Lung Lymph Flow Research Articles

Intravital imaging of pulmonary lymphatics in inflammation and metastatic cancer.

Intravital microscopy has enabled the study of immune dynamics in the pulmonary microvasculature, but many key events remain unseen because they occur in deeper lung regions. We therefore developed a technique for stabilized intravital imaging of bronchovascular cuffs and collecting lymphatics surrounding pulmonary veins in mice. Intravital imaging of pulmonary lymphatics revealed ventilation-dependence of steady-state lung lymph flow and ventilation-independent lymph flow during inflammation. We imaged the rapid exodus of migratory dendritic cells through lung lymphatics following inflammation and measured effects of pharmacologic and genetic interventions targeting chemokine signaling. Intravital imaging also captured lymphatic immune surveillance of lung-metastatic cancers and lymphatic metastasis of cancer cells. To our knowledge, this is the first imaging of lymph flow and leukocyte migration through intact pulmonary lymphatics. This approach will enable studies of protective and maladaptive processes unfolding within the lungs and in other previously inaccessible locations.

102 Vaping of Vitamin E Acetate Causes Acute Lung Injury in a Dose-dependent Manner in Sheep

IntroductionThe Centers for Disease Control and Prevention and the Food and Drug Administration have reported an increasing number of clinical cases of pulmonary injury following the use of e-cigarette/vaping products. Although the causative factors for the national outbreak of electronic-cigarette, or vaping product use-associated lung injury (EVALI) has not been established, CDC reported that vitamin E acetate (VEA) is strongly linked to the EVALI outbreak. In this study, we tested the hypothesis that VEA vaping causes acute lung injury in a dose-dependent manner in a sheep model.MethodsSheep were surgically prepared under anesthesia and analgesia with multiple vascular catheters (pulmonary arterial, left atrial, and femoral arterial). To assess pulmonary edema, the mediastinal lymph node vessel draining the lung was cannulated. After a 5-day surgical recovery, a tracheostomy tube and urinary catheter were placed. Then, the sheep were placed on a mechanical ventilator and VEA vaping was immediately started in the following groups: (1) vaped with glycerol (n=1); (2) vaped with 0.4mg of VEA (n=2); (3) vaped with 0.6mg of VEA (n=1); (4) vaped with 0.8mg of VEA (n=7); and (5) not injured, not treated (Sham, n=6). Sheep were resuscitated with lactated Ringer’s solution (4mL/kg/hr). Sheep in a conscious state was monitored with 4 hrs intervals for cardiopulmonary variables for 48 hrs.ResultsPulmonary gas exchange, represented by the PaO2/FiO2 ratio, was unchanged in sham, glycerol, and 0.4 mg VEA groups. In the 0.6 VEA group, the PaO2/FiO2 ratio was decreased from 42 to 48 hrs, while in the 0.8 mg VEA group, it was strongly decreased starting at 24 hrs and remained low throughout the remaining period. Lung lymph flow, an index of pulmonary microvascular permeability, was increased more than 2-fold in 0.6 and 0.8 mg VEA groups. Lung compliance also tended to decrease in all VEA groups.ConclusionsVEA vaping causes acute lung injury in a dose-dependent manner in sheep. Further studies should investigate underlying mechanistic aspects that cause increased microvascular permeability.

Cutaneous burn diminishes beneficial effect of intravenously administered mesenchymal stem cells on acute lung injury induced by smoke inhalation in sheep

