Bronchial Artery Perfusion Research Articles

Hypoxic perfusion of pulmonary arterial vasa vasorum increases pulmonary arterial pressure.

The pathophysiology of pulmonary hypertension (PH) is not fully understood. Here, we tested the hypothesis that hypoxic perfusion of the vasa vasorum of the pulmonary arterial (PA) wall causes PH. Young adult pig lungs were explanted and placed into a modified ex vivo lung perfusion unit (organ care system, OCS) allowing the separate adjustment of parameters for mechanical ventilation, as well as PA perfusion and bronchial arterial (BA) perfusion. The PA vasa vasorum are branches of the BA. The lungs were used either as the control group (n = 3) or the intervention group (n = 8). The protocol for the intervention group was as follows: normoxic ventilation and perfusion (steady state), hypoxic BA perfusion, steady state, and hypoxic BA perfusion. During hypoxic BA perfusion, ventilation and PA perfusion maintained normal. Control lungs were kept under steady-state conditions for 105 min. During the experiments, PA pressure (PAP) and blood gas analysis were frequently monitored. Hypoxic perfusion of the BA resulted in an increase in systolic and mean PAP, a reaction that was reversible upon normoxic BA perfusion. The PAP increase was reproducible during the second hypoxic BA perfusion. Under control conditions, the PAP stayed constant until about 80 min of the experiment. In conclusion, the results of the current study prove that hypoxic perfusion of the vasa vasorum of the PA directly increases PAP in an ex situ lung perfusion setup, suggesting that PA vasa vasorum function and wall ischemia may contribute to the development of PH.NEW & NOTEWORTHY Hypoxic perfusion of the vasa vasorum of the pulmonary artery directly increased pulmonary arterial pressure in an ex vivo lung perfusion setup. This suggests that the function of pulmonary arterial vasa vasorum and wall ischemia may contribute to the development of pulmonary hypertension.

Pulmonary lesions: correlative study of dynamic triple-phase enhanced CT perfusion imaging with tumor angiogenesis and vascular endothelial growth factor expression

BackgroundTo investigate value of the quantitative perfusion parameters of dynamic triple-phase enhanced CT in differential diagnosis of pulmonary lesions, and explore the correlation between perfusion parameters of lung cancer with microvessel density (MVD) and vascular endothelial growth factor (VEGF).Methods73 consecutive patients with lung lesions who successfully underwent pre-operative CT perfusion examination with dynamic triple-phase enhanced CT and received a final diagnosis by postoperative pathology or a clinical follow-up. The cases were divided into malignant and benign groups according to the pathological results. CT perfusion parameters, such as Median, Mean, Standard deviation (Std), Q10, Q25, Q50, Q75, Q90 of pulmonary artery perfusion (PAP), bronchial artery perfusion (BAP), perfusion index (PI) and arterial enhancement fraction (AEF) were obtained by performing computed tomography perfusion imaging (CTPI). Computed tomography perfusion (CTP) parameters were compared between malignant and benign lesions. The receiver operating characteristic (ROC) curve was used to assess the diagnostic efficiency of CTP parameters in diagnosing malignant lesions. The correlations between CTP parameters with MVD and VEGF were analysed in 36 lung cancer patients who had extra sections be used for immunohistochemistry staining of CD34 and VEGF.ResultsBAP (Mean, Std, Q90) and PI Std of benign lesions were higher than malignant lesions (p < 0.05), and PAP (Q10, Q25), PI (Median, Mean, Q10, Q25, Q50) of malignant lesions were higher than the benign (p < 0.05). The area under the ROC curve of PI Mean, PI Q10 and PI Std was 0.722 (95% CI = [0.595–0.845]), 0.728 (95% CI = [0.612–0.844]) and 0.717 (95% CI = [0.598–0.835]) respectively. Partial perfusion parameters of BAP and AEF Q10 were positively correlated with MVD (p value range is < 0.001–0.037, ρ value range is 0.483–0.683), and partial perfusion parameters of PI were negatively correlated with MVD (p value range is 0.001–0.041,ρvalue range is − 0.523–− 0.343). Partial perfusion parameters of BAP and AEF Q10 were positively correlated with VEGF (p value range is 0.001–0.016, ρvalue range is 0.398–0.570), meanwhile some perfusion parameters of PAP and PI were negatively correlated with VEGF (p value range is 0.001–0.040, ρ value range is − 0.657–0.343).ConclusionsQuantitative parameters of dynamic triple-phase enhanced CT can provide diagnostic basis for the differentiation of lung lesions, and there were connection with tumor angiogenesis and vascular endothelial growth factor expression.

