Effect of changing vascular volume on measurement of protein reflection coefficient in ischemic lungs.

In ischemic organs, the protein reflection coefficient (sigma) can be estimated by measuring blood hematocrit (Hct) and protein after increasing static vascular pressure (P(v)). Our original equation for sigma (J Appl Physiol 73: 2616-2622, 1992) assumed a constant vascular volume during convective fluid flux (). In this study, we 1) quantified the rate of vascular volume change (dV/dt) still present in ischemic single ferret lungs after 20 min of P(v) = 30 Torr and 2) developed an equation for sigma that allowed a finite dV/dt. In 25 lungs, we estimated the dV/dt after 20 min at P(v) = 30 Torr by subtracting from the rate of lung weight gain (W(L)). The relationship between (0.15 +/- 0.02 ml/min) and W(L) (0.24 +/- 0.02 g/min) was significant (R = 0.66, P < 0.001), but the slope was <1 (0.41 +/- 0.10, P < 0.05). dV/dt (0.10 +/- 0.02 ml/min) was similar in magnitude to at 20 min. The modified equation for sigma revealed that a finite dV/dt caused the original sigma measurement to underestimate true sigma. A low sigma, high, high baseline Hct, and long filtration time enhanced the error. The error was small, however, and could be minimized by adjusting experimental parameters.

Effect of time and vascular pressure on permeability and cyclic nucleotides in ischemic lungs.

We previously found that increased intravascular pressure decreased ischemic lung injury by a nitric oxide (NO)-dependent mechanism (Becker PM, Buchanan W, and Sylvester JT. J Appl Physiol 84: 803-808, 1998). To determine the role of cyclic nucleotides in this response, we measured the reflection coefficient for albumin (sigma(alb)), fluid flux (), cGMP, and cAMP in ferret lungs subjected to either 45 min ("short"; n = 7) or 180 min ("long") of ventilated ischemia. Long ischemic lungs had "low" (1-2 mmHg, n = 8) or "high" (7-8 mmHg, n = 6) vascular pressure. Other long low lungs were treated with the NO donor (Z)-1-[N-(3-ammoniopropyl)-N-(n-propyl)amino]diazen-1-ium -1, 2-diolate (PAPA-NONOate; 5 x 10(-4) M, n = 6) or 8-bromo-cGMP (5 x 10(-4) M, n = 6). Compared with short ischemia, long low ischemia decreased sigma(alb) (0.23 +/- 0.04 vs. 0.73 +/- 0.08; P < 0.05) and increased (1.93 +/- 0.26 vs. 0.58 +/- 0.22 ml. min(-1). 100 g(-1); P < 0.05). High pressure prevented these changes. Lung cGMP decreased by 66% in long compared with short ischemia. Lung cAMP did not change. PAPA-NONOate and 8-bromo-cGMP increased lung cGMP, but only 8-bromo-cGMP decreased permeability. These results suggest that ischemic vascular injury was, in part, mediated by a decrease in cGMP. Increased vascular pressure prevented injury by a cGMP-independent mechanism that could not be mimicked by administration of exogenous NO.

Effect of the NADPH oxidase inhibitor apocynin on ischemia-reperfusion lung injury.