ObjectiveTo investigate effects of intravenously administered allogeneic mesenchymal stem cells (MSCs) on burn/smoke-induced lung injury. MethodsSheep were subjected to 40%, third-degree flame skin burn and smoke inhalation under deep anesthesia and analgesia. One-hour after injury, PlasmaLite A (control) or 200 million MSCs (treatment) were intravenously administered. Pulmonary oxygenation index, PaO2/FiO2 ratio, lung–lymph flow, and bloodless lung wet-to-dry weight ratio were measured. Distribution of MSCs and stromal cell-derived factor-1 (Sdf-1) protein level were determined in lung and skin tissues. Effects of burn exudate on MSCs migration were characterized. ResultsMSCs did not attenuate pulmonary dysfunction. The number of MSCs was significantly higher in lungs of sheep with smoke inhalation compared with those with burn/smoke injury. In contrast, number of MSCs was significantly higher beneath burned skin in sheep with burn/smoke than in unburned skin of sheep with smoke inhalation only. Expression of Sdf-1 protein was increased in the burned skin compared to unburned skin. Effects of burn exudate on cultured MSCs proliferation differed depending on collection time. ConclusionSkin burn diminishes beneficial effects of MSCs on smoke-induced lung injury, by promoting migration of MSCs from the pulmonary tissue to the injured skin area, possibly via expression of Sdf-1 protein.

Adipose-derived stem cells attenuate pulmonary microvascular hyperpermeability after smoke inhalation.

BackgroundPulmonary edema is a hallmark of acute respiratory distress syndrome (ARDS). Smoke inhalation causes ARDS, thus significantly increasing the mortality of burn patients. Adipose-derived stem cells (ASCs) exert potent anti-inflammatory properties. The goal of the present study was to test the safety and ecfficacy of ASCs, in a well-characterized clinically relevant ovine model of ARDS.MethodsFemale sheep were surgically prepared. ARDS was induced by cooled cotton smoke inhalation. Following injury, sheep were ventilated, resuscitated with lactated Ringer’s solution, and cardiopulmonary hemodynamics were monitored for 48 hours in a conscious state. Pulmonary microvascular hyper-permeability was assessed by measuring lung lymph flow, extravascular lung water content, protein content in plasma and lung lymph fluid. Sheep were randomly allocated to two groups: 1) ASCs: infused with 200 million of ASCs in 200mL of PlasmaLyteA starting 1 hours post-injury, n = 5; 2) control, treated with 200mL of PlasmaLyteA in a similar pattern, n = 5.ResultsLung lymph flow increased 9-fold in control sheep as compared to baseline. Protein in the plasma was significantly decreased, while it was increased in the lung lymph. The treatment with ASCs significantly attenuated these changes. Treatment with ASCs almost led to the reversal of increased pulmonary vascular permeability and lung water content. Pulmonary gas exchange was significantly improved by ASCs. Infusion of the ASCs did not negatively affect pulmonary artery pressure and other hemodynamic variables.ConclusionsASCs infusion was well tolerated. The results suggest that intravenous ASCs modulate pulmonary microvascular hyper-permeability and prevent the onset of ARDS in our experimental model.

Abstract 19670: Adipose-derived Mesenchymal Stem Cells Attenuate Pulmonary Microvascular Hyperpermeability After Smoke Inhalation

Pulmonary edema is a hallmark of acute respiratory distress syndrome (ARDS). Smoke inhalation causes ARDS, significantly increasing the mortality of burn patients. Mesenchymal stem cells (MSCs) exert potent anti-inflammatory properties. The goal of the present study was to test the safety and efficacy of MSCs in a well-characterized clinically relevant ovine model of ARDS. Methods: Female sheep (30-40 kg) were surgically prepared 5-7 days prior the study. ARDS was induced by cooled cotton smoke inhalation. Following the injury, sheep were ventilated, resuscitated with lactated Ringer’s solution and cardiopulmonary hemodynamics was monitored for 48 h in a conscious state. Pulmonary microvascular hyper-permeability was assessed by measuring lung lymph flow, extravascular lung water content, protein in plasma and lung lymph. Sheep were randomly allocated to two groups: 1) MSCs: infused with 5 million/kg of intravenous MSCs over 30min starting 1 h post-injury, n=5; 2) control, treated with a vehicle in a similar pattern (200ml of PlasmaLyte A), n=5. Results: Lung lymph flow, an index of pulmonary transvascular fluid flux was ~7-fold increased in control sheep compared to baseline. This was associated with a significant protein decrease in plasma and its increase in lung lymph. The treatment with MSCs significantly attenuated these changes (Table). Moreover, the treatment with MSCs almost reversed increased pulmonary vascular permeability index {(lung lymph proteinхlung lymph flow)/plasma protein} and reduced lung water content (Lung wet-to-dry weight ratio). Pulmonary gas exchange was significantly improved by MSCs (PaO2/FiO2 was 406±101 in MSCs and 262±127 in control at 24 hrs, p<0.05). Infusion of the MSCs did not affect pulmonary artery pressure and other hemodynamic variables. Conclusions: MSCs infusion was well tolerated. The results suggest that intravenous MSCs modulate pulmonary microvascular hyper-permeability and prevent onset of ARDS.

