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Systemic to Pulmonary Bronchial Blood Flow in Heart Failure* Pier Giuseppe Agostoni, MD, FCCP; Elisabetta Doria, MD; Franco Bortone, MD; Carlo Antona, MD; and Paolo Moruzzi, MD Study objective: The aim of this study was to measure systemic to pulmonary blood flow from bronchial circulation (Qbr[s-p]) in patients with heart failure. Design: In the absence of pulmonary and coronary flows, Qbr(s-p) is the volume of blood accumulating in the left side of the heart; Qbr(s-p) was measured during total cardiopulmonary bypass for coronary artery surgery; bronchial blood was vented through a cannula introduced into the left side of the heart and its volume was measured. Patients: Patients were subdivided according to the presence for more than 6 months (group 1, n=6) or less than 2 months (group 2, n=7), or the absence of heart failure (group 2, n=15). Measurements and results: Qbr(s-p) was 89 ± 18* mL/ min, 27 ± 3, 22±2, in groups 1, 2, and 3, respectively (*=p<O.Ol group 1 vs groups 2 and 3). During total cardiopulmonary bypass, pulmonary venous pressure approximates atmospheric pressure and no differences between groups were observed in systemic artery pres- sure, extracorporeal circulation pump flow, and airway pressure. Therefore, vascular resistance through the bronchial vessels draining into the pulmonary circulation is reduced in patients with heart failure for more than 6 months (group 1). Conclusions: During total cardiopulmonary bypass, Qbr(s-p) is increased in patients with chronic heart failure. Since with elevated pulmonary vascular pressure blood flow through Qbr(s-p) vessels is from the pulmonary to the systemic circulation, the lower resistance observed in group 1 suggests that bronchial vessels might contribute to reduced lung fluid overload in patients with chronic heart failure. (Chest 1995; 107:1247-52) n heart failure, fluid content of the lung is increased; its removal is achieved through several ways, including lung lymphatics, pulmonary circulation, bronchial circulation, airways, pleural spaces, and mediastinal spaces.1 2 The fractional contribution of each of these pathways is not defined and we do not know whether the removal of lung fluid excess is affected by the time course of heart failure. A likely role of lymph vessels has been stressed repeatedly. However, albeit a manyfold increase of lung lymph flow after acute and chronic pulmonary vascular pressure elevation has been reported,36 lung lymph flow remains in the order of a few milliliters per hour.4-7 Therefore, lymph flow does not seem capable of maintaining lung water homeostasis in chronic heart failure and reverting to normal lung water content after acute heart failure. A role of bronchial circulation seems more likely. Indeed, the bronchial arteries drain into a vascular plexus located around the airways where most extravascular lung fluid accumulates. These vessels have two drainage pathways: 1) the bronchial veins which, through the azygos and the hemiazygos, drain into the superior vena cava, and 2) the anastomoses with the small pulmonary vessels.8'9 Hence, the intrapulmonary bronchial vasculature allows communication between pulmonary and systemic circulations.8-10 Bronchial circulation might participate in the reduction of excessive lung water in heart failure because pulmonary hypertension reverses blood flow through the bronchopulmonary anastomoses.11'12 Although several reports suggest an increase of bronchial blood flow in the presence of chronic lung infections, pulmonary vascular obstruction, and mitral stenosis,10'13-16 to our knowledge, no information is available for heart failure. This study was undertaken to evaluate whether, in humans, systemic to pulmonary bronchial blood flow is modified in acute and chronic heart failure. *From the Istituto di Cardiologia dell' Universita degli Studi di Milano, Centro Cardiologico-Fondazione "Monzino" IRCCS, Centro di Studi per le Ricerche Cardiovascolari del Consiglio Nazionale delle Ricerche, Milan, Italy. Manuscript received June 22, 1994; revision accepted November 16. Reprint requests: C. N. R. Centro di Studio per Ricerche Cardiovascolari, clo Cattedra di Cardiologia dell' Universita di