i!I
..:.5 ...
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Pulmonary Venous Infarction* Warren A. WiUiamson, M.D., F.C.C.f; Broce S. 1fvnic, M.D.; Nathan levitan, M.D.; David G. Webb-Johnson, M.D.; David M. Shahian, M.D., F.G.G.R; and F. Henry Ellis, Jr., M.D., Ph.D.t
(Chat 1992; 102:931-40)
pulmonary venous infarction rarely occurs because of the rich network ofvenous collateral vessels that drains the lung. However, certain clinical conditions can lead to obstruction of the pulmonary veins and subsequent infarction. Twenty-two cases ofpulmonary venous obstruction and infarction from a variety of causes have been reported in the literature. 1-16 Causes include sclerosing mediastinitis, atrial myxoma, congenital pulmonary venous narrowing, squamous cell carcinoma, acute thrombosis after lobectomy and bilobectomy, .and mitral stenosis with an obstructing left atrial clot (Table 1). CLINICAL FEATURES
Despite different causes, the common clinical presentation of pulmonary venous obstruction and infarction includes the triad ofcough, dyspnea, and hemoptysis,· 'which may be paroxysmal in nature. Frequent bouts of respiratory tract infection are common. Because pulmonary venous obstruction occurs gradually in many of these processes, the symptoms may be protracted, and the diagnosis is elusive. In advanced disease with more than one pulmonary vein involved, recurrent episodes of pulmonary edema and intractable heart failure may occur and are usually the cause of death. 1 Physical findings vary, depending on whether one or more pulmonary veins are occluded. With lobar involvement, the findings may be minimal and may suggest lobar consolidation or a pleural effusion. However, venous obstruction of an entire lung results in severe pulmonary venous hypertension, pulmonary congestion, and rales. DIAGNOSIS
It is difficult to diagnose this syndrome by conven*From the Departments of Thoracic and Cardiovascular Surgery and Anatomic Pathology, and the Sections of Medical Oncology and Pulmonary and Critical Care Medicine, Lahey Clinic Medical Center, Burlington, Mass. tPresent address: Division ofThoracic ~d Cardiovascular Surgery, New England Deaconess Ilospital, Boston. Reprint requests: Dr. Williamson, Lahey Clinic Medical Center, 41
MaU
Road, Burlington, MA 01805
tional roentgenologic means. The findings on standard roentgenography of the chest are nonspecific and variable and include pulmonary consolidation, atelectasis, increased pulmonary vascular markings, and increased hilar size. A mitral configuration with enlargement of the pulmonary conus and increased hilar markings suggest more extensive pulmonary venous obstruction. The contribution of computed tomography (CT) or magnetic resonance (MR) imaging in making this diagnosis is unclear because most cases described in the literature were reported before cr became available. Bronchoscopic features, as described by Dye et al,2 are also nonspecific and show inflammatory changes with mucosal friability. Caution should be exercised during bronchoscopy in these patients because minimal trauma can result in profuse bleeding. 2 Ventilation and perfusion scans may be of some value. In one reported instance,2 ventilation was normal, but perfusion to the lower lung field was poor in a patient with pulmonary venous occlusion of the right lower lobe because of sclerosing mediastinitis. The most useful diagnostic test to demonstrate pulmonary venous obstruction is pulmonary arteriography with delayed venous phase. Kittredge and Nash3 demonstrated a normal pulmonary arterial tree with large dilated pulmonary veins just before entrance into the left atrium in a patient with pulmonary venous infarction of the right lower lobe secondary to sclerosing mediastinal fibrosis. Dye and associates2 likewise demonstrated obstruction of the inferior pulmonary vein and middle lobe branch ofthe superior pulmonary vein on the venous phase of pulmonary arteriography in a similar patient. Table I-Reported Caaea of Pulmonary Venoua Ob_ruction and Infarction Causes
No. of Cases
Sclerosing mediastinitis2-14 Left atrial myxoma10.15 Thrombosis after pulmonary resection I6•17 Left atrial clot from mitral stenosis 1o Congenital stenosis of pulmonary veins 10 Squamous cell carcinoma
15
CHEST I 102 I 3 I SEPTEMBER, 1992
2 2
1 1 1
137
Yacoub and Thompson4 evaluated differential tests of lung function in a patient with pulmonary venous obstruction because of chronic idiopathic pulmonary hilar fibrosis. They demonstrated evidence of obstructive and restrictive disease as well as reduced diffusion capacity in the affected lung compared with the normal lung. Hemodynamic studies in these patients demonstrated postcapillary vascular obstruction with normal left atrial and left ventricular pressures. Pulmonary capillary wedge pressure and pulmonary arterial pressure were increased. The gradient between the pulmonary capillary wedge pressure and the left ventricular end-diastolic pressure and the absence of such a gradient between the left atrium and the left ventricle place the obstruction at the level of the pulmonary veins. 5 Normal left atrium and left ventricle pressures help rule out left heart disease as the cause of pulmonary hypertension. Botticelli and coworkers6 were able to pass a catheter through a small radicle of an obstructed pulmonary vein through the left atrial appendage in a patient with right superior and inferior pulmonary venous narrowing secondary to chronic fibrosing mediastinitis. A pull-back pressure gradient of 40 mm Hg was found between the smaller pulmonary veins and the left atrium. PATHOLOGY
