Aspiration pneumonia: beneficial and harmful effects of positive end-expiratory pressure.

With an ex vivo, isolated, ventilated, perfused canine pulmonary lobe, the effects of various levels of positive end-expiratory pressure (PEEP) were evaluated following acid injury. Following intrabronchial instillation of hydrochloric acid, eight lobes were ventilated with 5 cm of H2O of PEEP, 12 lobes with 10 cm of PEEP, and eight lobes with 15 cm of PEEP during a 4 hour perfusion period. Blood flow was kept constant in all preparations. Lobes with 5 cm of PEEP developed a 39% intrapulmonary shunt and increased their weight by 220%. When PEEP was increased to 10 cm, weight gain was similar (184%), but shunting decreased markedly, to 7%. When PEEP was increased further to 15 cm, shunting remained low (13%), but weight gain increased markedly, to 411% of the initial lobe weight. This study demonstrates the beneficial effects of PEEP in aspiration pneumonia, but it also points out that increasing levels of PEEP can magnify acid-pulmonary injury by causing a further increase in interstitial and intralveolar edema.     

Respiratory failure in acute pancreatitis: a possible role for triglycerides.

Respiratory failure is a frequent complication of acute pancreatitis. Two clinical studies of this association have demonstrated a high incidence of concomitant hypertriglyceridemia. Experimental studies were carried out using an ex vivo, isolated, perfused, ventilated, canine pulmonary lobe to evaluate the effects of triglyceride elevations on pulmonary mechanics and gas exchange. Control lobes perfused for a four hour period remained stable. When 5g and 10g of triglyceride were added to the perfusate, the lobes became grossly edematous and hemorrhagic. Intrapulmonary shunting developed (23 and 46%), weight gain occurred (130 and 189g), effective compliance decreased, and the pressure-volume deflation curves became abnormal. Free fatty acid (FFA) levels increased markedly during the perfusion periods. When small quantities of FFA were infused directly into the pulmonary artery, similar changes, but less severe, occurred. These studies demonstrate that triglyceride elevations are capable of adversely affecting pulmonary gas exchange and mechanics. Such changes probably occur secondary to FFA release. These data thus add support to the concept that the respiratory insufficiency that is seen in acute pancreatitis could be mediated through triglyceride elevations.     

Partial Liquid Ventilation Reduces Fluid Filtration of Isolated Rabbit Lungs with Acute Hydrochloric Acid-induced Edema

Background: Hydrochloric acid aspiration increases pulmonary microvascular permeability. The authors tested the hypothesis that partial liquid ventilation has a beneficial effect on filtration coefficients in acute acid-induced lung injury.

Methods: Isolated blood-perfused rabbit lungs were assigned randomly to one of four groups. Group 1 (n = 6) served as a control group without edema. In group 2 (n = 6), group 3 (n = 6), and group 4 (n = 6), pulmonary edema was induced by intratracheal instillation of hydrochloric acid (0.1 N, 2 ml/kg body weight). Filtration coefficients were determined 30 min after this injury (by measuring loss of perfusate after increase of left atrial pressure). Group 2 lungs were gas ventilated, and group 3 lungs received partial liquid ventilation (15 ml perfluorocarbon/kg body weight). In group 4 lungs, the authors studied the immediate effects of bronchial perfluorocarbon instillation on ongoing filtration.

Results: Intratracheal instillation of hydrochloric acid markedly increased filtration coefficients when compared with noninjured control lungs (2.3 +/- 0.7 vs. 0.31 +/- 0.08 ml [middle dot] min-1 [middle dot] mmHg-1 [middle dot] 100 g-1 wet lung weight, P < 0.01). Partial liquid ventilation reduced filtration coefficients of the injured lungs (to 0.9 +/- 0.3 ml [middle dot] min-1 [middle dot] mmHg-1 [middle dot] 100 g-1 wet lung weight, P = 0.022). Neither pulmonary artery nor capillary pressures (determined by simultaneous occlusion of inflow and outflow of the pulmonary circulation) were changed by hydrochloric acid instillation or by partial liquid ventilation. During ongoing filtration, bronchial perfluorocarbon instillation (5 ml/kg body weight) immediately reduced the amount of filtered fluid by approximately 50% (P = 0.027).     

