Pulmonary Artery Perfusion Research Articles

Airway smooth muscle shortening in excised canine lung lobes

To estimate the importance of lung parenchymal airway interdependence in attenuating airway narrowing, airway smooth muscle shortening in response to nebulized carbachol was measured in excised canine lung lobes and compared with the calculated load applied by lung elastic recoil. Pulmonary resistance of matched right and left upper lobes of five dogs was measured in a pressure-compensated volume plethysmograph by forced oscillation (6 Hz) before and after administration of an aerosol of carbachol (250 mg/ml) or saline. Matched lobes were studied at transpulmonary pressures (PL) of 5, 7, 10, 12, and 15 cmH2O. The lungs were then fixed at that PL by pulmonary arterial perfusion with formaldehyde, and cross sections of multiple airways from each lobe (n = 275) were examined by use of morphometric techniques to measure luminal area and smooth muscle length. By use of the saline lobe as a control, percentage of muscle shortening and decrease in airway lumen area caused by carbachol could be calculated. Passive and active smooth muscle stresses in each airway were calculated from PL and the calculated change in peribronchial pressure for a given change in airway diameter. The increase in pulmonary resistance and average smooth muscle shortening after administration of carbachol was greater in lobes held at lower PL. There was marked variation in narrowing between airways within a lobe: smooth muscle shortening ranged between 0 and 65% but averaged < 45% at all levels of PL.(ABSTRACT TRUNCATED AT 250 WORDS)

Central pulmonary thromboembolism: diagnosis with spiral volumetric CT with the single-breath-hold technique--comparison with pulmonary angiography.

Forty-two patients were prospectively evaluated with spiral volumetric computed tomography (CT) and selective pulmonary angiography of each lung to detect central pulmonary thromboembolism. Spiral volumetric CT images obtained with either 90 mL of 30% contrast material or 120 mL of 12% contrast material were graded as excellent or good in 98% of the examinations (41 patients). Diagnosis of pulmonary embolism with spiral volumetric CT was based on the direct visualization of intraluminal clots: partial filling defects (n = 41; 37%), complete filling defects (n = 51; 46%), "railway track" signs (n = 6; 5%), and mural defects (n = 14; 12%). All 23 patients with normal findings of spiral volumetric CT had normal findings of pulmonary angiography. With spiral volumetric CT, the finding of 112 central emboli (eight main, 28 lobar, and 76 segmental) corresponded exactly to the angiographic findings, but nine intersegmental lymph nodes were erroneously interpreted as filling defects. In one case of normal pulmonary angiographic findings, asymmetry in pulmonary arterial perfusion was misinterpreted as pulmonary embolism with spiral volumetric CT. Spiral volumetric CT can reliably depict thromboemboli in second- to fourth-division pulmonary vessels.

Pulmonary vasodilation by inhaled nitric oxide after endothelial injury.

Inhaled nitric oxide gas (NO) has recently been shown to reverse experimentally induced pulmonary vasoconstriction. To examine the effect of free radical injury and methylene blue exposure on inhaled NO-induced pulmonary vasodilation we studied ventilated rabbit lungs perfused with Krebs solution containing 3% dextran and indomethacin. When NO gas (120 ppm) was added to the inhaled mixture for 3 min, the elevated pulmonary arterial perfusion pressure (Ppa) induced by the thromboxane analogue U-46619 was significantly reduced [8 +/- 2 (SE) mmHg]. Acetylcholine similarly reduced Ppa (9 +/- 1 mmHg). After free radical injury and methylene blue exposure, inhaled NO again produced significant vasodilation (5 +/- 1 and 9 +/- 2 mmHg, respectively), but acetylcholine resulted in an increase in Ppa (-9 +/- 3 and -4 +/- 1 mmHg, respectively). These data demonstrate that pulmonary vasodilation produced by inhaled NO is unaffected by free radical injury or methylene blue in the intact lung despite concomitant reversal of acetylcholine-induced vasodilation.

Pulmonary circulatory dysfunction in rats with biliary cirrhosis. An animal model of the hepatopulmonary syndrome.