The two common pathologic patterns are infarction with hemorrhagic necrosis ofa lobe or lung and diffuse interstitial fibrosis. These two presentations may simply reflect an acute and chronic phase in the evolution of pulmonary venous infarction or they may represent different degrees of pulmonary venous obstnlction with or without infarction. During the hemorrhagic phase ofpulmonary venous infarction, the lobe is firm and purple. A patchy septal distribution of necrosis exists with subpleural infarcts separated by larger areas ofviable parenchyma. These areas of infarction are multifocal and are located septally near venules in contrast to pulmonary arterial infarction. The lumina of these venules are occluded by cellular and fibrous tissue. Intra-alveolar hemorrhage is also present. 7 ,8 The small arterioles and arteries show medial muscular hypertrophy with intimal fibrous thickening, the same findings seen in chronic pulmonary artery hypertension. The bronchial submucosa distal to the pulmonary venous obstruction demonstrates prominent ectasia of venous and lymphatic channels. 1 In the chronic phase of pulmonary venous obstruction, interstitial6brosis occurs. Proliferating capillaries and fibroblasts are present, with fibrous thickening of the adventitia of intrapulmonary veins. Intra-alveolar septa become greatly thickened by fibrous connective tissue. Intimal hypertrophy of pulmonary arterioles 938
and considerable venous dilation are noted in the involved areas. With lobar occlusion, these changes are striking compared with nlinimal to mild alteration in the other lobes. The visceral plenra of the involved lobe is weatly thickened and contains moderately large collateral channels. These pleural collateral channels \\'ere demonstrated experimentally by Kistner and coworkers 17 to be capable of carrying up to 20 percent of the normal pulmonary flo\\~ Visceral pleural collateral channels and other intrapulmonary venous collateral channels may prevent pulmonary infarction in many patients with pulmonary venous occlusion. Although these collateral channels may prevent infarction, they may not adequately prevent the sequelae of chronic pulmonary venous hypertension and its resulting fibrosis. It is not clear \\,hether chronic fibrosis represents a recovery phase from venous infarction or simply the end result of chronic pulmonary venous hypertension \\rithout infarction. DIFFERENTIAL DIAC';N()SIS
Pulmonary venous obstruction and infarction should not he confused \\;th pulmonary veno-occlusive disease; IH.19 in the latter condition, the microscopic pathologic findin~s may closely mimic lobar venous obstruction, but the cause and diffuse distribution are distin~uishinJ1; features. The process is obliterative venulitis, \vhich presents as diffuse hlnJ1; disease and pulmonary hypertension. Multiple proposed etiol()~ic factors exist, of \vhich chemotherapeutic a~ents are the most common, particularly bleomycin. Other factors include viral infections, inhaled toxins, and immune complex deposition in the lun~s. EXPERI~IENTAL STlTDIES
Early investig;ators2(l-2,1) reported conflicting results when ligation of pulmonary veins was studied in dOJ(s. The earliest studies by Tiegel in 1911 20 fi)und that pulmonary fibrosis resulted from partial Ii~ation of pulmonary veins in rabbits and do~s. Mathes and coworkers 21 in 1932 found that complete liJ1;ation of a lobar pulmonary vein in dogs usually resulted in death. Six years later, Swan and Mulligan 22 cited a study by Ameuille and colleaJ1;ues,2.1 \\,ho reported survival of hnlr of ten do~s after pulmonary venous ligation. In the animals that survived . all had collateral venous channels and enlargement of the bronchial arteries. S\van and Muni~an22 found that healthy do~s would survive lobar pulmonary vein ligation hut not li~ati()n of the entire pulmonary venous drainage of one lun~. Hurnrilz and coneagues2.t.2.~ found that \vhen the d()~s were treated \\;th antibiotics.. all survived Ii~ation of the pulmonary veins from one lun~. From these studies,20-2.; a useful chr()nolo~ of the patholo~ic events that occurred after li~ation of pulPulmonary Venous Infarction (Williamson et 81)
monary veins can be obtained. With lobar venous ligation in healthy dogs, the initial reaction was a fibrinopurulent pleuritis with adhesions of the lobe to the parietal pleura. This reaction was followed by hemorrhage and edema into the alveoli and bronchioles. Thrombosis of lobar veins occurred and was frequently accompanied by bronchopneumonia. The recovery period ensued, starting with the development of vascular adhesions, especially of the pleural surfaces, through which collateral venous drainage developed. Some focal interstitial 6brosis and hemosiderosis persisted, but by three to four months at least 80 percent of the lobe was reexpanded. Because of the persistence of focal interstitial 6brosis, it is unclear how much function actually returned. These observations led Swan and Mulligan22 to conclude that lobar venous ligation did not result in signi6cant. destruction of pulmonary tissue and was not a fatal event in healthy dogs. Wyatt and associates26 believed that pulmonary venous occlusion alone was incapable of causing infarction because of the lack of permanent microscopic changes in the lungs. In another shldy, Hanlon and associates27 showed that with ligation ofthe pulmonary . veins on the left side, the animals survived. They were not as successful with right-sided ligations; the chance of survival was improved, however, with the addition of antibiotics. Hurwitz and colleagues24 •25 found that survival \\'as also possible when the entire pulmonary venous drainage to one lung was interrupted in dogs that were treated with antibiotics. They further demonstrated that three groups of venous collateral channels developed in these dogs: expanded bronchial venous collateral channels, transpleural hilar venous collateral channels, and transpleural terminal veins. The expanded bronchial collateral veins communicate with the major pulmonary veins through multiple intrapulmonary connections. These bronchial veins then empty by means of the hilum into intercostal veins and the azygos veins. The transpleural hilar vessels arise from the capillaries that develop in granulation tissue in pleural adhesions. These vessels drain through the pericardiophrenic and intercostal veins. The transpleural terminal veins develop connections with the distal ends of pulmonary veins and likewise penetrate the pleura by means of pleural adhesions and drain through the pericardiophrenic, intercostal, and internal mammary veins. Similar collateral channels have been demonstrated in patients with pulmonary venous obstnlction. 2 •4 The potential for rich collateral venous drainage of the lung by means of the bronchial venous system was well described by Zuckerkandl28 in 1882 (as cited by Liebow29), by Ferguson and associates30 in 1944, and by Liebow and coworkers31 in 1950.