Milano, Via C. Parea, 4-20138 Milano, Italy Qbr(s-p)-systemic to pulmonary blood flow from bronchial circulation. Key words: edema; extracorporeal circulation; lung water; lymph flow MATERIAL AND METHODS We studied 28 patients who had undergone total cardiopulmonary bypass for coronary artery surgery. Patients with previous cardiac surgery, lung diseases, history of asthma, primitive valvular heart diseases, pulmonary hypertension, and congenital cardiac malformations were excluded from the study. PreoperaCHEST / 107/5/ MAY, 1995 Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21713/ on 05/08/2017 1247 tively, patients were subdivided into three groups according to the presence and duration of heart failure. To do so, inclusion criteria for each group were observed. Patients not fulfilling all the group inclusion criteria were excluded. The main inclusion criteria were the following: Group 1 consisted of patients with heart failure due to coronary artery disease for at least 6 months as suggested by long-term history of heart failure (at least 1 episode of acute pulmonary edema more than 6 months before cardiac surgery), reduced left ventricle ejection fraction (<40%), and increased pulmonary wedge pressure (>12 mm Hg) at preoperative echocardiogram and catheterization, respectively. Group 2 consisted of patients with heart failure due to coronary artery disease for less than 2 months. A first episode of myocardial infarction in the 2 months preceding cardiac surgery and evidence of heart failure since were among the inclusion criteria. Heart failure before the acute episode of myocardial infarction had to be excluded. Just as for group 1, left ventricle ejection fraction and pulmonary wedge pressure had to be, preoperatively, less than 40% and more than 12 mm Hg, respectively. Group 3 included patients with coronary artery disease but no evidence of heart failure, as suggested by the patient's history, absence of myocardial infarction, and normal left ventricle ejection fraction (>60%) and pulmonary wedge pressure (<12 mm Hg) at preoperative evaluation. Study enrolling time was between January 1992 and May 1993. All patients fullfilling the group 1 and 2 criteria who underwent coronary artery surgery at the Department of Cardiology of the University of Milan participated in the study. All subjects provided written informed consent to both the surgical and experimental procedures. The study had been approved by the local ethics committee; the investigation conforms with the principles outlined in the declaration of Helsinki. Total cardiopulmonary bypass was achieved using a standard technique. A two-stage venous cannula (William Harvey extracorporeal cannula, 34-46 F Bard) was connected, in series, to an 02-heat exchanger (Monolyth, Sorin Saluggia, Italy), to a cardiopulmonary bypass pump (Stockert-Smiley, Munich, Germany), and finally to an aortic cannula (21 to 24F). The pulmonary artery and the aorta were clamped so that no blood could leave the pulmonary circulation through the pulmonary valve or leak into the left side of the heart from the aorta. To drain the blood arriving into the left side of the heart, a cannula was inserted in the right superior pulmonary vein, advanced into the left side of the heart, and positioned into what the surgeon felt was the lowest portion of the left heart. This cannula was connected to a roller pump and then to a calibrated cylinder from which blood reached the extracorporeal circuit reservoir by gravity. The position of the left heart cannula was adjusted when needed; the aspiration from the roller pump was the lowest possible to keep the left side of the heart empty of blood. To avoid sucking of the cannula against the left ventricle wall and to obtain an adequate venting, a three-way stopcock with one end open to atmosphere was inserted between the left heart cannula and the roller pump. During total cardiopulmonary bypass, lungs were kept inflated by a constant flow of air (2 to 8 L/min, fully humidified, 24°C); airway pressure was kept unchanged throughout the procedure and was regulated by a positive end-expiratory pressure (PEEP) valve. We monitored airway and systemic blood pressures, extracorporeal circulation pump flow (cardiac output), and