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Ann Thorac Surg 2000;69:193-197
© 2000 The Society of Thoracic Surgeons

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Original Articles

Pulmonary vascular changes induced by congenital obstruction of pulmonary venous return

^a Department of Thoracic and Cardiovascular Surgery, Tohoku University School of Medicine, Sendai, Japan

Address reprint requests to Dr Endo, Department of Thoracic and Cardiovascular Surgery, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan

	Abstract

Top Abstract Introduction Patients and methods Results Comment References

 
Background. Pulmonary venous obstruction (PVO) induces pulmonary arterial hypertension, as well as pulmonary venous hypertension, and jeopardizes the repair of cardiac lesions.

Methods. Four cases of congenital mitral stenosis and 4 cases of cor triatriatum (Lucas type A), ages ranging from 2 months to 16 years, were histologically examined on pulmonary vasculature. Histometrical analysis was performed on medial thickness and intimal changes of both pulmonary arteries and veins. For comparison, the examination of pulmonary vasculature in ventricular septal defect (VSD) cases was also performed.

Results. Medial thickening and intimal fibrosis, in both pulmonary arteries and veins with widespread lymphangiectasia, were characteristic vascular changes of PVO cases. Medial thickness of pulmonary arteries was correlated with preoperative pulmonary arterial pressure (PAP) (r = 0.77, p = 0.03 for systolic PAP), and greater than that of VSD cases. Medial thickness of pulmonary veins was also greater in PVO cases. Intimal fibrosis of pulmonary arteries and veins was seen extensively at the advanced ages, whereas no plexiform lesions or more advanced stages of pulmonary vascular disease were present.

Conclusions. Congenital PVO induced progressive medial thickening and intimal fibrosis in pulmonary arteries and veins accompanied by lymphangiectasia. However, no plexiform lesions or more advanced stages of pulmonary vascular disease were present, which may explain the reversibility of pulmonary hypertension due to congenital PVO.

	Introduction

Top Abstract Introduction Patients and methods Results Comment References

 
Despite the major advances in the treatment of congenital heart diseases, obstruction of pulmonary venous return remains as a significant risk factor for their surgical repair [1–4]. Pulmonary hypertension during perioperative period is a serious complication for patients with congenital pulmonary venous obstruction (PVO) [1–3]. However, the pathogenesis of pulmonary hypertension associated with PVO is not fully understood. From the histological viewpoint, medial thickening and intimal fibrosis are characteristic pulmonary vascular changes in PVO cases [5, 6]. Our previous study showed that the medial layer of pulmonary arteries, in the case of congenital mitral stenosis, was thicker than that in the case of ventricular septal defect (VSD) or complete transposition of the great arteries [7]. In spite of those prominent pulmonary vascular changes, the reversibility of pulmonary hypertension due to congenital mitral stenosis has been recognized [8, 9]. We formed the hypothesis that histological changes in these patients are progressive but unique, and result in a type of pulmonary hypertension, which is reversible, and hence would make these patients lesions more amenable to operation, even at advanced ages. To test this hypothesis, we examined the histological changes of pulmonary vasculature and hemodynamic data in 8 surgical cases of congenital PVO.

	Patients and methods

Top Abstract Introduction Patients and methods Results Comment References

 
Eight cases of congenital PVO without significant left-to-right shunt, who underwent the repair between 1980 and 1997, were included in this study. There were 4 cases of congenital mitral stenosis and 4 cases of cor triatriatum (Lucas type A) with the age ranging from 2 months to 16 years, as shown in Table 1. Pulmonary arterial pressure (PAP) was measured preoperatively under spontaneous breathing in room air. Postoperative PAP was also measured in 6 patients before discharge. Lung specimens were taken during the operations. For the purpose of comparing pulmonary vascular changes between PVO cases and left-to-right shunt anomalies, 20 cases of VSD, aged 1 month to 5 years, were also examined for pulmonary vascular changes. Lung specimens were stained with Masson stain. As a histometrical analysis, medial hypertrophy and intimal fibrosis were quantitatively assessed as follows. First medial thicknesses of pulmonary arteries and pulmonary veins were measured using the computarized method proposed by Yamaki and Tezuka [7]. The cross-section of the vessel was transformed to the hypothetical state in which the internal elastic lamina was completely stretched to the circle and surrounded by the ring of medial muscular layer. In this state, the radius (R), the distance from the center of the lumen to the middle point of the muscular layer, and the medial thickness (D) were calculated. In each case, R and D were calculated on more than 15 cross-sections of pulmonary arteries and pulmonary veins. Subsequently, the regression line was made between logR and logD for each case. D at the R = 100 µm was obtained from the regression line and expressed as DR = 100 µm, representing the medial thickness of each case.