PATIIOPHYSH )(.()(;Y
Which patients \\ith pulmonary venous obstruction ,viII go on to the development of infarction is unclear. I ntuitivel~ it \vould seem that \\'ith acute venous obstruction, the venous (.'ol1ateral channels would not have a chance to dilate to accommodate the increased demand fi)r drainage. Ho,vever, in dog studies,24.25 treatment with antibiotics resulted in survival and prowession to a 6brotic sta~e in most situations. The de~ee oflymphatic obstnl('tion or dilation may also be important. Like the venous channels, lymphatic channels are greatly dilated in patients with pulmonary venous infarction. This lymphatic dilation may be secondary to the inDammatory response or may actually reflect lymphatic obstnlction as well. It may be that lymphatic obstruction and venous obstruction account for the progression to infarction in some patients. Pulmonary arteriolar changes may also play a role in venous infarction. In patients ,,,ith severe chronic pulmonary venous occlusion, hypertrophic changes occur within the pulmonary arterioles. Perhaps the pulmonary arteriolar sclerosis that develops in some patients over time serves to deerease How to the lobe or lobes with outDo\\' occlusion and prevents hemorrha~c infarction. Finally, the bronchial arterial circulation may also playa role in pulmonary venous obstnlction, as it does in pulmonary arterial occlusion ..12 ,1.1 Patients ,,,ith an t'xpanded hronchial arterial circulation may be more prone to the development of hemorrhagic infarction with outf)O\V occlusion. lTltimately, it is probably a comhination of many factors, in('ludin~ acuteness of development, extent of occlusion, adequacy of venous collaterals, and some component of lymphatic obstnlction, that determines why pulmonary venous infarction develops in some patients. TREAT~tENT
The management of this syndronlt~ is dependent on the canse. The most common cause, idiopathic 6brosing mediastinitis, is not amenable to resection as a nIle, and conservative therapy \vith antibiotics seems warranted. Inpatients \vith sclerosing mediastinitis secondary to histoplasmosis, impro\·ed mana~('ment has been demonstrated \\rith the lise of keto('onazole (Nizoral).34 With more local ohstruction from tnmor, myxoma, obstructing ('lot, or cOllgenital narro\\;ng, the treatment can he directed at tilt' specific pathologic entity. Su~t~tARY
Pulmonary venous infarction.. althou~h rare, can develop in patients \vith the various pathologic conditions outlined. The triad of ('(}n~h, dyspnea, and CHEST I 102 I 3 I SEPTEMBER, 1992
931
hemoptysis should raise clinical suspicion. The venous phase of pulmonary arteriography is the best way to document pulmonary venous obstruction, although MR imaging may also prove useful in the future. Treatment of patients with pulmonary venous infarction should be determined on the basis ofthe obstructing pathologic findings. Antibiotic therapy is important, as evidenced by the early experimental experience with this condition. It may be the only treatment available to patients with idiopathic 6brosing mediastinitis. Pulmonary resection, however, can be accomplished when a localized obstructing lesion is identi6ed. REFERENCES 1 Bindelglass IL, Trubowitz S. Pulmonary vein obstruction: an uncommon sequel to chronic fibrous mediastinitis. Ann Intern Med 1958; 48:876-91 2 Dye TE, Saab SB, Almond CH, Watson L. Sclerosing mediastinitis with occlusion of pulmonary veins: manifestations and management. J Thorac Cardiovasc Surg 1977; 74:137-41 3 Kittredge RD, Nash AD. The many facets of sclerosing fibrosis. AJR 1974; 122:288-98 4 Yacoub M H, Thompson VC. Chronic idiopathic pulmonary hilar fibrosis: a clinicopathological entity. Thorax 1971; 26:365-75 5 Nasser WK, Feigenbaum H, Fisch C. Clinical and hemodynamic diagnosis of pulmonary venous obstruction due to sclerosing mediastinitis. Am J Cardioll967; 20:725-29 6 Botticelli JT, Schlueter D ~ Lange RL. Pulmonary venous and arterial hypertension due to chronic fibrous mediastinitis: hemodynamics and pulmonary function. Circulation 1966; 33:86271 7 Katzenstein AL, Mazur MT. Pulmonary infarct: an unusual