Value of dual-input perfusion of 320 row CT on the efficacy evaluation of small cell lung cancer

Objective To discuss the value of dual-input perfusion of 320 row CT on the efficacy evaluation of small cell lung cancer (SCLC). Methods A total of 18 patients with SCLC confirmed by pathology who received cisplatin plus etoposide chemotherapy between June 2016 and June 2018 in the 8th Medical Center of Chinese PLA General Hospital were collected. All patients received 320 row CT perfusion scan at 3 time points before chemotherapy, after 2 cycles and 4 cycles of chemotherapy. Tumor size, perfusion pseudo color map and bronchial arterial blood flow (BF), pulmonary flow (PF) and perfusion index (PI) were obtained. The efficacy and adverse reactions were evaluated. The single factor analysis was used to make the group comparison. Pearson test was used to make correlation analysis. Results Two patients after 2 cycles of chemotherapy had complete remission (CR), another 2 patients after 4 cycles of chemotherapy had CR, and 3 patients of the above 4 cases with CR had abundant BF; after 4 cycles of chemotherapy, 7 cases had partial remission (PR), 6 cases had stable disease (SD), 1 patient had progression of disease (PD). Dual-input perfusion of 320 row CT showed that 10 cases had the tumor area 15 cm2 before the treatment. There was a negative correlation between PI and the tumor area (r=-0.694, P = 0.026) on patients with the tumor area 15 cm2 (P > 0.05). One case had Ⅳ degree of bone marrow suppression, and obvious adverse reactions were not seen in the rest of the patients. Conclusion Dual-input perfusion of 320 row CT based on the simple imaging can make an accurate quantitative judgement of the effect of SCLC according to perfusion parameter, which provides a new basis for curative effect evaluation on SCLC. Key words: Small cell lung carcinoma; Pulmonary perfusion imaging; Dual-input perfusion CT; Treatment outcome

Clinical effect of selective bronchial artery infusion chemotherapy for central squamous cell carcinoma of the lung

Objective To investigate the clinical effect of selective bronchial artery infusion chemotherapy for central squamous cell carcinoma of the lung. Methods 93 cases of central lung squamous cell carcinoma patients who were treated in our hospital from February 2015 to February 2017 were enrolled in the study. They were divided into the observation group (n=45) and the control group (n=48) according to the patients' final treatment. The observation group was treated with bronchial artery perfusion chemotherapy, and the control group was treated with systemic venous chemotherapy. The short-term effect and the improvement of lung function in the two groups were observed, and the prognosis of the patients was followed up. Results The short-term effect of the observation group was better than that of the control group (P<0.05), and the total effective rate of the observation group was 95.56%; The forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1) of the observation group were (75.39±6.88)% and (78.19±7.79)%, respectively, which were significantly higher than those in the control group (P<0.05). The reoperation ratio of the observation group was 44.44% after chemotherapy, which was significantly higher than that of the control group, with statistically significant difference (P<0.05). The median total survival time of the observation group was 17 months, which was significantly higher than that of the control group, with statistically significant difference (P<0.05). The incidence of adverse reaction in the observation group was 6.67%, which was significantly lower than that in the control group, with statistically significant difference (P<0.05). Conclusions Selective bronchial artery infusion chemotherapy for central lung cancer is effective and worthy of clinical application. Key words: Carcinoma, squamous cell/DT; Lung neoplasms/DT; Bronchial arteries/SU; Chemotherapy, cancer, regional perfusion

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.

