Experimental investigation of right-left flow balance concepts for a total artificial heart.

A total artificial heart (TAH) must be designed to autonomously balance the flows of the systemic and pulmonary circulation to prevent potentially lethal lung damage. The flow difference between the systemic and pulmonary circulation is mainly caused by the bronchial (arteries) shunt flow and can change dynamically. The ReinHeart TAH consists of only one actuator that ejects blood alternately from the right and left pump chamber. This design entails a coupling of the right and left stroke and thus, complicates the independent adaptation of the right and left flow. In this experimental study on the ReinHeart TAH, four concepts to keep the flows well balanced were investigated using an active mock circulation loop for data acquisition. Three concepts are based on mechanical design changes (variation of pusher plate shape, flexible right pump chamber housing, and reduced right stroke volume) to achieve a static flow difference. In combination with these static concepts, a concept influencing the ratio of systole and diastole duration to respond to dynamic changes was studied. In total, four measurement series, each with 270 operating points, to investigate the influence of circulatory filling volume, heart rate, bronchial shunt flow, and lung resistance were recorded. In the course of this study, we introduce a concept deviation indicator, providing information about the efficiency of the concepts to balance the flows based on changes in lung's blood pressures. Furthermore, the distribution of the measured data was evaluated based on bubble plot visualizations. The investigated variation of the right pusher plate shape results in high lung pressures which will cause lethal lung damage. In comparison, a flexible right pump chamber housing shows lower lung pressures, but it still has the potential to damage the lungs. Reducing the stroke volume of the right pump chamber results in proper lung pressures. The flow balance can dynamically be influenced with a positive effect on the lung pressures by choosing a suitable systole-diastole-ratio. The results of this study suggest that an adequate right-left flow balance can be achieved by combining the mechanical concept of a reduced right stroke volume with an active control of the systole-diastole-ratio.

The Bronchial Arterial Circulation in Lung Transplantation: Bedside to Bench to Bedside, and Beyond.

Chronic allograft dysfunction (CLAD) remains a major complication, causing the poor survival after lung transplantation (Tx). Although strenuous efforts have been made at preventing CLAD, surgical approaches for lung Tx have not been updated over the last 2 decades. The bronchial artery (BA), which supplies oxygenated blood to the airways and constitutes a functional microvasculature, has occasionally been revascularized during transplants, but this technique did not gain popularity and is not standard in current lung Tx protocols, despite the fact that a small number of studies have shown beneficial effects of BA revascularization on limiting CLAD. Also, recent basic and clinical evidence has demonstrated the relationship between microvasculature damage and CLAD. Thus, the protection of the bronchial circulation and microvasculature in lung grafts may be a key factor to overcome CLAD. This review revisits the history of BA revascularization, discusses the role of the bronchial circulation in lung Tx, and advocates for novel bronchial-arterial-circulation sparing approaches as a future direction for overcoming CLAD. Although there are some already published review articles summarizing the surgical techniques and their possible contribution to outcomes in lung Tx, to the best of our knowledge, this review is the first to elaborate on bronchial circulation that will contribute to prevent CLAD from both scientific and clinical perspectives: from bedside to bench to bedside, and beyond.

Prediction of Therapeutic Effect of Chemotherapy for NSCLC Using Dual-Input Perfusion CT Analysis: Comparison among Bevacizumab Treatment, Two-Agent Platinum-based Therapy without Bevacizumab, and Other Non-Bevacizumab Treatment Groups.

Purpose To determine whether dual-input perfusion computed tomography (CT) can predict therapeutic response and prognosis in patients who underwent chemotherapy for non-small cell lung cancer (NSCLC). Materials and Methods The institutional review board approved this study and informed consent was obtained. Sixty-six patients with stage III or IV NSCLC (42 men, 24 women; mean age, 63.4 years) who underwent chemotherapy were enrolled. Patients were separated into three groups: those who received chemotherapy with bevacizumab (BV) (n = 20), those who received two-agent platinum-based therapy without BV (n = 25), and those who received other non-BV treatment (n = 21). Before treatment, pulmonary artery perfusion (PAP) and bronchial artery perfusion (BAP) of the tumors were calculated. Predictors of tumor reduction after two courses of chemotherapy and prognosis were identified by using univariate and multivariate analyses. Covariates included were age, sex, patient's performance status, baseline maximum diameter of the tumor, clinical stage, pretreatment PAP, and pretreatment BAP. For multivariate analyses, multiple linear regression analysis for tumor reduction rate and Cox proportional hazards model for prognosis were performed, respectively. Results Pretreatment BAP was independently correlated with tumor reduction rate after two courses of chemotherapy in the BV treatment group (P = .006). Pretreatment BAP was significantly associated with a highly cumulative risk of death (P = .006) and disease progression after chemotherapy (P = .015) in the BV treatment group. Pretreatment PAP and clinical parameters were not significant predictors of therapeutic effect or prognosis in three treatment groups. Conclusion Pretreatment BAP derived from dual-input perfusion CT seems to be a promising tool to help predict responses to chemotherapy with BV in patients with NSCLC. © RSNA, 2017.

