Comparative Pathophysiology of Pulmonary Hypertension: Development of a Model

  • P. J. Friedman
  • R. A. Harley
  • A. A. Liebow
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 241)


The lesser circulation is affected by a considerable variety of diseases that involve the heart or lungs. Blood flow in the pulmonary vessels may be compromised by destruction of lung parenchyma and excessive positive alveolar pressure as in chronic obstructive lung disease, by frank obstruction of vessels, large or small, as in pulmonary thrombo-embolic disease, by obstruction to the outflow of blood as in diseases of the pulmonary veins, mitral valve or left ventricle, or by changes in the arteries due to chronic overloading as in several congenital heart conditions with left-to-right shunts. The response of the pulmonary circulation is conditioned by the necessity of maintaining sufficient perfusion of the lungs for effective gas exchange to take place, without allowing hydrostatic pressures in the capillaries to exceed plasma oncotic pressure so much as to result in frank edema. Ignoring for the moment the role of the lymphatics in draining away interstitial transudate to dispel such edema, it seems reasonable that one of the responses of the pulmonary arteries will be to protect the capillary bed by developing increased resistance to perfusion.


Pulmonary Artery Pulmonary Hypertension Pulmonary Vascular Resistance Ventricular Septal Defect Bronchial Artery 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Auld, P.A.M., Gibbons, J.E., and McGregor, M.: Vasomotor tone in the pulmonary vascular bed in patients with left-to-right shunts. British Heart Journal 25: 257, 1963.PubMedCrossRefGoogle Scholar
  2. 2.
    Boerema, B.: Appearance and regression of pathological changes in the pulmonary arterial wall after repeated air embolism. J. Cardiovasc. Surg. 6: 160, 1965.Google Scholar
  3. 3.
    Bolt, W.: Clinical and pharmacological studies on the peripheral pulmonary circulation by using selective pulmonary angiography. Bibl. Anat. 7: 92, 1965.PubMedGoogle Scholar
  4. 4.
    Braunwald, N.S., Braunwald, E., and Morrow, A.: The effects of surgical abolition of left-to-right shunts on the pulmonary vascular dynamics of patients with pulmonary hypertension. Circulation 26: 170, 1962.Google Scholar
  5. 5.
    Callahan, J.A., J.W. Kirklin, H.B. Burchell and E.H. Wood: Hemodynamic studies before, during, and after operation in 10 cases of PDA with equivalent pulmonary and systemic arterial pressures. J. Lab. Clin. Med. 44: 778, 1954.Google Scholar
  6. 6.
    Crispin, A.R., Goodwin, J.F. and Steiner, R.E.: The radiology of obliterative pulmonary hypertension and thrombo-embolism. Brit. J. Radiol. 36: 705, 1963CrossRefGoogle Scholar
  7. 7.
    Dalen, J., Matloff, J.M., Evans, G.L., Hoppin, F.G., Jr., Bhardwaj, P., Harken, D.E. and Dexter, L.: Early reduction of pulmonary vascular resistance after mitral-valve replacement. New Eng. J. Med. 277: 387, 1967.CrossRefGoogle Scholar
  8. 8.
    Dammann, J.F., Jr., Baker, J.P. and Muller, W.H., Jr.: Pulmonary vascular changes induced by experimentally produced pulmonary arterial hypertension. Surg. Gynec. & Obst. 105: 16, 1967.Google Scholar
  9. 9.
    Dammann, J.F., Jr., McEachen, J.A., Thompson, W.M., Jr., Smith, R. and Muller, W.H.,Jr.: Regression of pulmonary vascular dis-ease after the creation of pulmonary stenosis. J. Thor. Cardiovasc. Surg. 42: 722, 1961.Google Scholar
  10. 10.
    Dart, C.H., Montgomery, T. and Peters, R.M.: Experimental hyperkinetic pulmonary hypertension, tolerance after biventricular hypertrophy produced by a femoral arteriovenous fistula. J. Thor. Cardiovasc. Surg. 56: 817, 1968.Google Scholar
  11. 11.
