial stenosis, and (f) arterial occlusions. Pathologic correlations reveal that lytic loss of medial muscle causes arterial dilatation, dilated arterial gaps form aneurysms, dissections develop at arterial–medial gap junctions or from reparative granulation tissue and reparative alterations, and thrombi cause stenosis and occlusions. The most common radiologic findings at onset are aneurysms, arterial dilatation, and occlusions, while dissections and stenotic lesions often are delayed. These images correlate with the histologic evolution of segmental arterial mediolysis.ConclusionsSegmental arterial mediolysis is an acute limited disease. Sequelae recognized radiologically include aneurysms, dissecting hematomas, arterial stenosis, and occlusions. Generally, these persist, become smaller, or resolve, but symptomatic dissections with delayed onset occur. Sequelae of subclinical forms of segmental arterial mediolysis may cause isolated idiopathic aneurysms or may evolve into arterial lesions indistinguishable from fibromuscular dysplasia.     

Repeated pulmonary thromboembolism in rabbits.

Ten rabbits received 24 to 76 intravenous injections of finely divided thrombi prepared by a modification of Chandler's apparatus. Eight rabbits were killed soon after the last injection (group A) and two rabbits were allowed to survive for 4 months after the last introduction of thrombi (group B). Ten rabbits received repeated saline injections only, and six animals underwent no manipulation whatever. Six test rabbits and six control rabbits underwent catheterization of the pulmonary artery. The pulmonary arteries of each lung received injections of radiopaque material and were x-rayed; multiple blocks were selected from each lobe of each lung, cut, and stained with Weigert's elastic Van Gieson's stain, which permitted measurement of arterial medial thickness. Sections were also stained with hematoxylin and eosin and Martius scarlet blue. The results of catheterization showed that only mild pulmonary hypertension had been induced. Histologically, thromboemboli had become incorporated into the wall of the arteries. Concentric intimal thickening included an "onionskin" arrangement and was more prevalent than eccentric configuration. Medial hypertrophy of almost all vessels was found. The onionskin arrangement in an occasional precapillary vessel was also encountered. More severe histologic grades of pulmonary hypertension were not seen. The two group B animals showed recent thrombi, which suggested that once intimal thickening had occurred the process of fresh thrombotic superimposition continues, resulting in progression of the lesions. The experimental findings were compared with 13 patients (thromboembolic pulmonary hypertension (eight) and primary pulmonary hypertension (five)) and with 181 patients reported in the literature. Features such as the onionskin type of intimal thickening in muscular arteries and precapillary vessels have been suggested as points of distinction between these two conditions. These features have been reproduced in these experiments. Despite the fact that more severe histologic grades of pulmonary hypertension were not produced, it is suggested that these experiments lend support to the concept that primary pulmonary hypertension may have a thromboembolic etiology in at least some patients.     

Pathogenesis of portal sclerosis in the liver with idiopathic portal hypertension. Observations of 19 autopsy cases and animal experiments

The pathomorphological changes of intrahepatic portal veins were studied in 19 autopsy cases of idiopathic portal hypertension (IPH), and the pathogenesis of portal sclerosis was discussed by the observations on the human and experimental materials. The degree and morphological appearance of intimal lesions vary from vessel to vessel. Fibro-cellular proliferation of subendothelial tissue and incorporation of organized mural thrombi were suggested as the cause of intimal thickening in the portal veins. Animal experiment showed that injury of portal vein wall was followed by intimal hyperplasia and/or incorporation of mural thrombi, and resulted in portal sclerosis similar to that of IPH liver. The cause of portal phlebosclerosis in IPH can not be explained by passive congestion alone. There might be a certain possibility of direct injurious effect in the vessel wall in the pathogenesis of portal lesions of IPH. The following pathogenesis of portal sclerosis in IPH is postulated: phlebo-sclerotic changes of the portal veins are initiated by injury to the vessel wall due to unknown cause(s) and accelerated by secondary thrombosis and/or mechanical injury due to increased portal pressure.     

Comparison of biomechanical and histological properties in dog carotid arteries injured by neointima or intimal thickening

A general formula (Oka and Azuma's equation) has been rigorously derived for the circumferential wall tension in a hollow cylindrical tube in equilibrium. To evaluate the validity and usefulness of Oka and Azuma's equation, T = P(1) x r(1) - P(2) x r(2) (T, circumferential wall tension; P(1) and P(2), internal and external pressures of the tube; r(1) and r(2), the corresponding internal and external radii), we experimentally investigated changes in circumferential wall tension of noninjured (control) and injured dog common carotid arteries by using a newly developed apparatus with a photo- and X-ray-sensitive image sensor. We also studied histological features of the control and injured arteries with special reference to the relation of biomechanical properties. Two types of animal models with injured arteries--balloon-induced neointima or external collar-induced intimal thickening--were adopted in the present study. In the control arteries, the circumferential wall tension was experimentally confirmed to change from negative to positive by an increase in intraluminal pressure ranging from 50 to 180 mmHg. The critical intraluminal pressure that produced 0 dyne/cm of the circumferential wall tension was around 135 mmHg. The activation of arterial smooth muscles caused a significant increase in the critical pressure in the control arteries. In the arteries injured by neointima, the critical intraluminal pressure was significantly lower than that in the control. The activation of smooth muscles also significantly increased the critical pressure in the injured arteries. Histological examination demonstrated the existence of a circumferential neointimal formation along with a shortening of the internal diameter. In other arteries injured by intimal thickening, the circumferential wall tension was always negative at intraluminal pressure ranging from 50 to 180 mmHg. Newly developed structures consisted of elastic and collagen fibers, smooth muscles, and extracellular matrix in the intima and media of the injured arteries. These experimental findings suggest that the circumferential wall tension of dog common carotid arteries has been confirmed experimentally to become negative. We have also concluded that circumferential wall tension calculated with Oka-Azuma's equation may be one of the best parameters for evaluating changes in the biomechanical and histological properties of pathologically injured arteries.     