Pulmonary microvascular hyperpermeability and expression of vascular endothelial growth factor in smoke inhalation- and pneumonia-induced acute lung injury

IntroductionAcute lung injury (ALI) and sepsis are major contributors to the morbidity and mortality of critically ill patients. The current study was designed further evaluate the mechanism of pulmonary vascular hyperpermeability in sheep with these injuries. MethodsSheep were randomized to a sham-injured control group (n=6) or ALI/sepsis group (n=7). The sheep in the ALI/sepsis group received inhalation injury followed by instillation of Pseudomonas aeruginosa into the lungs. These groups were monitored for 24h. Additional sheep (n=16) received the injury and lung tissue was harvested at different time points to measure lung wet/dry weight ratio, vascular endothelial growth factor (VEGF) mRNA and protein expression as well as 3-nitrotyrosine protein expression in lung homogenates. ResultsThe injury induced severe deterioration in pulmonary gas exchange, increases in lung lymph flow and protein content, and lung water content (P<0.01 each). These alterations were associated with elevated lung and plasma nitrite/nitrate concentrations, increased tracheal blood flow, and enhanced VEGF mRNA and protein expression in lung tissue as well as enhanced 3-nitrotyrosine protein expression (P<0.05 each). ConclusionsThis study describes the time course of pulmonary microvascular hyperpermeability in a clinical relevant large animal model and may improve the experimental design of future studies.

Beneficial Effects of Concomitant Neuronal and Inducible Nitric Oxide Synthase Inhibition in Ovine Burn and Inhalation Injury

Different isoforms of nitric oxide (NO) synthase are critically involved in the development of pulmonary failure secondary to acute lung injury. Here we tested the hypothesis that simultaneous blockade of inducible and neuronal NO synthase effectively prevents the pulmonary lesions in an ovine model of acute respiratory distress syndrome induced by combined burn and smoke inhalation injury. Chronically instrumented sheep were allocated to a sham-injured group (n = 6), an injured and untreated group (n = 6), or an injured group treated with simultaneous infusion of selective inducible and neuronal NO synthase inhibitors (n = 5). The injury was induced by 48 breaths of cotton smoke and a third-degree burn of 40% total body surface area. All sheep were mechanically ventilated and fluid resuscitated. The injury induced severe pulmonary dysfunction as indicated by decreases in PaO2/FiO2 ratio and increases in pulmonary shunt fraction, ventilatory pressures, lung lymph flow, and lung wet/dry weight ratio. The treatment fully prevented the elevations in lymph and plasma nitrate/nitrite levels, pulmonary shunting, ventilatory pressures, lung lymph flow, and wet/dry weight ratio and significantly attenuated the decline in PaO2/FiO2 ratio. In conclusion, simultaneous blockade of inducible and neuronal NO synthase exerts beneficial pulmonary effects in an ovine model of acute respiratory distress syndrome secondary to combined burn and smoke inhalation injury. This novel treatment strategy may represent a useful therapeutic adjunct for patients with these injuries.