Perfusion Evaluation of Lung Cancer

The aim of this study was to investigate the feasibility of separately evaluating bronchial (BAP) and pulmonary arterial perfusion (PAP) of lung cancers using dual-input perfusion computed tomography. Twenty-nine lesions from 28 patients [19 men and 9 women; age, 65.8±11.3 y (mean±SD); range, 39 to 85 y] were included in this study (1 patient had 2 tumors). From computed tomography data, quantitative maps of PAP and BAP were created using the dual-input maximum-slope method. Total blood perfusion (TBP) was defined as the sum of PAP and BAP, and the percentage of PAP to TBP was defined as %PAP. Correlation of these values with tumor size, location, and pathologic type was statistically analyzed. PAP ranged from 2.0 to 93.1 mL/min/100 mL (mean±SD, 26.8±26.4), BAP was 0 to 65.4 (25.1±19.12), TBP was 20.7 to 132.0 (52.0±29.0), and %PAP was 4% to 100% (48.8%±31.9%). PAP, TBP, and %PAP correlated negatively with tumor size (P<0.05). PAP and %PAP were higher in the peripheral zone than in the central zone (P<0.05). There was significant correlation between pathologic type and the respective perfusion parameters (P>0.05). We were successful in separating the dual vascular supply to assess dual-input perfusion of lung cancer. We found perfusion of lung cancers to depend on tumor size and location. Acknowledging and assessing the dual vascular supply in lung perfusion may have clinical implications in the management of lung cancer treatment.

A New Lung Preservation Technique through Bronchial Artery Perfusion on Ex-Vivo Lung

Purpose Airway hypoxia due to microvascular loss may be a predisposing factor for subsequent fibrotic remodeling in allografts, resulting in suboptimal transplant outcomes in lung transplantation. Ex-vivo lung perfusion (EVLP) is a novel strategy for lung allograft preservation that keeps the organs at physiological protective conditions. Modifying EVLP strategy, we have developed a new lung preservation technique focusing on airway protection through bronchial artery perfusion. Methods and Materials Using heart-lung blocks harvested from Lewis rats, we have developed a model where bronchial circulation (using another cannula from descending aorta, retrogradely) was synchronously perfused in addition to pulmonary circulation with acellular Steen solution on EVLP (the scheme of the model is shown in Fig 1 ). Rat lungs after 1 hour cold preservation, perfused and ventilated on EVLP for 4 hours were evaluated and lungs with bronchial artery perfusion were compared with those without bronchial perfusion on EVLP. The studies were performed based on our rat EVLP protocol that has proven to be reliable with at least 4 hours of duration with stable results. Results At 4 hours on EVLP, bronchial artery perfusion was associated with significantly better preserved oxygenation and better compliance in lung allografts through reduced glucose consumption and increased ATP level as compared to the control group. Conclusions Bronchial artery perfusion on EVLP may be a new lung preservation strategy that breaks through the current major limitation in hypoxic transplant airways after lung transplantation.

Perfusion abnormalities in congenital and neoplastic pulmonary disease: comparison of MR perfusion and multislice CT imaging