Partial liquid ventilation reduces fluid filtration of isolated rabbit lungs with acute hydrochloric acid-induced edema

BACKGROUND: Hydrochloric acid aspiration increases pulmonary microvascular permeability. The authors tested the hypothesis that partial liquid ventilation has a beneficial effect on filtration coefficients in acute acid-induced lung injury. METHODS: Isolated blood-perfused rabbit lungs were assigned randomly to one of four groups. Group 1 (n = 6) served as a control group without edema. In group 2 (n = 6), group 3 (n = 6), and group 4 (n = 6), pulmonary edema was induced by intratracheal instillation of hydrochloric acid (0.1 N, 2 ml/kg body weight). Filtration coefficients were determined 30 min after this injury (by measuring loss of perfusate after increase of left atrial pressure). Group 2 lungs were gas ventilated, and group 3 lungs received partial liquid ventilation (15 ml perfluorocarbon/kg body weight). In group 4 lungs, the authors studied the immediate effects of bronchial perfluorocarbon instillation on ongoing filtration. RESULTS: Intratracheal instillation of hydrochloric acid markedly increased filtration coefficients when compared with non-injured control lungs (2.3 +/- 0.7 vs. 0.31 +/- 0.08 ml.min(-1). mmHg(-1).100 g(-1) wet lung weight, P < 0.01). Partial liquid ventilation reduced filtration coefficients of the injured lungs (to 0.9 +/- 0.3 ml.min(-1).mmHg(-1).100 g(-1) wet lung weight, P = 0.022). Neither pulmonary artery nor capillary pressures (determined by simultaneous occlusion of inflow and outflow of the pulmonary circulation) were changed by hydrochloric acid instillation or by partial liquid ventilation. During ongoing filtration, bronchial perfluorocarbon instillation (5 ml/kg body weight) immediately reduced the amount of filtered fluid by approximately 50% (P = 0.027). CONCLUSIONS: In the acute phase after acid injury, partial liquid ventilation reduced pathologic fluid filtration. This effect started immediately after bronchial perfluorocarbon instillation and was not associated with changes in mean pulmonary artery, capillary, or airway pressures. The authors suggest that in the early phase of acid injury, reduction of fluid filtration contributes to the beneficial effects of partial liquid ventilation on gas exchange and lung mechanics.     

Evaluation of the efficacy of Alka-Seltzer Effervescent in gastric acid neutralization

A commercially available antacid, a mixture of sodium and potassium bicarbonates and citric acid (Alka-Seltzer Effervescent), was evaluated experimentally and clinically for its efficacy in neutralizing 0.1 N HCl and gastric contents. In an in vitro titration study, Alka-Seltzer Effervescent buffered 5-30 times the volume of HCl with a pH between 1.0 and 2.0 to above a pH of 2.5. In an isolated canine pulmonary lobe model, aspiration of the antacid or acid-antacid mixture caused only a mild increase in lobe weight and did not increase intrapulmonary shunting. In the clinical study, when the antacid was given 5-40 min before administration of general anesthesia in a group of patients for emergency surgery, the pH of the gastric contents in each patient was increased to above 4.0. This contrasts with the control group of patients, which showed 50% (P less than 0.05) of the patients were at risk when no antacid was administered. Preoperative administration of Alka-Seltzer effectively increases the pH of the gastric contents in patients undergoing emergency surgery.     

Evaluation of ventilatory therapy for acid aspiration.

