Expression of TGFbeta1 in pulmonary vein stenosis after radiofrequency ablation in chronic atrial fibrillation of dogs.

The development of pulmonary vein stenosis has recently been described after radiofrequency ablation (RF) to treat atrial fibrillation (AF). The purpose of this study was to examine expression of TGFbeta1 in pulmonary vein stenosis after radiofrequency ablation in chronic atrial fibrillation of dogs. About 28 mongrel dogs were randomly assigned to the sham-operated group (n = 7), the AF group (n = 7), AF + RF group (n = 7), and RF group (n = 7). In AF or AF + RF groups, dogs underwent chronic pulmonary vein (PV) pacing to induce sustained AF. RF application was applied around the PVs until electrical activity was eliminated. Histological assessment of pulmonary veins was performed using hematoxylin and eosin staining; TGFbeta1 gene expression in pulmonary veins was examined by RT-PCR analysis; expression of TGFbeta1 protein in pulmonary veins was assessed by Western blot analysis. Rapid pacing from the left superior pulmonary vein (LSPV) induced sustained AF in AF group and AF + RF group. Pulmonary vein ablation terminated the chronic atrial fibrillation in dogs. Histological examination revealed necrotic tissues in various stages of collagen replacement, intimal thickening, and cartilaginous metaplasia with chondroblasts and chondroclasts. Compared with sham-operated and AF group, TGFbeta1 gene and protein expressions was increased in AF + RF or RF groups. It was concluded that TGFbeta1 might be associated with pulmonary vein stenosis after radiofrequency ablation in chronic atrial fibrillation of dogs.

Endothelial VE-cadherin expression in human lungs.

Cell adhesion molecule vascular endothelial cadherin (VE-cadherin) is the major component of endothelial adherence junctions, maintaining endothelial cell integrity. Studies dealing with constitutive VE-cadherin expression patterns in different pulmonary vessel types (arteries, arterioles, capillaries, venules, veins) or with the influence of physiological factors such as age or sex on VE-cadherin expression have not been published yet. Knowledge of constitutive resp. varying expression patterns not only fundamentally contribute to understanding the role of VE-cadherin in the pathogenesis of pulmonary diseases but also help to develop therapies based on immunotargeting. Hence, endothelial VE-cadherin expression was studied in regular lung tissue. Fifty-eight specimens of regular lung tissue (30 females, 28 males between 1 month and 75 years old) were immunohistochemically stained with an antibody against VE-cadherin. There was strong endothelial expression of VE-cadherin in arteries, arterioles, and capillaries but almost no expression in veins and venules. Neither age nor sex had any influence on the expression pattern or staining intensity. There is a vessel type-specific expression pattern for VE-cadherin in regular human lung tissue, which is not influenced by age or sex. Further studies will have to prove whether this is influenced by pathological conditions, e.g., ARDS.

Extended atrial conduction system characterised by the expression of the HCN4 channel and connexin45.

OBJECTIVE: In the heart, there are multiple supraventricular pacemakers involved in normal pacemaking as well as arrhythmias and the objective was to determine the distribution of HCN4 (major isoform underlying the pacemaker current, I(f)) in the atria. METHODS: In the atria of the rat, the localisation of HCN4 and connexins was determined using immunohistochemistry, and electrical activity was recorded using extracellular electrodes. RESULTS: As expected, HCN4 and Cx45 (but not Cx43) were expressed in the sinoatrial node extending from the superior vena cava down the crista terminalis. The same pattern of expression of HCN4 and connexins was observed in a novel tract of nodal-like cells extending from the superior vena cava down the interatrial groove. Although the sinoatrial node was usually the leading pacemaker site, the novel tract of HCN4-expressing cells was capable of pacemaking and could act as the leading pacemaker site; there was evidence of a hierarchy of pacemakers. The same pattern of expression of HCN4 and connexins was also observed in the atrioventricular ring bundle (including the atrioventricular node) encircling the tricuspid valve, but not in the atrioventricular ring bundle encircling the mitral valve. HCN4 was not expressed in the pulmonary veins. CONCLUSIONS: The widespread distribution of HCN4 can explain the widespread location of the leading pacemaker site during sinus rhythm, the extensive region of tissue that has to be ablated to stop sinus rhythm, and the widespread distribution of ectopic foci responsible for atrial tachycardia.

Sex steroid receptor expression in idiopathic pulmonary fibrosis.