The aim of this work was to assess magnetic resonance (MR) perfusion patterns of chronic, non-embolic pulmonary diseases of congenital and neoplastic origin and to compare the findings with results obtained with pulmonary, contrast-enhanced multislice computed tomography (CT) imaging to prove that congenital and neoplastic pulmonary conditions require MR imaging over the pulmonary perfusion cycle to successfully and directly detect changes in lung perfusion patterns. Twenty-five patients underwent concurrent CT and MR evaluation of chronic pulmonary diseases of congenital (n=15) or neoplastic (n=10) origin. Analysis of MR perfusion and contrast-enhanced CT datasets was realized by defining pulmonary and vascular regions of interest in corresponding positions. MR perfusion calculated time-to-peak enhancement, maximal enhancement and the area under the perfusion curve. CT datasets provided pulmonary signal-to-noise ratio measurements. Vessel center-lines of bronchial arteries were determined. Underlying perfusion type, such as pulmonary arterial or systemic arterial supply, as well as regions with significant variations in perfusion were determined statistically. Analysis of the pulmonary perfusion pattern detected pulmonary arterial supply in 19 patients; six patients showed systemic arterial supply. In pulmonary arterial perfusion, MR and multislice CT imaging consistently detected the perfusion type and regions with altered perfusion patterns. In bronchial arterial supply, MR perfusion and CT imaging showed significant perfusion differences. Patients with bronchial arterial supply had bronchial arteries ranging from 2.0 to 3.6 mm compared with submillimeter diameters in pulmonary arterial perfusion. Dynamic MR imaging of congenital and neoplastic pulmonary conditions allowed characterization of the pulmonary perfusion type. CT imaging suggested the presence of systemic arterial perfusion by visualizing hypertrophied bronchial arteries.

A novel technique for semiselective in situ bronchial artery perfusion in human lung retrieval

A novel technique for semiselective in situ bronchial artery perfusion in human lung retrieval

Angiogenesis and blood supply during the course of pulmonary carcinogenesis in experimental rat

To investigate the origin of tumor blood vessel and blood supply during pulmonary carcinogenesis, and the relationship between vascular endothelial growth factor (VEGF), its receptor Flk-1 and angiogenesis. One hundred Wistar rats were instilled with 3-methylcholanthrene (MCA) and diethylinitrosamine (DEN) to induce pulmonary squamous cell carcinoma through left lower lobe bronchus. To acquire different pathological phase during the carcinogenesis, rats were killed in 15, 35, 55, 65, 75 days after instillation. Yellow and green silastics were respectively injected into the bronchial and pulmonary arteries of 30 rats in 55, 65, 75 days after instillation. Intertumor microvessel density (MVD) was marked by anti-von Willebrand factor monoantibody. VEGF and Flk-1 expression were examined by immunohistochemistry. In the tumor area the tumor blood vessels were yellow and connected with distorted bronchial artery and very few green incomplete branches of pulmonary artery were seen. Silastic particles could be seen in the disordered tumor blood vessels by microscope after bronchial artery perfusion. There was no silastic particles in the carcinoma interstitial blood vessels after pulmonary artery perfusion. MVD count significantly increased in carcinoma in situ (39.50±12.60) and infiltrative carcinoma (61.05±19.92) as compared to atypical hyperplasia (8.92±3.80)(both P < 0.01), and the increased vessels originated from bronchial artery, but not pulmonary artery. The expression of VEGF and Flk-1 increased during pulmonary carcinogenesis. The positive coefficients of VEGF and FLK-1 expressions became higher and higher from epithelial proliferation to squamous metaplasia, to atypical hyperplasia, to carcinoma in situ and finally to infiltrative carcinoma. There was significant correlation between MVD and VEGF expression (r=0.979 8, P < 0.005), as well as between MVD and Flk-1 expression (r=0.907 8, P < 0.05). Angiogenesis is the important phenomenon of the rat pulmonary carcinogenesis and the newly formed blood vessels in tumor connect with the branches of bronchial artery, but not pulmonary artery. This confirms that the blood supply of pulmonary carcinoma is from bronchial artery, not from pulmonary artery. VEGF and Flk-1 are closely related to angiogenesis of tumor.

Pulmonary and bronchial circulations: contributions to heat and water exchange in isolated lungs.