Aspiration of hydrochloric acid in experimental animals results in severe, progressive hypoxia which is due to intrapulmonary shunting and depressed cardiac output. This preparation is useful therefore in studying the therapy of hypoxia. Mongrel dogs were subjected to acid aspiration and the effects of several ventilatory patterns on intrapulmonary shunt fractions and lung water accumulation observed. The combination of large tidal volumes (30 c.c. per kilogram) with positive end-expiratory pressure was effective in preventing intrapulmonary shunting and other ventilatory patterns were ineffective. Pulmonary edema uniformly followed acid aspiration and was not affected by ventilatory therapy. When ventilatory therapy was delayed for 4 hours, the progression of shunting apparently was limited, but the existing shunt was not reduced.     

A critical comparison of the hematologic, cardiovascular, and pulmonary response to steroids and nonsteroidal anti-inflammatory drugs in a model of sepsis and adult respiratory distress syndrome

Improved survival of patients receiving high-dose steroid therapy in sepsis and adult respiratory distress syndrome (ARDS) has been reported, but such therapy and its benefits remain controversial. Recently research has been directed toward manipulation of the arachidonic acid cascade. Improved survival and hemodynamics with administration of nonsteroidal anti-inflammatory drugs (NSAID) have been reported in animal models of sepsis and ARDS. The purpose of this study was to compare the effects of steroids (methylprednisolone) and NSAID (ibuprofen) in a porcine model of septic ARDS induced by a continuous infusion of live Pseudomonas aeruginosa. Cardiopulmonary parameters were monitored in animals intubated, paralyzed, and ventilated at a 250 ml tidal volume and 0.5 Fio2. Pigs were randomly assigned to one of five groups: groups I and II received respective doses of 12.5 mg/kg ibuprofen and 30 mg/kg methylprednisolone at 20 and 210 minutes after baseline; group III had P. aeruginosa only; groups IV and V received respective doses of ibuprofen and methylprednisolone at 20 and 210 minutes of sepsis. Significant pulmonary edema, increased intrapulmonary shunting, hypoxemia, hemoconcentration, and systemic hypotension occurred with P. aeruginosa infusion. In septic animals treated with ibuprofen normal systemic arterial pressure was maintained, hemoconcentration was decreased, and oxygenation was improved with a significant decrease in shunting and pulmonary edema. Administration of methylprednisolone improved hemoconcentration and cardiac index, but no significant effect on pulmonary edema, intrapulmonary shunting, or oxygenation was observed. The results of this study demonstrated a significant beneficial effect of ibuprofen and we would encourage controlled clinical trials of this drug in the management of sepsis and ARDS. On the other hand, methylprednisolone was found to be relatively ineffective in treatment of circulatory collapse and ARDS associated with sepsis.     

Sodium nitroprusside mitigates oleic acid-induced acute lung injury

BACKGROUND: Acute lung injury (ALI) is associated with pulmonary hypertension, intrapulmonary shunting, and increased microvascular permeability, leading to altered oxygenation capacity. Oleic acid (OA) creates a significant ALI that physiologically mimics human adult respiratory distress syndrome (ARDS). It has been hypothesized that pulmonary vasodilatation may improve ALI. Studies in our laboratory using this model and nitric oxide (NO) have shown that NO inhalation is detrimental and worsens the effects of OA. We studied the effect of pretreatment with a potent vasodilator, sodium nitroprusside (SNP), on ALI induced by OA in an isolated lung model. We hypothesized that pretreatment with SNP will worsen pulmonary hypertension and oxygenation in OA-induced ALI, similar to the effects seen with inhaled NO in this model. METHODS: Rabbit heart lung blocks were isolated, flushed in vivo, harvested, immediately perfused with whole blood, and ventilated with 50% oxygen. Pulmonary artery pressure was determined every 15 seconds for 90 minutes of perfusion. Oxygenation was determined by blood gas analysis of pulmonary venous effluent at 0, 20, 40, 60, and 90 minutes after initiation of OA infusion. Four groups were studied: saline control (SC), oleic acid control (OAC; 20-minute infusion of 50% OA/ethanol into pulmonary circulation), SNP control (NPC; 10 microg/ kg/min SNP infused without subsequent OA infusion), and SNP treatment (NPRx); 10 microg/kg/min SNP infused before OA/ethanol. Pulmonary artery pressure (PAP), oxygenation (arterio-venous oxygen difference [AVO2], compliance (CPL), and wet/dry lung weight were determined. RESULTS: No significant differences were found between the NPRx group and SC. Pretreatment with SNP eliminated the detrimental effects of OA infusion. CONCLUSIONS: Contrary to our hypothesis, pretreatment with SNP eliminates the decrease in oxygenation and increase in lung weight, and ameliorates pulmonary hypertension in our isolated lung model of OA-induced ALI.     