Usual interstitial pneumonia (UIP) is characterized by progressive scarring of the lungs and is associated with high morbidity and mortality despite therapeutic interventions. Sex steroid receptors have been demonstrated to play an important role in chronic lung conditions; however, their significance is unknown in patients with UIP. We retrospectively reviewed 40 idiopathic UIP cases for the expression of hormonal receptors. Forty cases including 10 normal lung, 10 cryptogenic organizing pneumonia, 10 idiopathic organizing diffuse alveolar damage, 7 hypersensitivity pneumonitis, and 3 nonspecific interstitial pneumonitis served as controls. Immunohistochemistry for estrogen receptor α, progesterone receptor (PR), and androgen receptor was performed in all groups. Expression of these receptors was assessed in 4 anatomic/pathologic compartments: alveolar and bronchiolar epithelium, arteries/veins, fibroblastic foci/airspace organization, and old scar. All UIPs (100%) stained positive for PR in myofibroblasts in the scarred areas, whereas among the control cases, only 1 nonspecific interstitial pneumonitis case stained focally positive and the rest were negative. PR was positive in myocytes of the large-sized arteries within the fibrotic areas in 31 cases (77.5%). PR was negative within the alveolar and bronchial epithelium, airspace organization, and center of fibroblastic foci; however, weak PR positivity was noted in the peripheral fibroblasts of the fibroblastic foci where they merged with dense fibrous connective tissue scar. All UIP and control cases were negative for androgen receptor and estrogen receptor α. This is the first study to show the expression of PR within the established fibrotic areas of UIP, indicating that progesterone may have profibrotic effects in UIP patients. Hormonal therapy by targeting PR could be of potential benefit in patients with UIP/IPF.

[Pulmonary veins and atrial fibrillation: a pathological study of 100 hearts]. / Plicní zíly a fibrilace síní - studie 100 srdcí.

Pathogenesis of atrial fibrillation (AF), the most common sustained heart arrhythmia, is not yet fully elucidated. Recent electrophysiological studies have shown that in most patients with AF the arrhythmia is triggered by ectopic beats originating from extensions of left atrial myocardium over the pulmonary veins (PVs), so called myocardial sleeves (MSPV). A total of 100 hearts (393 PVs) obtained at autopsy were prospectively studied - 50 from patients with chronic AF (average age 76.9 +/- 7.3 yrs.) and a control group of 50 with a sinus rhythm (aver. age 71.7 +/- 9.5 yrs.). This is a largest study published on this topic so far. It appeared that MSPV frequently harbour pathological lesions, particularly senile atrial amyloid, and scarring. These two pathological changes were evaluated semiquantitatively on a grade 0-3 basis in individual PVs, comparing the results in the AF vs. the control group. Amyloidosis of MSPV was found in 68 % of all hearts and in 55 % of all sleeves. The deposits were most marked in the right superior PV. Amyloidosis was more frequent and more severe in MSPV of patients with AF (58.5 %; average grade 0.89) than of those without AF (51.7 %; aver. grade 0.76); the differences, however, lack statistical significance. Scarring of MSPV was present in all 349 sleeves, more markedly in the left inferior, left superior, and right superior PVs. It was significantly more severe in patients with AF compared to those without the arrhythmia. By an injection metod, we have shown that MSPV are supplied by coronary arteries. However, the degree of scarring of the sleeves did not correlate with the degree of coronary atherosclerosis. We suggest that genesis of the scarring is not postnecrotic but degenerative, due to diffuse hypoxia of the sleeve myocardium. To conclude, amyloidosis and particularly scarring of MSPV appear generally in the elderly population as an arrhythmogenic substrate for AF.

Tissue structure and connexin expression of canine pulmonary veins.

OBJECTIVE: Rapid electrical activity in pulmonary veins (PVs) has been proposed as a mechanism for focal atrial fibrillation. The way in which the myocardial sleeve inside PVs can form a substrate for focal activity is not well understood. Therefore, we have studied tissue structure and connexin distribution at the veno-atrial transition in the dog. METHODS: In adult mongrel dogs, the anatomy of the PV area was studied. Tissue structure in individual veins was assessed in formalin fixed sections using Masson's Trichrome staining. Gap junction protein distribution was examined using antibodies against connexin40 (Cx40) and connexin43 (Cx43). The ultrastructure of myocytes in myocardial sleeves was studied using electron microscopy. RESULTS: Individual PVs in the dog had a gross morphology similar to that observed in the human, with myocardial sleeves extending into the veins for 4-20 mm. In all veins examined, myocytes in myocardial sleeves had a normal atrial morphology and anti-desmin staining pattern. Cx43 was expressed throughout the sleeve at levels comparable to normal atrial myocardium. By contrast, Cx40 expression was lower in myocardial sleeves than in the rest of the left atrium. Myocytes in the sleeve, which were ultrastructurally similar to normal atrial myocytes, were predominantly organized in a circumferential pattern. CONCLUSIONS: PVs in the dog and various canine models of heart disease will be a suitable model for (patho)physiology of the veno-atrial transition. Myocytes in myocardial sleeves are similar to normal atrial myocytes. The circumferential orientation of these myocytes may provide a substrate for rapid circular reentry.

Evidence for a M(1) muscarinic receptor on the endothelium of human pulmonary veins.