The unpaired Student’s t test was applied to assess differences in each value between the PVO group and the VSD group. All values are expressed as the mean ± standard error of the mean (SEM). The correlations of the histometrical values and hemodynamic data were examined in each group. Data were considered significantly different if p was less than 0.05.

	Results

Top Abstract Introduction Patients and methods Results Comment References

 
Pulmonary arterial pressure
PAPs before and after the operation were shown in Table 1. In 6 cases, for which both preoperative and postoperative PAP were obtained, mean PAP significantly decreased from 58.2 ± 6.6 mm Hg preoperatively to 31.5 ± 5.4 mm Hg (p < 0.05) postoperatively. Between PVO and VSD cases, there were no differences in systolic PAP (82.0 ± 7.4 versus 73.2 ± 3.2 mm Hg) and mean PAP (59.8 ± 5.3 versus 49.7 ± 2.7 mm Hg), but diastolic PAP was higher in PVO cases other than in VSD cases (44.0 ± 5.4 versus 31.0 ± 2.5 mm Hg, p < 0.02).

Histological changes of pulmonary vasculature
Thickened medial layers of pulmonary arteries and veins were seen in all 8 patients (Fig 1). Arterialization of pulmonary veins with well developed external elastic lamina, which was previously demonstrated in the cases of total anomalous pulmonary venous connection [10, 11], was also seen in all congenital PVO cases. Intimal fibrosis was seen extensively in pulmonary arteries and veins in 5 older patients, although it was not seen in any patient younger than 18 months. Cellular intimal fibrosis of pulmonary arteries was not clearly seen in any case. Proliferation and dilatation of lymph vessels (lymphangiectasia) were seen in the interlobular septa and the subpleural layers in all 8 cases. In case 6, dilated lymph vessels were seen even around peripheral bronchioles and within lung parenchyma in contact with alveoli (Fig 2). Interstitial edema and fibrosis were also seen in the subpleural layer, around peripheral bronchioles and in alveolar walls.

View larger version (114K): [in this window] [in a new window]   Fig 1. (A) Medial thickening and intimal fibrosis of the small pulmonary artery in case 6 and (B) marked medial thickening with intimal fibrosis of small pulmonary vein in case 5. (Elastica Masson stain, x 100.)

View larger version (134K): [in this window] [in a new window]   Fig 2. Lymphangiectasia in lung parenchyma in case 6. (Lym = lymph vessel; Alv = alveolus.) (Elastica Masson stain, x 100.)

View larger version (21K): [in this window] [in a new window]   Fig 3. The correlations between medial thicknesses (DR = 100 µm) of pulmonary arteries and preoperative systolic pulmonary arterial pressures in 8 PVO cases and in 20 VSD cases. The slope of the regression line in PVO cases is greater than that of VSD cases (0.24 versus 0.07, p < 0.025). (PAP = pulmonary arterial pressure; PVO = pulmonary venous obstruction; VSD = ventricular septal defect.)

View larger version (12K): [in this window] [in a new window]   Fig 4. The medial thickness (DR = 100 µm) of pulmonary veins in PVO cases and in VSD cases. (PVO = pulmonary venous obstruction; VSD = ventricular septal defect, *p = 0.001.)

View larger version (16K): [in this window] [in a new window]   Fig 5. Progression of intimal changes, expressed as the percentage of the numbers of the vessels with intimal changes, (A) of pulmonary arteries and (B) pulmonary veins in PVO and VSD cases. (PVO = pulmonary venous obstruction; VSD = ventricular septal defect.)