The relative contribution of the pulmonary and bronchial circulatory systems to heat and water exchange in normal lungs was evaluated in 20 isolated, in situ perfused dog lungs and in four patients undergoing elective cardiopulmonary bypass. In isolated dog lungs, if the pulmonary artery was perfused at a nominal flow rate (0.5 l/min), bronchial artery perfusion (up to 70 ml/min) did not significantly affect the expired gas temperature. When the lungs were not perfused through either system, 8 min of ventilation with cool, dry gas decreased the temperature of the expired gas by 6.2 +/- 1.4 degrees C. Selective perfusion of bronchial arteries at 68 +/- 10 mmHg resulted in a mean flow rate of 28 +/- 16 ml/min and increased the average temperature of the expired gas by 0.6 degrees C. An increase in the rate of bronchial arterial perfusion to 55 +/- 14 ml/min increased the average temperature of the expired gas by 1.3 degrees C. The time constant for equilibration of tritiated water between the perfusate and the lung parenchyma was 130 +/- 33 min for pulmonary arterial perfusion and 35 +/- 13 min for combined bronchial and pulmonary perfusion, which indicated that filtration of water from high-pressure bronchial vessels facilitated water exchange in the lung interstitium. The rate of tracer equilibration was similar between the perfusate and gas in both variants of perfusion, but the ratios of tracer gas to perfusate were different (0.42 +/- 0.06 for pulmonary, 0.98 +/- 0.07 for combined), which indicates that bronchial vessels contribute mainly to the hydration of the bronchial mucosa. In humans, the bronchial blood flow was capable of maintaining heat supply after the initiation of cardiopulmonary bypass. Before bypass, when both pulmonary and bronchial blood flow were present, the mean time constant of the temperature decay after a switch to ventilation with cool, dry gas was 35 +/- 12 s. The average temperature difference between the blood and expired gas was 2.4 +/- 0.50 degrees C. After 5 min of dry gas ventilation, the temperature difference between the expired gas and initial blood temperature decreased an average of 3.8 +/- 0.06 degrees C (P < 0.05). The time constant of temperature decay increased to 56 +/- 14 s (P < 0.05). We conclude that bronchial perfusion has a less important role in the temperature balance of the respiratory tract compared with pulmonary arterial perfusion because heat flux is "flow limited" but is important in providing water for hydration of the mucosal surface and interstitial compartments of peribronchial tissues.

Maximal preservation time of tracheal allografts

Our objective was to study the maximal preservation time of directly revascularized tracheal allografts in immunosuppressed piglets. Donor grafts were flushed with Euro-Collins solution (65 mL/kg at 4 degrees C) by simultaneous inferior thyroid artery and bronchial artery perfusion through a 15-cm aortic segment and heterotopically implanted on their own vascular pedicle after 3 (group 1), 6 (group 2), 15 (group 3), and 24 (group 4) hours of static storage in Euro-Collins solution at 4 degrees C (n = 5 each). The animals were observed for 4 weeks after transplantation and then sacrificed. Histologic evaluation of the tracheal allografts was routinely done using specimens from open biopsies. The overall length of tracheal grafts was 12.4 +/- 0.6 cm, and this variable was not significantly different between the four groups. Graft exocrine (mucous secretion) function began 1.3 +/- 0.5 days after transplantation in groups 1 through 3 but was absent in all group 4 grafts (p < 0.0001). All grafts in groups 1 through 3 were viable at the time of sacrifice and showed little discernible intergroup and intragroup histologic and functional (tracheal smooth muscle contraction and relaxation) variations except for a significantly higher (p < 0.001) incidence of rejection in group 3 allografts. In contrast, all grafts in group 4 became completely necrotic 4 days after transplantation (p < 0.001) despite full patency of all the vascular anastomoses. These results demonstrate that tracheal allografts may be safely preserved for as long as 15 hours and that longer periods of ischemia are likely to result in irreversible allograft damage.