esophageal, rectal, and blood temperatures. The Qbr(s-p) was measured as the volume of blood returning to the left side of the heart.'15"7 '9 This blood was collected in the calibrated cylinder and measured continuously during the extracorporeal circulation. We discarded data obtained in the first 10 min of the procedure, during patients' rewarming (+2°C of esophageal, rectal, or blood temperature from the lowest achieved), and in the 10 min following cardioplegia if repeated. With this exception, Qbr(s-p) is the average of the entire run per patient. During Qbr(s-p) measurements, pulmonary artery and venous pressures were approximately 0 mm Hg. Assuming that the relationship between pulmonary venous pressure and Qbr(s-p) is linear'2,20 and that the pressure at which flow in the intrapulmonary bronchial vessels starts to be from the pulmonary to the systemic circulation=20 mm Hg,20 the relationship between pulmonary wedge pressure/Qbr(s-p) was drawn and Qbr(s-p) at real pulmonary vascular pressure was estimated. Statistical Analysis Data are reported as mean ± standard error of mean (SEM). Differences were analyzed by Student's unpaired t test applying the Bonferroni correction for multiple comparisons. RESULTS Patient characteristics are reported in Table 1. Preoperative treatment included the following: (1) group 1-digitalis, 6/6 patients; angiotensin-converting enzyme inhibitors, 5/6; nitrates, 5/6; diuretics, Table 1-Patient Characteristics* Patient/Age, yr/ Sex Smoke CI, Ppaw, LVEF, Ppa, % mm Hg mm Hg L/min/m2 43 21 64 23 26 22 2.3 2.2 2.4 2.4 2.0 3.1 Group 1 1/55/M 2/68/M 3/61/F 4/56/M 5/71/M 6/72/M + + + + + + + + + 21 15 28 43 37 43 22 16 13 22 17 35 30 20 34+61 30±111 22+81 1/50/M 2/55/M + + 3/70/M 4/68/F 5/56/M 6/62/M 7/68/M 8/71/F - 10/44/M 11/49/M 12/62/M 13/60/M 14/68/M 15/71/M Mean+SE 60+9 30 42 38 34 39 30 27 + - Mean±SE 61±6 Group 3 9/50/M 29 15 49 17 15 20 33+71 33±174 24+131 2.4+0.4f Mean+SE 64±7 Group 2 1/62/M 2/65/F 3/53/M 4/61/M 5/69/F 6/65/M 7/53/M 30 39 20 32 39 35 + 2.2 2.2 2.4 2.9 2.7 2.3 2.6 2.5±0.3f 10 8 16 18 16 10 9 12 14 16 14 12 12 16 12 7 4 3 10 7 2 6 6 4 10 7 6 2 8 1 3.3 3.6 3.0 2.8 3.8 3.7 4.2 3.0 4.1 3.0 4.1 4.0 3.3 2.9 3.1 63+5 13+3 6+3 3.5+0.5 60 55 70 66 68 56 59 72 60 66 58 56 62 64 68 + + + + + + + + + *LVEF=left ventricular ejection fraction; Ppa=mean pulmonary artery pressure; Ppaw=pulmonary artery wedge pressure; Cl= cardiac index; +=smoker; -=nonsmoker; + =ex-smoker; SE= standard error. Echocardiographic and hemodynamic data were obtained preoperatively. fp<0.01 vs group 3. Jp<0.03 vs group 3. 1248 Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21713/ on 05/08/2017 Clinical Investigations To further strengthen this point, Qbr(s-p) was not measured in patients with an intermediate duration of heart failure. Patient grouping was made a priori. A significant increase of intrapulmonary bronchial blood flow has been reported previously in several chronic diseases that affect the lungs.8"13-'6 In models of acute pulmonary embolism, bronchial blood flow is reduced21-23 but it is increased in lungs of animals with previous pulmonary embolism.'4 Beside the duration of heart failure, the severity of the pulmonary hemodynamic impairment might contribute to Qbr(s-p) changes. Patients in groups 1 and 2 had comparable hemodynamics at preoperative evaluation. However, this is a single measurement obtained at rest, and is possibly not representative of real pulmonary hemodynamic behavior. Therefore, although several mechanisms might be postulated,'4 the influence of time course and severity of heart failure on intrapulmonary bronchial circulation remains unsettled. The differences in Qbr(s-p) between groups might have some relevance for lung fluid balance in heart failure. Indeed, in chronic heart failure, elevated pulmonary vascular pressures are tolerated better than in acute heart failure, both at rest and during exercise, and there is evidence that similar elevations of left atrial pressure produce a less severe pulmonary edema when attained chronically.2'24 This means that one or more of the several pathways that can participate to removal of the excessive lung fluids have undergone some adaptive changes. Excessive extravascular lung fluids