Apocynin (4-hydroxy-3-methoxy-acetophenone) inhibits NADPH oxidase in activated polymorphonuclear (PMN) leukocytes, preventing the generation of reactive oxygen species. To determine if apocynin attenuates ischemia-reperfusion lung injury, we examined the effects of apocynin (0.03, 0.3, and 3 mM) in isolated in situ sheep lungs. In diluent-treated lungs, reperfusion with blood (180 min) after 30 min of ischemia (ventilation 28% O(2), 5% CO(2)) caused leukocyte sequestration in the lung and increased vascular permeability [reflection coefficient for albumin (sigma(alb)) 0.47 +/- 0.10, filtration coefficient (K(f)) 0.14 +/- 0.03 g. min(-1). mmHg(-1). 100 g(-1)] compared with nonreperfused lungs (sigma(alb) 0.77 +/- 0. 03, K(f) 0.03 +/- 0.01 g. min(-1). mmHg(-1). 100 g(-1); P < 0.05). Apocynin attenuated the increased protein permeability at 0.3 and 3 mM (sigma(alb) 0.69 +/- 0.05 and 0.91 +/- 0.03, respectively, P < 0. 05); K(f) was decreased by 3 mM apocynin (0.05 +/- 0.01 g. min(-1). mmHg(-1). 100 g(-1), P < 0.05). Diphenyleneiodonium (DPI, 5 microM), a structurally unrelated inhibitor of NADPH oxidase, worsened injury (K(f) 0.32 +/- 0.07 g. min(-1). mmHg(-1). 100 g(-1), P < 0.05). Neither apocynin nor DPI affected leukocyte sequestration. Apocynin and DPI inhibited whole blood chemiluminescence and isolated PMN leukocyte-induced resazurin reduction, confirming NADPH oxidase inhibition. Apocynin inhibited pulmonary artery hypertension and perfusate concentrations of cyclooxygenase metabolites, including thromboxane B(2). The cyclooxygenase inhibitor indomethacin had no effect on the increased vascular permeability, suggesting that cyclooxygenase inhibition was not the explanation for the apocynin results. Apocynin prevented ischemia-reperfusion lung injury, but the mechanism of protection remains unclear.

Effect of ventilation on vascular permeability and cyclic nucleotide concentrations in ischemic sheep lungs.

Ventilation during ischemia attenuates ischemia-reperfusion lung injury, but the mechanism is unknown. Increasing tissue cyclic nucleotide levels has been shown to attenuate lung ischemia-reperfusion injury. We hypothesized that ventilation prevented increased pulmonary vascular permeability during ischemia by increasing lung cyclic nucleotide concentrations. To test this hypothesis, we measured vascular permeability and cGMP and cAMP concentrations in ischemic (75 min) sheep lungs that were ventilated (12 ml/kg tidal volume) or statically inflated with the same positive end-expiratory pressure (5 Torr). The reflection coefficient for albumin (sigmaalb) was 0.54 +/- 0.07 and 0.74 +/- 0. 02 (SE) in nonventilated and ventilated lungs, respectively (n = 5, P < 0.05). Filtration coefficients and capillary blood gas tensions were not different. The effect of ventilation was not mediated by cyclic compression of alveolar capillaries, because negative-pressure ventilation (n = 4) also was protective (sigmaalb = 0.78 +/- 0.09). The final cGMP concentration was less in nonventilated than in ventilated lungs (0.02 +/- 0.02 and 0.49 +/- 0. 18 nmol/g blood-free dry wt, respectively, n = 5, P < 0.05). cAMP concentrations were not different between groups or over time. Sodium nitroprusside increased cGMP (1.97 +/- 0.35 nmol/g blood-free dry wt) and sigmaalb (0.81 +/- 0.09) in nonventilated lungs (n = 5, P < 0.05). Isoproterenol increased cAMP in nonventilated lungs (n = 4, P < 0.05) but had no effect on sigmaalb. The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester had no effect on lung cGMP (n = 9) or sigmaalb (n = 16) in ventilated lungs but did increase pulmonary vascular resistance threefold (P < 0.05) in perfused sheep lungs (n = 3). These results suggest that ventilation during ischemia prevented an increase in pulmonary vascular protein permeability, possibly through maintenance of lung cGMP by a nitric oxide-independent mechanism.

Microsphere-induced bronchial artery vasodilation: role of adenosine, prostacyclin, and nitric oxide.

We previously found that injection of 15-micron microspheres into the bronchial artery of sheep decreased bronchial artery resistance. This effect was inhibited partially by indomethacin or 8-phenyltheophylline, suggesting that microspheres caused release of a dilating prostaglandin and adenosine. To identify the prostaglandin and confirm adenosine release, we perfused the bronchial artery in anesthetized sheep. In 12 sheep, bronchial artery blood samples were obtained before and after the infusion of 1 x 10(6) microspheres or microsphere diluent into the bronchial artery. Microspheres, but not diluent, decreased bronchial artery resistance by 40% and increased bronchial artery plasma 6-ketoprostaglandin F1 alpha (194.7 +/- 45.0 to 496.5 +/- 101.3 pg/ml), the stable metabolite of prostacyclin, and prostaglandin (PG) F2 alpha (28.1 +/- 4.4 to 46.2 +/- 9.7 pg/ml). There were no changes in PGD2, PGE2, thromboxane B2, adenosine, inosine, or hypoxanthine. Pretreatment with dipyridamole, an adenosine uptake inhibitor, did not affect bronchial artery nucleoside concentrations (n = 7). Microsphere-induced vasodilation was not enhanced by dipyridamole (n = 9) and was not inhibited by either the adenosine receptor antagonist xanthine amine congener (n = 4) or the nitric oxide (NO) synthase inhibitor NG-monomethyl-L-arginine (n = 8). These results do not support a role for either adenosine or NO and suggest that microspheres caused bronchial artery vasodilation through release of prostacylin and an unidentified vasodilator.