    Downing, S.E., Vidone, R.A., Brandt, H.M., and Liebow, A.A.: The pathogenesis of vascular lesions in experimental hyper-kinetic pulmonary hypertension. Am. J.Path. 43: 739, 1963.PubMedGoogle Scholar
  12. 12.
    Enson, Y., Giuntini, C., Lewis, M.L., Morris, T.Q., Ferrer, M. I. and Harvey, R.M.: The influence of hydrogen ion concentration and hypoxia on the pulmonary circulation. J. Clin. Invest. 43: 1146, 1964.PubMedCrossRefGoogle Scholar
  13. 13.
    Evans, R.H., Bresler, H.L., Lancaster, J.R., Stewart, P.B., Harrison, R.W., and Moulder, P.V.: Large systemic artery to pulmonary artery shunt afforded by biventricular hypertrophy. J. Thor. Cardiovasc. Surg. 47: 472, 1964.Google Scholar
  14. 14.
    Ferguson, D.J., and Vareo, RL.: The relation of blood pressure and flow to the development and regression of experimentally induced pulmonary arteriosclerosis. Circ. Res. 3: 152, 1955.PubMedGoogle Scholar
  15. 15.
    Friedman, P.J.: Direct magnification angiography and correlative pathophysiology in experimental pulmonary hypertension. In preparation.Google Scholar
  16. 16.
    Friedman, P.J. and Greenspan, R.H.: Observations on magnification radiography. Radiology, 92: 549, 1969.PubMedGoogle Scholar
  17. 17.
    Fowler, N.O.: The normal pulmonary arterial pressure-flow relationships during exercise. Am. J. Med. 47: 1, 1969.PubMedCrossRefGoogle Scholar
  18. 18.
    Gilbert, J.W., Jr., Berglund, E., Dahlgren, S., Ovenfors, C.O. and Barnes, R.: Experimental pulmonary hypertension in the dog: a preparation involving repeated air embolism. J. Thor. Cardiovasc. Surg. 55: 565, 1968.Google Scholar
  19. 19.
    Gyepes, M.T., Abrams, H.L., and Mesel, E.: Pulmonary vascular responses to acute hypoxia. Radiol. 91: 223, 1968.Google Scholar
  20. 20.
    Hales, M.R. and Carrington, C.B.: A pigmented gelatin mass for vascular injection. The Yale J. Biol. Med. 43: 257, 1971.Google Scholar
  21. 21.
    Hallman, G.L., Cooley, D.A., Wolfe, R.R. and McNamara, D.G.: Surgical treatment of ventricular septal defect associated with pulmonary hypertension. J. Thor. Cardiovasc. Surg. 48: 588, 1964.Google Scholar
  22. 22.
    Harley, R.A., Friedman, P.J., Johnson, R.M., and Liebow, A.A.: The sequential development of lesions in experimental severe pulmonary hypertension. In preparation.Google Scholar
  23. 23.
    Heath, D. and Edwards, J.E.: The pathology of hypertensive pulmonary vascular disease. Circ. 18: 533, 1958.Google Scholar
  24. 24.
    Heath, D., Helmholz, H.F.,Jr., Burchell, H.B., DuShane, J.W. and Edwards, J.E.: Relation between structural changes in the small pulmonary arteries and the immediate reversibility of pulmonary hypertension following closure of ventricular and atrial septal defects. Circ. 18: 1167, 1958.Google Scholar
  25. 25.
    Hirschmann, J.C. and Boucek, R.J.: Angiographic evidence of pulmonary vasomotion in the dog. Brit. Heart J. 25: 375, 1963.CrossRefGoogle Scholar
  26. 26.
    Hunt, C.E., Formanek, G., Levine, M.A., Castañeda, A. and Moller, J.H.: Banding of the pulmonary artery: Results in 111 children. Circ. 43: 395, 1971.Google Scholar
  27. 27.
    Jacobsen, G.: Peripheral pulmonary (wedge) arteriography - a standard technique for the single film arteriogram. Clin. Radiol. 14: 326, 1963.CrossRefGoogle Scholar
  28. 28.
    Josephson, S.: Pulmonary hemodynamics during experimental air embolism. Evidence of vasoconstriction. Scand. J. Clin. Lab. Invest. 26:Supp. 115, 1970.Google Scholar
  29. 29.
    Kanjuh, V.I., Sellers, R.D., and Edwards, J.E.: Pulmonary vascular plexiform lesions. Arch. Path. 78: 513, 1964.PubMedGoogle Scholar
  30. 30.
    Leachman, R.D. and Pereyo, J.A.: Decrease in pulmonary vascular resistance following surgical closure of a ventricular septal defect associated with elevated capillary wedge pressure and severe pulmonary arterial hypertension. Amer. Heart J. 76: 816, 1968.PubMedCrossRefGoogle Scholar