Predictive role of arterial carboxyhemoglobin concentrations in ovine burn and smoke inhalation-induced lung injury

ABSTRACTInhalation injury frequently occurs in burn patients and contributes to the morbidity and mortality of these injuries. Arterial carboxyhemoglobin has been proposed as an indicator of the severity of inhalation injury; however, the interrelation between arterial carboxyhemoglobin and histological alterations has not yet been investigated. Chronically instrumented sheep were subjected to a third degree burn of 40% of the total body surface area and inhalation of 48 breaths of cotton smoke. Carboxyhemoglobin was measured immediately after injury and correlated to clinical parameters of pulmonary function as well as histopathology scores from lung tissue harvested 24 hours after the injury. The injury was associated with a significant decline in pulmonary oxygenation and increases in pulmonary shunting, lung lymph flow, wet/dry weight ratio, congestion score, edema score, inflammation score, and airway obstruction scores. Carboxyhemoglobin was negatively correlated to pulmonary oxygenation and positively correlated to pulmonary shunting, lung lymph flow, and lung wet/dry weight ratio. No significant correlations could be detected between carboxyhemoglobin and histopathology scores and airway obstruction scores. Arterial carboxyhemoglobin in sheep with combined burn and inhalation injury are correlated with the degree of pulmonary failure and edema formation, but not with certain histological alterations including airway obstruction scores.

Beneficial pulmonary effects of a metalloporphyrinic peroxynitrite decomposition catalyst in burn and smoke inhalation injury

During acute lung injury, nitric oxide (NO) exerts cytotoxic effects by reacting with superoxide radicals, yielding the reactive nitrogen species peroxynitrite (ONOO(-)). ONOO(-) exerts cytotoxic effects, among others, by nitrating/nitrosating proteins and lipids, by activating the nuclear repair enzyme poly(ADP-ribose) polymerase and inducing VEGF. Here we tested the effect of the ONOO(-) decomposition catalyst INO-4885 on the development of lung injury in chronically instrumented sheep with combined burn and smoke inhalation injury. The animals were randomized to a sham-injured group (n = 7), an injured control group [48 breaths of cotton smoke, 3rd-degree burn of 40% total body surface area (n = 7)], or an injured group treated with INO-4885 (n = 6). All sheep were mechanically ventilated and fluid-resuscitated according to the Parkland formula. The injury-related increases in the abundance of 3-nitrotyrosine, a marker of protein nitration by ONOO(-), were prevented by INO-4885, providing evidence for the neutralization of ONOO(-) action by the compound. Burn and smoke injury induced a significant drop in arterial Po(2)-to-inspired O(2) fraction ratio and significant increases in pulmonary shunt fraction, lung lymph flow, lung wet-to-dry weight ratio, and ventilatory pressures; all these changes were significantly attenuated by INO-4885 treatment. In addition, the increases in IL-8, VEGF, and poly(ADP-ribose) in lung tissue were significantly attenuated by the ONOO(-) decomposition catalyst. In conclusion, the current study suggests that ONOO(-) plays a crucial role in the pathogenesis of pulmonary microvascular hyperpermeability and pulmonary dysfunction following burn and smoke inhalation injury in sheep. Administration of an ONOO(-) decomposition catalyst may represent a potential treatment option for this injury.

Case Scenario: Acute Postoperative Negative Pressure Pulmonary Edema

A 25-yr-old man (weight, 68 kg; height, 183 cm) presentedto the surgery center for excision of back and thigh schwan-nomas on the same day. The patient’s medical history wassignificant only for his history of multiple schwannoma re-sections and a history of smoking one pack of cigarettes perweek for the past 5 yr. He denied previous problems withgeneral anesthesia, and his baseline peripheral oxygen satu-ration was 99% on ambient air.Thepatientwaspremedicatedwith2mgmidazolam,andanesthesia was induced with 250 mg fentanyl, 500 mg thio-pental, and 8 mg vecuronium given for facilitation of tra-cheal intubation. He was atraumatically intubated with a7-mm ID endotracheal tube using a no. 3 Macintosh laryn-goscope (Teleflex Medical, Research Triangle Park, NC) onthe first attempt with direct visualization of the vocal cords.The patient was turned prone, bilateral breath sounds werereconfirmed, and schwannoma excisions were performed ontheleftthighandtheleftflank.Atotalof0.5mghydromor-phone was administered for analgesia. The intraoperativecoursewasunremarkable.Thepatientwashemodynamicallystable with minimal blood loss and was easily ventilated andoxygenated. A total of 500 ml lactated Ringer’s solution wasadministeredduringthe65-minsurgicalprocedure.Thepa-