Vaporized Perfluorohexane Attenuates Ventilator-induced Lung Injury in Isolated, Perfused Rabbit Lungs

Background: The authors tested the hypothesis that administration of vaporized perfluorohexane may attenuate ventilator-induced lung injury.

Methods: In isolated, perfused rabbit lungs, airway pressure-versus-time curves were recorded. At baseline, peak inspiratory pressure and positive end-expiratory pressure of mechanically ventilated lungs were set to obtain straight pressure-versus-time curves in both the lower and upper ranges, which are associated with less collapse and overdistension, respectively. After that, peak inspiratory pressure and positive end-expiratory pressure were set at 30 cm H2O and 0, respectively, and animals were randomly assigned to one of two groups: (1) simultaneous administration of 14% perfluorohexane vapor in room air (n = 7) and (2) control group-ventilation with room air (n = 7). After 20 min of cycling collapse and overdistension, tidal volume and positive end-expiratory pressure were set back to baseline levels, administration of perfluorohexane in the therapy group was stopped, and mechanical ventilation was continued for up to 60 min. Lung weight, mean pulmonary artery pressure, and concentration of thromboxane B2 in the perfusate were measured. In addition, the distribution of pulmonary perfusate flow was assessed by using fluorescent-labeled microspheres.

Results: Significantly higher peak inspiratory values developed in control lungs than in lungs treated with perfluorohexane. In addition, upper ranges of pressure-versus-time curves were closer to straight lines in the perfluorohexane group. Lung weight, mean pulmonary arterial pressure, and release of thromboxane B2 were significantly higher in controls than in perfluorohexane-treated lungs. Also, redistribution of pulmonary perfusate flow from caudal to cranial zones was less important in the treatment group.     

Vaporized perfluorohexane attenuates ventilator-induced lung injury in isolated, perfused rabbit lungs

BACKGROUND: The authors tested the hypothesis that administration of vaporized perfluorohexane may attenuate ventilator-induced lung injury. METHODS: In isolated, perfused rabbit lungs, airway pressure-versus-time curves were recorded. At baseline, peak inspiratory pressure and positive end-expiratory pressure of mechanically ventilated lungs were set to obtain straight pressure-versus-time curves in both the lower and upper ranges, which are associated with less collapse and overdistension, respectively. After that, peak inspiratory pressure and positive end-expiratory pressure were set at 30 cm H2O and 0, respectively, and animals were randomly assigned to one of two groups: (1) simultaneous administration of 14% perfluorohexane vapor in room air (n = 7) and (2) control group-ventilation with room air (n = 7). After 20 min of cycling collapse and overdistension, tidal volume and positive end-expiratory pressure were set back to baseline levels, administration of perfluorohexane in the therapy group was stopped, and mechanical ventilation was continued for up to 60 min. Lung weight, mean pulmonary artery pressure, and concentration of thromboxane B2 in the perfusate were measured. In addition, the distribution of pulmonary perfusate flow was assessed by using fluorescent-labeled microspheres. RESULTS: Significantly higher peak inspiratory values developed in control lungs than in lungs treated with perfluorohexane. In addition, upper ranges of pressure-versus-time curves were closer to straight lines in the perfluorohexane group. Lung weight, mean pulmonary arterial pressure, and release of thromboxane B2 were significantly higher in controls than in perfluorohexane-treated lungs. Also, redistribution of pulmonary perfusate flow from caudal to cranial zones was less important in the treatment group. CONCLUSION: The authors conclude that the administration of perfluorohexane vapor attenuates the development of ventilator-induced lung injury in isolated, perfused rabbit lungs.     