We studied hypoxic pulmonary vasoconstriction (HPV) and pulmonary gas exchange in unanesthetized rats with biliary cirrhosis induced by chronic bile duct ligation (BDL) (5 to 6 wk) and compared pulmonary vascular reactivity in perfused lungs isolated from BDL and control rats. Awake, catheter-implanted, cirrhotic rats exhibited increased cardiac output, normal systemic and pulmonary arterial pressures, and decreased total systemic (TSR) and pulmonary (TPR) vascular resistances in comparison with those in sham-operated control rats. HPV was markedly depressed in cirrhotic rats (percent increase in TPR while breathing 8% O2: 42.3 +/- 13.7% in control and 0.9 +/- 3.6% in cirrhotic rats, p less than 0.05), and this was associated with an increased AaPO2 (control rats, 15.7 +/- 1.1 mm Hg; cirrhotic rats, 23.1 +/- 1.9 mm Hg; p less than 0.05). In contrast, the pulmonary pressor response to angiotensin II was intact, and the depression of HPV in cirrhotic rats was ameliorated after angiotensin II infusion. These changes in cirrhotic rats were not due to the accompanying cholestasis since noncirrhotic rats with severe cholestasis had intact HPV and normal AaPO2. Lungs isolated from cirrhotic rats and perfused with blood from normal rats exhibited two patterns of response to hypoxia. In one group, HPV was blunted compared with that in control rats (change in pulmonary arterial perfusion pressure after 3% O2: control rats, 23.2 +/- 2.8 mm Hg; cirrhotic rats, 4.8 +/- 1.4 mm Hg; p less than 0.01). Similar to the result in intact rat, angiotensin-II-induced vasoconstriction was preserved in lungs from cirrhotic rats, and HPV increased significantly after angiotensin II infusion (to 17.3 +/- 4.8 mm Hg). In the second group, baseline pulmonary arterial pressure progressively increased during normoxia, and this increase was attenuated by hypoxic ventilation (hypoxic vasodilation).(ABSTRACT TRUNCATED AT 250 WORDS)

Paraquat-induced lung injury: prevention by N-tert-butyl-alpha-phenylnitrone, a free-radical spin-trapping agent.

The herbicide paraquat causes lung injury that is believed to be oxygen-radical mediated. To further characterize this injury and explore new methods of preventing it, we used the spin-trapping agent N-tert-butyl-alpha-phenylnitrone (PBN) to identify the paraquat radical in lung tissue and to reduce the injury resulting from the subsequent generation of reactive oxygen species. The formation of a paraquat free radical by guinea pig lung was detected under anaerobic conditions by electron paramagnetic resonance spectrometry. Infused (25, 50, or 100 mg/kg) into guinea pig lungs (perfused at constant flow with Krebs solution containing 4% bovine serum albumin and ventilated with 95% O2-5% CO2), paraquat produced dose-dependent increases in peak airway pressure (Paw), mean pulmonary arterial perfusion pressure (Ppa), and wet-to-dry (W/D) lung weight ratio. At 100 mg/kg, paraquat increased Paw by 589.6 +/- 59.8% (mean +/- SE, n = 8) and W/D ratio from 5.33 +/- 0.07 to 6.29 +/- 0.11 (P less than 0.001). Pulmonary vascular leak index increased from 0.40 +/- 0.09 to 1.96 +/- 0.45 (P less than 0.02), without changes in pulmonary microvascular pressure. Perfusate concentrations of thromboxane B2 and 6-ketoprostaglandin F1 alpha increased, but indomethacin did not reduce the injury. PBN (2.3 mM) markedly attenuated all evidence of lung injury, which was also reduced by catalase, mannitol, ethanol, and vitamin E.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical and experimental studies on the mechanism of abnormal accumulation in lung scanning with 123I-IMP

To investigate the intrapulmonary kinetics of N-isopropyl-p-I-123-iodoamphetamine (123I-IMP), lung scanning with 123I-IMP was performed in patients with various lung disorders. Compared with the normal lung field, abnormal accumulation of 123I-IMP was detected in all patients in delayed imaging performed 24 h after 123I-IMP injection. These sites were within areas of absent or reduced perfusion observed by pulmonary perfusion scanning using 99Tcm-macroaggregated albumin (99Tcm-MAA). A similar phenomenon was seen in additional experiments in rabbits with regional pulmonary arterial hypoperfusion resulting from a balloon catheter-induced bronchial occlusion. 123I-IMP accumulation in areas where 99Tcm-MAA images are absent or decreased may be explained by the ability of 123I-IMP to penetrate significantly narrowed microvascular beds with reduced perfusion. Our clinical and experimental results indicate that pulmonary arterial perfusion, particularly hypoperfusion, influence the pulmonary kinetics of 123I-IMP. This compound is a potentially useful non-particulate agent for the assessment of pulmonary arterial perfusion.