Role of neutrophils in lung injury after intestinal ischemia and reperfusion in dogs

We studied the role of neutrophils in lung injury after intestinal ischemia and reperfusion (I/R) in anesthetized dogs with lung lymph fistulae. One group was subjected to 2.5 hours of balloon occlusion of the superior mesenteric artery without laparotomy, followed by 3 hours of reperfusion (I/R group, n = 7). The other group was subjected to the same procedures, except for intestinal I/R (sham operation group, n = 6). In the sham operation group, lung fluid balance, hemodynamics, extravascular water volume (Qw 1: ml/g BFDW), myeloperoxidase activity in the lung (MPO: unit/g DW), H2O2 production by neutrophils in blood (mean DCF/cell), and migration of neutrophils into the lung lymphatic system did not significantly change. In the I/R group, both lung lymph flow (Jv) and protein clearance (Qp) increased more than 2.5 fold as compared with the baseline values, while capillary pressure (Ppc) and the ratio of lymph to plasma protein concentration (CL/Cp) remained almost the same as the baseline values. Qw1 also moderately increased. MPO activity, H2O2 production, and migration of neutrophils into the lung lymphatic system increased after I/R, and were more remarkable than in the sham operation group. These results suggest that activation and migration of primed neutrophils contributes to lung injury after intestinal ischemia and reperfusion.

Activated pulmonary intravascular macrophages increase pulmonary microvascular permeability in sheep

Pulmonary intravascular macrophages (PIMs) reside in the alveolar capillaries of sheep lung. However, the role of PIMs activation in the mechanism of increasing pulmonary microvascular permeability is not clear. We determined, using awake sheep with chronic lung lymph fistulas, the effects of intraarterial infusion of latex beads emulsion (1 microns in diameter) on lung lymph-dynamics. Sheep were divided into 3 groups; control, low dose latex and high dose latex groups. In control group, their lymph-dynamics were stable during the experimental period. In low dose latex group (5.46 x 10(9) beads/kg), lung lymph flow increased during the infusion period, but lung lymph protein clearance did not change. In high dose latex group (5.46 x 10(10) beads/kg), lung lymph flow began to increase during the infusion period and remained high, and lung lymph protein clearance increased significantly during and after the infusion of latex beads emulsion. The latex beads mainly distributed to lungs, and 70% of the beads were caught by PIMs in their phagosomes. These findings suggest that the activation of PIMs through their phagocytic uptake of circulating microparticles increases pulmonary microvascular permeability.

Role of calcitonin gene-related peptide (CGRP) in ovine burn and smoke inhalation injury.

Concomitant smoke inhalation trauma in burn patients is a serious medical problem. Previous investigations in our sheep model revealed that these injuries lead to significant airway hyperemia, enhanced pulmonary fluid extravasation, and severely impaired pulmonary function. However, the pathophysiological mechanisms are still not fully understood. The lung is innervated by sensory nerves containing peptides such as substance P and calcitonin gene-related peptide. Noxious stimuli in the airways can induce a neurogenic inflammatory response, which has previously been implicated in several airway diseases. Calcitonin gene-related peptide is known to be a potent vasodilator. We hypothesized that calcitonin gene-related peptide is also a mediator of the pulmonary reaction to toxic smoke and planned experiments to evaluate its role in this model. We tested the effects of pretreatment with a specific antagonist of the major receptor for calcitonin gene-related peptide (BIBN4096BS; 32 microg/kg, followed by continuous infusion of 6.4 microg.kg(-1).h(-1)) until the animal was killed 48 h after injury in an established ovine model of burn (40% total body surface, third degree) and smoke inhalation (48 breaths, <40 degrees C) injury. In treated animals (n = 7), the injury-related increases in tracheal blood flow and lung lymph flow were significantly attenuated compared with untreated controls (n = 5). Furthermore, the treatment significantly attenuated abnormalities in respiratory gas exchange. The data suggest that calcitonin gene-related peptide contributes to early airway hyperemia, transvascular fluid flux, and respiratory malfunction following ovine burn and smoke inhalation injury. Future studies will be needed to clarify the potential therapeutic benefit for patients with this injury.

