Unilateral Pulmonary Artery Occlusion Research Articles

Oleuropein ameliorated lung ischemia-reperfusion injury by inhibiting TLR4 signaling cascade in alveolar macrophages

Lung ischemia–reperfusion (I/R) injury is a common postoperative complication in patients with lung transplantation, pulmonary embolism, and cardiopulmonary bypass. Lung I/R injury is a sterile inflammatory process that leads to lung dysfunction, and is an important cause of patient death. Effectively alleviating lung I/R injury can thus improve the prognosis of patients. In this study, we created a mouse model of lung I/R injury by transient unilateral left pulmonary artery occlusion. 6–8 weeks male C57BL/6 mice were randomly assigned to four groups: Sham, I/R, I/R + oleuropein (OLE) and OLE. OLE (50 mg/kg) was orally 24 h and 30 min before anesthesia. Measurement of lung pathohistological, isolated alveolar macrophages (AMs), inflammatory mediators, TLR4 and its downstream factors (MyD88, NF-κB) were performed. We then evaluated the ability of oleuropein (OLE) to ameliorate I/R-induced lung injury and explored the possible molecular mechanisms. OLE ameliorated I/R-induced lung injury and edema and decreased inflammatory factors in lung tissue and bronchoalveolar lavage fluid. This protection required toll-like receptor 4 (TLR4). OLE significantly inhibited I/R-induced expression of TLR4 and its downstream factors in lung tissue and alveolar macrophages. In addition, hypoxia-inducible factor 1α protein accumulated in TLR4-mediated lung I/R injury, and further induced the production of inflammatory factors. Collectively, these data suggest that OLE ameliorates I/R-induced lung injury. The mechanism responsible for its protective effect may involve inhibition of the I/R-induced inflammatory response by downregulating the TLR4 signaling cascade in AMs.

Short-term Physiologic Consequences of Regional Pulmonary Vascular Occlusion in Pigs.

After pulmonary artery occlusion (mimicking a pulmonary embolism), perfusion is redistributed to the rest of the lung tissue, but the distribution of ventilation is uncertain. Data from anesthetized pigs (uninjured lungs) indicate that the perfusion is redistributed as suspected. Similarly, ventilation is redistributed from nonperfused to perfused lung tissue. This limits the increase in dead space and is accompanied by less density in the occluded lung. Acute unilateral pulmonary arterial occlusion causes ventilation-perfusion mismatch of the affected lung area. A diversion of ventilation from nonperfused to perfused lung areas, limiting the increase in dead space, has been described. The hypothesis was that the occlusion of a distal branch of the pulmonary artery would cause local redistribution of ventilation and changes in regional lung densitometry as assessed with quantitative computed tomography. In eight healthy, anesthetized pigs (18.5 ± 3.8 kg) ventilated with constant ventilatory settings, respiratory mechanics, arterial blood gases, and quantitative computed tomography scans were recorded at baseline and 30 min after the inflation of the balloon of a pulmonary artery catheter. Regional (left vs. right lung and perfused vs. nonperfused area) quantitative computed tomography was performed. The balloon always occluded a branch of the left pulmonary artery perfusing approximately 30% of lung tissue. Physiologic dead space increased (0.37 ± 0.17 vs. 0.43 ± 0.17, P = 0.005), causing an increase in PaCO2 (39.8 [35.2 to 43.0] vs. 41.8 [37.5 to 47.1] mmHg, P = 0.008) and reduction in pH (7.46 [7.42 to 7.50] vs. 7.42 [7.38 to 7.47], P = 0.008). Respiratory system compliance was reduced (24.4 ± 4.2 vs. 22.8 ± 4.8 ml · cm H2O, P = 0.028), and the reduction was more pronounced in the left hemithorax. Quantitative analysis of the nonperfused lung area revealed a significant reduction in lung density (-436 [-490 to -401] vs. -478 [-543 to -474] Hounsfield units, P = 0.016), due to a reduction in lung tissue (90 ± 23 vs. 81 ± 22 g, P < 0.001) and an increase in air volume (70 ± 22 vs. 82 ± 26 ml, P = 0.022). Regional pulmonary vascular occlusion is associated with a diversion of ventilation from nonperfused to perfused lung areas. This compensatory mechanism effectively limits ventilation perfusion mismatch. Quantitative computed tomography documented acute changes in lung densitometry after pulmonary vascular occlusion. In particular, the nonperfused lung area showed an increase in air volume and reduction in tissue mass, resulting in a decreased lung density.