Bronchial Artery Angiogenesis Drives Lung Tumor Growth.

Angiogenesis is vital for tumor growth but in well-vascularized organs such as the lung its importance is unclear. This situation is complicated by the fact that the lung has two separate circulations, the pulmonary and the systemic bronchial circulation. There are few relevant animal models of non-small cell lung cancer, which can be used to study the lung's complex circulations, and mice, lacking a systemic bronchial circulation cannot be used. We report here a novel orthotopic model of non-small cell lung cancer in rats, where we have studied the separate contributions of each of the two circulations for lung tumor growth. Results show that bronchial artery perfusion, quantified by fluorescent microspheres (206% increase in large tumors) or high-resolution computed tomography scans (276% increase in large tumors), parallels the growth in tumor volume, whereas pulmonary artery perfusion remained unchanged. Ablation of the bronchial artery after the initiation of tumor growth resulted in a decrease in tumor volume over a subsequent course of 4 weeks. These results demonstrate that although the existing pulmonary circulation can supply the metabolic needs for tumor initiation, further growth of the tumor requires angiogenesis from the highly proliferative bronchial circulation. This model may be useful to investigate new therapeutic approaches that target specifically the bronchial circulation. Cancer Res; 76(20); 5962-9. ©2016 AACR.

A New Method for Discriminating between Bronchial and Pulmonary Arterial Phases using Contrast-Enhanced Ultrasound.

This study aimed to explore the value of a real-time comparative observation method using contrast-enhanced ultrasound (CEUS) for discriminating between bronchial and pulmonary arterial phases in diagnosing lung diseases. Forty-nine patients with 50 pulmonary lesions (45 peripheral lesions and five central lesions with obstructive atelectasis, including 36 malignant tumors, five tuberculomas, four inflammatory pseudotumors and five pneumonia lesions) detected via computed tomography and visible on ultrasonography were enrolled in this study. The arterial phases were determined by comparing contrast agent arrival time (AT) in the peripheral lung lesion with that in adjacent lung tissue, referred to as a real-time comparative observation method. Detection rates of this observation method were 100% (50/50) for pulmonary arterial phase and 88% (44/50) for bronchial arterial phase. Using the instrument's built-in graphing and analysis software, a time-intensity curve was constructed based on a chosen region of interest within the lesion where enhancement was the most obvious. Commonly used perfusion indicators in CEUS, such as AT, time-to-peak and peak intensity, were obtained from the time-intensity curve. Percutaneous puncture biopsies were performed under ultrasound guidance, and specimens of all 50 lesions were examined pathologically. AT was significantly shorter in patients with pneumonia than in those with malignant tumors or chronic inflammation (p < 0.05), whereas no difference was seen between those with malignant tumors and those with chronic inflammation. No significant differences in time-to-peak or peak intensity were seen among those with various lung diseases (p > 0.05). This is the first description of a real-time comparative observation method using CEUS for determining the arterial phases in the lungs. This method is accurate, simple to perform and provides a direct display. It is expected to become a practical and feasible tool for diagnosing lung diseases.

Bronchial arteries: anatomy, function, hypertrophy, and anomalies.