manifestation of fibrosin~ mediastinitis. Chest 1980; 77:521-24 8 Mendelson EB, Mintzer RA, Hidveg OF. Veno-occlusive pulmonary infarct: an unusual complication of fibrosing mediastinitis. AJR 1983; 141:175-76 9 Andrews EC Jr. Five cases of an undescribed form of pulmonary interstitial fibrosis caused by obstnlction of the pulmonary veins. BuD Johns Hopkins Hosp 1957; 100:28-42 10 Edwards JE, Burchell HB. Multilobar pulmonary venous obstruction with pulmonary hypertension: "protective" arterial lesions in the involved lobes. Arch Intern Med 1951; 87:372-78 11 Davis ~ Andrus EC. Mitral stenosis in facsimile. N Eng) J Med 1954; 251:297-302 12 Leech TR, Meckstroth C~ Kla.'isen K~ Exploratory thoracotomy in chronic lymphadenitis of the mediastinum. Arch Surg 1955; 71:383-91 13 Hegglin R, Zollinger H U. A case of pulmonary sclerosis of particular etiolo~ (scar tissue of the mediastinum). Cardiologia 1954; 24:92-5 14 Stevens LH, Ilormuth DA, Schmidt PE, Atkins S, Fehrenbacher JW Left atrial myxoma: pulmonary infarction caused by pulmonary venous O(.-clusion. Ann Thorac Surg 1987; 43:215-17 15 Hovaguimian II, Morris JF, Gately HL, Floten HS. Pulmonary
940
vein thrombosis following bilobectomy. Chest 1991; 99:1515-16 16 Venter C~ Dannheimer IE Pulmonary venous thrombosis complicating lobectom~ S Afr Med J 1973; 47:2339-42 17 Kistner WF, Mudd JG, Hanlon CR. Bronchospirometric determinations of pulmonary function in dogs after unilateral ligation of the pulmonary vein and artery [abstract]. Circulation 1955; 12:733 18 Lombard CM, Churg A, Winokur S. Pulmonary veno-occlusive disease following therapy for malignant neoplasms. Chest 1987; 92:871-76 19 Joselson R, Warnock M. Pulmonary veno-occlusive disease after chemotherapy. Hum Patholl983; 14:88-91 20 Tiegel M. Operative lungenstauung und deren einOuss auf die tuberkulose. Arch fClin Chir 1911; 95:810 21 Mathes ME, Holman E, Reichert FL. A study of the bronchial, pulmonary, and lymphatic circulation of the lung under various pathologic conditions experimentally produced. J Thorac Surg 1932; 1:339-62 22 Swan H, Mulligan RM. An experimental study of the effect of ligation of pulmonary veins in the dog. J Thorac Surg 1948; 17:44-56 23 Ameuille ~ Lemoine JM, Nouaille J. Suppleance circulatoire par las adherences apres ligature des veines pulmonaires. Ann Anat Pathol 1938; 15:85-8 24 Hurwitz A, Calabresi M, Cooke ~ Liehow AA. An experimental study of the venous collateral circulation of the lung: anatomical observations. Am J Patholl954; 30:1085-115 25 Hurwitz A, Calabresi M, Cooke ~ Liebow AA. Experimental study of the venous collateral circulation of the lung: functional observations. J Thorac Surg 1954; 28:241-46 26 Wyatt J~ Burke DR, Hanlon CR. Morphologic study of canine lungs after ligation of the pulmonary veins. Am J Pathol 1953; 29:291-303 27 Hanlon CR, Sabiston DC Jr, Burke DR. Expetimental pulmonary venous occlusion. J Thorac Surg 1952; 24:190-200 28 Zuckerkandl E. tiber die anastomosen der venae pulmonales mit den bronchialvenen und mit dem mediastinaIen venennetze. Sitzungsb Akad Wiss Math-naturw CI 1882; 849(pt 3):110-52 29 Liehow AA. The bronchopulmonary venous collateral circulation with special reference to emphysema. Am J Patholl953; 29:25189 30 Ferguson FC, Kobilak RE, Deitrick JE. Varices of the bronchial veins as a source of hemoptysis in mitral stenosis. Am Heart J 1944; 28:445-56 31 Liehow AA, Hales MR, Bloomer WE, Harrison Lindskog GE. Studies on the lung after ligation of the pulmonary artery: anatomical changes. Am J Patholl950; 26: 177-95 32 Ellis FH Jr, Grindlay JH, Edwards JE. The bronchial arteries: their role in pulmonary embolism and infarction. Surgery 1952; 31:167-79 33 Chapman DW: Gugle LJ, Wheeler PW Experimental pulmonary infarction: abnormal pulmonary circulation as a prerequisite for pulmonary infarction following an embolus. Arch Intern Moo 1949; 83:158-63 34 Urschel HC Jr, Razzuk MA, Netto GJ, Disiere J, Chung SY. Sclerosing mediastinitis: improved management with histoplasmosis titer and ketoconazole. Ann Thorac Surg 1990; 50:215-21
w:
Pulmonary venous Infarction (Williamson et 81)
..:.5 ...
