Candiduria in intensive care units: association with heavy colonization and candidaemia.

Candiduria is increasingly detected in intensive care unit (ICU) patients and often coexists with candidal colonization at other anatomical sites. Studies involving surgical and medical ICU patients have consistently reported a relationship between candiduria and heavy colonization. This suggests that candiduria could be considered as a marker for heavy colonization. Risk factors that predispose to heavy colonization are generally similar to those predisposing to candidaemia. Candiduria in ICU patients is characterized by a high mortality, largely through a significant relationship with candidaemia, which in some patients may reach 50%. Therapeutic interventions should be strongly considered in the critically ill patient who presents with candiduria and concurrent clinical risk factors predisposing to dissemination.

Tuberculosis treatment for the beginning of the next century.

As we move into the next century it appears that new antituberculosis drugs will arise from four categories: 1) new use of old drugs, 2) new delivery of old drugs, 3) new drugs within old classes, and 4) new classes of drugs. Old drugs such as clofazimine and its analogues, rifabutin, the macrolides, aminoglycosides, quinolones and perhaps vitamin D may find a way into better regimens. New therapy may also arise from new combinations and new uses of current antituberculosis drugs. New drugs are being developed in the rifamycin, fluoroquinolone, and nitroimidazole families. Several immune amplifiers, such as interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and interleukin-12 (IL-12) have undergone pilot testing. Counteracting adhesion molecules is being tested for several infectious diseases. With the unraveling of the tuberculosis genome, attacking enzymes unique to Mycobacterium tuberculosis is easier and allows us to hit elements in both a metabolic pathway and its alternate pathway. Interfering with transcription factors that bind DNA but do not promote RNA production could interrupt transcription. Genetic products of mycobacteria can be modified to cause their own death. Phages may deliver antisense nucleic acids for inhibition of mycobacterial gene expression. The distinction between drugs, immunotherapies and vaccines may blur.

Pulmonary lymphatic filling is increased in spontaneously hypertensive rats.

Extravascular lung liquid must rely on tissue-space pressure gradients to drive it into the lymphatics because the fluid is outside the lymphatic contractile pumping and valve control. Focal tissue pressure changes could result from muscular contraction in the blood vessel walls. Perivascular lymphatics usually lie within the adventitia of pulmonary blood vessels, and are generally more noticeable in veins than arteries. Spontaneously hypertensive rats have exaggerated focal pulmonary venous muscle (venous sphincters). These muscular tufts are often near initial lymphatics; if their contraction was important for lymph transport, spontaneously hypertensive rats could have more lymphatic filling in the areas of the pulmonary venous sphincters than normotensive rats. Because the focal muscularity is found in pulmonary veins more than arteries, veins may have more focal lymphatic filling than arteries. To test these hypotheses, lung histology and vascular and lymphatic casts of spontaneously hypertensive and normotensive rats were examined. Contracted venous sphincters were found on 108 of 127 veins with lymphatics in the spontaneously hypertensive rats and 5 of 41 in the normotensive rats P<0.01). The spontaneously hypertensive rats had deeper venous contractions and more lymphatic filling around both arteries and veins (P<0.01). In the hypertensive rats, the venous was greater than the arterial lymphatic filling (P<0.01). On the pleural surface, hypertensive rats also had greater lymphatic filling than controls (P<0.01). This anatomic evidence suggests that pulmonary venous sphincters are associated with focal lymphatic filling, and perivascular muscle action might be a component of the pulmonary lymphatic system.

Staining tissue with methacrylate casts for light microscopy.