Inhibition of lung permeability changes after burn and smoke inhalation by an anti-interleukin-8 antibody in sheep

To evaluate the effects of a monoclonal antibody against interleukin-8 (K2.2) on the microvascular fluid flux after combined injury by burn and smoke inhalation. Fourteen sheep were prepared surgically by placing a lung lymph catheter and a flank lymph catheter to examine the microvascular fluid flux. After a recovery period, they were subjected to a combined injury of 40% third-degree burns on the flank and smoke inhalation. This combined injury induced a rapid increase in burned tissue lymph flow (b-Q(L)) and a delayed-onset increase in lung lymph flow (l-Q(L)). The initial increase in b-Q(L) was associated with an elevation of the lymph-to-plasma oncotic pressure ratio, which led to a predominant increase in the burned tissue permeability index (b-PI). Pretreatment with K2.2 had no effect on the permeability change seen in the burned tissue; however, the lung permeability changes were attenuated by pretreatment with K2.2. These findings indicate that the pathogenesis of the increase in microvascular fluid flux seen after the combined injury differs in burned tissue and the lung.

Pulmonary vascular permeability changes in an ovine model of methicillin-resistant Staphylococcus aureus sepsis

IntroductionEndothelial dysfunction is a hallmark of sepsis, associated with lung transvascular fluid flux and pulmonary dysfunction in septic patients. We tested the hypothesis that methicillin-resistant Staphylococcus aureus (MRSA) sepsis following smoke inhalation increases pulmonary transvascular fluid flux via excessive nitric oxide (NO) production.MethodsEwes were chronically instrumented, and randomised into either a control or MRSA sepsis (MRSA and smoke inhalation) group.ResultsPulmonary function remained stable in the control group, whereas the MRSA sepsis group developed impaired gas exchange and significantly increased lung lymph flow, permeability index and bloodless wet-to-dry weight-ratio (W/D ratio). The plasma nitrate/nitrite (NOx) levels, lung inducible nitric oxide synthases (iNOS) and endothelial nitric oxide synthases (eNOS), vascular endothelial growth factor (VEGF) protein expressions and poly-(ADP)-ribose (PAR) were significantly increased by MRSA challenge.ConclusionsThese results provide evidence that excessive NO production may mediate pulmonary vascular hyperpermeability in MRSA sepsis via up regulation of reactive radicals and VEGF.

Assessment of vascular permeability in an ovine model of acute lung injury and pneumonia-induced Pseudomonas aeruginosa sepsis

To assess the time changes and mechanism of pulmonary and peripheral vascular permeability in sheep with acute lung injury and sepsis. Prospective, controlled, randomized trial. University research laboratory. A total of 21 chronically instrumented, adult female sheep. Sheep were instrumented with lung and prefemoral lymph fistulas and allocated to either an uninjured control group (n = 5) or sepsis group (n = 5). The sheep in the sepsis group received cotton smoke inhalation injury followed by instillation of Pseudomonas aeruginosa into the lungs. All sheep were mechanically ventilated and fluid resuscitated for the entire duration of the 24-hr experiment. Additional sheep (n = 11) received injury and were killed at different time points for the measurement of vascular endothelial growth factor in lung tissue. The injury induced a hypotensive-hyperdynamic circulation; increases in pulmonary capillary pressure, net fluid balance, lung and prefemoral lymph flow and protein content, lung water content, abdominal and thoracic fluid and protein content, neutrophil accumulation in the lung, and vascular endothelial growth factor expression in lung tissue; and decreases in PaO2/FiO2 ratio, plasma protein concentration, plasma oncotic pressure, and myocardial contractility. Lung edema formation in this model was the result of marked increases in both pulmonary microvascular permeability and pressure. Pulmonary vascular hyperpermeability peaked 12 hrs postinjury and was related to vascular endothelial growth factor overexpression. Early myocardial failure was a potential contributor to the constant increase in pulmonary capillary pressure. The sepsis-induced increase in peripheral microvascular permeability was associated with significant accumulation of fluid and protein in the third space.