	Comment

Top Abstract Introduction Patients and methods Results Comment References

 
Obstruction of pulmonary venous return is caused by intracardiac obstructive lesions [5, 6, 12–20], as well as extracardiac obstructive lesions of pulmonary veins [1–4, 19, 20]. Classical cor triatriatum (Lucas type A) and congenital mitral stenosis show the clinical and pathological pictures of pure PVO, because they are not complicated by an intracardiac shunt. However, patients with congenital PVO are frequently complicated by a left-to-right shunt. In these cases, the clinical courses and pulmonary vascular changes are affected, not only by pulmonary venous obstruction, but also by increased pulmonary blood flow. Haworth and Reid [20] examined pulmonary vascular disease in the cases of total anomalous pulmonary venous connection, and mentioned that pulmonary vascular changes and cardiac morphological changes were related to the combined effects of PVO and large left-to-right shunts.

In the present study, we demonstrated that pure PVO induced progressive medial thickening and intimal fibrosis in both pulmonary arteries and pulmonary veins. Medial thickness of pulmonary arteries in PVO cases was correlated with PAP, and greater than that of VSD cases, which indicated that medial thickening in PVO cases was regulated not only by the increase of PAP, but also by factors most likely associated with pulmonary venous hypertension. Pulmonary veins of congenital PVO also had thickened media and intimal fibrosis. Yamaki and associates [12] showed that medial thickness of pulmonary veins stayed at low levels during childhood, in both normal children and left-to-right shunt cases. They demonstrated that DR = 100 µm of pulmonary veins remained constant at about 3 µm in normal children and 5 µm in VSD cases. On the contrary, we revealed that the pulmonary veins of PVO cases had very thick media with mean DR = 100 µm of 16.5 µm.

Intimal changes of pulmonary arteries were not present in the congenital PVO cases younger than 18 months, though those changes were detected in more than half of VSD cases younger than 12 months. Cellular intimal proliferation, which is one of the common vascular changes in left-to-right shunt cardiac anomalies [7], was rarely observed in pulmonary arteries or veins in congenital PVO cases. In addition, plexiform lesions or more advanced vascular changes, which are regarded as irreversible changes and observed in the advanced stage of the left-to-right shunt-related pulmonary vascular obstructive disease, were not seen in any congenital PVO case in this study. Thus, the pathogenesis of pulmonary vascular disease due to PVO seems to be different from that of left-to-right shunt cardiac anomalies. Physiological characteristics of PVO cases, compared with left-to-right shunt cases, are as follows: (1) pulmonary blood flow is not increased in PVO cases, whereas it is increased in left-to-right shunt cases; (2) PVO cases suffer from increased pulmonary venous pressure as well as increased pulmonary arterial pressure; (3) PVO cases are accompanied by chronic pulmonary congestion. We speculate that medial hypertrophy in pulmonary arteries is accelerated by synergistic effects of the increases in pulmonary arterial and venous pressures. In addition, long-standing pulmonary venous hypertension and congestion presumably induce medial thickening and intimal fibrosis of pulmonary veins.

Of great interest is the fact that case 6, with a 7-year history of congenital mitral stenosis and preoperative Pp/Ps of 1.0, had an uneventful postoperative course with postoperative Pp/Ps of 0.66, even though in this case there was very thickened media and diffuse intimal fibrosis in both the pulmonary arteries and veins. Furthermore, the PAP decreased to a normal level 2 years postoperatively. This postoperative normalization of PAP seemed to be related to the reversibility of pulmonary vascular changes associated with congenital PVO. In short, the severity of medial hypertrophy or intimal fibrosis did not mean a poor postoperative prognosis. However, our study suggested the importance of careful postoperative respiratory management for congenital PVO cases. Because of very thickened media of pulmonary arteries and veins, reactive pulmonary hypertension is likely to be induced by triggers such as hypoxia. In addition, high airway pressure induces progressive interstitial emphysema in the lung complicated with lymphangiectasia [12].

In summary, congenital PVO induced progressive medial thickening and intimal fibrosis, in both pulmonary arteries and veins accompanied by lymphangiectasia. However, these lesions and pulmonary hypertension seemed to be reversible, which makes congenital PVO amenable to operation even at an advanced age.

