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Pulmonary vascular remodeling in rats with unilaterally banded lobar pulmonary veins

Published online by Cambridge University Press:  19 August 2008

Carol M. Cottrill*
Affiliation:
From theUniversity of Kentucky College of Medicine, Department of PediatricsLexington
William N. O'Connor
Affiliation:
Department of PathologyLexington
Robert Fitz
Affiliation:
University of Kentucky College of Pharmacy, Lexington
Mark N. Gillespie
Affiliation:
University of Kentucky College of Pharmacy, Lexington
*
University of Kentucky College of Medicine, Department of Pediatrics, MN-472 Chandler Medical Center, 800, Rose Street, Lexington, KY 40536-0084, USA. Tel. 606-233-5494; F. 606-258-5499.

Abstract

Although pulmonary vascular disease occurs in association with pulmonary venous obstruction, a model of pulmonary vascular lesions in this setting in small laboratory animals has yet to be described. The objective of this study was to determine if unilateral banding of pulmonary veins in the rat would produce pulmonary vascular disease that mimicked key aspects of the human disorder. Rats were anesthetized and, after mechanical ventilation and thoracotomy, one of the four pulmonary veins was banded to reduce its external diameter by approximately 65–75% to 0.8 mm. Additional animals, sham-operated controls, were treated identically except for venous banding. Mortality did not differ between groups and was less than 20%. Eight weeks after surgical preparation, moderate pulmonary hypertension was demonstrated with a mean pressure in the pulmonary artery of 24.9 mm Hg (range 19.25 – 30.0) in the banded group versus 18.7 mm Hg (range 16.6 – 19.3) for sham-operated animals. Pulmonary cineangiography in rats with banded pulmonary veins demonstrated marked pulmonary congestion and a prolonged residence time of contrast medium in the capillary circulation of the lung region subjected to banding. Angiographically, non-banded lungs were similar to shams. Histopathology of the vein-banded region revealed venous congestion, arterialization of veins, perivenular edema, and sparse to moderate inflammation. Prominent bronchial vessels, pulmonary arterial medial and occasional intimal thickening, and periarterial inflammation were also observed in banded regions. Similar inflammation around pulmonary arterial and pulmonary venous vessels was noted in contralateral lung lobes but not in sham-operated control rats. Morphometric evaluation of all muscular pulmonary arteries from 50–200μ external diameter accompanying airways to the level of terminal and respiratory bronchioles indicated that the medial area in lung regions subjected to venous banding was over three times greater than in shams. Pulmonary arteries from the contralateral, unbanded lungs of treated animals also exhibited a two-fold increase in medial area. These findings indicate that a modest degree of pulmonary venous banding in rats produces congestion and causes alterations in lung vessels which are reminiscent of those observed in humans with pulmonary venous outflow obstruction. Such a model in a cost-effective laboratory animal should be useful for delineating the specific mechanisms underlying these alterations.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 1992