Safe lung preservation for twenty-four hours with perfadex

The function of six porcine left lung allografts was studied after pulmonary (140 mL/kg) and bronchial (50 mL/kg) artery perfusion with Perfadex (Kabi Pharmacia, Uppsala, Sweden) at room temperature, followed by 24-hour storage of the lungs in an atelectatic state in 6 ° to 8 °C Perfadex, which is a low-potassium-dextran solution. Left lung transplantation was done followed by right pneumonectomy, thereby making all the animals 100% dependent for their survival on the transplanted lungs. The pigs (mean weight = 56 kg, range = 51 to 58 kg, n = 18; 6 donors, 6 recipients, and 6 shamoperated) were ventilated with a volume-controlled ventilator (20 breaths/min, 500 ml tidal volume, 8 cm H 2O positive end-expiratory pressure, inspired oxygen fraction = 0.5). All the transplanted animals were in good condition throughout the 24-hour observation period with arterial oxygen tensions around 25 kPa (188 mm Hg) and arterial carbon dioxide tensions around 5 kPa (38 mm Hg). The mean pulmonary arterial pressure was around 30 mm Hg, and the pulmonary vascular resistance around 500 dyn · s · cm −5; neither showed any tendency to change with time. After 24 hours the inspired oxygen fraction was increased to 1.0 and the arterial oxygen tension increased to 43.3 ± 5 kPa (325 ± 38 mm Hg) (mean ± standard error of the mean; n = 6). A sham operation (bilateral thoracotomy, right pneumonectomy) was done in 6 pigs, which were followed up for 24 hours. The arterial oxygen tensions in these pigs were around 30 kPa and the mean pulmonary arterial pressure and pulmonary vascular resistance around 24 mm Hg and 350 dyn · s · cm −5, respectively. This study demonstrates excellent pulmonary function after pulmonary and bronchial artery perfusion with Perfadex at room temperature followed by 24 hours of cold atelectatic storage in Perfadex.

Role of the bronchial circulation in ischemia-reperfusion lung injury

Bronchial arterial (BA) perfusion could modify pulmonary arterial (PA) ischemia-reperfusion (IR) injury by promoting clearance of peribronchial edema or limiting edema formation through maintenance of pulmonary vessel integrity via bronchopulmonary anastomotic or pulmonary vasa vasorum flow. The purpose of this study was to determine the effect of BA perfusion on IR injury in isolated sheep lungs. In 12 lungs (BA++) the BA was perfused throughout 30 min of PA ischemia and 180 min of reperfusion. In 12 lungs (BA-+) BA perfusion was begun with PA reperfusion, and in 15 lungs (BA--) the BA was never perfused. After 180 min, extravascular lung water was less (P < 0.05) in BA++ and B-+ lungs [4.70 +/- 0.16 and 4.57 +/- 0.18 g/g blood-free dry lung (bfdl)] than in BA-- lungs (5.23 +/- 0.19 g/g bfdl). The reflection coefficient for albumin was greater (P < 0.05) in BA++ and BA-+ (0.57 +/- 0.06 and 0.75 +/- 0.03) than in BA-- lungs (0.44 +/- 0.04). The filtration coefficient in BA++ and BA-+ lungs (0.016 +/- 0.006 and 0.015 +/- 0.006 g.min-1 x mmHg-1 x kg-1) was not different from that in BA-- lungs (0.025 +/- 0.006 g.min-1 x mmHg-1 x kg-1). These results suggest that BA perfusion decreased reperfusion edema by attenuating the increase in pulmonary vascular permeability caused by IR injury. Moreover the result in BA-+ lungs suggests that the protective effect was mediated by BA perfusion of PA vasa vasorum rather than bronchopulmonary anastomotic flow, which was trivial compared with PA blood flow.