~.§...a
-----.• •t---r_e_vie_w
_
Pulmonary Venous Infarction* Warren A. WiUiamson, M.D., F.C.C.f; Broce S. 1fvnic, M.D.; Nathan levitan, M.D.; David G. Webb-Johnson, M.D.; David M. Shahian, M.D., F.G.G.R; and F. Henry Ellis, Jr., M.D., Ph.D.t
(Chat 1992; 102:931-40)
pulmonary venous infarction rarely occurs because of the rich network ofvenous collateral vessels that drains the lung. However, certain clinical conditions can lead to obstruction of the pulmonary veins and subsequent infarction. Twenty-two cases ofpulmonary venous obstruction and infarction from a variety of causes have been reported in the literature. 1-16 Causes include sclerosing mediastinitis, atrial myxoma, congenital pulmonary venous narrowing, squamous cell carcinoma, acute thrombosis after lobectomy and bilobectomy, .and mitral stenosis with an obstructing left atrial clot (Table 1). CLINICAL FEATURES
Despite different causes, the common clinical presentation of pulmonary venous obstruction and infarction includes the triad ofcough, dyspnea, and hemoptysis,· 'which may be paroxysmal in nature. Frequent bouts of respiratory tract infection are common. Because pulmonary venous obstruction occurs gradually in many of these processes, the symptoms may be protracted, and the diagnosis is elusive. In advanced disease with more than one pulmonary vein involved, recurrent episodes of pulmonary edema and intractable heart failure may occur and are usually the cause of death. 1 Physical findings vary, depending on whether one or more pulmonary veins are occluded. With lobar involvement, the findings may be minimal and may suggest lobar consolidation or a pleural effusion. However, venous obstruction of an entire lung results in severe pulmonary venous hypertension, pulmonary congestion, and rales. DIAGNOSIS
It is difficult to diagnose this syndrome by conven*From the Departments of Thoracic and Cardiovascular Surgery and Anatomic Pathology, and the Sections of Medical Oncology and Pulmonary and Critical Care Medicine, Lahey Clinic Medical Center, Burlington, Mass. tPresent address: Division ofThoracic ~d Cardiovascular Surgery, New England Deaconess Ilospital, Boston. Reprint requests: Dr. Williamson, Lahey Clinic Medical Center, 41
MaU
Road, Burlington, MA 01805
tional roentgenologic means. The findings on standard roentgenography of the chest are nonspecific and variable and include pulmonary consolidation, atelectasis, increased pulmonary vascular markings, and increased hilar size. A mitral configuration with enlargement of the pulmonary conus and increased hilar markings suggest more extensive pulmonary venous obstruction. The contribution of computed tomography (CT) or magnetic resonance (MR) imaging in making this diagnosis is unclear because most cases described in the literature were reported before cr became available. Bronchoscopic features, as described by Dye et al,2 are also nonspecific and show inflammatory changes with mucosal friability. Caution should be exercised during bronchoscopy in these patients because minimal trauma can result in profuse bleeding. 2 Ventilation and perfusion scans may be of some value. In one reported instance,2 ventilation was normal, but perfusion to the lower lung field was poor in a patient with pulmonary venous occlusion of the right lower lobe because of sclerosing mediastinitis. The most useful diagnostic test to demonstrate pulmonary venous obstruction is pulmonary arteriography with delayed venous phase. Kittredge and Nash3 demonstrated a normal pulmonary arterial tree with large dilated pulmonary veins just before entrance into the left atrium in a patient with pulmonary venous infarction of the right lower lobe secondary to sclerosing mediastinal fibrosis. Dye and associates2 likewise demonstrated obstruction of the inferior pulmonary vein and middle lobe branch ofthe superior pulmonary vein on the venous phase of pulmonary arteriography in a similar patient. Table I-Reported Caaea of Pulmonary Venoua Ob_ruction and Infarction Causes
No. of Cases
Sclerosing mediastinitis2-14 Left atrial myxoma10.15 Thrombosis after pulmonary resection I6•17 Left atrial clot from mitral stenosis 1o Congenital stenosis of pulmonary veins 10 Squamous cell carcinoma
15
CHEST I 102 I 3 I SEPTEMBER, 1992
2 2
1 1 1
137
Yacoub and Thompson4 evaluated differential tests of lung function in a patient with pulmonary venous obstruction because of chronic idiopathic pulmonary hilar fibrosis. They demonstrated evidence of obstructive and restrictive disease as well as reduced diffusion capacity in the affected lung compared with the normal lung. Hemodynamic studies in these patients demonstrated postcapillary vascular obstruction with normal left atrial and left ventricular pressures. Pulmonary capillary wedge pressure and pulmonary arterial pressure were increased. The gradient between the pulmonary capillary wedge pressure and the left ventricular end-diastolic pressure and the absence of such a gradient between the left atrium and the left ventricle place the obstruction at the level of the pulmonary veins. 5 Normal left atrium and left ventricle pressures help rule out left heart disease as the cause of pulmonary hypertension. Botticelli and coworkers6 were able to pass a catheter through a small radicle of an obstructed pulmonary vein through the left atrial appendage in a patient with right superior and inferior pulmonary venous narrowing secondary to chronic fibrosing mediastinitis. A pull-back pressure gradient of 40 mm Hg was found between the smaller pulmonary veins and the left atrium. PATHOLOGY