Does increased pulmonary blood flow redistribute towards edematous lung units?

Unilobar pulmonary edema secondary to increased capillary permeability was produced utilizing oleic acid infusion into the left lower lobe pulmonary artery of seven dogs. This model was used to determine whether random changes in cardiac output produced by opening and closing arteriovenous fistulae were associated with changes in fractional perfusion to the edematous lobe (as determined by differentially labeled radiomicrospheres) thus explaining changes in intrapulmonary shunt. With an increase in cardiac output from a mean (+/- SD) of 1.6 +/- 0.5 liters/min to 2.6 +/- 0.8 liters/min (P less than 0.01), mean (+/- SD) injured lobar shunt as measured from O2 contents of lower lobar pulmonary venous blood and mixed venous blood increased from 54.4 +/- 3.0% to 74.4 +/- 22.1% while total intrapulmonary shunt increased from 12.0 +/- 4.0% to 16.0 +/- 3.7% (P less than 0.01). This increase in intrapulmonary shunt was, however, not associated with preferential perfusion of the edematous lobe, the mean (+/- SD) of the perfusion to the edematous lobe expressed as a percentage of the cardiac output being 16.6 +/- 1.6% at the low cardiac output and 16.9 +/- 1.4% at the high cardiac output. It is concluded that redistribution of blood flow towards the edematous lobe does not occur with increases in cardiac output and therefore does not account for the increased intrapulmonary shunt.     

Effect of arachidonic and eicosapentaenoic acids on acute lung injury induced by hypochlorous acid

BACKGROUND: Hypochlorous acid (HOCl) is the main oxidant of activated polymorphonuclear neutrophil granulocytes (PMN) and generated by myeloperoxidase during respiratory burst. This study investigates the effects of HOCl on pulmonary artery pressure (PAP) and vascular permeability and characterises the influence of arachidonic acid (AA) and eicosapentaenoic acid (EPA) on the observed effects. METHODS: HOCl (500, 1,000, 2,000 nmol/min) was continuously infused into the perfusate (Krebs-Henseleit buffer solution, KHB). AA or EPA in subthreshold doses (both 2 nmol/min) or buffer were simultaneously infused using a separate port. PAP, pulmonary venous pressure (PVP), ventilation pressure, and lung weight gain were continuously recorded. The capillary filtration coefficient (Kf,c) was calculated before and 30, 60, and 90 minutes after starting the HOCl infusion. RESULTS: HOCl application resulted in a dose dependent increase in PAP and Kf,c. The onset of these changes was inversely related to the HOCl dose used. The combined infusion of AA with HOCl resulted in a significant additional rise in pressure and oedema formation which forced premature termination of all experiments. The combination of EPA with HOCl did not result in an enhancement of the HOCl induced rise in pressure and oedema formation. CONCLUSIONS: Changes in the pulmonary microvasculature caused by HOCl are differently influenced by omega-6 and omega-3 polyunsaturated free fatty acids, suggesting a link between neutrophil derived oxidative stress and pulmonary eicosanoid metabolism.     

High-dose nitric oxide inhalation increases lung injury after gastric aspiration.