Losartan, an angiotensin II receptor blocker, fails to attenuate pulmonary dysfunction in ovine burn and smoke model

Elevated levels of angiotensin II (AngII) in the lung have been shown in response to burn and smoke inhalation injury. AngII has been associated with increased nitric oxide levels, leading to nuclear oxidative damage in Type II lung epithelial cells. Losartan is an AngII receptor blocker, specific to AT1A receptors. Using an ovine model of acute respiratory distress, we hypothesized that blocking AngII receptors with losartan would improve the clinical conditions seen in response to the injury. Chronically prepared adult ewes received a 40% total body surface area third degree flame burn followed by 48 breaths of cotton smoke. The sheep were randomly divided into two groups: control (injury, no treatment, n=6) and treatment (injury + losartan, n= 6). Losartan was given intravenously as a bolus (50 mg) at 1hour post‐injury. All animals received 4ml/kg/%burn of Ringer's lactate and were mechanically ventilated. Control animals showed severe signs of acute lung injury evidenced by deterioration of pulmonary gas exchange (PaO2/FiO2, pulmonary shunt fraction), increased lung water content, and increased pulmonary transvascular fluid flux, and vascular permeability index. Although there was a trend for reduction of lung lymph flow and permeability index, these alterations could not be shown as statistically affected by this dosage of losartan in this 24‐hour ovine model of acute lung injury. SBI 8450, PPG 5P01GM066312

Lymphatics and lymph in acute lung injury

Lymph flow will be discussed as part of the drainage and fluid balance of lung tissue and abdomen as well as a qualitative analysis of inflammatory processes. Measurement of lung lymph is still a technical challenge. Mechanical ventilation and positive end-expiratory pressure impede lung lymph flow by increased intrathoracic pressure and increased central venous pressure. Positive end-expiratory pressure may thus enhance edema formation of the lung. Inflammatory spread from abdomen to the lung via the lymphatic system has been shown in a number of experimental studies. Ligation or diversion of the thoracic duct has been proposed to blunt the effects of noxious stimuli mediated by lymphatics to the lungs. Lymphatics have a major role on abdominal fluid balance while draining extravascular fluid accumulation and edema, especially during sepsis. Mechanical ventilation with high airway pressure increases abdominal edema (ascites) and spontaneous breathing protects from edema formation. Lymph flow measurements are still a difficult task to perform; however, new results show an important function in the fluid balance of the lung and abdomen. Inflammatory spread may occur from the lung to the periphery by the blood stream and from the abdomen to the lung by lymph flow.

Effect of ablated airway blood flow on systemic and pulmonary microvascular permeability after smoke inhalation in sheep

The bronchial circulation plays a significant role in the pathogenesis of smoke inhalation. We investigated the physiological manifestations in both the systemic and the pulmonary circulation after smoke inhalation injury, and determined whether ablation of the bronchial circulation had any effect on these changes. We used a chronically instrumented ovine model with lung and prefemoral lymph fistulae to determine the changes in pulmonary and systemic microvascular permeability. Fourteen animals were divided into two groups. The injection group had bronchial circulation ablation with an ethanol injection into the bronchial artery, whereas it was left intact in the sham group. The sham group showed a four-fold increase in lung lymph flow (l- Q L) and a two-fold increase in prefemoral lymph flow (s- Q L) 24 h after injury. The increase in s- Q L was associated with a decrease in lymph oncotic pressure. Therefore, systemic colloid clearance (s-CC), an indicator of systemic microvascular permeability to protein, was unchanged. The ablated bronchial circulation reversed the pulmonary but not the systemic manifestations after smoke inhalation. In conclusion, the pathophysiological events occurring after smoke inhalation were confined to the lung with increased bronchial blood flow delivering inflammatory mediators directly to the lung parenchyma.

Flat beer vs. physiological improvement: effect of acetazolamide during hypoxic exercise

Flat beer <i>vs.</i> physiological improvement: effect of acetazolamide during hypoxic exercise