Measurement of relative lung perfusion with electrical impedance and positron emission tomography: an experimental comparative study in pigs

BackgroundElectrical impedance tomography (EIT) with indicator dilution may be clinically useful to measure relative lung perfusion, but there is limited information on the performance of this technique. MethodsThirteen pigs (50–66 kg) were anaesthetised and mechanically ventilated. Sequential changes in ventilation were made: (i) right-lung ventilation with left-lung collapse, (ii) two-lung ventilation with optimised PEEP, (iii) two-lung ventilation with zero PEEP after saline lung lavage, (iv) two-lung ventilation with maximum PEEP (20/25 cm H2O to achieve peak airway pressure 45 cm H2O), and (v) two-lung ventilation under unilateral pulmonary artery occlusion. Relative lung perfusion was assessed with EIT and central venous injection of saline 3%, 5%, and 10% (10 ml) during breath holds. Relative perfusion was determined by positron emission tomography (PET) using 68Gallium-labelled microspheres. EIT and PET were compared in eight regions of equal ventro-dorsal height (right, left, ventral, mid-ventral, mid-dorsal, and dorsal), and directional changes in regional perfusion were determined. ResultsDifferences between methods were relatively small (95% of values differed by less than 8.7%, 8.9%, and 9.5% for saline 10%, 5%, and 3%, respectively). Compared with PET, EIT underestimated relative perfusion in dependent, and overestimated it in non-dependent, regions. EIT and PET detected the same direction of change in relative lung perfusion in 68.9–95.9% of measurements. ConclusionsThe agreement between EIT and PET for measuring and tracking changes of relative lung perfusion was satisfactory for clinical purposes. Indicator-based EIT may prove useful for measuring pulmonary perfusion at bedside.

GW29-e1126 Chronic Thromboembolic Pulmonary Hypertension(CTEPH): Outcomes of Surgical Effect in Patients with Unilateral Main Pulmonary Artery Occlusion

To summarize the clinical characteristics and the effect of pulmonary endarterectomy(PEA) in CTEPH patients with unilateral main pulmonary artery occlusion. Of 160 CTEPH patients operated between January 2004 and March 2018 at our center,13(8.1%) had complete main pulmonary artery occlusion.

Unilateral pulmonary artery pre-operative occlusion test: technical feasibility and safety prior to pneumonectomy or pleuropneumonectomy for malignancy.

The aim of the present study was to assess the technical feasibility and safety of the unilateral pulmonary artery occlusion (UPAO) test in pre-operative evaluation of pneumonectomy or pleuropneumonectomy for lung or pleural tumours. The UPAO test was performed on 91 patients who were scheduled to undergo or were being considered for pneumonectomy or pleuropneumonectomy between June 2003 and July 2016. There were 74 males and 17 females, with a median age of 65 years (range, 23-80). The technical success rate, procedure time and complication rate were evaluated. Technical success was defined as completion of the UPAO test. The diagnoses of the 91 patients were as follows: lung cancer in 63, malignant pleural mesothelioma in 21, thymoma in 5, lung metastasis in 1 and lung carcinoid in 1. The UPAO test was performed successfully on 88 out of 91 patients (technical success rate: 97%). The median procedure time was 57 min (range, 34-120). Cardiac arrest due to migration of the balloon catheter to the pulmonary trunk occurred in 1 patient (complication rate: 1.1%). The UPAO test in pre-operative evaluation of pneumonectomy or pleuropneumonectomy for lung or pleural tumours appears to be technically feasible. However, it needs to be performed with care in order to avoid severe complications. Advances in knowledge: The UPAO test can be safely performed and is helpful in evaluating patients for pneumonectomy or pleuropneumonectomy.

Surgical embolectomy for high-risk acute pulmonary embolism is standard therapy.