Comparison of the University of Wisconsin preservation solution and other crystalloid perfusates in a 30-hour rabbit lung preservation model

The University of Wisconsin solution, which contains a high potassium concentration (120 mmol/L), was evaluated for rabbit lung preservation by comparing it with a modified University of Wisconsin solution with low potassium (4 mmol/L), a low-potassium dextran solution (4 mmol/L), and simple surface cooling. In the first three groups rabbit lungs were flushed in situ with the solution (n = 5 in each group); then the lung-heart block was harvested and stored at 10 degrees C for 30 hours. In the surface cooling group the lungs were harvested without flushing and then simply immersed in saline and stored. For assessment, the stored lung was ventilated with room air and perfused with fresh venous blood at a rate of 40 ml/min for 10 minutes. Assessment of lung function included gas analysis of effluent blood, mean pulmonary artery perfusion pressure, and peak airway pressure. Among these parameters, oxygen tension was most sensitive. Oxygen tension at 10 minutes' perfusion in the modified University of Wisconsin (95 +/- 6 mm Hg) and low-potassium dextran (99 +/- 4 mm Hg) groups was significantly higher than that in the surface cooling (61 +/- 7 mm Hg) and University of Wisconsin (51 +/- 7 mm Hg) groups. There was no difference between the modified University of Wisconsin and low-potassium dextran groups or between the surface cooling and University of Wisconsin groups. We conclude that the low-potassium University of Wisconsin solution is superior to the high-potassium University of Wisconsin solution and that the lactobionate and raffinose included in the University of Wisconsin solution as impermeants do not improve lung preservation in this model.

Phorbol myristate acetate-induced lung injury: involvement of reactive oxygen species.

Using lucigenin-enhanced chemiluminescence, isolated rat lungs perfused with physiological salt-Ficoll solution were studied to test whether phorbol myristate acetate (PMA)-induced lung injury was mediated by reactive oxygen species (ROS). PMA (0.03 micrograms ml-1) caused small but significant increases in lung ROS levels and pulmonary arterial perfusion pressure (Ppa) but did not induce lung oedema. PMA (0.15 micrograms ml-1) induced lung oedema with large increases in ROS production and Ppa. Superoxide dismutase (SOD) inhibited the increases in ROS, Ppa, and lung oedema. Catalase and dimethylthiourea inhibited lung oedema but did not attenuate the increases in ROS and Ppa entirely. Indomethacin attenuated lung oedema partially but did not inhibit the increases in ROS and Ppa. These data indicate that PMA-induced lung injury is dependent on PMA concentration and ROS are responsible for such lung injury. Thromboxane plays a minor role for PMA-induced lung injury. The different effects of oxygen radical scavengers suggest that different radical species contribute to the increased pulmonary vascular response and lung injury.

Long-term Results after Right Ventricular Outflow Tract Reconstruction with Porcine and Allograft Conduits

From 1975 to 1989, a total of 353 patients were operated for complex cardiac malformations with impaired pulmonary artery perfusion using 53 non-valved and 300 valved right heart to pulmonary artery conduits. In 108 patients a porcine conduit (Hancock or Carpentier-Edwards) 12-30 mm was used; the age range was 14 days to 37 years (mean 4.3 years) and body weight 2.9-68 kg (mean 15.3 kg). One hundred and ninety-two patients had an allograft of 9-29 mm implanted at the age of 17 days to 26 years (mean 3.8 years), body weight 2.7-73 kg (mean 14.2 kg). So far, 32 of the porcine valved conduits have had to be exchanged 2.5-10.5 years (mean 6.1 +/- 2.1 years) after the first implantation. In 3 patients, reoperated before 1982, another porcine valved conduit was used. After 1982, 29 exchanges were all performed using allografts. The main reason for xenograft conduit malfunction was degeneration and/or calcification of the valves. Some conduits, however, with rather small sizes of 12 and 14 mm had to be exchanged in spite of still sufficient function because the children had "outgrown" the conduit and needed a bigger one. Out of 192 patients with allografts implanted since 1982, so far 5 patients have had to be reoperated 2 months to 6 years (mean 4.6 +/- 2.8 years) after the first operation. The causes of allograft failure were degeneration and, in one case, infection of the conduit. Even though allografts seem to be the conduit of choice for right ventricular outflow tract reconstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-Term Results After Right Ventricular Outflow Tract Reconstruction with Porcine Bioprosthetic Conduits