The two main sources of blood supply to the lungs and their supporting structures are the pulmonary and bronchial arteries. The bronchial arteries account for 1% of the cardiac output but can be recruited to provide additional systemic circulation to the lungs in various acquired and congenital thoracic disorders. An understanding of bronchial artery anatomy and function is important in the identification of bronchial artery dilatation and anomalies and the formulation of an appropriate differential diagnosis. Visualization of dilated bronchial arteries at imaging should alert the radiologist to obstructive disorders that affect the pulmonary circulation and prompt the exclusion of diseases that produce or are associated with pulmonary artery obstruction, including chronic infectious and/or inflammatory processes, chronic thromboembolic disease, and congenital anomalies of the thorax (eg, proximal interruption of the pulmonary artery). Conotruncal abnormalities, such as pulmonary atresia with ventricular septal defect, are associated with systemic pulmonary supply provided by aortic branches known as major aortopulmonary collaterals, which originate in the region of the bronchial arteries. Bronchial artery malformation is a rare left-to-right or left-to-left shunt characterized by an anomalous connection between a bronchial artery and a pulmonary artery or a pulmonary vein, respectively. Bronchial artery interventions can be used successfully in the treatment of hemoptysis, with a low risk of adverse events. Multidetector computed tomography helps provide a vascular road map for the interventional radiologist before bronchial artery embolization.

Differential effects of inhaled methacholine on circumferential wall and vascular smooth muscle of third-generation airways in awake sheep.

Evolution and natural selection ensure that specific mechanisms exist for selective airway absorption of inhaled atmospheric molecules. Indeed, nebulized cholinoceptor agonists used in asthma-challenge tests may or may not enter the systemic circulation. We examined the hypothesis that inhaled cholinoceptor agonists have selective access. Six sheep were instrumented under general anesthesia (propofol 5 mg/kg iv, 2-3% isoflurane-oxygen), each with pulsed-Doppler blood flow transducers mounted on the single bronchial artery and sonomicrometer probes mounted on the intrapulmonary third-generation lingula lobe bronchus. Continuous measurements were made of bronchial blood flow (Q(br)), Q(br) conductance (C(br)), bronchial hemicircumference (CIRC(br)), and bronchial wall thickness (WALL TH(br)) in recovered, standing, awake sheep. Methacholine (MCh; 0.125-2.0 µg/kg iv), at the highest dose, caused a 233% rise in Q(br) (P < 0.05) and a 286% rise in C(br) (P < 0.05). CIRC(br) fell to 90% (P < 0.05); WALL TH(br) did not change. In contrast, nebulized MCh (1-32 mg/ml), inhaled through a mask at the highest dose, caused a rise in ventilation and a rise in Q(br) proportional to aortic pressure without change in C(br). CIRC(br) fell to 91% (P < 0.01), and WALL TH(br) did not change. Thus inhaled MCh has access to cholinoceptors of bronchial circumferential smooth muscle to cause airway lumen narrowing but effectively not to those of the systemic bronchovascular circulation. It is speculated that the mechanism is selective neuroparacrine inhibition of muscarinic acetylcholine receptors (M3 bronchovascular cholinoceptors) by prostanoids released by intense MCh activation of epithelial and mucosal cells lining the airway.

Integration of baroreflex and autoregulation control of bronchial blood flow in awake dogs.

AIM: Baroreflex control of the bronchial circulation is unresolved. Early studies suggested that baroreflexes dilate or have no effect, but recent studies in awake dogs suggested baroreflexes did not normally engage tonic vasoconstrictor efferents but during excitement systemic pressure rises may also trigger local sensory-motor dilator reflexes. We examined the postulate that bronchial flow is normally regulated at rest during controlled changes in pressure gradient (Pg) by integration of tonic autonomic activity with autoregulation. METHODS: Twelve greyhounds were instrumented under general anaesthesia by surgical implantation of pulsed Doppler flow transducers on the right bronchial artery (BA). After recovery baroreflex effects were evoked by raising and lowering aortic pressure using a lower thoracic aortic balloon in 11 animals, and in six of these after cholinoceptor plus adrenoceptor blockade. RESULTS: The right BA bed showed pressure-passive responses and the time-dependent bronchial bed effects in the autonomically intact state (INT) were largely similar to those in the blocked state (TAB). When results were replotted as pressure-flow relationships and analysed using covariance, the regression line over the pressure range 70-135 mmHg for TAB demonstrated a significant slope (P < 0.05), a linear regression elevated 120% (P = 0.006) above and parallel to INT (Y(Q) = 0.034 + 0.00033(X(Pg) - 104.6). The regression fell on the line of equal proportional change. CONCLUSION: Baroreflexes do not functionally engage the autonomic outflow to the bronchial circulation. Under controlled conditions of systemic Pg change, the bronchial circulation is normally controlled by the integration of resting autonomic tone, myogenic autoregulation and pressure-passive effects.

[A simulating excorporeal experimental system for automatic drug injection based on predictive control in vascular interventional therapy].