Vascular injury in isolated sheep lungs. Role of ischemia, extracorporeal perfusion, and oxygen.

Extracorporeal perfusion of isolated sheep lungs with blood after 30 min of ischemia caused injury manifested by polymorphonuclear (PMN) leukocyte sequestration, pulmonary hypertension, thromboxane release, and increased pulmonary vascular permeability. To determine the roles of ischemia, extracorporeal perfusion, and oxygen in this injury, lungs ventilated with 28% O2-5% CO2 and subjected to 30 min of ischemia followed by 180 min of perfusion (ischemic-perfused, n = 23) were compared with lungs subjected to (1) ischemia without perfusion (ischemic, n = 7), (2) perfusion without ischemia (perfused, n = 20), or (3) both ischemia and perfusion during ventilation with 95% N2 (anoxic ischemic-perfused, n = 15). Compared with ischemic-perfused lungs, ischemic lungs had an increased reflection coefficient for albumin (sigma alb, 0.82 +/- 0.03 versus 0.54 +/- 0.05) and decreased filtration coefficient (Kf, 0.05 +/- 0.01 versus 0.11 +/- 0.03 g.min-1.mm Hg-1.100 g-1). Perfused lungs had increased pulmonary hypertension, lung PMN leukocytes, and sigma alb (0.74 +/- 0.05); Kf was not different. Anoxic ischemic-perfused lungs had decreased pulmonary hypertension and thromboxane release, but sigma alb and Kf were not altered. These results suggest that extracorporeal perfusion caused PMN leukocyte sequestration, thromboxane release, and pulmonary hypertension, whereas ischemia caused derecruitment of vascular surface area. Injury required both ischemia and perfusion, but it was not decreased by anoxia, suggesting that oxygen radicals were not involved.

Three-dimensional structure of the bronchial microcirculation in sheep.

BACKGROUND: The bronchial circulation affects both pulmonary vascular and airway activity. Fundamental to understanding the role of the bronchial microcirculation in health and disease is understanding its anatomy. This study sought to identify specific structural elements that might contribute to the drop that occurs between the systemic blood pressure of the bronchial artery and the low pressure of the pulmonary bed into which the bronchial circulation flows and to better describe the connections of the bronchial and pulmonary circulations. METHODS: To do this, the lungs of five sheep were cast by injecting a resin through bronchial and pulmonary arteries. After taking samples for light microscopy, the tissue was digested and the casts were viewed with a scanning electron microscope. RESULTS: Casts of extrapulmonary bronchial arteries were structurally similar to other systemic arteries. Tortuous ones spiraled around bronchi and large blood vessels. Intrapulmonary bronchial arteries, about 100-300 microns in diameter, had sharp branching and deep focal constrictions with great rugosity that completely shut off the flow of the resin. These vessels correspond to the Sperrarterien described by von Hayek (and could cause the resistance associated with the pressure drop). Vasa vasorum ran in the walls of intrapulmonary pulmonary arteries for a variable distance before they entered the lumens of the pulmonary arteries. The smallest blood vessel found that was supplied with vasa vasorum was a bronchial artery 42 microns in diameter. Capillary-like networks with large luminal diameters were found on the pleural surface. CONCLUSIONS: Scanning electron microscopy of microvascular casts provides a fresh description of the bronchial circulation, further delineates the communications of these two circulations, and may structurally account for some pressure drop between the bronchial and pulmonary circulations.

Polystyrene microspheres decrease bronchial artery resistance in anesthetized sheep.