Scanning electron microscopy (SEM) of methyl methacrylate casts and light microscopy (LM) of tissue are well-established methods for studying the microcirculation. The two are complimentary, but methacrylate is transparent and thus its presence is often not appreciated by LM. Applying histologic stains to sections of tissue embedded in methyl methacrylate would allow the relationships of light microscopic and scanning electron microscopic views of cast vasculature to be better appreciated. We sought to test different stains on cast tissue to find one that would accent the cast. Surgically removed and autopsied human lungs were cast with methacrylate and processed by routine light microscopic methods. They were stained with the hematoxylin and eosin, Masson trichome, elastic--van Gieson, Grocott methenamine silver, Brown-Brennan, and Ziehl-Neelsen methods. The Ziehl-Neelsen procedure stained the methacrylate best, giving it a red color. This procedure also worked well without heating. We conclude that (1) cast methacrylate lung can be processed for routine LM with excellent results; (2) methacrylate stains well with the Ziehl-Neelsen technique; (3) the acid--fast stained cast lung shows capillaries and cells in both normal and diseased lung better than the routine hematoxylin and eosin stain; (4) this technique can be used to assess filling and correlate findings on the same tissue with the two different microscopic methods.

Giant cell arteritis manifesting as chronic cough and fever of unknown origin.

A 57-year-old white man sought medical attention because of chronic cough and fever of unknown origin. An extensive work-up over 4 weeks, including repeated blood cultures, chest roentgenograms, a gallium scan, and computed tomographic scans of the sinuses, chest, and abdomen, was nondiagnostic. The patient was referred to our institution for bronchoscopy. Further analysis of his history revealed that he had a headache in conjunction with the cough and an episode of a flashing color design in his left eye 1 week before assessment. The erythrocyte sedimentation rate was 115 mm in 1 hour. A biopsy of the temporal artery showed granulomatous inflammation of the vessel wall with multinucleated giant cells, histiocytes, lymphocytes, plasma cells, and few eosinophils. The multinucleated giant cells were closely related to the fragmented elastic lamina. Corticosteroid therapy resulted in prompt resolution of the chronic cough and fever. Giant cell arteritis should be considered in the differential diagnosis of chronic cough.

Endothelin-1 causes luminal constrictions in rat cochlear veins.

Serum levels of the vasoconstrictor endothelin-1 (ET-1) increase in ischemia and systemic hypertension. We examined the effects of ET-1 on the cochlear microvasculature. Blood vessels were cast with methacrylate in adult male Wistar Kyoto rats, 10 min after intravenous injection of ET-1 (1.0 microg/kg); control animals received saline. Systemic blood pressure was recorded continuously. ET-1 increased the average systolic pressure by 18% and average diastolic pressure by 22% (P < 0.01). Scanning electron microscopy of cast vessels showed multiple circumscribed luminal constrictions on: (1) postcapillary venules; (2) collecting veins; (3) where collecting veins merged with the spiral modiolar vein; (4) on the spiral modiolar vein itself. Circumscribed constrictions in arteries were not observed. In ET-1 injected animals focal contractions of collecting veins reduced luminal width by 13.4% +/- 2.9 (P < 0.01). In control rats, constrictions on venous casts were minimal and constrictions on arteries were not observed. The present study shows that ET-1 is involved in local control of cochlear blood flow in that it focally contracts cochlear veins. It is suggested that this might be due to the high affinity of ET-1 receptors and/or the large number of ET-1 receptors on contractile cells in venous walls.

Lung capillary changes in hepatic cirrhosis in rats.

The hypoxemia of the hepatopulmonary syndrome may result from dilated intrapulmonary vascular segments. Knowledge of the size, density, and branching frequency of the lung capillaries might confirm this hypothesis and suggest that the pathogenesis may involve vascular dilatation or angiogenesis. To investigate these changes, the common bile duct of rats was tied off to cause biliary cirrhosis. Later (4 wk), the pulmonary vasculature of these animals was cast, and the casts were studied with scanning electron microscopy. In the ligated animals, evidence for enhancement of the bronchial to pulmonary circulation was found: cast vasa vasorum of the pulmonary arteries and cast bronchial veins emptying into pulmonary veins. Ligated animals had more adherent intracapillary cells per alveolus than the sham-operated animals. The diameters of all capillary beds were larger in the ligated animals. The alveolar capillary density was increased, but the branching frequency was not. A few areas suggesting angiogenesis were found. Induction of biliary cirrhosis enhances the pulmonary-systemic circulation, increases intracapillary adherent cells, capillary diameter, and density, and may be associated with angiogenesis.