This paper discusses an in vitro simulating experiment for drug injection based on predictive control in vascular interventional therapy. The relationship between the model of drug injection and the pulsatile blood flow was studied. The experimental model for predictive control of drug injection was tested and verified so as to support the future animal experimental modeling with the data acquired from the in vitro simulating experiment.

The airway vasculature: recent advances and clinical implications.

It is increasingly recognised that the airway circulation plays an important role in airway diseases, either through a change in blood flow or through microvascular leakage. Most of the information available regarding the anatomy and physiology of bronchial blood flow and its regulation has necessarily derived from animal studies. However, there have recently been important advances in understanding airway blood flow in airway disease in humans through the development of non-invasive methods and in the quantification of microvascular leakage using plasma markers. These studies have shown that bronchial blood flow is increased in patients with asthma but not in those with chronic obstructive pulmonary disease, confirming previous pathology investigations. Changes in bronchial blood flow may in part reflect the generation of new vascular vessels, a process known as "angiogenesis" which is caused by airway inflammation. Angiogenesis and the resulting plasma leak affect airway physiology, drug clearance and its bioavailability. This review discusses the anatomy, physiology and regulation of bronchial blood flow in the normal and diseased lung, In addition, it analyses the effect of current medical treatment and discusses the potential use of new anti-angiogenesis medications. The development of non-invasive assessment of bronchial blood flow and the study of angiogenesis have provided a tool to investigate airway physiology in vivo; these advances will contribute to a better understanding of inflammatory airway diseases as well as the implication of these findings to management.

[Successful treatment of a primary racemose hemangioma using ligation and transection of the bronchial artery decided on the basis of the intra-operative arterial pressure].

An 80-year-old woman presented with hemoptysis. Fiberoptic bronchoscopy revealed a blue, non-pulsatile, polypoid lesion at the orifice of the left upper division bronchus. Bronchial arteriography demonstrated convolution, dilatation, and pooling of contrast material in the left upper lobe. Since the bronchial arterial pressure decreased to the predicted pulmonary artery pressure after transient interruption between the aorta and proximal bronchial artery, the racemose hemangioma was presumed to be supplied mainly from the bronchial artery. She underwent ligation and transaction of the left bronchial artery, and had no further hemoptysis. Measurement of the bronchial arterial pressure is important for determining how to treat racemose hemangioma.

Dilatation of bronchial arteries correlates with extent of central disease in patients with chronic thromboembolic pulmonary hypertension.

BACKGROUND: Dilatation of the bronchial arteries is a well-recognized feature in patients with chronic thromboembolic pulmonary hypertension (CTEPH). The purpose of the current study was to use computed tomography (CT) to assess the relationship between dilated bronchial arteries and the extent of thrombi, and to evaluate the predictive value of the former for surgical outcome. METHODS AND RESULTS: Fifty-nine patients with CTEPH and 16 with pulmonary arterial hypertension (PAH) were retrospectively evaluated. The total cross-sectional area of bronchial arteries was measured by CT and its relationship with the central extent of thrombi or surgical outcome was assessed. The total area of the bronchial arteries in CTEPH patients was significantly larger than that in PAH patients (median [range], 6.9 [1.7-29.5] mm(2) vs 3.2 [0.8-9.4] mm(2)), with the total area of bronchial arteries correlating with the central extent of thrombi. In patients who had undergone pulmonary thromboendarterectomy (PTE) (n=22), the change in PaO(2) after surgery had a tendency to correlate with the total area of the bronchial arteries. CONCLUSION: The total cross-sectional area of the bronchial arteries correlated with the extent of central disease in patients with CTEPH, and it might predict gas exchange improvement after PTE.

Vascular endothelial growth factor gene therapy induces early re-establishment of canine bronchial circulation.