Acute massive pulmonary embolism (AMPE) is a life-threatening condition that often induces rapid haemodynamic deterioration. The mortality of surgical embolectomy is still poor in patients with preoperative cardiopulmonary arrest (CPA). We analysed the outcome of surgical pulmonary embolectomy for haemodynamically unstable patients. Thirty-one patients underwent surgical embolectomy for haemodynamically unstable AMPE. The indications for surgical embolectomy were (i) <7 days from onset, (ii) haemodynamically unstable, (iii) massive clots in bilateral pulmonary arteries or unilateral pulmonary artery occlusion with a floating clot in the main pulmonary artery or right atrium and (iv) right ventricular dilatation in transthoracic echocardiography. Eight (25.8%) patients had cardiopulmonary arrest. Nine (29.0%) patients received preoperative percutaneous cardiopulmonary support (PCPS). The mean original Pulmonary Embolism Severity Index (PESI) and simplified PESI scores were 158 ± 51 and 2.4 ± 0.9, respectively. The hospital mortality rate was 12.9% (n = 4). Two patients died of hypoxia. Multiorgan failure occurred by sepsis and by right ventricular failure in 1 patient each. No hospital deaths occurred in patients with preoperative PCPS (n = 9). The mean follow-up period was 47.7 ± 35.9 months (range, 3 - 134 months) and the 5-year survival rate was 83.2 ± 6.9%. Postoperative pulmonary artery pressure significantly decreased from 52.7 to 25.8 mmHg. Surgical embolectomy for high-risk AMPE patients has an excellent operative mortality and long-term outcome. Preoperative PCPS may lead to an immediate stable haemodynamic state and improve surgical embolectomy results, especially in high-risk patients (e.g. those with preoperative CPA). Surgical embolectomy for AMPE is an established operation and considered as the first-line therapy.

Pulmonary vascular remodeling in broiler and Leghorn chickens after unilateral pulmonary artery occlusion

Morphological and physiological responses to unilateral pulmonary artery occlusion (PAO) were evaluated in male broiler (B) and Leghorn (L) chickens. All birds were fed a diet containing 3,200 kcal of ME/kg of feed and 23% CP. Broilers (18-21 d old; 507 ± 40 g of BW) and L (61-64 d old, 861 ± 87 g of BW) had surgical PAO (n = 40 each strain) or were sham-operated (SHAM; n = 40 each strain). Hematocrit (%, Hc), relative lung weight (wet right + left lung weight/BW × 100), right ventricle to total ventricle weight ratio (RV/TV), and resistance pulmonary arterioles (RPA) thickness were measured in 6 chickens per group one day presurgery, and at 7 and 14 d postsurgery. Data were analyzed using one-way ANOVA. Relative lung weight was higher in L-chickens than in B-chickens at all sampling times. There were no differences in Hc between B and L presurgery, but at d 7 and 14, L-PAO chickens had the highest Hc (35 ± 1.4 and 40 ± 1.9, respectively); the B-SHAM had a lower Hc (28 ± 1.2, and 29 ± 1.0) than the L-SHAM (32 ± 1.2 and 34 ± 1.1) and the B-PAO (32 ± 1.2 and 34 ± 2.0) chickens, with no differences between L-SHAM and B-PAO. The RV/TV ratio was highest in the B-PAO at d 7 and d 14, with no differences among the other groups. The B-PAO chickens had the thickest RPA at 7 d and 14 d postsurgery than the rest of the groups, whereas B had thicker RPA than L at presurgery. Broilers had a lower ventilation capacity than L, and after PAO they developed right ventricular hypertrophy and small arteriole remodeling, whereas the L-PAO showed a higher degree of hypoxemia (high Hct), but without changes in RV/TV ratios or small arterial remodeling, suggesting that L-chickens had a better pulmonary arterial vasodilation even after chronic increases in blood flow through a single lung.

Alveolar Macrophages and Toll-like Receptor 4 Mediate Ventilated Lung Ischemia Reperfusion Injury in Mice