The two common pathologic patterns are infarction with hemorrhagic necrosis ofa lobe or lung and diffuse interstitial fibrosis. These two presentations may simply reflect an acute and chronic phase in the evolution of pulmonary venous infarction or they may represent different degrees of pulmonary venous obstnlction with or without infarction. During the hemorrhagic phase ofpulmonary venous infarction, the lobe is firm and purple. A patchy septal distribution of necrosis exists with subpleural infarcts separated by larger areas ofviable parenchyma. These areas of infarction are multifocal and are located septally near venules in contrast to pulmonary arterial infarction. The lumina of these venules are occluded by cellular and fibrous tissue. Intra-alveolar hemorrhage is also present. 7 ,8 The small arterioles and arteries show medial muscular hypertrophy with intimal fibrous thickening, the same findings seen in chronic pulmonary artery hypertension. The bronchial submucosa distal to the pulmonary venous obstruction demonstrates prominent ectasia of venous and lymphatic channels. 1 In the chronic phase of pulmonary venous obstruction, interstitial6brosis occurs. Proliferating capillaries and fibroblasts are present, with fibrous thickening of the adventitia of intrapulmonary veins. Intra-alveolar septa become greatly thickened by fibrous connective tissue. Intimal hypertrophy of pulmonary arterioles 938
and considerable venous dilation are noted in the involved areas. With lobar occlusion, these changes are striking compared with nlinimal to mild alteration in the other lobes. The visceral plenra of the involved lobe is weatly thickened and contains moderately large collateral channels. These pleural collateral channels \\'ere demonstrated experimentally by Kistner and coworkers 17 to be capable of carrying up to 20 percent of the normal pulmonary flo\\~ Visceral pleural collateral channels and other intrapulmonary venous collateral channels may prevent pulmonary infarction in many patients with pulmonary venous occlusion. Although these collateral channels may prevent infarction, they may not adequately prevent the sequelae of chronic pulmonary venous hypertension and its resulting fibrosis. It is not clear \\,hether chronic fibrosis represents a recovery phase from venous infarction or simply the end result of chronic pulmonary venous hypertension \\rithout infarction. DIFFERENTIAL DIAC';N()SIS
Pulmonary venous obstruction and infarction should not he confused \\;th pulmonary veno-occlusive disease; IH.19 in the latter condition, the microscopic pathologic findin~s may closely mimic lobar venous obstruction, but the cause and diffuse distribution are distin~uishinJ1; features. The process is obliterative venulitis, \vhich presents as diffuse hlnJ1; disease and pulmonary hypertension. Multiple proposed etiol()~ic factors exist, of \vhich chemotherapeutic a~ents are the most common, particularly bleomycin. Other factors include viral infections, inhaled toxins, and immune complex deposition in the lun~s. EXPERI~IENTAL STlTDIES
Early investig;ators2(l-2,1) reported conflicting results when ligation of pulmonary veins was studied in dOJ(s. The earliest studies by Tiegel in 1911 20 fi)und that pulmonary fibrosis resulted from partial Ii~ation of pulmonary veins in rabbits and do~s. Mathes and coworkers 21 in 1932 found that complete liJ1;ation of a lobar pulmonary vein in dogs usually resulted in death. Six years later, Swan and Mulligan 22 cited a study by Ameuille and colleaJ1;ues,2.1 \\,ho reported survival of hnlr of ten do~s after pulmonary venous ligation. In the animals that survived . all had collateral venous channels and enlargement of the bronchial arteries. S\van and Muni~an22 found that healthy do~s would survive lobar pulmonary vein ligation hut not li~ati()n of the entire pulmonary venous drainage of one lun~. Hurnrilz and coneagues2.t.2.~ found that \vhen the d()~s were treated \\;th antibiotics.. all survived Ii~ation of the pulmonary veins from one lun~. From these studies,20-2.; a useful chr()nolo~ of the patholo~ic events that occurred after li~ation of pulPulmonary Venous Infarction (Williamson et 81)
monary veins can be obtained. With lobar venous ligation in healthy dogs, the initial reaction was a fibrinopurulent pleuritis with adhesions of the lobe to the parietal pleura. This reaction was followed by hemorrhage and edema into the alveoli and bronchioles. Thrombosis of lobar veins occurred and was frequently accompanied by bronchopneumonia. The recovery period ensued, starting with the development of vascular adhesions, especially of the pleural surfaces, through which collateral venous drainage developed. Some focal interstitial 6brosis and hemosiderosis persisted, but by three to four months at least 80 percent of the lobe was reexpanded. Because of the persistence of focal interstitial 6brosis, it is unclear how much function actually returned. These observations led Swan and Mulligan22 to conclude that lobar venous ligation did not result in signi6cant. destruction of pulmonary tissue and was not a fatal event in healthy dogs. Wyatt and associates26 believed that pulmonary venous occlusion alone was incapable of causing infarction because of the lack of permanent microscopic changes in the lungs. In another shldy, Hanlon and associates27 showed that with ligation ofthe pulmonary . veins on the left side, the animals survived. They were not as successful with right-sided ligations; the chance of survival was improved, however, with the addition of antibiotics. Hurwitz and colleagues24 •25 found that survival \\'as also possible when the entire pulmonary venous drainage to one lung was interrupted in dogs that were treated with antibiotics. They further demonstrated that three groups of venous collateral channels developed in these dogs: expanded bronchial venous collateral channels, transpleural hilar venous collateral channels, and transpleural terminal veins. The expanded bronchial collateral veins communicate with the major pulmonary veins through multiple intrapulmonary connections. These bronchial veins then empty by means of the hilum into intercostal veins and the azygos veins. The transpleural hilar vessels arise from the capillaries that develop in granulation tissue in pleural adhesions. These vessels drain through the pericardiophrenic and intercostal veins. The transpleural terminal veins develop connections with the distal ends of pulmonary veins and likewise penetrate the pleura by means of pleural adhesions and drain through the pericardiophrenic, intercostal, and internal mammary veins. Similar collateral channels have been demonstrated in patients with pulmonary venous obstnlction. 2 •4 The potential for rich collateral venous drainage of the lung by means of the bronchial venous system was well described by Zuckerkandl28 in 1882 (as cited by Liebow29), by Ferguson and associates30 in 1944, and by Liebow and coworkers31 in 1950.