OBJECTIVE: To evaluate the usefulness of gene therapy with human vascular endothelial growth factor 165 (phVEGF(165)) to promote the early re-establishment of systemic arterial perfusion in canine bronchi deprived of bronchial circulation. METHODS: To disrupt bronchial circulation, dogs were submitted to transversal bronchotomy dividing the left mainstem bronchus into a proximal and a distal portion. phVEGF(165) (VEGF group, n=8) or physiologic saline solution (control group, n=8) were then delivered to the left distal bronchus. After that, the airway was reconstituted with interrupted suture. On day 3, nine dogs (four VEGF and five controls) were euthanized and their left distal bronchi were harvested to evaluate VEGF(165) gene expression by reverse transcription-polymerase chain reaction. In the other dogs (four VEGF and three controls), a microvascular dye was injected through the canine aorta to verify the re-establishment of arterial blood supply to the distal bronchus. Additionally, VEGF immunohistochemistry was performed in distal airway specimens. RESULTS: Microvascular dye was observed in 100% of specimens transfected with phVEGF(165) compared to none in controls. VEGF gene expression (p<0.01) and VEGF protein expression (p<0.05) were higher in VEGF(165)-treated bronchi. CONCLUSIONS: Local transfection with phVEGF(165) promoted the early re-establishment of systemic arterial perfusion to bronchi previously deprived of bronchial circulation. Gene therapy with phVEGF(165) may be a useful tool to restore bronchial circulation by promoting early airway angiogenesis.

Bronchial arterial imaging using helical computed tomography.

The bronchial arteries, which provide the systemic arterial supply to the lungs, are involved in a variety of disease processes in humans, including congenital disorders, infection, and pulmonary thromboembolism. In these conditions, the bronchial arteries hypertrophy and bronchial blood flow increases. Consequently, in many disorders, such as bronchiectasis, the bronchial arteries are a frequent source of haemoptysis, which may be massive and life-threatening. Evaluation of the bronchial circulation has typically required invasive imaging with angiography to determine the location of bleeding. Non-invasive assessment of bronchial arterial anatomy and morphology is currently being investigated with the use of helical computed tomography (CT). We evaluated eight patients with various lung diseases with helical CT (GE Medical Systems, LS16, Milwaukee, WI) to determine the imaging features of the bronchial circulation. Non-ionic contrast medium (iopromide) was injected intravenously (80-1000ml/30s) and scanning was triggered once contrast material was present in the pulmonary artery (average delay=15s) or ascending aorta (average delay=20s). Detector collimation (16-row unit) was 10mm. Imaging parameters included a section thickness of 0.6mm, kilovolt peak of 120, 150-440mA, pitch factor of 1.375, matrix of 512x512, and tube rotation time of 0.8s. The images were reconstructed and scanned isotropically (Advantage Workstation 4.1,GE Medical Systems). We conclude that helical computed tomography may provide a non-invasive means of evaluating the bronchial arteries and their role in pulmonary disease processes.

Drainage routes of bronchial blood flow in anaesthetized sheep.

The systemic circulation to the lung supplies the trachea and airway walls and may be important in the pathophysiology of asthma and pulmonary oedema. An understanding of the venous drainage pathways of this bronchial blood flow may be therapeutically important. The purpose of this study was to understand the normal drainage pathways in sheep. In seven anaesthetized, ventilated sheep we injected echo contrast agents into a systemic vein or into the bronchial artery while performing echocardiography to determine whether the drainage could be observed to the right heart and/or to the left heart. During transoesophageal echo (n=5) or heart surface echo (n=2), cephalic vein injection of <8 microm diameter gelatin microballoons promptly opacified the right but never the left-sided circulation. Air in agitated saline in the seven animals showed the same result. By contrast, injection into the bronchial artery promptly opacified the left atrium, left ventricle, and aorta but not the right-sided circulation in all seven microballoon injections and all but one of the air in agitated saline injections. The failure of the echo agents to pass through the pulmonary circulation may be related to sheep pulmonary intravascular macrophages or the surface forces on air bubbles of small size promoting collapse. The main conclusion is that there are bronchopulmonary anastomoses that connect the bronchial circulation to the pulmonary venous circulation connecting distal to the pulmonary capillaries. Any bronchial venous drainage to the right-sided circulation must have been below the detection level of the instruments and would in any case appear to be much less that the post-pulmonary capillary anastomoses noted. Pulmonary venous hypertension would be expected to have a direct effect on the bronchial circulation.

Injection of prostaglandin F2alpha into the bronchial artery in sheep increases the pulmonary vascular permeability to protein.