Ischemia-reperfusion (I-R) injury is a sterile inflammatory process that is commonly associated with diverse clinical situations such as hemorrhage followed by resuscitation, transient embolic events, and organ transplantation. I-R injury can induce lung dysfunction whether the I-R occurs in the lung or in a remote organ. Recently, evidence has emerged that receptors and pathways of the innate immune system are involved in recognizing sterile inflammation and overlap considerably with those involved in the recognition of and response to pathogens. The authors used a mouse surgical model of transient unilateral left pulmonary artery occlusion without bronchial involvement to create ventilated lung I-R injury. In addition, they mimicked nutritional I-R injury in vitro by transiently depriving cells of all nutrients. Compared with sham-operated mice, mice subjected to ventilated lung I-R injury had up-regulated lung expression of inflammatory mediator messenger RNA for interleukin-1β, interleukin-6, and chemokine (C-X-C motif) ligand-1 and -2, paralleled by histologic evidence of lung neutrophil recruitment and increased plasma concentrations of interleukin-1β, interleukin-6, and high-mobility group protein B1 proteins. This inflammatory response to I-R required toll-like receptor-4 (TLR4). In addition, the authors demonstrated in vitro cooperativity and cross-talk between human macrophages and endothelial cells, resulting in augmented inflammatory responses to I-R. Remarkably, the authors found that selective depletion of alveolar macrophages rendered mice resistant to ventilated lung I-R injury. The data reveal that alveolar macrophages and the pattern recognition receptor toll-like receptor-4 are involved in the generation of the early inflammatory response to lung I-R injury.

TLR4 and alveolar macrophages mediate lung ischemia reperfusion (IR) sterile inflammatory injury in a mouse model of ventilated lung ischemia (67.6)

Abstract Background: Ischemia reperfusion (IR) injury is sterile inflammatory process associated with diverse clinical situations, for example, hemorrhage followed by resuscitation, transient embolic events, and organ transplantation. IR injury can result in lung dysfunction whether the IR occurs in the lung itself or in a remote organ. Increasingly it appears that receptors and pathways of the innate immune system are involved in recognizing sterile inflammation and overlap considerably with those involved in recognition and response to pathogens and pathogen-derived products. Methods: We used a mouse surgical model of transient unilateral pulmonary artery occlusion to the left lung without bronchial involvement to create IR injury and tracked injury in vivo and ex vivo. Additionally, we mimicked IR injury in vitro by transiently depriving cells of nutrients. Results: In the mouse ventilated lung IR model we demonstrate an upregulation of inflammatory markers and recruitment of neutrophils that is characteristic of IR injury. We show that the early inflammatory response to IR requires TLR4. Furthermore, we demonstrate in vitro that cooperativity and cross-talk exists between macrophages and endothelial cells resulting in an augmented inflammatory response to nutritional deprivation and that in vivo macrophages are indeed required for early sensing of IR injury. Remarkably, we find that selective depletion of alveolar macrophages rendered mice resistant to lung IR injury.

Correlation between slopes of pulmonary blood flow-driving pressure curve and routine pulmonary function

In 91 preoperative cases of lung cancer, an attempt was made to correlate the slopes of pulmonary blood flow-driving pressure curve (delta DP/delta CI), as constructed from unilateral pulmonary arterial occlusion (UPAO) test values and pulmonary blood flow fraction values as measured by scintigraphy, with total pulmonary vascular resistance index (TPVRI) and pulmonary vascular resistance index (PVRI) and routine pulmonary function. FVC and FEV per unit body surface (BSA) were found to correlate, to same degree, with delta DP/delta CI, TPVRI and PVRI (p less than 0.05). delta DP/delta CI correlated significantly with FRC/BSA, whereas TPVRI and PVRI did not. 3) The inverse of the cardiac index (1/cardiac index) was shown to significantly correlate with TPVRI and PVRI (r = 0.64, 0.48), but poorly with delta DP/delta CI (r = 0.32). These results suggest that delta DP/delta CI might possibly provide a more useful quantitative index for the pulmonary vascular bed than TPVRI and PVRI.

Extension of functional limitation for surgery of lung cancer by unilateral pulmonary arterial occlusion test

We performed unilateral pulmonary arterial occlusion test to determine the indication for lung resection functionally, and investigated 32 cases whose total pulmonary vascular resistance was over 700 dyne.sec.cm-5/M2. Thirteen out of 32 cases underwent surgery. There was no difference in lung function tests between surgical and non-surgical cases. Nine out of 12 cases whose pulmonary vascular resistance was less than 800 dyne by unilateral pulmonary arterial occlusion test underwent surgery, and none of these cases died within 3 months after surgery. In non-surgical cases, two were aged patients and one had chronic renal failure. Four out of 20 cases whose total pulmonary vascular resistance was over 800 dyne underwent surgery. Two cases that underwent surgery died within 3 months after surgery. These results suggest that the functional limitation of lung resection can be extended from 700 dyne.sec.cm-5/M2 to 800 dyne.sec.cm-5/M2 total pulmonary vascular resistance by application of unilateral pulmonary arterial occlusion test.