Pulmonary artery adventitial changes and venous involvement in primary pulmonary hypertension.

Primary pulmonary hypertension (PPH) is associated with a spectrum of structural changes in the pulmonary arteries: increased medial thickness, eccentric and concentric intimal thickening, obliteration and recanalization of arteries, and appearance of plexiform and dilatation lesions. The purpose of the present study was to further characterize these structural changes with particular emphasis on arterial adventitial thickness and alterations in the walls of the pulmonary veins. In addition, to determine whether the characteristic structural changes of PPH were size related, each was related to external diameter. With quantitative techniques, the pulmonary vasculature of 19 patients with PPH and 7 controls was examined by light microscopy. In all 19 patients, we found a striking increase in adventitial, as well as intimal and medial, thickness in arteries of all sizes when compared with controls (P < 0.05). In addition, we found intimal and adventitial thickening of pulmonary veins < 250 mu in diameter in approximately half of the PPH cases (P < 0.05). The frequency of arterial obliteration, concentric intimal thickening, and recanalization was 16, 18, and 11 of 19 cases, respectively. These changes were most prevalent in arteries less than 200 mu in diameter whereas eccentric intimal thickening and plexiform lesions occurred in 15 and 6 of the patients, respectively, and were most widespread in arteries > 200 mu. We conclude that remodeling of the pulmonary vasculature in PPH routinely includes thickening of the arterial adventitia and frequently also includes changes in the walls of the pulmonary veins. The finding that recanalization occurs predominantly in the smaller arteries whereas eccentric intimal thickening occurs mainly in the larger ones suggests that recanalization should not be considered a consequence of thromboemboli but may also occur at sites of more fibrotic intimal change.     

Focal veno-occlusive lesions following metastasis of cancer in the liver with special reference to obstruction of lymphatics in hepatic veins

Summary Focal veno-occlusive lesions and congestion of the liver are found frequently at autopsy in patients with metastatic carcinoma in the liver. In 6 cases, intimal proliferation of loose connective tissue with dilatation of lymphatic capillaries was seen continuously from the terminal hepatic venule to the hepatic vein, and cancer cells were found only in lymphatic capillaries in the wall of the hepatic vein. In 7 cases, cancer cells infiltrated directly into the adventitia of the sublobular vein and intimai proliferation of loose connective tissue with or without formation of recent thrombi was observed. A main causative factor of hepatic veno-occlusive disease is thought to be leakage of plasma due to endothelial injury to the terminal hepatic venule and sublobular vein. Lymphatic obstruction, in addition to a direct reaction to invasion of cancer cells to the vessel wall, may also cause veno-occlusive lesions due to stasis and leakage of lymph fluid into the intima of the terminal hepatic venule, sublobular vein and hepatic vein.     

Morphology of the internal elastic lamina in arteries from pulmonary hypertensive patients: a confocal laser microscopy study.

The development and progression of pulmonary hypertension lesions involve continuous remodeling of the arterial wall, including the extracellular matrix components. The integrity of the internal elastic lamina may represent a barrier to cell migration and formation of intimal proliferative lesions. Some patients with congenital cardiac shunts develop precocious intimal occlusive lesions,whereas others evolve with isolated medial hypertrophy. We studied the 2-D and 3-D morphology of the internal elastic lamina of peripheral pulmonary arteries to search for any difference regarding the type of histological lesion. Fifteen lung biopsies collected for diagnostic purposes from patients with congenital shunts and 6 control lungs (mean ages, 15.8 and 14.7 mo) were studied using the confocal laser scanning microscope, under predetermined conditions of laser intensity, brightness and contrast. We measured the thickness of the internal elastic lamina and determined the number of gaps and projections of elastic tissue towards the medial and intimal layers. The mean internal elastic lamina thickness was significantly higher in arteries from cases with isolated medial hypertrophy when compared with controls and to those with proliferative lesions (P <.05). The number of gaps of the internal elastic lamina was higher in arteries >100 micro m in diameter from the group with intimal lesions when compared to the cases presenting with isolated hypertrophy, but did not differ from the controls. There was a positive linear correlation between the external arterial diameter and the thickness of the internal elastic lamina (r =.74, P <.001) in cases presenting isolated medial hypertrophy. The increased thickness and smaller number of gaps of the internal elastic lamina may act as a barrier that prevents smooth muscle cell migration in patients with pulmonary hypertension without intimal proliferative lesions. On the other hand, a greater number of gaps does not represent, by itself, unrestrained migration, because controls also showed fenestrated laminae.