Lung injury and oedema following smoke inhalation are associated with eicosanoid release and the injury is heavily influenced by the tracheobronchial circulation. We hypothesized that injection of a vasoactive eicosanoid, prostaglandin F2alpha (PGF2alpha), into the tracheobronchial circulation would induce a permeability leak in that circulation as measured in lung lymph flow and protein content. PGF2alpha when injected into the bronchial artery increased lung lymph flow, protein content and lymph protein flux (protein times flow). The increase in lymph to plasma protein concentration after injection of PGF2alpha is consistent with an increase in vascular protein permeability since an increase in pressure alone would cause an increase in fluid flow in excess of protein with a fall in protein concentration. Ligation of the bronchial artery 3min after injection of the PGF2alpha largely prevented the late changes suggesting that the protein leak into the lymph was from the bronchial arteries.

Anastomoses between bronchial and coronary circulation in a porcine model: computed tomographic and angiographic demonstration.

INTRODUCTION: Although the importance of the bronchial arteries is evident in modern day thoracic surgery, the significance of their communications with coronary arteries has yet to be appreciated, especially in cases of heart-lung transplantation and aortic aneurysm repair. We conducted a study to demonstrate the coronary-bronchial anastomotic routes in a porcine model using angiography and computed tomography. METHODS: Six young female white pigs were used. The heart and lungs were removed en bloc, including the lower trachea and oesophagus. Digital subtraction angiography of the bronchial circulation and spiral computed tomography scan were performed in a three-phase study before and after administration of contrast medium. This was achieved by infusion either into the cannulated bronchial artery or into the aortic root. Macroscopic evaluation was carried out using latex infusion into the bronchial or coronary circulation. RESULTS: We demonstrated communications between the bronchial and coronary systems in 5 of 6 subjects. This communication was located at the left atrial wall and the posterior and anterior wall of the left ventricle. In one case there were further anastomoses around the right atrial wall. CONCLUSIONS: There were communications between the left coronary arteries and the bronchial arteries in the majority of cases. Digital subtraction angiography and spiral computer tomography scan can demonstrate these communications directly and indirectly by measurements of contrast enhancement within the heart wall. Our study emphasises the importance of the bronchial arteries in cases of heart-lung transplantation and repair of thoracic aortic aneurysms.

[A simulating experimental system for interventional treatment of lung cancer].

In order to go deeply into the researches on the theory of hemodynamics for interventional treatment of lung cancer, we have designed a simulating experimental system. Using the experimental system, we can simulate the operation process and test the effect of drug infusion under a variety of physiological parameters. The parameters that admit of adjustment are: cardiac output, blood pressure of aorta, waveform of pressure, pulse period, blood flow in bronchial artery and different types of catheter, injecting velocity, injecting technique, etc. In addition, the entrance position and blood vessel diameter of small embranchment artery can be changed. In this paper are presented the application of our pH-testing method to natural infusion region and the determined representational shape and size.

Effect of bronchial artery blood flow on cardiopulmonary bypass-induced lung injury.

Cardiovascular surgery requiring cardiopulmonary bypass (CPB) is frequently complicated by postoperative lung injury. Bronchial artery (BA) blood flow has been hypothesized to attenuate this injury. The purpose of the present study was to determine the effect of BA blood flow on CPB-induced lung injury in anesthetized pigs. In eight pigs (BA ligated) the BA was ligated, whereas in six pigs (BA patent) the BA was identified but left intact. Warm (37 degrees C) CPB was then performed in all pigs with complete occlusion of the pulmonary artery and deflated lungs to maximize lung injury. BA ligation significantly exacerbated nearly all aspects of pulmonary function beginning at 5 min post-CPB. At 25 min, BA-ligated pigs had a lower arterial Po(2) at a fraction of inspired oxygen of 1.0 (52 +/- 5 vs. 312 +/- 58 mmHg) and greater peak tracheal pressure (39 +/- 6 vs. 15 +/- 4 mmHg), pulmonary vascular resistance (11 +/- 1 vs. 6 +/- 1 mmHg x l(-1) x min), plasma TNF-alpha (1.2 +/- 0.60 vs. 0.59 +/- 0.092 ng/ml), extravascular lung water (11.7 +/- 1.2 vs. 7.7 +/- 0.5 ml/g blood-free dry weight), and pulmonary vascular protein permeability, as assessed by a decreased reflection coefficient for albumin (sigma(alb); 0.53 +/- 0.1 vs. 0.82 +/- 0.05). There was a negative correlation (R = 0.95, P < 0.001) between sigma(alb) and the 25-min plasma TNF-alpha concentration. These results suggest that a severe decrease in BA blood flow during and after warm CPB causes increased pulmonary vascular permeability, edema formation, cytokine production, and severe arterial hypoxemia secondary to intrapulmonary shunt.