The use of microspheres to measure tissue blood flow requires that the microspheres themselves do not alter regional arterial tone. To determine whether microspheres affected bronchial artery resistance, we cannulated and perfused the bronchial artery in anesthetized sheep. In seven sheep, the change in bronchial artery pressure at constant flow was recorded during infusion of 5 doses (1 x 10(5), 2 x 10(5), 5 x 10(5), 1 x 10(6), and 1.5 x 10(6)) of 15-microns microspheres. Microspheres produced a dose-dependent, self-limited decrease in bronchial artery pressure (1.5 x 10(6) microspheres decreased bronchial artery pressure by 36% for 31 min). This was a decrease in bronchial artery resistance, as evidenced by a shift in the slope, but not the intercept, of a pressure-flow curve (n = 4 sheep). Left atrial injection of 1 x 10(7) microspheres decreased bronchial artery resistance by 17% in six sheep with intact bronchial arteries in which flow was measured by ultrasound probe. The adenosine-receptor antagonist 8-phenyltheophylline attenuated the fall in resistance by 79% (n = 4 sheep). Cyclooxygenase inhibition by indomethacin attenuated the response by 37% (n = 4 sheep). These results suggest that microspheres caused the release of adenosine and a vasodilator prostaglandin. Repetitive measurements of bronchial blood flow by microspheres could overestimate true bronchial blood flow if the interval between measurements is < 30 min.

Role of the bronchial circulation in ischemia-reperfusion lung injury.

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

Effects of oxygen tension and glucose concentration on ischemic injury in ventilated ferret lungs.

In the ventilated ischemic lung, oxygen tension will increase at a time when glucose depletion may impair antioxidant defenses, thereby predisposing the lung to injury mediated by oxygen radicals. In the unventilated ischemic lung, however, glucose depletion in the setting of low oxygen tension may decrease production of ATP, leading to injury by a different mechanism. In this study, we evaluated the role of both oxygen tension and glucose concentration on ischemic injury in isolated ferret lungs. Injury, defined as an increase in vascular permeability, was assessed by measurement of filtration coefficient (Kf) and osmotic reflection coefficient for albumin (sigma alb) after 3 h of normothermic (37 degrees C) ischemia without reperfusion. Lungs were ventilated with either 95% O2-5% CO2 or 0% O2-5% CO2. The vasculature was flushed with physiological salt solution containing either 15 mM glucose (hyperoxia-glucose, anoxia-glucose), 15 mM sucrose (hyperoxia-sucrose, anoxia-sucrose), or no substrate (hyperoxia-no substrate, anoxia-no substrate) (n = 6 for each condition). Kf and sigma alb in hyperoxia-no substrate group did not differ from values in minimally ischemic normoxic normoglycemic ferret lungs. Without glucose, ischemic injury was worse in anoxic than in hyperoxic lungs. With glucose, ischemic injury was worse in hyperoxic than in anoxic lungs. Glucose exacerbated injury in hyperoxic, but not anoxic, lungs. These results indicate that ischemic injury in these lungs depended on both oxygen tension and glucose concentration and suggest that both oxygen radical generation and ATP depletion during ischemia may contribute to the development of this injury.

Edema clearance in isolated sheep lungs.

Edema may be cleared from the lung by lymphatic drainage, transudation across the visceral pleural, vascular reabsorption, and movement into the mediastinum. To determine the quantity and mechanisms of edema clearance associated with spontaneous edema formation in isolated sheep lungs, we perfused six lungs for 180 min with blood (100 ml.kg-1.min-1) at subatmospheric left atrial pressure (Pla) from a weighed reservoir. In six other lungs, Pla was increased to 20 mmHg at 30-75 min to further augment edema. Fluid drainage from the lung was fractionated into blood and water components by serial measurements of drainage and perfusate hematocrit. Changes in weight of circulating intravascular blood and extravascular lung water (EVLW) were also directly measured by dye dilution and standard gravimetric techniques, respectively. From these measurements, we calculated that 3.04 +/- 0.53 g/g blood-free dry lung of water filtered into the extravascular space during perfusion. Of this amount, 42% was reabsorbed into the pulmonary vasculature; 18% drained from the lung via lymphatics, visceral pleura, and mediastinum; and 40% was retained in the lung. Compared with low Pla lungs, transient elevation of Pla increased lung hemorrhage and the final change in reservoir weight, but the quantity and clearance of cumulative filtered water and the final values of EVLW and wet-to-dry weight ratio (WW/DW) were not altered. These results suggest that 1) significant edema clearance occurred in isolated sheep lungs, primarily by vascular reabsorption, and 2) measurements of EVLW and WW/DW under-estimated injury in the presence of lung hemorrhage and significant edema clearance.