BACKGROUND: Inhaled nitric oxide is often used in patients with adult respiratory distress syndrome. However, nitric oxide also may be significantly toxic, especially if administered concurrently with hyperoxia. The authors evaluated the isolated effect of nitric oxide and the combined effects of nitric oxide and hyperoxia on lung injury in rats after acid aspiration. METHODS: Animals were injured by instillation of 1.2 ml/kg hydrogen chloride in low-pH saline (the acid group) or acidified gastric particles (the casp group) into the lungs under halothane anesthesia via a tracheal catheter. Controls received no injury vehicle but rather underwent the surgical process. After recovery from anesthesia, the animals were exposed to 20% or 90% oxygen with or without 20, 40, or 80 ppm nitric oxide for 5 h. The permeability index, alveolar-arterial oxygen difference, the ratio of oxygen pressure to the inspired fraction of oxygen, and the ratio of wet to dry weight were assessed 5 h after injury as indices of lung injury. Data were assessed using analysis of variance. RESULTS: Each group included 6-10 rats. Exposure to nitric oxide (80 ppm) in air increased protein permeability in the lungs to a permeability index of 1.42+/-0.12 after acid aspiration. The combination of nitric oxide (80 ppm) and hyperoxia further increased protein leakage to a permeability index of 2.1+/-0.25. Exposure to lower concentrations of nitric oxide (e.g., 20 and 40 ppm) increased the permeability index of the lungs (1.44+/-0.21, 1.75+/-0.29, respectively) in the presence of hyperoxia, although it did not affect the permeability index of the lungs during exposure to air. Pretreatment of animals with deferoxamine and methylene blue partially inhibited the adverse effect of hyperoxia and nitric oxide, which suggested a complex underlying mechanism involving both reactive-species generation and pulmonary vasomotor changes. CONCLUSIONS: These results show that inhaled nitric oxide at 80 ppm for a short duration (5 h) increases the severity of the inflammatory microvascular lung injury after acid aspiration. The pulmonary damage is exacerbated further in the presence of high oxygen concentrations. Although lower concentrations of nitric oxide did not increase the extent of lung injury, longer exposure times need to be assessed.     

Systemic perfluorocarbons suppress the acute lung inflammation after gastric acid aspiration in rats

Perflurocarbons (PFCs) are used during liquid ventilation and as hemoglobin substitutes. PFCs reduce free radical generation and damage to the lung during liquid ventilation. Thus, we examined the effects of parenteral administration of PFCs on lung injury after acid aspiration. Rats were treated with intraperitoneal injection of either FC-77 or IV injection of Fluosol. Controls received intraperitoneal or IV normal saline (NS) before or at the time of injury and then were injured by instillation of NS + HCl (pH = 1.25) into their lungs via a tracheotomy. The animals were exposed to air or 98% oxygen, breathing spontaneously. The rats were injected with 0.05 microCi of (125)I-albumin (bovine serum albumin) before injury. The extent of lung injury was assessed 5 h postinjury by compliance and lung albumin permeability index measurement. Myeloperoxidase (MPO) activity and histologic examination were used to assess neutrophilic infiltration. Both FC-77 and Fluosol decreased the permeability index compared with controls (1.05 +/- 0.08; 1.08 +/- 0. 12, respectively, versus 1.34 +/- 0.21) and improved lung compliance after intratracheal instillation of 1.2 mL/kg of HCl/NS, pH = 1.25 + hyperoxia injury (P < 0.05). Lung MPO activity decreased in the FC-77 group and was associated with a concomitant decrease in neutrophil infiltration. MPO activity of the spleen increased after FC-77 treatment. The administration of FC-77 decreased the severity of lung permeability changes associated with acid in the presence or absence of hyperoxia exposure. These data suggest that attenuation of neutrophilic infiltration by PFCs decreases lung injury. IMPLICATIONS: Intraperitoneally administered perfluorocarbons in rats attenuate the neutrophilic infiltration in the lung after acid aspiration, thereby decreasing the alveolar protein leakage and improving pulmonary compliance.     