Pulmonary venous sphincters in cattle.

BACKGROUND: The pulmonary veins of rats have regular focal narrowing by tufts of smooth muscle (sphincters) that can contract in response to a variety of stimuli, but these structures are not well studied in other species, and there is little information about their innervation and control. METHODS: The pulmonary veins of 21 cattle were cast with methacrylate, and the casts were studied by scanning electron microscopy, or the fixed tissue was studied by light microscopy with immunocytochemistry and transmission electron microscopy. RESULTS: Constrictions occurred in series along the course of veins (9.6/500 microns), giving the cast veins a string-of-pearl look, with narrowing of 33-81% of the outer diameter. No resin appeared beyond the most narrowed veins. The percentage of contraction did not correlate with the diameter of the veins. With immunohistochemistry using antibodies to S-100, protein gene peptide 9.5, neuron-specific enolase, neurofilament 200, and glial fibrillary acidic protein and with transmission electron microscopy, we could identify no neuronal elements associated with the venous smooth muscle tufts. Bronchial smooth muscle bundles in the same sections stained positively. CONCLUSIONS: The veins of cattle are unlike the rat because the focal venous smooth muscle protrudes deeply into the venous lumen and may completely obstruct perfusion. If the focal venous muscle has no innervation (this study) and can constrict without blood flow (as shown previously), then the venous constriction and, hence, local blood flow regulation must be controlled by local mediators.

Structural and pathologic changes in the lung vasculature in chronic liver disease.

The hepatopulmonary syndrome results from erythrocytes bypassing the lung without oxygenation. In addition to ventilation-perfusion mismatching, the hypoxemia may result from portapulmonary shunting, passage around alveoli through pleural and hilar blood vessels, and intrapulmonary vascular dilatations. Dilated vascular channels between arteries and veins on the pleural surface are seen more often than dilated intrapulmonary capillaries in chronic liver disease. These anastomoses appear grossly as vascular "spider nevi" on the pleura. Portal vein-to-pulmonary vein anastomoses could produce arterial hypoxemia because the deoxygenated portal venous blood can mix with oxygenated pulmonary venous blood. There is an association of esophageal varices with the hepatopulmonary syndrome and anastomoses between the portal veins and pulmonary veins have been found in both animals and humans. As portal pressures increase, the mediastinal veins enlarge, enhancing the chance that they may penetrate the pleura and drain into pulmonary veins. Direct splenic injections in patients, however, suggest that this shunt pathway is uncommon and small. Pulmonary artery injection studies have demonstrated dilated intrapulmonary vascular segments in humans and animals. Dilation of capillaries may allow a more rapid flow through the lung and the greater distance between the erythrocyte and alveolar wall may make it more difficult to oxygenate rapidly passing erythrocytes. Pulmonary capillary dilation can explain the abnormalities of the perfusion lung scan and contrast echocardiogram that portapulmonary shunting cannot. Pulmonary hypertension may occur in chronic liver disease even without arterial hypoxemia, but it is rare. The prevalence of hypertensive pulmonary vascular disease in patients with cirrhosis of the liver is less than 1%, although a higher percentage (2%) has been found when patients with portal hypertension were studied by cardiac catheterization. The hypertensive pulmonary vascular disease (pulmonary arteriopathy with plexiform lesions) that occurs in patients with liver disease appears identical to that encountered in patients with congenital cardiac shunts and unexplained (primary) pulmonary hypertension.

Human alveolar capillaries undergo angiogenesis in pulmonary veno-occlusive disease.