accumulate in cuffs around peribronchial and perivascular loose connective tissue where a network of bronchial capillaries is located. Recent evidence supporting the role of intrapulmonary bronchial circulation as a significant pathway for removal of excessive lung fluids has been reported.",25'26 In particular, it has been documented that, even in the absence of pulmonary blood flow, bronchial circulation is able to clear interstitial liquid.27 Blood flow in the intrapulmonary bronchial circulation is from the systemic to the pulmonary vessels but changes to from the pulmonary to the systemic circulation in case of elevation of pulmonary venous pressure.11'12 In experimental models, the relationship between pulmonary venous pressure and blood flow in the intrapulmonary bronchial vessels has been found to be linear,'2'20 but this relationship can be affected by systemic artery and right heart pressures.12'28 The blood pressure in pulmonary circulation at which the direction of blood flow through the intrapulmonary bronchial vessels changes has been questioned.'2'20 Recently, Wagner20 showed that this pressure is around 20 mm Hg. Therefore, considering that Qbr(s-p) was measured in our study with pulmonary vascular pressure around 0 mm Hg, assuming the existence of a linear relationship between Qbr(s-p) and pulmonary vascular pressure also in humans and assuming 20 mm Hg as the pressure at which blood flow in the bronchial vessels starts to be from the pulmonary to the systemic circulation, a diagram of Qbr(s-p) vs pulmonary wedge pressure can be drawn for each of the groups we studied (Fig 2). Using the same assumptions and considering the pulmonary wedge pressure measured preoperatively, we estimated the Qbr(s-p) during normal conditions and observed that flow in the intrapulmonary bronchial vessels was probably reversed in patients with heart failure. From Figure 2 it may also be suggested that in long-term heart failure with pulmonary hypertension, the magnitude of blood leaving the lung vasculature is relevant and so bronchial circulation might significantly contribute to lung fluid removal in chronic heart failure. It is recognized that when drawing the Qbr(s-p)/pulmonary wedge pressure diagram, right atrial pressure changes due to chronic heart failure were not considered and actually the animal experimental models, from which this relationship was derived, assume a low right atrial pressure; on the contrary, it is known that increasing right atrial pressure reduces bronchial blood flow through the bronchial veins (to the right heart) and worsens pulmonary edema.25'29 Therefore, the hemodynamic model we propose is limited because it applies to the condition of elevated pulmonary venous pressure and low right heart pressure, because it is based on several assumptions and because it does not take into account the other pathways that contribute to lung fluid homeostasis in heart failure." 2 In conclusion, our data show that with chronic heart failure, bronchial circulation undergoes changes that produce a reduction of vascular resistances. We hypothesized that low resistance allows a significant blood flow out of the lungs when pressures in the pulmonary vasculature are elevated. REFERENCES 1 Matthay MA. The bronchial and systemic circulation in lung and pleural fluid and protein balance. In: Butler J, ed. The bronchial circulation. New York: Marcel Dekker, 1992; 389-415 2 Matthay MA. Resolution of pulmonary edema: mechanisms of liquid, protein and cellular clearance from the lung. Clin Chest Med 1985; 6:521-45 3 Staub NC. Pulmonary edema. Physiol Rev 1974; 54:678-811 4 Erdmann J III, Vaughan TR, Brigham KL, et al. Effect of increased vascular pressure on lung fluid balance in unanesthetized sheep. Circ Res 1975; 37:271-84 5 Gee MH, Spath JA. The dynamics of the lung fluid filtration system in dogs with edema. Circ Res 1980; 46:796-801 6 Grimbert FA, Martin D, Packer JC, et al. Lymph flow during increase in pulmonary blood flow and microvascular pressure in dogs. Am J Physiol 1988; 255:H1149-H1155 CHEST / 107/ 5 / MAY, 1995 Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21713/ on 05/08/2017 1251 Table 2-Duration, Extracorporeal Circulation Pump Flow, and Body Temperature During