  31. 31.
    Liebow, A.A.: Arteriosclerosis of the Pulmonary Circulation. In: Arteriosclerosis - A Survey of the Problem. Chap. 14. (Ed.) H.T. Blumenthai, C.C. Thomas, Springfield, 111., pp. 248–328, 1966.Google Scholar
  32. 32.
    Linde, L.M., Goldberg, S.J., Takahashai, M., Momma, K. and Groveman, G.: Pulmonary vasoreactivity in animals with relatively increased pulmonary blood flow. Cardiovasc. Res. 4: 99, 1970.PubMedCrossRefGoogle Scholar
  33. 33.
    Marshall, H.W., Swan, J.J., Burchell, H.B., and Wood, E.H.: Effect of breathing oxygen on pulmonary artery pressure and pulmonary vascular resistance in patients with ventricular septal defect. Circ. 23: 241, 1961.Google Scholar
  34. 34.
    Milne, E.N.C.: A technique of macroradiography and macro-angiography of the minute peripheral pulmonary vessels in vivo. Vase. Dis. 2: 195, 1965.Google Scholar
  35. 35.
    Moss, A.J. and Duffie, E.R.,Jr.: The use of isoproterenol (Isuprel) in the evaluation of congenital cardiac defects. Circ. 27: 51, 1963.Google Scholar
  36. 36.
    Moulder, P.V., Rams, J.J., Diacoff, G.R., and Cassels, D.E.: Surgical treatment of severe pulmonary hypertension. Dis. Chest 51: 39, 1967.PubMedCrossRefGoogle Scholar
  37. 37.
    Muller, W.H., Dammann, J.F. and Head, W.H.,Jr.: Changes in the pulmonary vessels produced by experimental pulmonary hypertension. Surg. 34: 363, 1953.Google Scholar
  38. 38.
    Naeye, R.L. and Vennart, G.P.: The structure and significance of pulmonary plexiform structures. Am. J. Path. 36: 593, 1960.PubMedGoogle Scholar
  39. 39.
    Naeye, R.L.: Hypoxemia and pulmonary hypertension. Arch. Path. 71: 447, 1961.PubMedGoogle Scholar
  40. 40.
    O’Rourke, M.F.: Impact pressure, lateral pressure, and impedance in the proximal aorta and pulmonary artery. J. Appl. Physiol. 25: 533, 1968.PubMedGoogle Scholar
  41. 41.
    Park, C.D., Nicodemus, H., Downes, J.J., Miller, W.W. and Waldhausen, J.A.: Changes in pulmonary vascular resistance following closure of ventricular septal defects. Circ. 39: Suppl. 1: 193, 1969.Google Scholar
  42. 42.
    Quiroz, A.C., Sanchez, G., Giles, T.D. and Burch, G.E.: Angiographic demonstration of pulmonary venomotor reactions in the intact dog. Angiology 21: 724, 1970.PubMedCrossRefGoogle Scholar
  43. 43.
    Raphael, M. and Steiner, R.E.: Selective cine-fluoroscopic studies of pulmonary circulatory disorders. Brit. Heart J. 28: 523, 1966.PubMedCrossRefGoogle Scholar
  44. 44.
    Rashkind, W.J., Waldhausen, J., Miller, W., Dodd, P. and Friedman, S.: “Test-banding” of the pulmonary artery with a balloon-tipped catheter. Technique for evaluation of pulmonary arteriolar reactivity in children with pulmonary hypertension secondary to ventricular septal defects. Suppl. I:Circ. 39: 1–201, 1969.Google Scholar
  45. 45.
    Rodbard, S. and Kira, S.: Mechanical forces and pulmonary vascular conductance. Am. Heart J. 72: 498, 1966.PubMedCrossRefGoogle Scholar
  46. 46.
    Rudolph, A.M. and Yuan, S.: Response of the pulmonary vasculature to hypoxia and H+ ion concentration changes. J. Clin. Invest. 45: 399, 1966.PubMedCrossRefGoogle Scholar
  47. 47.
    Rudolph, A.M. and Scarpelli, E.M.: Drug action on pulmonary circulation of unanesthetized dogs. Am. J. Physiol. 206:1201, 1964,Google Scholar
  48. 48.
    Saldana, M.E., Harley, R.A., Liebow, A.A., and Carrington, C. B.: Experimental extreme pulmonary hypertension and vascular disease in relation to polycythemia. Am. J. Patli. 52: 935, 1968.Google Scholar
  49. 49.