Basic physiopathological patterns of perfusion and inhalation pulmonary scintigraphy

^113mIn is an excellent radiopharmaceutical for pulmonary scanning. Seven physiopathological patterns are described after the study of the results of successive perfusion and inhalation pulmonary scans—pulmonary artery obstruction, complete bronchial obstruction, partial bronchial obstruction, bronchiolar obstruction, anatomical changes in the pulmonary parenchyma, pathological pulmonary dead space, and intrapulmonary arterio-venous shunting. Pulmonary artery obstruction can be diagnosed early, precisely, and safely by this method. Pathological pulmonary dead space and intrapulmonary shunting have well-defined characteristics; the ability to demonstrate their topography and size in patients with pulmonary emphysema may lead to surgical removal of the affected regions, thus improving overall pulmonary function. The scintigraphic procedures used revealed that bronchial obstruction is associated with absent pulmonary arterial perfusion in the corresponding bronchial territory; this finding is of the utmost importance, as it may permit the diagnosis of bronchial carcinoma before any radiological changes occur.     

High-dose Nitric Oxide Inhalation Increases Lung Injury after Gastric Aspiration

Background: Inhaled nitric oxide is often used in patients with adult respiratory distress syndrome. However, nitric oxide also may be significantly toxic, especially if administered concurrently with hyperoxia. The authors evaluated the isolated effect of nitric oxide and the combined effects of nitric oxide and hyperoxia on lung injury in rats after acid aspiration.

Methods: Animals were injured by instillation of 1.2 ml/kg hydrogen chloride in low-pH saline (the acid group) or acidified gastric particles (the casp group) into the lungs under halothane anesthesia via a tracheal catheter. Controls received no injury vehicle but rather underwent the surgical process. After recovery from anesthesia, the animals were exposed to 20% or 90% oxygen with or without 20, 40, or 80 ppm nitric oxide for 5 h. The permeability index, alveolar-arterial oxygen difference, the ratio of oxygen pressure to the inspired fraction of oxygen, and the ratio of wet to dry weight were assessed 5 h after injury as indices of lung injury. Data were assessed using analysis of variance.

Results: Each group included 6-10 rats. Exposure to nitric oxide (80 ppm) in air increased protein permeability in the lungs to a permeability index of 1.42 +/- 0.12 after acid aspiration. The combination of nitric oxide (80 ppm) and hyperoxia further increased protein leakage to a permeability index of 2.1 +/- 0.25. Exposure to lower concentrations of nitric oxide (e.g., 20 and 40 ppm) increased the permeability index of the lungs (1.44 +/- 0.21, 1.75 +/- 0.29, respectively) in the presence of hyperoxia, although it did not affect the permeability index of the lungs during exposure to air. Pretreatment of animals with deferoxamine and methylene blue partially inhibited the adverse effect of hyperoxia and nitric oxide, which suggested a complex underlying mechanism involving both reactive-species generation and pulmonary vasomotor changes.     

Hemodynamic and oxygenation changes of combined therapy with inhaled nitric oxide and inhaled aerosolized prostacyclin

OBJECTIVE: To evaluate hemodynamic and oxygenation changes of combined therapy with inhaled nitric oxide (iNO) and inhaled aerosolized prostcyclin (IAP) during lung transplantation. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Ten patients scheduled for lung transplantation. INTERVENTIONS: Ten patients, with a mean age of 38 years (range, 24 to 56 years), were scheduled for lung transplantation (2 single-lung transplantations and 8 double-lung transplantations). During first lung implantation with single-lung perfusion and ventilation, hemodynamic and oxygenation data were analyzed in 3 phases: (1) baseline, 5 minutes after pulmonary artery clamping; (2) inhaled NO phase, 15 minutes after inhaled NO administration (20 ppm) in 100% oxygen; and (3) IAP-inhaled NO phase, 15 minutes after combined administration of inhaled NO (20 ppm) and IAP (10 ng/kg/min) in 100% oxygen. MEASUREMENTS AND MAIN RESULTS: During the inhaled NO phase, reductions of mean pulmonary arterial pressure (p < 0.05) and intrapulmonary shunt (p < 0.05) were noted. After the start of prostacyclin inhalation, a further decrease in mean pulmonary arterial pressure (p < 0.05) was observed. PaO2/FIO2 increased during the IAP-inhaled NO phase (p < 0.05), whereas intrapulmonary shunt decreased (p < 0.05). CONCLUSION: This study confirms the action of inhaled NO as a selective pulmonary vasodilator during lung transplantation. Combined therapy with IAP and inhaled NO increases the effects on pulmonary arterial pressure and oxygenation compared with inhaled NO administered alone without any systemic changes.     