Changes in right ventricular function with unilateral pulmonary artery occlusion test for pre-operative evaluation prior to lung resection

We measured the right ventricular ejection fraction (RVEF) before and during unilateral pulmonary artery occlusion test (UPAO) by thermodilution method. We also measured the right ventricular end-diastolic volume index (RVEDVI), right ventricular end-systolic volume index (RVESVI), and right ventricular stroke volume index (RVSVI). RVEF and RVSVI were significantly decreased by UPAO (p less than 0.05), but there were no obvious changes in RVEDVI and RVESVI. Some cases showed only a small decrease in RVEF by UPAO, even though their total pulmonary vascular resistance indices were over 700 dyne.sec.cm-5/m2 during UPAO. On the other hand, some cases had a decreased in RVEF of more than 10% by UPAO, even though their total pulmonary vascular resistance indices were under 400 dyne.sec.cm-5/m2 during UPAO. We consider that it is important to measure right ventricular functions such as RVEF together with pulmonary vascular hemodynamics in the pre-operative evaluation of cases of lung resection.

Changes in right ventricular hemodynamic function by unilateral pulmonary arterial occlusion test

We performed unilateral pulmonary arterial occlusion test (UPAO) for the preoperative evaluation of lung function in patients undergoing lung resection. In this test, the main pulmonary artery of either side is occluded to simulate postoperative functional status. In order to evaluate the right ventricular hemodynamic function, we measured right ventricular ejection fraction (RVEF) and right ventricular end-diastolic volume index (RVEDVI) throughout UPAO by thermodilution method. We investigated the relationships between changes in right ventricular hemodynamic function and postoperative complications related to cardiac functions, namely arrhythmias or heart failure. Thirty-four patients without heart disease prior to lung resection were examined by UPAO, and RVEF and RVEDVI were measured. Analyses demonstrated that changes in RVEF were inversely correlated with changes in RVEDVI. In 6 cases, RVEDVI increased from control by over 20% during UPAO. All of these patients had postoperative cardiac complications. The hypothetical ventricular function curves showed a large increase in RVEDVI relative to right ventricular stroke work index (RVSWI), suggesting a decrease in right ventricular function. In conclusion, these results suggest that changes in RVEDVI during UPAO may predict postoperative cardiac complications in patients undergoing pulmonary resection.

Retrospective investigation of pulmonary resection in patients with high total pulmonary vascular resistance during preoperative unilateral pulmonary artery occlusion

The aim of this study was to evaluate the indications for pulmonary resection (lobectomy) in patients with increased total pulmonary vascular resistance (TPVR) during a preoperative unilateral pulmonary artery occlusion (UPAO) test. According to our previous report, the feasibility of performing lobectomy in patients with a high risk of cardiopulmonary complications is determined on the basis of the increase in TPVR after 15 min of obstruction during the UPAO test (occluded TPVR). A total of 19 high-risk [occluded TPVR > or =700 dynes/s/cm(-5)/m(2) (dynes)] patients who underwent lobectomy or pneumonectomy were studied and a detailed analysis of postoperative cardiopulmonary complications was performed. The subjects were divided into four groups based on the occluded TPVR (700-799 dynes, 800-899 dynes, 900-999 dynes, or > or =1000 dynes) to compare the incidence of postoperative complications. Two patients died after surgery. One of them had an occluded TPVR >1000 dynes and died 313 days after right upper lobectomy; the other had an occluded TPVR of 783 dynes and died 20 days after right pneumonectomy. Postoperative cardiopulmonary complications occurred in 6 of 19 patients (31.6%), and all three patients with an occluded TPVR > or =900 dynes developed cardiopulmonary complications. Limited surgery should be performed in patients with an occluded TPVR > or =900 dynes.