    Scebat, L., Ferrang, J. and LeNégre, J.: La reserve artérielle pulmonaire dans les cardiopathies congénitales avec hypertension artérielle pulmonaire. II. Etude angiocariographique fonctionelle. Arch. Mal. Coeur. 52: 656, 1959.PubMedGoogle Scholar
  50. 50.
    Schuster, B., Chin Woo Lum, Yauuz, F. and Johnson, G.F.: Pulmonary arteriolar changes in congenital heart disease, as demonstrated by pre-wedge arteriography; a physiologic-radiologic correlation. Angiology. 15: 239, 1964.PubMedCrossRefGoogle Scholar
  51. 51.
    Sham, G.B., White, F.C., and Bloor, C.M.: A constrictive and occlusive cuff for medium and large blood vessels. J. Appl. Physiol. 28: 510, 1970.PubMedGoogle Scholar
  52. 52.
    Stark, J., Tynan, M., Tatooles, J., Aberdeen, E. and Waterston, D.J.: Banding of the pulmonary artery for transposition of the great arteries and ventricular septal defect. Circ. (Suppl I.): 116, 1970.Google Scholar
  53. 53.
    Takahashi, S., Sakuma, S., Kaneko, M. and Koga, S.: Clinical and hemodynamic effects of pulmonary artery banding. Am. J. Cardiol. 21: 174, 1968.PubMedCrossRefGoogle Scholar
  54. 54.
    Thilenius, D.G., Hoffer, P.B., Fitzgerald, R.S. and Perkins, J.F., Jr.: The response of the pulmonary circulation of resting unanesthetized dogs to acute hypoxia. Am. J. Physiol. 206: 867, 1964.PubMedGoogle Scholar
  55. 55.
    Valdivia, E., Rowe, G.G., Usher, M.: Pulmonary cineangiography in experimental chronic hypoxia. Angiology. 18: 610, 1967.PubMedCrossRefGoogle Scholar
  56. 56.
    Viles, P.: The spectrum of pulmonary vascular disease in transposition of the great arteries. Circ. 40: 31, 1969.Google Scholar
  57. 57.
    Vogel, J.H.K., Cameron, D. and Jamieson, G.: Chronic pharmacologic treatment of experimental hypoxic pulmonary hyper-tension. Am. Heart J. 72: 50, 1966.PubMedCrossRefGoogle Scholar
  58. 58.
    Vogel, J.H.K., McNamara, D.G., and Blount, S.G.,Jr.: Role of hypoxia in determining pulmonary vascular resistance in infants with ventricular septal defects. Am. J. Cardiol. 20: 346, 1967.PubMedCrossRefGoogle Scholar
  59. 59.
    Vogel, J.H.K., Grover, R.F. and Blount, S.G.,Jr.: Pathphysiologic correlations in patients with ventricular septal defect and elevated pulmonary vascular resistance. Am. J. Cardiol. 19: 154, 1967.CrossRefGoogle Scholar
  60. 60.
    Voridis, E. Scebat, L., Renais, J. and LeNégre, J.: La Réserve artérielle pulmonaire dans les cardiopathies congénitales avec hypertension artérielle pulmonaire. I. Etude hemodynamique. Arch. Mal. Coeur. 52: 639, 1959.Google Scholar
  61. 61.
    Wagenvoort, C.A., Heath, D. and Edwards, J.E.: The Pathology of the Pulmonary Vasculature. A. Chapter V., B. Chapter VIII, C.C. Thomas, Springfield, 111., 1964.Google Scholar
  62. 62.
    Wagenvoort, C.A.: The morphology of certain vascular lesions in pulmonary hypertension. J. Path. Bact. 78: 503, 1959.CrossRefGoogle Scholar
  63. 63.
    Wagenvoort, C.A., Nauta, J., van der Schaar, P.J., Weeda, H. W.H. and Wagenvoort, N.: Effect of flow and pressure on pulmonary vessels. Circ. 35: 1028, 1967.Google Scholar
  64. 64.
    Yu, P.N., Glick, G., Schreiner, B.F., Jr., and Murphy, G.W.: Effects of acute hypoxia on the pulmonary vascular bed of patients with acquired heart diseaspae.(with special reference to the demonstration of active vasomotion). Circ. 27: 541, 1963.Google Scholar

Copyright information

© Plenum Press, New York 1972

Authors and Affiliations

  • P. J. Friedman
    • 1
    • 2
    • 3
  • R. A. Harley
    • 1
    • 2
    • 3
  • A. A. Liebow
    • 1
    • 2
    • 3
  1. 1.Departments of Radiology and PathologyYale University School of MedicineUSA
  2. 2.Departments of Radiology and PathologyUniversity of California, San Diego, School of MedicineUSA
  3. 3.Department of PathologyUniversity of South Carolina, College of MedicineUSA

Personalised recommendations