From 1975 to 1990, a total of 110 patients were operated for complex cardiac malformations with impaired pulmonary artery perfusion using porcine valved right heart to pulmonary artery conduits. Twelve- to 30-mm porcine valved conduits (Hancock or Carpentier-Edwards) were implanted at the age of 4 weeks to 28 years (mean 4.3 years). The patients' body weights were 2.9-68 kg (mean 15.3 kg). Early mortality was 5.5% (six patients), late mortality was 12.7% (14 patients), and 90 patients could be included in this long-term follow-up (426 patient-years). So far, 41 of the conduits had to be exchanged 4 months to 15 years (mean 6.5 years) after the first implantation. Forty-nine of the conduits are still in place. At reoperation, 38 patients received an allograft; three patients, reoperated before 1982, had a second xenograft. The main reason for porcine conduit malfunction was degeneration and/or calcification of the valves. In 11 patients, however, with 12- and 14-mm conduits implanted at a mean age of 3.1 years, a reoperation was necessary after a mean time of 6.8 years because these children had "outgrown" the conduit and needed a bigger one. We conclude that even though allografts seem to be the conduit of choice for right ventricular outflow tract reconstruction, our clinical experience shows that porcine valved conduits can be used just as well since most of them function sufficiently well for as long as 5 to 10 years, and early valve failure is relatively rare.

Ventilation-perfusion scintigram in diabetics

We carried out ventilation and perfusion scintigraphies and pulmonary function tests in 20 diabetics under 50 years of age. 99mTc-MAA perfusion scintigrams showed evidence of minimal nonuniformity (MNU) in four cases (20%) and nonsegmental defect (NSD) in eight cases (40%). There was a ventilation defect in the single-breath image in one case (5%) and a delayed washout in three cases (15%) upon 133Xe ventilation scintigram. In the NSD group, the mean diffusing capacity value was abnormally low and the mean duration of the diabetes was long compared with other groups. The frequency of perfusion defects was higher than that of ventilation abnormalities; moreover, abnormal findings on ventilation scintigrams were very mild compared with those of perfusion defects. Perfusion defects correlated significantly with a decrease in diffusing capacity. These findings suggest that the disturbance in pulmonary arterial perfusion caused a decrease in diffusing capacity in diabetics.

Contribution of the bronchial circulation to lung preservation

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

Analysis of pulmonary and systemic vascular responses to cromakalim, an activator of K+ATP channels

Cardiovascular and pulmonary responses to cromakalim, a member of a novel class of antihypertensive agents that open ATP-sensitive K+ (K+ATP) channels, were investigated in the anesthetized cat. Intravenous injections of cromakalim in doses of 30-300 micrograms/kg decreased arterial pressure (AP), pulmonary arterial pressure (PAP), and increased cardiac output (CO), while producing small changes in right and left atrial pressures. Pulmonary and systemic vascular resistances were decreased and vasodilator responses to cromakalim were blocked by glybenclamide, a K+ATP channel-blocking agent. The low dose of cromakalim caused a reflex increase in heart rate (HR) and right ventricular contractile force (RVCF), whereas the high dose decreased HR and RVCF. Under constant-flow conditions the K+ATP channel opener caused dose-dependent decreases in hindquarters perfusion pressure, and when tone was elevated in the pulmonary vascular bed, dose-dependent decreases in pulmonary lobar arterial perfusion pressure. Hindquarters and pulmonary lobar vasodilator responses to cromakalim were inhibited in a specific manner by glybenclamide. The present data show that cromakalim has significant vasodilator activity in both the systemic and pulmonary vascular beds and suggest that responses to this agent result from activation of glybenclamide-sensitive K+ATP channels. These data show that cromakalim can cause substantial decreases in systemic and pulmonary vascular resistance in a dose that has little effect on RVCF.