The bronchial circulation undergoes angiogenesis in several pathological conditions, such as lung neoplasm and bronchiectasis, but whether the pulmonary circulation can do this has been questioned. A woman treated with mitomycin C and 5-fluorouracil developed progressive, fatal pulmonary hypertension over 5 months. In addition to light and transmission electron microscopic examination of her lung, her pulmonary vasculature was cast and the casts were studied with scanning electron microscopy. Light microscopy showed that she had pulmonary veno-occlusive disease and angiomatoid capillary growth in the alveolar walls. Transmission electron microscopy confirmed the presence of pulmonary hypertension and showed thickened endothelial basement membrane. Scanning electron microscopy of the cast blood vessels showed distortion and destruction of alveolar capillaries prohibiting the passage of erythrocytes. Large new capillaries developed on top of, and were connected to, the shrivelled capillaries that made up the alveolar wall. The new capillaries were larger and fewer, which reduced the alveolar-capillary interface. Arteries and veins were irregularly narrowed and the veins had broad muscularity. Oedema was present, and the pulmonary lymphatics were extensively cast, especially in the lobular septa, but the lymphatics had a normal appearance. It appears that this patient suffered extensive capillary damage and venous occlusion and that the response was extensive new capillary formation, sometimes in angiomatoid configurations, and hypertrophy of pulmonary veins and arteries. Casting the microvasculature and viewing it with scanning electron microscopy identified new alveolar capillaries in this patient with acquired pulmonary hypertension.

Spontaneously hypertensive rats develop pulmonary hypertension and hypertrophy of pulmonary venous sphincters.

This study explored the spontaneously hypertensive rat as an animal model of pulmonary hypertension and sought to identify anatomic changes in its pulmonary microvasculature, especially focal constrictions of pulmonary veins (sphincters). The average systemic and pulmonary artery blood pressures were 172/139 (+/- 9/9) and 36/14 (+/- 4/3), respectively, for spontaneously hypertensive Wistar Kyoto rats (SHR), and 134/83 (+/- 8/2) and 20/10 (+/- 2/2) for normotensive Wistar Kyoto rats (WKY) (P < 0.01 for both). Light microscopy of the lungs in SHR showed muscularization of both arteries and veins, but this was more pronounced in the small pulmonary veins. Perivascular edema was also present. There were 20 (+/- 4) leukocytes per 100 microns of capillary length in SHR and 9 (+/- 2) in WKY (P < 0.001). Transmission electron microscopy showed focal venous smooth muscle was greater in SHR than in WKY. Scanning electron microscopy of vascular casts showed the average maximal focal venous contraction (sphincter) was 54% (+/- 10) of its diameter in SHR, but was only 6% (+/- 4) in WKY (P < 0.01). Arterial contraction occurred in the hypertensive rats as bourglass narrowings of the casts, but was less conspicuous than venous constrictions. The mean alveolar capillary diameter was 8.1 microns (+/- 1.6) in SHR, compared with 6.3 microns (+/- 1.0) in WKY (P < 0.01). The central interspace between capillaries was 3.2 microns (+/- 1.6) in SHR and 6.0 microns (+/- 3.6) in WKY (P < 0.01). The venous contraction, capillary size, and capillary interspace distance correlated with the pulmonary blood pressure. The spontaneously hypertensive rat can be a model of pulmonary hypertension with its most notable structural change being increased muscularity in the small pulmonary veins.

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.

Carboxypeptidase M activity is increased in bronchoalveolar lavage in human lung disease.

Carboxypeptidase M (CPM) cleaves the C-terminal arginine and lysine of peptides; it is expressed in the lung, especially on the plasma membrane of alveolar type I cells. Here, we report on CPM in human bronchoalveolar lavage (BAL) collected from 69 patients and analyzed for activity, cell number and type, and protein level. Seventy-six percent of CPM activity, measured at pH 7.5 with 5-dimethylamino-naphthalene-1-sulfonyl-alanyl-arginine (Dansyl-Ala-Arg) substrate, was immunoprecipitated with polyclonal antibody to purified human enzyme. In patients without active lung disease, CPM activity in BAL was 7.69 (+/- 2.12) nmol/h/mg protein, but in patients with acute pneumonia, it was 29.25 (+/- 4.06) (p < 0.01). In patients with Pneumocystis carinii pneumonia, CPM activity was elevated to 26.00 (+/- 4.85) (p < 0.01) and in patients with lung cancer, to 30.95 (+/- 4.12) (p < 0.01). The activity was not associated with the cellular elements of BAL. The highest specific activity was in the large aggregate fraction of surfactant, which also contained the highest concentration of phosphorus. Transmission electron microscopy of this fraction revealed the presence of typical lamellar bodies and tubular myelin structures. The high CPM activity may stem from its induction and release in acute lung disease. In addition, CPM may be a marker of infection with certain pathogens and an indicator of type I cell injury in parenchymal lung diseases.