Separate effects of ischemia and reperfusion on vascular permeability in ventilated ferret lungs.

In systemic organs, ischemia-reperfusion injury is thought to occur during reperfusion, when oxygen is reintroduced to hypoxic ischemic tissue. In contrast, the ventilated lung may be more susceptible to injury during ischemia, before reperfusion, because oxygen tension will be high during ischemia and decrease with reperfusion. To evaluate this possibility, we compared the effects of hyperoxic ischemia alone and hyperoxic ischemia with normoxic reperfusion on vascular permeability in isolated ferret lungs. Permeability was estimated by measurement of filtration coefficient (Kf) and osmotic reflection coefficient for albumin (sigma alb), using methods that did not require reperfusion to make these measurements. Kf and sigma alb in control lungs (n = 5), which were ventilated with 14% O2-5% CO2 after minimal (15 +/- 1 min) ischemia, averaged 0.033 +/- 0.004 g.min-1.mmHg-1.100 g-1 and 0.69 +/- 0.07, respectively. These values did not differ from those reported in normal in vivo lungs of other species. The effects of short (54 +/- 9 min, n = 10) and long (180 min, n = 7) ischemia were evaluated in lungs ventilated with 95% O2-5% CO2. Kf and sigma alb did not change after short ischemia (Kf = 0.051 +/- 0.006 g.min-1.mmHg-1.100 g-1, sigma alb = 0.69 +/- 0.07) but increased significantly after long ischemia (Kf = 0.233 +/- 0.049 g.min-1 x mmHg-1 x 100 g-1, sigma alb = 0.36 +/- 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Spontaneous injury in isolated sheep lungs: role of resident polymorphonuclear leukocytes.

Perfusion of isolated sheep lungs with homologous blood caused pulmonary hypertension and edema that was not altered by depletion of perfusate polymorphonuclear (PMN) leukocytes (D. B. Pearse et al., J. Appl. Physiol. 66: 1287-1296, 1989). The purpose of this study was to evaluate the role of resident PMN leukocytes in this injury. First, we quantified the content and activation of lung PMN leukocytes before and during perfusion of eight isolated sheep lungs with a constant flow (100 ml.kg-1.min-1) of homologous blood. From measurements of myeloperoxidase (MPO) activity, we estimated that the lungs contained 1.2 x 10(10) PMN leukocytes, which explained why the lung PMN leukocyte content, measured by MPO activity and histological techniques, did not increase significantly with perfusion, despite complete sequestration of 2.0 x 10(9) PMN leukocytes from the perfusate. MPO activities in perfusate and lymph supernatants did not increase during perfusion, suggesting that lung PMN leukocytes were not activated. Second, we perfused lungs from 6 mechlorethamine-treated and 6 hydroxyurea-treated sheep with homologous leukopenic blood and compared them with 11 normal lungs perfused similarly. Despite marked reductions in lung PMN leukocyte concentration, there were no differences in pulmonary arterial pressure, lymph flow, or reservoir weight between groups. Extravascular lung water was greater in both groups of leukopenic lungs. These results suggest that resident PMN leukocytes did not contribute to lung injury in this model.

Energy state and vasomotor tone in hypoxic pig lungs.