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References

1.Reeves, JT, Groves, BM. Pulmonary hypertension. In: Weir, EK, Reeves, JT (eds), Pulmonary Hypertension. Futura Publishing Co.,, Mt. Kisco NY, 1984, pp 144.Google Scholar
2.Wagenvoort, CA, Wagenvoort, N. Pulmonary venous hyper tension. In: Pathology of Pulmonary Hy pertension. John Wiley & Sons, New York, 1977, pp 177216.Google Scholar
3.Ferencz, C, Dammann, JF JrSignificance of the pulmonary vascular bed in congenital heart disease. Lesions of the left side of the heart causing obstruction of the pulmonary venous return. Circulation 1957; 16: 10461056.CrossRefGoogle ScholarPubMed
4.Fong, LV, Anderson, RH, Park, SC, Zuberbuhler, JR. Morpho logic features ofstenosis of the pulmonary veins. Am J Cardiol 1988; 62: 11361138.CrossRefGoogle Scholar
5.Bini, RM, Cleveland, DC, Ceballos, R, Bargeron, LM, PacIfico, AD, Kirklin, JW. Congenital pulmonary vein stenosis. Am J Cardiol 1984; 54: 369375.CrossRefGoogle ScholarPubMed
6.Driscoll, DJ, Hesslein, PS, Mullins, CE. Congenital stenosis of individual pulmonary veins: clinical spectrum and unsuccess ful treatment by transvenous balloon dilatation. Am J Cardiol 1982; 49: 17671772.CrossRefGoogle Scholar
7.Silove, ED, Tavernor, WD, Berry, CL. Reactive pulmonary arterial hypertension after pulmonary venous constriction in the calf. Cardiovasc Res 1972; 6: 3644.CrossRefGoogle ScholarPubMed
8.LaBourene, JI, Coles, JG, Johnson, DJ, Mehra, A, Keeley, FW, Rabinovitch, M. Alterations in elastin and collagen related to the mechanism of progressive pulmonary venous obstruction in a piglet model: a hemodynamic, ultrastructural, and bio chemical study. Circ Res 1990; 66: 438456.CrossRefGoogle Scholar
9.Kay, JM, Heath, D. Morbid anatomical effects on rats of a diet containing crotalaria spectabilis seeds. In: Kugelmass IN (ed). Crotalaria Spectabilis: The Pulmonary Hypertension Plant. Thomas, Charles C., Springfield, IL, 1969, pp 62–77.Google Scholar
10.Meyrick, B, Reid, L. Normal postnatal development of the media of the rat hilar pulmonary artery and its remodeling by chronic hypoxia. Lab Invest 1982; 46: 505514.Google ScholarPubMed
11.Wagenvoort, CA, Dingemans, KP, Lotgering, GG. Electron microscopy of pulmonary vasculature after application of fulvine. Thorax 1974; 29: 511521.CrossRefGoogle ScholarPubMed
12.Schaefer, CF, Brackett, DJ, Downs, P, Tompkins, P, Wilson, MF. Laryngoscopic intubation of rats for inhalation anesthe sia.. J AppI Physiol; 1984; 56: 533535.CrossRefGoogle Scholar
13.Stinger, RB, lacopino, VJ, Alter, I, Fitzpatrick, TM, Rose, JC, Kot, PA. Catheterization of the pulmonary artery in the closed-chest rat. J AppI Physiol 1981; 51: 10471050.CrossRefGoogle ScholarPubMed
14.O'Connor, WN, Valle, S. A combination Verhoeffs elastic and Masson's trichrome stain for routine histology. Stain Tech nology 1982; 57: 207210.CrossRefGoogle Scholar
15.Fernie, JM, Lamb, D. A new method for quantitating the medial component of pulmonary arteries. The measurements. Arch Pathol Lab Med 1985; 109: 156162.Google ScholarPubMed
16.Fernie, JM, McClean, A, Lamb, D. New method for quanritat ing the medial component of pulmonary arteries. Factors a the measurements. Arch Pathol Lab Med 1985; 109: 843848.Google Scholar
17.Shone, J, Amplatz, M, Anderson, R, Adams, P, Edwards, J. Congenitalstenosisofindividualpulmonaryveins. Circ 1962; 26: 574581.CrossRefGoogle Scholar
18.Hu, LM, Jones, R. Injury and remodeling of pulmonary veins by high oxygen: a morphometric study. Am J Pathol 1989; 134: 253262.Google ScholarPubMed
19.Kay, JM, Heath, D. Anatomy of the lungs and heart and pulmonary vasculature in the normal rat. In: Crotalaria Specatabilis: the pulmonary hypertension plant. Kugelmass IN (ed). Thomas, Charles C., Springfield, IL, 1969, pp 23–40.Google Scholar
20.Hislop, A, Reid, L. Normal structure and dimensions of the pulmonary arteries in the rat. J Anat 1978; 125: 7183.Google ScholarPubMed
21.Meyrick, B, Hislop, A, Reid, L. Pulmonary arteries of the normal rat: the thick-walled oblique muscle segment. J Anat 1978; 125: 109221.Google ScholarPubMed
22.Meyrick, B, Reid, L. Ultrastructural features of the distended pulmonary arteries of the normal rat. Anat Rec 1979; 193: 7198.CrossRefGoogle ScholarPubMed
23.Meyrick, B, Reid, L. Ultrastructural findings in lung biopsy material from children with congenital heart defects. Am J Pathol 1980; 101: 527537.Google ScholarPubMed
24.Reid, L. Structure and function in pulmonary hypertension. New perceptions. Chest 1986; 89: 279288.CrossRefGoogle ScholarPubMed
25.Wagenvoort, CA. Morphologic changes in intrapulmonary veins. Human Pathology 1970; 1: 205213.CrossRefGoogle ScholarPubMed
26.Kelley, KM, Cheatham, JP, Kugler, JD, Fleming, WH, McManus, BM. Postnatal atresia of extraparenchymal pulmonary veins, fulminant necrotizing pulmonary arteritis and elevated circu lating immune complexes. J Am Coll Cardiol 1987; 9: 10431048.CrossRefGoogle Scholar
27.Stenmark, KR, Morganroth, ML, Remigo, LK, Voelkel, NF, Murphy, RC, Henson, PM, Mathias, MM, Reeves, JT. Alveolar inflammation and arachidonate metabolism in monocrotaline induced pulmonary hypertension. Am J Physiol 1985; 248: H859. [Abstruct]Google ScholarPubMed
28.Jones, R, Zapol, WM, Reid, L. Pulmonary artery remodeling and pulmonary hypertension after exposure to hyperoxia for seven days. Am J Pathol 1984; 117: 273285.Google Scholar