Pulmonary lymphatics and their spatial relationship to venous sphincters.

BACKGROUND: Pulmonary lymphatics are critical to clearing lung fluid. Although their structure can be shown with light and transmission electron microscopy, scanning electron microscopy of their casts can better show their number, size, shape, distribution, and degree of filling. This technique has identified four forms of lung lymphatics, but these forms have not been fully evaluated by tissue microscopy. A most important site of pulmonary edema formation, the pulmonary capillary, is just upstream from small veins which have focal, smooth muscle tufts termed venous sphincters. Because of their constricting potential, these sphincters may control lung perfusion and cause edema. METHODS: With light and transmission electron microscopy of tissue and scanning electron microscopy of casts, the lymphatic forms were explored in relation to the tissue anatomy in rats without pulmonary edema and with mild-to-moderate edema caused by extended vascular rinsing. RESULTS: The edematous lungs had increased sacculo-tubular lymphatics adjacent to the venous sphincters. These lymphatics were in the adventitial connective tissue and were partially endothelialized. As lymphatics became more tubular their endothelium became more complete. Collagen fibers traversed the lumen of these lymphatics even where endothelial cells were present and caused the lines on the surface of the lymphatic casts. Overlapping endothelial cells caused clefts on the casts. CONCLUSIONS: Scanning electron microscopy of lymphatic casts better defines their ultrastructure and shows the spatial relationship of veins and their sphincters to venous lymphatics. Sphincter contraction may influence pulmonary lymph production which could affect other aspects of regional lung perfusion.

Endothelin-1 focally constricts pulmonary veins in rats.

Serum endothelin levels increase during sepsis, ischemia, reperfusion, pulmonary operations, and systemic hypertension after surgery. Despite extensive study, the site and extent of action of endothelin on the pulmonary microcirculation are not well established. To assess the effect of endothelin on the pulmonary vasculature, especially the veins, the circulation of the lung was cast with methyl methacrylate 10 minutes after endothelin-1 was given intravenously to rats. Endothelin-1, at concentrations of 0.1, 1.0, and 10.0 micrograms/kg of body weight, increased the mean systemic arterial blood pressure 8%, 7%, and 17% (p < 0.01) and mean pulmonary arterial blood pressure 15%, 28%, and 53%, respectively (p < 0.01). The proportional increases in the pulmonary pressures were greater than those of the systemic pressures (p < 0.01). Scanning electron microscopy of cast blood vessels showed more contraction of the veins than the arteries. For doses of 0, 0.1, 1.0, and 10.0 micrograms/kg, the respective focal contraction of small veins was 6.7% (+/- 4.4), 15.4% (+/- 9.1), 23.3% (+/- 10.1), and 14.4% (+/- 9.0) of the vessel diameter (p < 0.01). In addition, the diameter of capillaries increased (p < 0.01) and the capillary interspaces decreased (p < 0.01) after endothelin administration, but not in a linear dose-dependent manner. The dose of endothelin correlated with the change in the mean systemic (r = 0.82, p < 0.01) and the mean pulmonary (r = 0.80, p < 0.01) blood pressures. The mean pulmonary pressure change correlated with the focal venous contraction on the casts (r = 0.35, p < 0.01), capillary diameter (r = 0.64, p < 0.01), and capillary interspace distance (r = -0.34, p < 0.01). The venous contraction was related to the capillary diameter (r = 0.26, p < 0.01). The most notable effect of endothelin-1 in rat pulmonary microcirculation is focal constriction of small veins. Because this effect may lead to pulmonary edema, endothelin antagonists may be of benefit in a variety of clinical situations.