Reconditioning of an injured lung graft with intrabronchial surfactant instillation in an ex vivo lung perfusion system followed by transplantation

Background

We tested whether an injured lung graft from category-3 donation after cardiac death donor could be reconditioned with an ex vivo lung perfusion (EVLP) system by intrabronchial diluted surfactant lavage before transplantation.

Methods

In a pig model, cardiac arrest was induced by deconnecting from the ventilator. Left lung injury was done by intrabronchial instillation of 1 mL/kg pepsin + HCl. After retrieval, the heart–lung block was stored at 4°C for 2 h. In the treated group, transplantation was performed after reconditioning with intrabronchial diluted surfactant lavage in EVLP system.

Results

During EVLP, surfactant group showed better oxygenation and lower pulmonary vascular resistance. After transplantation, better oxygenation, lower mean pulmonary artery pressure, and lower lung edema were observed in surfactant group. Lower blood IL-1 beta and IL-6 cytokine levels were measured in the surfactant group. In bronchoalveolar lavage, the percentage of neutrophils, IL-1 beta and IL-6 cytokine levels, amount of protein, and neutrophil infiltration in the lung tissue at the end of the experiment were significantly lower in the surfactant group.

Conclusions

Our data demonstrate the feasibility of reconditioning and transplantation of an acutely damaged lung graft due to aspiration from a category-3 DCD donor. Implementation of an EVLP system is an efficacious tool to recondition and assess a questionable graft before transplantation.     

Aspiration of Blood and Pulmonary Host Defense Mechanisms

The effect of aspiration of blood on pulmonary host defenses was studied in the rat. Sham and experimental rats had 0.2 ml of saline or blood/100 g body weight injected into their tracheas. One or 24 hours after aspiration rats were challenged with aerosolized, radiolabeled ((32)P), S. aureus. Fourteen hours after bacterial challenge, lungs were removed and intrapulmonary bacterial inactivation was quantified. Significant impairment of bacterial inactivation occurred at both 15 and 38 hours after aspiration of blood, but not after saline. The pulmonary consolidation after aspiration of blood was focal in nature. The lung weight increased but fractional water content decreased. Arterial pH, pCO(2), or pO(2) were unaffected by aspiration of blood. The number and viability of macrophages recovered by lavage were similar in control, sham and experimental groups. If similar impairment in pulmonary host defenses occurred in man following aspiration of blood, the patient with aspiration of blood would have an increased susceptibility to bacterial infection.     

Triolein increases microvascular permeability in isolated perfused rabbit lungs: role of neutrophils

BACKGROUND: Pathophysiologic mechanisms of the fat embolism syndrome are poorly understood. Neutrophils are thought to play a role in the development of many forms of acute lung injury. The objective of this study was to examine the role of intrapulmonary neutrophils in lung injury resulting from fat infusion. METHODS: Triolein (0.08 mL/kg) was infused into isolated rabbit lungs perfused with Krebs-Henseleit buffer. Pulmonary arterial pressure was monitored, and pulmonary vascular resistance and microvascular permeability (Kf) were measured at baseline and 60 minutes after triolein infusion. RESULTS: Triolein produced increases in pulmonary arterial pressure, pulmonary vascular resistance, and Kf. Neutrophil depletion or inhibition of neutrophil elastase prevented the increase in Kf after triolein, and catalase partially blocked this Kf increase. CONCLUSION: These results suggest that activated intrapulmonary neutrophils play a major role in developing triolein-induced lung injury, intrapulmonary neutrophils act chiefly via neutrophil elastase release, and reactive oxygen species are involved in the lung injury.