Qbr(s-p) Measurements* Patient Co, Time, min L/min P Airways, mm Hg T Es, °C T Rectum, °C T Blood, °C 25 28 15 22 40 35 27+9 6.0 4.3 3.8 3.4 3.3 4.3 4.2+1.0 0 0 0 0 0 0 0+0 27.9 29.9 28.5 28.0 27.6 31.9 29.0+1.6 32.1 32.0 32.0 29.4 30.0 31.5 31.2+1.2 26.3 28.3 25.9 27.7 27.0 29.0 27.4+1.2 27 20 41 15 23 18 40 26+10 4.0 5.5 3.2 3.8 2.9 4.5 5.2 4.2+1.0 0 0 0 0 4 0 0 0.6+1.5 26.8 29.4 29.0 30.1 27.2 28.5 28.0 28.4+1.2 28.9 30.4 31.9 31.6 30.2 33.6 29.0 30.8+1.7 27.9 27.2 27.0 27.7 25.9 27.0 26.8 27.1+0.7 20 15 30 38 22 26 21 30 26 24 18 16 23 40 31 25+7 4.2 4.8 3.9 3.0 5.1 3.5 3.9 3.3 4.0 4.2 4.4 4.8 5.3 4.1 4.3 4.2+0.6 0 0 0 2 0 0 0 4 0 0 2 0 0 0 0 0.5+1.2 28.0 29.6 30.1 27.6 27.9 28.1 26.9 28.0 27.9 30.1 29.0 29.1 28.0 28.5 29.5 29.2 30.4 31.0 28.0 28.2 29.4 28.5 30.1 29.1 31.2 29.9 30.6 30.1 31.6 30.3 29.8+1.1 27.1 29.0 29.0 27.5 27.0 27.6 26.9 29.2 27.6 28.8 28.0 28.5 26.9 29.0 28.2 28.0+0.9 Group 1 1 2 3 4 5 6 Mean+SE Group 2 1 2 3 4 5 6 7 Mean+SE Group 3 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Mean+SE 28.6+1.0 *Time=duration of Qbr(s-p) measurements; CO=cardiac output (extracorporeal circulation pump flow); P pressure; T= temperature; Es=esophagus; SE=standard error. measured blood flow the lung weight changes.'2,21 It is not possible to measure lung weight changes in humans. However, changes of lung fluid' content during our measurements are unlikely because pulmonary vascular pressure was, by necessity, close to zero and so was airway pressure; therefore, fluid filtration in the lung interstitium or accumulation in the pulmonary vasculature is unlikely. Furthermore, we previously showed that Qbr(s-p) values obtained by this technique are constant with time18 and there is experimental evidence that lung weight remains constant under similar conditions.22 With our technique, the possible blood flow from the pulmonary circulation to the right side of the heart was impeded by the pulmonary artery clamp. Our technique does not interfere with the surgical procedure or prolong the extracorporeal circulation. It is recognized that Qbr(s-p) measurements were done in nonphysiologic conditions. Indeed, the surgical procedure, body temperature, inspired gas humidity, absence of pulmonary flow, and close to zero mm Hg pulmonary vascular pressure influence the results.19 However, body temperature, inspired gas humidity, and pulmonary hemodynamics were kept constant during Qbr(s-p) measurements and no differences in these parameters were observed between groups. Therefore, albeit our measurements probably do not apply to physiologic conditions, data between groups are at least comparable. Because during total cardiopulmonary bypass the pressures upstream (systemic artery), downstream (pulmonary circulation), and around the intrapulmonary bronchial vessels (airway pressure) were similar in the three groups, the differences in Qbr(s-p) imply differences in resistance through the intrapulmonary bronchial vessels. This means the existence in patients with chronic heart failure (group 1) of more dilated and/or larger and/or more numerous intrapulmonary bronchial vessels. Duration of heart failure was more than 6 months for group 1 and less than 2 months in group 2 and it is the sole relevant difference between these groups. 1250 Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21713/ on 05/08/2017 Clinical Investigations To further strengthen this point, Qbr(s-p) was not measured in patients with an intermediate duration of heart failure. Patient grouping was made a priori. A significant increase of intrapulmonary bronchial blood flow has been reported previously in several chronic diseases that affect the lungs.8"13-'6 In models of acute pulmonary embolism, bronchial blood flow is reduced21-23 but it is increased in lungs of animals with previous pulmonary embolism.'4 Beside the duration of heart failure, the severity of the pulmonary hemodynamic impairment might contribute to Qbr(s-p) changes. Patients in groups 1 and 2 had comparable hemodynamics at preoperative evaluation. However, this is a single measurement obtained at rest, and is possibly not representative of real pulmonary hemodynamic behavior. Therefore, although several mechanisms might be postulated,'4 the influence of