PATIIOPHYSH )(.()(;Y
Which patients \\ith pulmonary venous obstruction ,viII go on to the development of infarction is unclear. I ntuitivel~ it \vould seem that \\'ith acute venous obstruction, the venous (.'ol1ateral channels would not have a chance to dilate to accommodate the increased demand fi)r drainage. Ho,vever, in dog studies,24.25 treatment with antibiotics resulted in survival and prowession to a 6brotic sta~e in most situations. The de~ee oflymphatic obstnl('tion or dilation may also be important. Like the venous channels, lymphatic channels are greatly dilated in patients with pulmonary venous infarction. This lymphatic dilation may be secondary to the inDammatory response or may actually reflect lymphatic obstnlction as well. It may be that lymphatic obstruction and venous obstruction account for the progression to infarction in some patients. Pulmonary arteriolar changes may also play a role in venous infarction. In patients ,,,ith severe chronic pulmonary venous occlusion, hypertrophic changes occur within the pulmonary arterioles. Perhaps the pulmonary arteriolar sclerosis that develops in some patients over time serves to deerease How to the lobe or lobes with outDo\\' occlusion and prevents hemorrha~c infarction. Finally, the bronchial arterial circulation may also playa role in pulmonary venous obstnlction, as it does in pulmonary arterial occlusion ..12 ,1.1 Patients ,,,ith an t'xpanded hronchial arterial circulation may be more prone to the development of hemorrhagic infarction with outf)O\V occlusion. lTltimately, it is probably a comhination of many factors, in('ludin~ acuteness of development, extent of occlusion, adequacy of venous collaterals, and some component of lymphatic obstnlction, that determines why pulmonary venous infarction develops in some patients. TREAT~tENT
The management of this syndronlt~ is dependent on the canse. The most common cause, idiopathic 6brosing mediastinitis, is not amenable to resection as a nIle, and conservative therapy \vith antibiotics seems warranted. Inpatients \vith sclerosing mediastinitis secondary to histoplasmosis, impro\·ed mana~('ment has been demonstrated \\rith the lise of keto('onazole (Nizoral).34 With more local ohstruction from tnmor, myxoma, obstructing ('lot, or cOllgenital narro\\;ng, the treatment can he directed at tilt' specific pathologic entity. Su~t~tARY
Pulmonary venous infarction.. althou~h rare, can develop in patients \vith the various pathologic conditions outlined. The triad of ('(}n~h, dyspnea, and CHEST I 102 I 3 I SEPTEMBER, 1992
931
hemoptysis should raise clinical suspicion. The venous phase of pulmonary arteriography is the best way to document pulmonary venous obstruction, although MR imaging may also prove useful in the future. Treatment of patients with pulmonary venous infarction should be determined on the basis ofthe obstructing pathologic findings. Antibiotic therapy is important, as evidenced by the early experimental experience with this condition. It may be the only treatment available to patients with idiopathic 6brosing mediastinitis. Pulmonary resection, however, can be accomplished when a localized obstructing lesion is identi6ed. REFERENCES 1 Bindelglass IL, Trubowitz S. Pulmonary vein obstruction: an uncommon sequel to chronic fibrous mediastinitis. Ann Intern Med 1958; 48:876-91 2 Dye TE, Saab SB, Almond CH, Watson L. Sclerosing mediastinitis with occlusion of pulmonary veins: manifestations and management. J Thorac Cardiovasc Surg 1977; 74:137-41 3 Kittredge RD, Nash AD. The many facets of sclerosing fibrosis. AJR 1974; 122:288-98 4 Yacoub M H, Thompson VC. Chronic idiopathic pulmonary hilar fibrosis: a clinicopathological entity. Thorax 1971; 26:365-75 5 Nasser WK, Feigenbaum H, Fisch C. Clinical and hemodynamic diagnosis of pulmonary venous obstruction due to sclerosing mediastinitis. Am J Cardioll967; 20:725-29 6 Botticelli JT, Schlueter D ~ Lange RL. Pulmonary venous and arterial hypertension due to chronic fibrous mediastinitis: hemodynamics and pulmonary function. Circulation 1966; 33:86271 7 Katzenstein AL, Mazur MT. Pulmonary infarct: an unusual manifestation of fibrosin~ mediastinitis. Chest 