Lung lymphatics cast from the airspace.

Lymphatics are important in the resolution of pulmonary edema, but which lymphatics drain alveolar fluid and how they change during lung injury and edema is uncertain. To study this question 16 rats were exposed to 85% O2 for 7 days. At 0, 3, 7, and 14 days after removal from the hyperoxic chamber, the lungs of the rats were cast by instilling methyl methacrylate into the trachea. The lungs of four similar room-air breathing rats served as controls. Tissue was taken for light microscopy and the casts were examined for lymphatic filling with a scanning electron microscope. Rats exposed to hyperoxia had diffuse damage and extensive edema. On removal from hyperoxia (day 0), 29% of the rat bronchioles had saccular lymphatic casts around them and 6% of bronchioles were surrounded by these lymphatics. Twenty-five percent of bronchioles had conduit lymphatic casts. Fourteen percent of arteries had lymphatic casts around them. All were different from the rats kept in room air (P < 0.0001). Rats exposed to hyperoxia had lymphatics on the pleural surface, near alveoli and alveolar ducts, and around veins. The peribronchial and periarterial saccular lymphatics formed separate groups with communicating conduit lymphatics. The perivenous lymphatics had their own separate conduit lymphatics. Fourteen days after returning to ambient air, the lymphatics were similar to those of control animals. In this model, airway casting allows three-dimensional analysis of the lung lymphatics. It shows that lymphatic compartments expand during hyperoxic lung injury and that peribronchial and perivascular saccular lymphatics connect to conduit lymphatics of the bronchoalveolar bundle.

Lung lymphatics increase after hyperoxic injury. An ultrastructural study of casts.

The microscopic lymphatics of the lung can be cast and studied with scanning electron microscopy. This technique shows several different forms of lymphatics and the interstitial space that leads into lymphatics as no other method can. To study changes in lymphatic forms, rats were placed in 85% oxygen for 7 days to produce pulmonary edema. Methyl methacrylate resin was injected into the lung vasculature at various times after the animals were removed from hyperoxia. In the animals not exposed to hyperoxia, no artery, vein, or airway was surrounded by a lymphatic cast. However, in rats that were in the hyperoxic chamber, 22% of arteries, 30% of veins, and 51% of indeterminate blood vessels (which could be arteries or veins) were encompassed by saccular lymphatic casts. These lymphatics were still observed 7 days after recovery from hyperoxia. Fourteen days after hyperoxia, the lymphatics returned to control values. Only 9% of the pleural surface of the animals not exposed to hyperoxia had initial lymphatics. Fifty-two percent of the hyperoxia-exposed animals had initial lymphatics, measured 3 days after exposure. This decreased to 14% 14 days after exposure to hyperoxia (P < 0.01). Conduit lymphatics were found on the pleural surfaces of 33% of animals exposed to ambient air and 100% of animals exposed to the high-oxygen environment (P < 0.05). The median percentage of the pleural surface covered with lymphatics was 0 in the animals exposed to ambient air. It was 65% in animals exposed to hyperoxia, 3 days after returning to room air. It was again 0 in animals exposed to hyperoxia, 14 days after returning to room air (P < 0.001). The lymphatics around veins expanded more than around arteries (P < 0.0001). These results indicate that in the rat all compartments of the lung lymphatics expand after the injury and edema caused by oxygen and return to normal with the resolution of the edema.

Effect of age on the contraction of pulmonary venous sphincters in rats.