Lung Fluid Balance During Development

After completing this article, readers should be able to: 1. Describe the major driving forces for liquid formation in and liquid removal from the lumen of the fetal lung. 2. Delineate the role of a normal volume of liquid within the lumen of the fetal lung for normal lung growth during development. 3. Describe the effects of labor on Na,K-ATPase activity in lung epithelial cells and clearance of lung liquid after birth. 4. Explain the route by which most residual liquid drains from the lung. 5. List the conditions associated with preterm birth that may contribute to delayed removal of fetal lung liquid. Curious students of mammalian development recognized more than a century ago that the lungs are filled with liquid during fetal life, (1) but the origin of that liquid remained obscure until 1948, when an unexpected discovery by two French scientists dispelled the prevailing view that fetal lung liquid derived from intrauterine inhalation of amniotic fluid. In studies designed to explore the ontogeny of the pituitary-adrenal axis, tracheal ligation of fetal rabbits for 9 days resulted in fluid distention of the lungs. (2) This serendipitous finding, subsequently confirmed and embellished by others, (3)(4)(5) established that the fetal lung itself, rather than the amniotic sac, is the source of the liquid that fills the lung during development. This liquid forms a slowly expanding structural template that prevents collapse and promotes growth of the fetal lung. Subsequent studies, conducted mostly with sheep, showed that liquid in the lumen of the fetal lung forms as a result of chloride secretion in the respiratory epithelium, (6)(7) a process that can be inhibited by diuretics that block Na,K-2Cl cotransport. (8)(9) In vitro experiments using cultured explants of lung tissue and monolayers of epithelial cells harvested from human fetal lung have …

The Combination of Inhaled Nitric Oxide and Pulmonary Artery Balloon Inflation Improves Oxygenation During Whole-Lung Lavage

We present a case in which the use of inhaled nitric oxide associated with temporary partial unilateral pulmonary artery occlusion further improved oxygenation during whole-lung lavage. This is the first case in the literature describing the simultaneous use of these two modalities.

Intravenous micro-particle injections and pulmonary hypertension in broiler chickens: acute post-injection mortality and ascites susceptibility

Intravenously injected micro-particles become trapped within the pulmonary vasculature where they increase the resistance to blood flow and trigger pulmonary hypertension. We tested the hypothesis that i.v. micro-particle injections can be used to trigger acute (24 to 48 h) post-injection mortality in broilers having the most limited pulmonary vascular capacity, or ascites in broilers whose marginal cardiopulmonary capacity renders them susceptible to pulmonary hypertension syndrome (PHS). Progressive inflammation-associated responses were initiated within the lung parenchyma by 10 to 80 microm diameter dextran polymer (Sephadex) and 30 microm diameter cellulose micro-particles, leading to the scavenging of Sephadex micro-particles from the pulmonary vasculature by <5 d post-injection, whereas the cellulose micro-particles persisted for >7 d post-injection. The persistency and size of the cellulose apparently facilitated chronic occlusion of blood flow through precapillary arterioles, thereby triggering appreciable post-injection mortality and PHS at relatively low injection volumes (0.3 to 0.6 mL at 0.02 g/mL). In contrast, the small size of the polystyrene microspheres (15 microm), and the lack of persistency of the Sephadex micro-particles, apparently precluded the reliable occurrence of post-injection mortality or PHS until higher volumes (>0.8 mL at 0.02 g/mL) were injected. Values for the total susceptibility index (TSI: 24 to 48 h post-injection mortality + PHS mortality) following cellulose injections were higher for broilers reared at cool temperatures than at thermoneutral temperatures. The incidences of PHS induced by exposing broilers from different genetic lines to constant cool temperatures qualitatively paralleled the respective post-injection mortalities elicited by injecting the cellulose micro-particle suspension into the same lines. These observations indicate the micro-particle injection methodology potentially can replace unilateral pulmonary artery occlusion as the technique of choice for genetically selecting broilers that have a sufficiently robust pulmonary vascular capacity to resist the onset of pulmonary hypertension and PHS. The functional importance of the relative antigenicity of different micro-particle types, and the extent to which key immune-mediated responses, either beneficial or detrimental, might be co-selected by the micro-particle injection technology, remain to be clarified.