Successful double-lung transplantation with direct bronchial artery revascularization

Double-lung transplantation with tracheal anastomosis has previously resulted in unacceptable ischemic complications of airway healing. Three patients underwent double-lung transplantation at our institution in 1986 and 1987, and 2 of these required later retransplantation because of airway complications. Recently, we began to perform direct revascularization of the bronchial arteries at their origin on the donor descending thoracic aorta, using recipient internal thoracic artery. Eight patients (2 male and 6 female patients; ages, 10–51 years) underwent nine double-lung transplantations with revascularization. The preoperative diagnoses in these patients were cystic fibrosis (2 patients), atrial septal defect and Eisenmenger's syndrome (1 patient), lymphangioleiomyomatosis (1 patient), bronchiectasis (1 patient), α 1-antitrypsin deficiency (1 patient), and primary pulmonary hypertension (2 patients); 1 underwent retransplantation because of pulmonary emboli. There have been no significant airway complications in any patient. Two patients died early postoperatively, 1 of early pulmonary dysfunction (at 1 day postoperatively) and 1 of subarachnoid hemorrhage (at 16 days postoperatively; tracheal healing was excellent in this patient). Follow-up in the remaining 6 patients ranged from 5 to 9 months. Internal thoracic artery angiography was performed on seven grafts, which documented patency of the internal thoracic artery in all seven and bronchial artery perfusion in six. Bronchoscopic examinations have demonstrated excellent airway healing in all six of these grafts, with no dehiscence, granulation, or narrowing of the trachea or distal bronchi. Ulceration of the tracheal anastomosis developed anteriorly in the remaining patient, which has resolved. We conclude that double-lung transplantation is an acceptable therapeutic approach when combined with bronchial artery revascularization, and early airway healing has been excellent. This approach allows simultaneous bilateral lung transplantation with immediate revascularization of the airways to both lungs.

Contribution of the bronchial circulation to lung preservation

Short preservation time still severely limits lung transplantation. To determine the effect of bronchial arterial flush preservation, we studied 54 dogs using the isolated perfused working lung model. After baseline measurements, lungs were flushed with lactated Ringer's solution (60 ml/kg at 8 degrees C) by one of three methods: pulmonary artery perfusion, bronchial artery perfusion through a 15 cm closed aortic segment, or simultaneous pulmonary-bronchial artery perfusion. These groups were further subdivided and tested after 0, 4, and 17 hours of storage at 4 degrees C (n = 6 each). Lungs were ventilated (flow rate 140 ml/kg/min; inspired oxygen fraction 0.21) and continuously reperfused with normothermic deoxygenated autologous blood in a closed loop. Measured variables were hemodynamics, aerodynamics, and leukocytes in bronchoalveolar lavage. Survival time was determined from initial reperfusion to failure of the lung to oxygenate. After 0 and 4 hours of storage, there was no significant difference in survival times. After 17 hours, lungs subjected to pulmonary-bronchial artery perfusion survived longer than those perfused via either the pulmonary or bronchial arteries alone (120 +/- 24 versus 38 +/- 14 or 52 +/- 16 minutes; p less than 0.01). Pulmonary artery pressure and resistance in all groups except at failure were never different from baseline values in the intact animal. Shunts in the pulmonary-bronchial artery perfusion groups were closest to baseline at onset (8% +/- 4%) and remained lower throughout reperfusion than in the groups subjected to pulmonary or bronchial artery perfusion alone. After 17 hours, static compliance of pulmonary artery-perfused lungs was worse than baseline (1.1 +/- 0.2 x 10(-2) versus 3.2 +/- 0.7 x 10(-2) L/cm H2O/sec; p less than 0.05), whereas compliance in the pulmonary-bronchial artery perfusion groups remained constant (3.6 +/- 1.5 x 10(-2) L/cm H2O/sec). Elastic work performed by lungs subjected to pulmonary-bronchial artery flushing at onset was significantly lower when these lungs were reperfused immediately (201 +/- 14 versus 295 +/- 35 gm-m/min for pulmonary artery-flushed lungs) or after 4 hours of storage (229 +/- 30 versus 290 +/- 24 gm-m/min for pulmonary artery-flushed lungs). Bronchoalveolar lavage after 17 hours in the group subjected to pulmonary bronchial artery flushing demonstrated leukocyte counts similar to those of intact lungs (45 +/- 5 versus 29 +/- 8/mm3) and significantly less than in lungs subjected to pulmonary or bronchial artery flushing (137 +/- 18 or 82 +/- 10/mm3, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Morphometry of the Subepithelial Circulation in Sheep Airways: Effect of Vascular Congestion