	References

Top Abstract Introduction Patients and methods Results Comment References

 

1. Lupinetti F.M., Kulik T.J., Beekman R.H., Crowley D.C., Bove E.L. Correction of total anomalous pulmonary venous connection in infancy. J Thorac Cardiovasc Surg 1993;106:880-885.[Abstract]
2. Sinzobahamvya N., Arenz C., Brecher A.M., Blaschczok H.C., Urban A.E. Early and long-term results for correction of total anomalous pulmonary venous drainage (TAPVD) in neonates and infants. Eur J Cardiothorac Surg 1996;10:433-438.[Abstract]
3. Delius R.E., de Laval M.R., Elliott M.J., Stark J. Mixed total pulmonary venous drainage. J Thorac Cardiovasc Surg 1996;112:1581-1588.[Abstract/Free Full Text]
4. Endo M., Yamaki S., Itoh T., et al. Unilateral pulmonary venous obstruction. Kyoubu-Geka 1989;42:555-557.
5. Ferencz C. Significance of the pulmonary vascular bed in congenital heart disease. V. Lesion of the left side of the heart causing obstruction of the pulmonary venous return. Circulation 1957;16:1046-1056.[Medline]
6. Yamaki S., Endo M., Takahashi T. Different grades of medial hypertrophy and intimal changes in small pulmonary arteries among various types of congenital heart disease with pulmonary hypertension. Tohoku J Exp Med 1997;182:83-97.[Medline]
7. Yamaki S., Tezuka F. Qualitative analysis of pulmonary vascular disease in complete transposition of the great arteries. Circulation 1976;54:805-809.[Abstract/Free Full Text]
8. Carpentier A., Branchini B., Cour J.C., et al. Congenital malformations of the mitral valve in children. J Thorac Cardiovasc Surg 1976;72:854-866.[Abstract]
9. Collins-Nakai R.L., Rosenthal A., Castaneda A.R., Bernhard W.F., Nadas A.S. Congenital mitral stenosis. Circulation 1997;56:1039-1047.[Abstract/Free Full Text]
10. Petersen R.C., Edwards W.D. Pulmonary vascular disease in 57 necropsy cases of total anomalous pulmonary venous connection. Histopathol 1983;7:487-496.[Medline]
11. Wagenvoort C.A. Morphologic changes in the intrapulmonary veins. Human Pathology 1970;1:205-213.[Medline]
12. Yamaki S., Tsunemoto M., Shimada M., et al. Qualitative analysis of pulmonary vascular disease in total anomalous pulmonary venous connection in sixty infants. J Thorac Cardiovasc Surg 1992;104:728-735.[Abstract]
13. Atz A.M., Adatia I., Jonas R.A., Wessel D.L. Inhaled nitric oxide in children with pulmonary hypertension and congenital mitral stenosis. Am J Cardiol 1996;77:316-319.[Medline]
14. Banerjee A., Kohl T., Silverman N.H. Echocardiographic evaluation of congenital mitral valve anomalies in children. Am J Cardiol 1995;76:1284-1291.[Medline]
15. Tulloh R.M., Bull C., Elliott M.J., Sullivan I.D. Supravalvar mitral stenosis. Br Heart J 1995;73:164-168.[Abstract/Free Full Text]
16. Moore P., Adatia I., Spevak P.J., et al. Severe congenital mitral stenosis in infants. Circulation 1994;89:2099-2106.[Abstract/Free Full Text]
17. Salmone G., Tiraboschi R., Bianchi T., Ferri F., Crippa M., Parenzan L. Cor triatriatum. Clinical presentation and operative results. J Thorac Cardiovasc Surg 1991;101:1088-1092.[Abstract]
18. Sethia B., Sullivan I.D., Elliott M.J., de Leval M., Stark J. Congenital left ventricular inflow obstruction. Eur J Cardiothorac Surg 1988;2:312-317.[Abstract]
19. Van Son J.A., Danielson G.K., Puga F.J., Edwards W.D., Driscoll D.J. Repair of congenital and acquired pulmonary vein stenosis. Ann Thorac Surg 1995;60:144-150.[Abstract/Free Full Text]
20. Haworth S.G., Reid L. Structural study of pulmonary circulation and of heart in total anomalous pulmonary venous return in early infancy. Br Heart J 1977;39:80-92.[Abstract/Free Full Text]

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