Pathophysiology of heart/lung disorders: pulmonary hypertension syndrome in broiler chickens

Pulmonary hypertension syndrome (PHS, ascites) in broiler chickens provides an outstanding example of the pathophysiological interplay between the lungs and heart. Recent research has confirmed the hypothesis that PHS susceptible broilers have an inherent potential to outgrow their pulmonary vascular capacity. Definitive proof that pulmonary hypertension (PH) is initiated as a consequence of an excessive pulmonary arterial resistance was obtained through measurements of pulmonary wedge pressures. Definitive proof that a pulmonary diffusion limitation causes the hypoxaemia characteristic of susceptible broilers was demonstrated by the rapid return to full arterial blood oxygenation in pre-ascitic broilers when they were provided with 100% oxygen to breathe. Experiments involving acute and chronic unilateral pulmonary occlusion provided definitive proof that the entire pathogenesis of PHS can be replicated by reducing the pulmonary vascular capacity. These experiments conclusively demonstrate that the resistance of broilers to PHS depends upon the capacity of their pulmonary vasculature to accept the requisite cardiac output at blood flow rates and pressures sufficiently low to avoid triggering PH and systemic hypoxaemia. The chronic unilateral pulmonary artery occlusion technique was successfully applied to develop a broiler line that is highly resistant to PHS induced by fast growth and exposure to rigorous cool temperatures, demonstrating for the first time that a dominant gene codes for a highly significant proportion of the PHS susceptibility. We now possess the knowledge necessary to create broiler lines capable of maintaining extremely rapid growth under rigorous field conditions while retaining very low susceptibility to PHS.

Furosemide Does Not Facilitate Pulmonary Vasodilation in Broilers During Chronic or Acute Unilateral Pulmonary Arterial Occlusion

Furosemide (FURO) is a diuretic and a putative pulmonary vasodilator that, when added to broiler diets, previously has been shown to reduce the cumulative pulmonary hypertension syndrome (PHS) mortality induced by cold temperatures. The objective of the present study was to evaluate the influence of dietary FURO on the pulmonary vasculature in broilers undergoing chronic or acute unilateral pulmonary arterial occlusion. Broilers were fed a standard ration throughout the entire experiment (Control group) or the same ration supplemented with 0.015% (wt/wt) FURO from Day 14 to 42 (FURO group). In the present study chicks were chosen at random at 16 to 18 d of age to undergo sham surgery or a chronic unilateral pulmonary artery clamp (PAC) procedure. Diet and surgical treatments resulted in Control-Sham, FURO-Sham, Control-PAC, and FURO-PAC groups. The Control-PAC and FURO-PAC groups did not differ in body weight or right:total ventricular weight ratios (RV:TV). The postsurgical mortality, ascites mortality, and mortality due to other causes did not differ between the Control-PAC and FURO-PAC groups. Plasma Na+ (P 0.05) was lower in the FURO-Sham group than in the Control-Sham group. Broilers from the same hatch were fed Control or FURO diets and surgically prepared for acute unilateral pulmonary arterial occlusion by using a snare. Tightening of the snare triggered characteristic increases in pulmonary blood flow, pulmonary arterial pressure, and pulmonary vascular resistance. Across all of these variables, the Control and FURO groups did not differ during any sample interval. Dietary FURO did not affect body weight, hematocrit, or RV:TV. Dietary FURO at 0.015% (wt/wt) does not appear to influence the pulmonary vasculature in broilers, but it may prolong the survival of broilers during the pathophysiological progression of PHS.

Bullectomy is beneficial in the pulmonary blood flow/driving pressure relationship in bullous emphysema patients.

Few physiological studies have been on pulmonary circulation, including the relationship between pulmonary blood flow and driving pressure, and viscosity changes arising from hematocrit changes before versus after lung volume reduction Surgery or bullectomy in emphysematous patients. We studied the relationship between pulmonary blood flow and driving pressure before and after bullectomy using a unilateral pulmonary artery occlusion test based on pulmonary blood flow fractions obtained by pulmonary blood flow scintigraphy in 7 patients with pulmonary emphysema associated with bullae. Among the 7 undergoing bullectomy, the pulmonary blood flow/driving pressure relationship decreased in 5 and was unchanged in 2. Of the 11 lungs treated by bullectomy, this relationship decreased in 8 lungs, but not 3 (p < 0.01). No significant difference was seen in oxygen partial pressure in arterial and mixed venous blood or hematocrit. We concluded that bullectomy shifted the pulmonary blood flow/driving pressure relationship downword in some cases with significant bullae.