time course and severity of heart failure on intrapulmonary bronchial circulation remains unsettled. The differences in Qbr(s-p) between groups might have some relevance for lung fluid balance in heart failure. Indeed, in chronic heart failure, elevated pulmonary vascular pressures are tolerated better than in acute heart failure, both at rest and during exercise, and there is evidence that similar elevations of left atrial pressure produce a less severe pulmonary edema when attained chronically.2'24 This means that one or more of the several pathways that can participate to removal of the excessive lung fluids have undergone some adaptive changes. Excessive extravascular lung fluids accumulate in cuffs around peribronchial and perivascular loose connective tissue where a network of bronchial capillaries is located. Recent evidence supporting the role of intrapulmonary bronchial circulation as a significant pathway for removal of excessive lung fluids has been reported.",25'26 In particular, it has been documented that, even in the absence of pulmonary blood flow, bronchial circulation is able to clear interstitial liquid.27 Blood flow in the intrapulmonary bronchial circulation is from the systemic to the pulmonary vessels but changes to from the pulmonary to the systemic circulation in case of elevation of pulmonary venous pressure.11'12 In experimental models, the relationship between pulmonary venous pressure and blood flow in the intrapulmonary bronchial vessels has been found to be linear,'2'20 but this relationship can be affected by systemic artery and right heart pressures.12'28 The blood pressure in pulmonary circulation at which the direction of blood flow through the intrapulmonary bronchial vessels changes has been questioned.'2'20 Recently, Wagner20 showed that this pressure is around 20 mm Hg. Therefore, considering that Qbr(s-p) was measured in our study with pulmonary vascular pressure around 0 mm Hg, assuming the existence of a linear relationship between Qbr(s-p) and pulmonary vascular pressure also in humans and assuming 20 mm Hg as the pressure at which blood flow in the bronchial vessels starts to be from the pulmonary to the systemic circulation, a diagram of Qbr(s-p) vs pulmonary wedge pressure can be drawn for each of the groups we studied (Fig 2). Using the same assumptions and considering the pulmonary wedge pressure measured preoperatively, we estimated the Qbr(s-p) during normal conditions and observed that flow in the intrapulmonary bronchial vessels was probably reversed in patients with heart failure. From Figure 2 it may also be suggested that in long-term heart failure with pulmonary hypertension, the magnitude of blood leaving the lung vasculature is relevant and so bronchial circulation might significantly contribute to lung fluid removal in chronic heart failure. It is recognized that when drawing the Qbr(s-p)/pulmonary wedge pressure diagram, right atrial pressure changes due to chronic heart failure were not considered and actually the animal experimental models, from which this relationship was derived, assume a low right atrial pressure; on the contrary, it is known that increasing right atrial pressure reduces bronchial blood flow through the bronchial veins (to the right heart) and worsens pulmonary edema.25'29 Therefore, the hemodynamic model we propose is limited because it applies to the condition of elevated pulmonary venous pressure and low right heart pressure, because it is based on several assumptions and because it does not take into account the other pathways that contribute to lung fluid homeostasis in heart failure." 