In order to quantitate the subepithelial microvascular volume and its relation to the airway lumen, we conducted a morphometric analysis of the vascular compartment in the wall of the trachea (within a 55-microns depth from the epithelial basement membrane) and of 1.0 and 0.5-mm bronchioles of sheep. The lungs were fixed by bronchial and pulmonary artery perfusion with glutaraldehyde under three experimental conditions: (1) bronchial artery pressure, 100 mm Hg pulmonary artery pressure, 20 mm Hg (control); (2) bronchial artery pressure, 100 mm Hg, pulmonary artery pressure, 40 mm Hg (pulmonary hypertension, PH); (3) bronchial artery pressure, 100 mm Hg, pulmonary artery pressure, 40 mm Hg (pharmacologic vasodilation with sodium nitroprusside, PH + V). Venous pressures were atmospheric. Under control conditions, the microvascular volume fraction comprised 12, 16, and 15% of the subepithelial tissue in the trachea and 1-mm and 0.5-mm bronchioles, respectively. PH increased the microvascular volume fraction in the bronchioles (p less than 0.05), but it had no effect on the microvasculature in the trachea. PH + V approximately doubled the microvascular volume fraction in the trachea and the bronchioles. PH increased the mean wall thickness, and PH and PH + V decreased the airway cross-sectional area in the 1-mm bronchioles. These observations demonstrate that the microvasculature constitutes a considerable volume fraction of the subepithelial airway tissue and that vascular congestion can narrow the bronchiolar lumen.

Location of lung receptors mediating the breathing frequency response to pulmonary CO 2

Pulmonary stretch receptors are thought to mediate the breathing frequency (bf) response to changes in pulmonary CO 2. However, the location and distribution of these receptors is disputed. The purpose of this study was to determine what contribution the extrapulmonary receptors make in the pulmonary CO 2 bf response. Mongrel dogs were anesthetized and placed on cardiopulmonary bypass. The diaphragm electromyogram was used to monitor respiratory center output and to trigger a ventilator. Exposure of an upper airway segment to CO 2 or positive end-expired pressure failed to produce changes in the bf. Denervation of the upper airway down to but not including the hilum caused similar insignificant changes in the CO 2 bf response. Lungs collapsed by suction showed minimal Hering-Breuer inhibition when compared with inflated lungs. Bronchial arterial perfusion with hypocapnic followed by hypercapnic blood failed to produce changes in the bf while similar perfusion of the pulmonary arterial system resulted in significant increases in bf. It appears that the receptors mainly responsible for the pulmonary CO 2 response are located in the more peripheral regions of the lung.

Bronchial artery perfusion for treatment of advanced lung cancer.

Twenty-one patients with advanced lung cancer, limited to the chest, were treated by bronchial artery perfusion using 0.4 to 0.6 mg/kg of HN2 using a double lumen, double balloon aortic catheter. The infusion was made into the aorta between levels T4 and T8. Two patients were infused 2 times. There were no serious complications in these 21 patients. Average survival of the 21 treated patients was 8 months with a range from one day to 45 months. Symptoms were improved in the majority of treated patients. Cough was improved in 80%. Pain was completely relieved in 3, almost completely relieved in 2, and improved in 4–a total 9 of the 15 patients with severe, persistent pain. There was objective evidence of improvement in 12 patients. Five had objective measured improvement in pulmonary function and, in 7 of the 21 patients (32%), there was decrease in the size of the tumor mass as recorded on official x-ray reports. Average survival in 6 patients considered for perfusion but not completed, because of technical difficulties, was 1.8 months with a range from 1 to 3 months.

Bronchial arterial perfusion with cytotoxic agents for bronchogenic carcinoma. Preliminary report.

Bronchial arterial perfusion with cytotoxic agents for bronchogenic carcinoma. Preliminary report.