Tone-dependent responses to endothelin in the isolated perfused fetal sheep pulmonary circulation in situ

Pulmonary vascular responses to endothelin (ET-1), a peptide derived from endothelial cells in culture, were investigated in the ovine fetus delivered by cesarean section from chloralose-anesthetized ewes with intact umbilical circulation. Circulation to the lower left lobe of the fetal lung was isolated in situ and perfused at constant flow with blood withdrawn from the inferior vena cava. Injection of graded doses of ET-1 into the left pulmonary artery decreased pulmonary arterial perfusion pressure in a dose-related manner. At doses of 100, 300, and 1,000 ng, pulmonary vascular resistance per kilogram body weight (PVR/kg) was decreased 30, 40, and 42%, respectively. However, when fetuses were ventilated with 100% oxygen, 100- and 300-ng doses of ET-1 decreased PVR/kg by 5 and 9%, respectively. In contrast, injection of 1,000 ng of ET-1 resulted in a reversal of the response, and PVR/kg was increased by 70%. Ventilation of the right lung alone resulted in a similar reversal of the vasodilator response to 1,000 ng of ET-1, and a 138% increase in PVR/kg was recorded. These studies demonstrate for the first time that ET-1 has vasodilator activity in the normally high-tone ovine fetal pulmonary circulation. In addition, these results show that ET-1 has vasoconstrictor activity in the newly ventilated low-tone pulmonary vasculature. The present data indicate the pulmonary vascular responses to ET-1 are tone dependent in the ovine fetal pulmonary circulation.

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

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

Color Doppler flow mapping of fetal heart

Color Doppler flow mapping of fetal heart was performed in 582 fetuses between 16 and 38 weeks of gestation. Congenital heart diseases were excluded in 522 fetuses correctly. In 59 fetuses structural and/or functional cardiac abnormalities were diagnosed. In one fetus small multiple ventricular septal defects were missed. The most important additional information obtained by color Doppler flow mapping was: (1) Diagnosis of insufficiencies of atrioventricular valves; (2) Demonstration of turbulent high velocity jet in stenosis of semilunar valve; (3) Reverse flow in ascending aorta in atresia of aortic valves and on ductus arteriosus and main pulmonary artery in atresia of pulmonary valves; (4) Reverse perfusion of ductus arteriosus and main pulmonary artery as well as an antegrade turbulent high velocity jet in severe pulmonary stenosis as part of tetralogy of Fallot; (5) Bidirectional interventricular shunting of blood in ventricular septal defect. Color Doppler flow mapping allows rapid screening for flow abnormalities of the fetal heart. Exact localisation of sample volume by pulsed wave Doppler in area of abnormal flow pattern is possible, thus significantly reducing the Doppler examination time. The accuracy of prenatal diagnosis of congenital heart diseases is improved by application of color Doppler flow mapping, in particular in presence of complex cardiac defects.

Changes in circulating norepinephrine with hemofiltration in advanced congestive heart failure

In congestive heart failure (CHF), hemofiltration is associated with an obvious decrease in circulating norepinephrine. This method was used for investigating the mechanisms whereby plasma norepinephrine is increased in chronic CHF. In 23 cases of advanced CHF, hemofiltration (2,983 ± 1,228 ml) lowered plasma norepinephrine by 515 ± 444 pg/ml. This effect was prompt, persisted or became greater in the next 24 hours. It was not associated with significant changes in cardiac output, aortic pressure or systemic vascular resistance. It did not appear to depend on variations in parameters related to the sympathetic activity, such as plasma renin, right atrial, wedge pulmonary artery and renal perfusion pressures, and was independent of duration and amount of hemofiltration. These observations did not support the concept that the norepinephrine decrease was the main consequence of a neural sympathetic inhibition. Hemofiltration increased diuresis by 606 ± 415 ml; changes were prompt and correlated inversely (r = −0.7; p < 0.01) with those in plasma norepinephrine. The same unknown mechanism of the increased urinary output might potentiate the norepinephrine removal from the blood by the kidney, or hemofiltration and the augmented diuresis might result in a regression of congestion of lungs and kidneys, leading to an improved extraction of norepinephrine. In CHF, a relation may exist between fluid retention and norepinephrine and in advanced stages, circulating norepinephrine, although strikingly increased, is devoid of important cardiovascular effects. At these stages, plasma norepinephrine is probably unreliable as an index of the sympathetic neural activity.