Pulmonary veins of rats have regular focal ringlike muscular constrictions (sphincters) that deepen with stimuli, such as head injury, sufficient to cause pulmonary edema. The depth of the individual constrictions on the veins can be determined by casting the pulmonary circulation, fracturing the cast veins at their narrowed points, and measuring the constriction using a scanning electron microscope. A recent study in rats given a blow to the head showed that the venous constriction was attenuated by alpha-adrenergic antagonism, but interaction between the antagonist, the animal body weight, and sex was found. Older, heavier male animals constricted more. To clarify these factors and assess the change in pulmonary venous sphincter contraction with age, 20 female Sprague-Dawley rats aged 5, 10, 15, 20, and 30 wk had their lung vasculature cast with methyl methacrylate. Of the 4 animals in each age group 3 were given a blow to the head to constrict the veins while the plastic was solidifying. The lungs were digested and the casts of the blood vessels were fractured, exposing the constricted portions of the veins. The depths of these focal constrictions were measured. In animals that received the head blow the constrictions were 2.9 +/- 0.3% (5 wk), 4.1 +/- 0.3% (10 wk), 5.8 +/- 0.4% (15 wk), 6.8 +/- 0.4% (20 wk), and 7.1 +/- 0.5% (30 wk) (p < 0.0001). To separate age from weight, a multivariate regression that accounted for venous contraction was carried out. Although head blow, age, and weight were each individually important, the combined model showed age was insignificant (p = 0.9) when weight (p = 0.02) was present.(ABSTRACT TRUNCATED AT 250 WORDS)

Vasoactive intestinal peptide enhances lung preservation.

The outcome of lung transplantation is often dependent on the quality of the donor lungs. To explore a way to improve lung preservation, vasoactive intestinal peptide (VIP) was added to pneumoplegic solutions. The 4 solutions tested were Krebs solution, Krebs solution with VIP, University of Wisconsin solution, and the University of Wisconsin solution with VIP. The lungs of 8 male Sprague-Dawley rats were flushed and stored in these solutions for 24 hr. At regular intervals, tissue was sampled and examined by light, scanning, and transmission electron microscopy. Casts of the vasculature were made after 4 hr and viewed by a scanning electron microscope. Lungs appeared well preserved by light microscopy at all intervals. Although inflammatory cells around arteries, arterial constriction, bronchiolar epithelial detachment, peribronchiolar edema, and alveolar size inhomogeneity were greater with time, there was no significant difference among the 4 groups by light microscopy. Scanning microscopy of tissue at 24 hr confirmed the information found on light microscopy but did not allow separation of the groups. The vascular casts showed that edema around large vessels was less in the lungs treated with VIP (P < 0.01). Transmission electron microscopy showed that lungs stored in the solutions with VIP had significantly more normal-shaped mitochondria, less mitochondrial edema, less distortion of mitochondrial cristae, thinner basal lamina, and less aggregation of nuclear chromatin at most intervals sampled after 4 hr. We conclude that VIP added to certain pneumoplegic solutions improves the ultrastructure of rat lung stored in the cold for up to 24 hr. VIP may be an important additive to pneumoplegic solutions to improve preservation of lung before transplantation.

Pulmonary venous sphincter constriction is attenuated by alpha-adrenergic antagonism.

Pulmonary veins of rats have regular thin bands of constriction (sphincters) that deepen when the animals are given a blow to the head that is sufficient to cause pulmonary edema. Pulmonary edema caused by a stimulus to the brain is attenuated by alpha-adrenergic blockade. This study tested the hypothesis that alpha-adrenergic antagonism decreases this contraction in pulmonary veins. Male and female Sprague-Dawley rats were given prazosin, an alpha 1-specific antagonist, phentolamine, a combined alpha 1- and alpha 2-antagonist, or saline 10 min before their lungs were cast and they were given a blow on the head. The casts were fractured, causing the veins to break at the site of the constriction. Depth of contraction expressed as a percentage was 1 minus the ratio of the inner (constricted) and outer (total) diameters of the vein at the fracture. Resin that escaped the vascular space to cast alveoli and lymphatics was also measured. The average contraction of the veins at the site of the sphincters was 7.9 +/- 1.1% in the saline group, 5.4 +/- 0.7% in the phentolamine group, and 4.8 +/- 0.7% in the prazosin group (p < 0.05), although about a third of the constrictions were less than 2% in all groups. Arteries had no contraction. Contraction was greater in heavier and male animals, which were variables that interacted with the agent the animals were given in a multivariate analysis. Contrary to the hypothesis, lymphatic casts were greater in the animals receiving alpha-blockers (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)