2 In conclusion, our data show that with chronic heart failure, bronchial circulation undergoes changes that produce a reduction of vascular resistances. We hypothesized that low resistance allows a significant blood flow out of the lungs when pressures in the pulmonary vasculature are elevated. REFERENCES 1 Matthay MA. The bronchial and systemic circulation in lung and pleural fluid and protein balance. In: Butler J, ed. The bronchial circulation. New York: Marcel Dekker, 1992; 389-415 2 Matthay MA. Resolution of pulmonary edema: mechanisms of liquid, protein and cellular clearance from the lung. Clin Chest Med 1985; 6:521-45 3 Staub NC. Pulmonary edema. Physiol Rev 1974; 54:678-811 4 Erdmann J III, Vaughan TR, Brigham KL, et al. Effect of increased vascular pressure on lung fluid balance in unanesthetized sheep. Circ Res 1975; 37:271-84 5 Gee MH, Spath JA. The dynamics of the lung fluid filtration system in dogs with edema. Circ Res 1980; 46:796-801 6 Grimbert FA, Martin D, Packer JC, et al. Lymph flow during increase in pulmonary blood flow and microvascular pressure in dogs. Am J Physiol 1988; 255:H1149-H1155 CHEST / 107/ 5 / MAY, 1995 Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21713/ on 05/08/2017 1251 7 Matthay MA, Landolt CC, Staub NC. Differential liquid and protein clearance from the alveoli of anesthetized sheep. J Appl Physiol 1982; 53:96-104 8 Deffebach ME, Charan NB, Lakshminarayan S, et al. The bronchial circulation: small, but a vital attribute to the lung. Am Rev Respir Dis 1987; 135:463-81 9 Murata K, Itoh K, Todo G, et al. Bronchial venous plexus and its communication with pulmonary circulation. Invest Radiol 1986; 32:24-30 10 Ohimici M, Tagaki S, Tsunematsu K, et al. Endobronchial changes in pulmonary venous hypertension. Chest 1988; 93: 1127-32 11 Awad J, Ghys R, Lou WU, et al. Hemodynamic aspects of the pulmonary collateral circulation: an experimental study of an isolated pulmonary lobar circulation by means of tagged erythrocytes. J Thorac Cardiovasc Surg 1965; 50:596-600 12 Agostoni PG, Deffebach ME, Kirk W, et al. Upstream pressure for systemic to pulmonary bronchial blood flow in dogs. J Appl Physiol 1987; 63:485-91 13 Charan NB, Carvalho PG. The bronchial circulation in chronic lung infections. In: Butler J, ed. The bronchial circulation. New York: Marcel Dekker, 1992; 535-50 14 Shure D. The bronchial circulation in pulmonary vascular obstruction. In: Butler J, ed. The bronchial circulation. New York: Marcel Dekker, 1992; 579-98 15 Agostoni PG, Agrifoglio M, Arena V, et al. Systemic to pulmonary bronchial blood flow in mitral stenosis. Chest 1991; 99:642-45 16 Babic UU, Popovic Z, Grujicic S, et al. Systemic and pulmonary flow in mitral stenosis: evidence for a bronchial vein shunt. Cardiology 1991; 78:311-16 17 Baile EM, Ling H, Heyworth JR, et al. Bronchopulmonary anastomotic and non-coronary collateral blood flow in humans during cardiopulmonary bypass. Chest 1985; 87:749-54 18 Agostoni PG, Arena V, Biglioli P, et al. Increase of alveolar pressure reduces systemic-to-pulmonary bronchial blood flow in humans. Chest 1989; 96:1081-85 19 Agostoni PG, Baile EH, Godden DJ. Measurements of bronchial blood flow in humans. In: Butler J, ed. The bronchial circulation. New York: Marcel Dekker, 1992; 181-96 20 Wagner E. Mechanical aspects of physiological regulation of the bronchial circulation. In: Butler J, ed. The bronchial circulation. New York: Marcel Dekker, 1992; 219-48 21 Agostoni PG, Deffabach ME, Kirk W, et al. Temperature alters bronchial blood flow response to pulmonary artery obstruction. J Appl Physiol 1987; 62:1907-11 22 Charan NB, Albert RK, Lakshminarayan S, et al. Factors affecting bronchial blood flow through bronchopulmonary anastomoses in dogs. Am Rev Respir Dis 1986; 134:85-8 23 Malik AB, Tracy SE. Bronchovascular adjustments after pulmonary embolism. J Appl Physiol 1980; 49:476-81 24 Dash H, Lipton MJ, Chatterjee K, et al. Estimation of pulmonary arterial wedge pressure from the chest radiograph in patients with chronic congestive cardiopulmonary and ischemic cardiomyopathy. Br Heart J 1980; 44:322-29 25 Raj UJ, Band RD. Lung luminal liquid clearance in newborn lambs. Am Rev Respir Dis 1986; 134:305-10 26 Lakshminarayan S, Kowalski TF, Kirk W, et al. The effect of bronchial venous pressure on pulmonary edema in the dog. Respir Physiol 1990; 82:317-24 27 Jayr C, Matthay MA. Alveolar and lung liquid clearance in the absence of pulmonary blood flow. J Appl Physiol 1991; 71:1679-87 28 Salisbury PF, Weil P, State D. Factors influencing collateral blood flow to the dog's lung. Circ Res 1957; 5:303-09 29 Charan NB, Turk MG, Hey DH. Effect of increase bronchial venous pressure on lung lymph flow. J Appl Physiol 1985; 59: 1249-53 1252 Downloaded From: http://publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21713/ on 05/08/2017 Clinical Investigations