1980; 77:521-24 8 Mendelson EB, Mintzer RA, Hidveg OF. Veno-occlusive pulmonary infarct: an unusual complication of fibrosing mediastinitis. AJR 1983; 141:175-76 9 Andrews EC Jr. Five cases of an undescribed form of pulmonary interstitial fibrosis caused by obstnlction of the pulmonary veins. BuD Johns Hopkins Hosp 1957; 100:28-42 10 Edwards JE, Burchell HB. Multilobar pulmonary venous obstruction with pulmonary hypertension: "protective" arterial lesions in the involved lobes. Arch Intern Med 1951; 87:372-78 11 Davis ~ Andrus EC. Mitral stenosis in facsimile. N Eng) J Med 1954; 251:297-302 12 Leech TR, Meckstroth C~ Kla.'isen K~ Exploratory thoracotomy in chronic lymphadenitis of the mediastinum. Arch Surg 1955; 71:383-91 13 Hegglin R, Zollinger H U. A case of pulmonary sclerosis of particular etiolo~ (scar tissue of the mediastinum). Cardiologia 1954; 24:92-5 14 Stevens LH, Ilormuth DA, Schmidt PE, Atkins S, Fehrenbacher JW Left atrial myxoma: pulmonary infarction caused by pulmonary venous O(.-clusion. Ann Thorac Surg 1987; 43:215-17 15 Hovaguimian II, Morris JF, Gately HL, Floten HS. Pulmonary
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vein thrombosis following bilobectomy. Chest 1991; 99:1515-16 16 Venter C~ Dannheimer IE Pulmonary venous thrombosis complicating lobectom~ S Afr Med J 1973; 47:2339-42 17 Kistner WF, Mudd JG, Hanlon CR. Bronchospirometric determinations of pulmonary function in dogs after unilateral ligation of the pulmonary vein and artery [abstract]. Circulation 1955; 12:733 18 Lombard CM, Churg A, Winokur S. Pulmonary veno-occlusive disease following therapy for malignant neoplasms. Chest 1987; 92:871-76 19 Joselson R, Warnock M. Pulmonary veno-occlusive disease after chemotherapy. Hum Patholl983; 14:88-91 20 Tiegel M. Operative lungenstauung und deren einOuss auf die tuberkulose. Arch fClin Chir 1911; 95:810 21 Mathes ME, Holman E, Reichert FL. A study of the bronchial, pulmonary, and lymphatic circulation of the lung under various pathologic conditions experimentally produced. J Thorac Surg 1932; 1:339-62 22 Swan H, Mulligan RM. An experimental study of the effect of ligation of pulmonary veins in the dog. J Thorac Surg 1948; 17:44-56 23 Ameuille ~ Lemoine JM, Nouaille J. Suppleance circulatoire par las adherences apres ligature des veines pulmonaires. Ann Anat Pathol 1938; 15:85-8 24 Hurwitz A, Calabresi M, Cooke ~ Liehow AA. An experimental study of the venous collateral circulation of the lung: anatomical observations. Am J Patholl954; 30:1085-115 25 Hurwitz A, Calabresi M, Cooke ~ Liebow AA. Experimental study of the venous collateral circulation of the lung: functional observations. J Thorac Surg 1954; 28:241-46 26 Wyatt J~ Burke DR, Hanlon CR. Morphologic study of canine lungs after ligation of the pulmonary veins. Am J Pathol 1953; 29:291-303 27 Hanlon CR, Sabiston DC Jr, Burke DR. Expetimental pulmonary venous occlusion. J Thorac Surg 1952; 24:190-200 28 Zuckerkandl E. tiber die anastomosen der venae pulmonales mit den bronchialvenen und mit dem mediastinaIen venennetze. Sitzungsb Akad Wiss Math-naturw CI 1882; 849(pt 3):110-52 29 Liehow AA. The bronchopulmonary venous collateral circulation with special reference to emphysema. Am J Patholl953; 29:25189 30 Ferguson FC, Kobilak RE, Deitrick JE. Varices of the bronchial veins as a source of hemoptysis in mitral stenosis. Am Heart J 1944; 28:445-56 31 Liehow AA, Hales MR, Bloomer WE, Harrison Lindskog GE. Studies on the lung after ligation of the pulmonary artery: anatomical changes. Am J Patholl950; 26: 177-95 32 Ellis FH Jr, Grindlay JH, Edwards JE. The bronchial arteries: their role in pulmonary embolism and infarction. Surgery 1952; 31:167-79 33 Chapman DW: Gugle LJ, Wheeler PW Experimental pulmonary infarction: abnormal pulmonary circulation as a prerequisite for pulmonary infarction following an embolus. Arch Intern Moo 1949; 83:158-63 34 Urschel HC Jr, Razzuk MA, Netto GJ, Disiere J, Chung SY. Sclerosing mediastinitis: improved management with histoplasmosis titer and ketoconazole. Ann Thorac Surg 1990; 50:215-21
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Pulmonary venous Infarction (Williamson et 81)