Vascular smooth muscle-derived relaxing factor (MDRF) and its close similarity to nitric oxide

The principal finding in this study is that vascular smooth muscle generates a labile relaxing factor that possesses pharmacological and chemical properties that are similar to those of authentic nitric oxide. MDRF was generated by perfusion of endothelium-denuded bovine pulmonary artery as assessed by bioassay. In addition, endothelium-denuded arterial rings that were incubated at 37°C for 24 hr to lower endogenous L-arginine levels relaxed in response to L-arginine but not D-arginine. Freshly mounted, endothelium-denuded arterial rings were not relaxed by L-arginine but did relax in response to the dipeptide L-arginyl-L-alanine. Relaxant responses were accompanied by increases in smooth muscle levels of cyclic GMP and nitrite, and were inhibited by oxyhemoglobin, methylene blue, and NG-nitro-L-arginine. NG-Nitro-L-arginine also caused endothelium-independent contractile responses. Thus, a relaxing factor with the properties of nitric oxide can be generated from vascular smooth muscle.

PAF potentiates protamine-induced lung edema: role of pulmonary venoconstriction

We studied the synergistic interaction between platelet-activating factor (PAF) and protamine sulfate, a cationic protein that causes pulmonary endothelial injury, in isolated rat lungs perfused with a physiological salt solution. A low dose of protamine (50 micrograms/ml) increased pulmonary artery perfusion pressure (Ppa) but did not increase wet lung-to-body weight ratio after 20 min. Pretreatment of the lungs with a noninjurious dose of PAF (1.6 nM) 10 min before protamine markedly potentiated protamine-induced pulmonary vasoconstriction and resulted in severe lung edema and increased lung tissue content of 6-keto-prostaglandin F1 alpha, thromboxane B2, and leukotriene C4. Pulmonary microvascular pressure (Pmv), measured by double occlusion, was markedly increased in lungs given PAF and protamine. These potentiating effects of PAF were blocked by WEB 2086 (10(-5) M), a specific PAF receptor antagonist. Pretreatment of the lungs with a high dose of histamine (10(-4) M) failed to enhance the effect of protamine on Ppa, Pmv, or wet lung-to-body weight ratio. Furthermore, PAF pretreatment enhanced elastase-, but not H2O2-, induced lung edema. To assess the role of hydrostatic pressure in edema formation, we compared lung permeability-surface area products (PS) in papaverine-treated lungs given either protamine alone or PAF + protamine and tested the effect of mechanical elevation of Pmv on protamine-induced lung edema. In the absence of vasoconstriction, PAF did not potentiate protamine-induced increase in lung PS. On the other hand, mechanically raising Pmv in protamine-treated lungs to a level similar to that measured in lungs given PAF + protamine did not result in a comparable degree of lung edema. We conclude that PAF potentiates protamine-induced lung edema predominantly by enhanced pulmonary venoconstriction. However, a pressure-independent effect of PAF on lung vasculature cannot be entirely excluded.

Distant organ procurement in clinical lung- and heart-lung transplantation *1Cooling by extracorporeal circulation or hypothermic flush

The scarcity of suitable donors for single lung and heart-lung transplantation calls for methods of medium-term pulmonary preservation to allow for distant organ procurement. At our institution, the first five grafts (four heart-lung, one single lung) were cooled by means of a transportable extracorporeal circulation unit, while the last eight grafts (four heart-lung, four single lung) were flush-perfused with modified cold Euro-Collins solution. The technique of extracorporated circulation included aortic and right atrial cannulation and cooling to 12 degrees-14 degrees C (rectal temperature) using a bubble oxygenator. Bypass times ranged between 41 and 52 min. Following excision, the organs were transported in ice-cold donor blood for ischemic times from 171 to 310 min. For cold flush preservation, simultaneous coronary (cold St. Thomas's solution) and pulmonary artery perfusion (Euro-Collins solution, 50 ml/kg over 4 min) were initiated simultaneously. The organs were transported in cold Euro-Collins solution for ischemic times of 175 to 270 min. In heart-lung transplantations the first postoperative arterial PO2 upon arrival at the intensive care unit was 120 +/- 38 Torr in the extracorporeal circulation and 140 +/- 38 Torr in the Euro-Collins solution group. Six of eight patients were extubated within 48 h after cardiopulmonary grafting. We conclude that pulmonary function following heart-lung or single lung preservation with simple hypothermic flush is as good or better than that following extracorporeal circulation. Since distant organ retrieval is much more convenient without the latter, preservation using Euro-Collins solution is preferred.