To evaluate the role of energy state in pulmonary vascular responses to hypoxia, we exposed isolated pig lungs to decreases in inspired PO2 or increases in perfusate NaCN concentration. Lung energy state was assessed by 31P nuclear magnetic resonance spectroscopy or measurement of adenine nucleotides by high-pressure liquid chromatography in freeze-clamped biopsies. In ventilated lungs, inspired PO2 of 200 (normoxia), 50 (hypoxia), and 0 Torr (anoxia) did not change adenine nucleotides but resulted in steady-state pulmonary arterial pressure (Ppa) values of 15.5 +/- 1.4, 30.3 +/- 1.8, and 17.2 +/- 1.9 mmHg, respectively, indicating vasoconstriction during hypoxia and reversal of vasoconstriction during anoxia. In degassed lungs, similar changes in Ppa were observed; however, energy state deteriorated during anoxia. An increase in perfusate NaCN concentration from 0 to 0.1 mM progressively increased Ppa and did not alter adenine nucleotides, whereas 1 mM reversed this vasoconstriction and caused deterioration of energy state. These results suggest that 1) pulmonary vasoconstrictor responses to hypoxia or cyanide occurred independently of whole lung energy state, 2) the inability of the pulmonary vasculature to sustain hypoxic vasoconstriction during anoxia might be associated with decreased energy state in some lung compartment, and 3) atelectasis was detrimental to whole lung energy state.

Spontaneous injury in isolated sheep lungs: role of perfusate leukocytes and platelets.

Perfusion of isolated sheep lungs with blood causes spontaneous edema and hypertension preceded by decreases in perfusate concentrations of leukocytes (WBC) and platelets (PLT). To determine whether these decreases were caused by pulmonary sequestration, we continuously measured blood flow and collected pulmonary arterial and left atrial blood for cell concentration measurements in six lungs early in perfusion. Significant sequestration occurred in the lung, but not in the extracorporeal circuit. To determine the contribution of these cells to spontaneous injury in this model, lungs perfused in situ with a constant flow (100 ml.kg-1.min-1) of homologous leukopenic (WBC = 540 mm-3, n = 8) or thrombocytopenic blood (PLT = 10,000 mm-3, n = 6) were compared with control lungs perfused with untreated homologous blood (WBC = 5,320, PLT = 422,000, n = 8). Perfusion of control lungs caused a rapid fall in WBC and PLT followed by transient increases in pulmonary arterial pressure, lung lymph flow, and perfusate concentrations of 6-ketoprostaglandin F1 alpha and thromboxane B2. The negative value of reservoir weight (delta W) was measured as an index of fluid entry into the lung extravascular space during perfusion. delta W increased rapidly for 60 min and then more gradually to 242 g at 180 min. This was accompanied by a rise in the lymph-to-plasma oncotic pressure ratio (pi L/pi P). Relative to control, leukopenic perfusion decreased the ratio of wet weight to dry weight, the intra- plus extravascular blood weight, and the incidence of bloody lymph. Thrombocytopenic perfusion increased lung lymph flow and the rate of delta W, decreased pi L/pi P and perfusate thromboxane B2, and delayed the peak pulmonary arterial pressure. These results suggest that perfusate leukocytes sequestered in the lung and contributed to hemorrhage but were not necessary for hypertension and edema. Platelets were an important source of thromboxane but protected against edema by an unknown mechanism.

Reperfusion pulmonary edema after thrombolytic therapy of massive pulmonary embolism.

We report here the occurrence of acute focal pulmonary edema after thrombolytic therapy for massive pulmonary embolism. Symptomatic pulmonary edema developed in a 75-yr-old man after streptokinase infusion for a massive pulmonary embolism. Repeat radiographic studies demonstrated that the edema occurred in an area of early reperfusion. Right heart catheterization showed pulmonary hypertension, and there was no clinical evidence of left ventricular failure. The edema spontaneously resolved during a second course of thrombolytic therapy that successfully lysed the remaining thrombus. We conclude that reperfusion pulmonary edema is a potential, albeit rare, complication of thrombolytic therapy for pulmonary embolism.

31P NMR spectroscopy of isolated perfused lungs.

31P NMR spectra of isolated blood-perfused pig lungs were obtained by degassing the lungs in vivo to remove field inhomogeneities caused by air-tissue interfaces. The spectra show the presence of ATP, phosphodiester, inorganic phosphate, and phosphomonoester, but no phosphocreatine. All the metabolites remained stable for more than 4 h when the lungs were perfused with oxygenated blood. Blood gas tensions, glucose concentration, pH, and temperature were controlled throughout the experiment. During anoxia or ischemia, ATP and intracellular pH declined and Pi increased but returned to control levels during subsequent normoxia or reperfusion. These results demonstrate the applicability of NMR spectroscopy to isolated perfused lungs, enabling studies of metabolic processes in normal and pathologic lungs, as well as establishment of optimal conditions for lung preservation for transplantation.