1. To characterize the muscarinic receptors on human pulmonary veins associated with the acetylcholine (ACh)-induced relaxation, isolated venous and arterial preparations were pre-contracted with noradrenaline (10 microM) and were subsequently challenged with ACh in the absence or presence of selective muscarinic antagonists. 2. ACh relaxed venous preparations derived from human lung with a pD(2) value of 5.82+/-0.09 (n=16). In venous preparations where the endothelium had been removed, the ACh relaxations were abolished (n=4). ACh relaxed arterial preparations with a pD(2) value of 7. 06+/-0.14 (n=5). 3. Atropine (1 microM), the non selective antagonist for muscarinic receptors, inhibited ACh-induced relaxations in human pulmonary veins. The affinity value (pK(B) value) for atropine was: 8.64+/-0.10 (n=5). The selective muscarinic antagonists (darifenacin (M(3)), himbacine (M(2),M(4)), methoctramine (M(2)) and pFHHSiD (M(1),M(3))) also inhibited ACh-induced relaxations in venous preparations. The pK(B) values obtained for these antagonists were not those predicted for the involvement of M(2 - 5) receptors in the ACh-induced relaxation in human pulmonary veins. 4. The pK(B) value for darifenacin (1 microM) was significantly greater in human pulmonary arterial (8.63+/-0.14) than in venous (7.41+/-0.20) preparations derived from three lung samples. 5. In human pulmonary veins, the pK(B) values for pirenzepine (0.5 and 1 microM), a selective antagonist for M(1) receptors, were: 7.89+/-0.24 (n=7) and 8.18+/-0.22 (n=5), respectively. In the venous preparations, the pK(B) values derived from the functional studies with all the different muscarinic antagonists used were correlated (r=0.89; P=0.04; slope=0.78) with the affinity values (pK(i) values) previously published for human cloned m1 receptors in CHO cells. 6. These results suggest that the relaxations induced by ACh are due to the activation of M(1) receptors on endothelial cells in isolated human pulmonary veins.

Leukotriene receptors on human pulmonary vascular endothelium.

1. Cysteinyl-leukotrienes cause contractions and/or relaxations of human isolated pulmonary vascular preparations. Although, the localization and nature of the receptors through which these effects are mediated have not been fully characterized, some effects are indirect and not mediated via the well-described LT1 receptor. 2. In human pulmonary veins (HPV) with an intact endothelium, leukotriene D4 (LTD4) induced contraction above basal tone. This response was observed at lower concentrations of LTD4 in the presence of nitric oxide synthase inhibitor N omega-nitro-L-arginine (L-NOARG). Contractions (in the absence and presence of L-NOARG) were partially blocked by the LT1 antagonists (MK 571 and ICI 198615). 3. LTD4 relaxed HPV previously contracted with noradrenaline. This relaxation was potentiated by LT1 antagonists, but was abolished by removal of the endothelium. LTD4 also relaxed human pulmonary arteries (HPA) precontracted with noradrenaline but this effect was not modified by LT1 antagonists. 4. The results suggest that contraction of endothelium-intact HPV by LTD4 is partially mediated via LT1 receptors. Further, in endothelium-intact HPV, this contraction was opposed by a relaxation induced by LTD4, dependent on the release of nitric oxide, which was mediated, at least in part, via a non-LT1 receptor. In addition, LTD4 relaxation on contracted HPA was not mediated by LT1 receptors. 5. The mechanical effects of LTD4 on human pulmonary vasculature are complex and involve both direct and indirect mechanisms mediated via at least two types of cysteinyl-leukotriene receptors.

Prostacyclin release and receptor activation: differential control of human pulmonary venous and arterial tone.

1. In human pulmonary vascular preparations, precontracted arteries were more sensitive to the relaxant effect of acetylcholine (ACh) than veins (pD(2) values: 7.25+/-0.08 (n=23) and 5.92+/-0.09 (n=25), respectively). Therefore, the role of prostacyclin (PGI(2)) was explored to examine whether this mediator may be responsible for the difference in relaxation. 2. In the presence of the cyclooxygenase (COX) inhibitor, indomethacin (INDO), the ACh relaxations were reduced in arteries but not in veins. On the contrary, an inhibitor (l-NOARG) of the nitric oxide synthase blocked preferentially the relaxation in veins. 3. A greater release of 6-keto-PGF(1alpha), the stable metabolite of PGI(2), was observed in arterial preparations than in venous preparations when stimulated with either ACh or arachidonic acid (AA). 4. Exogenous PGI(2) produced a reduced relaxant effect in the precontracted vein when compared with the artery. In the presence of the EP(1)-receptor antagonist AH6809, the PGI(2) relaxation of veins was similar to arteries. 5. In veins, AA (0.1 mm) produced a biphasic response, namely, a contraction peak (0.4-0.5 g) followed by a relaxation. These contractions in venous preparations were abolished either in the absence of endothelium or in the presence of INDO or an EP(1)-receptor antagonist (AH6809, SC19220). In the arterial preparations AA induced only relaxations. 6. In both vascular preparations, COX-1 but not the COX-2 protein was detected in microsomal preparations derived from homogenized tissues or freshly isolated endothelial cells. 7. The differential vasorelaxations induced by ACh may be explained, in part, by a more pronounced production and release of PGI(2) in human pulmonary arteries than in the veins. In addition, while PGI(2) induced relaxation by activation of IP-receptors in both types of vessels, a PGI(2) constrictor effect was responsible for masking the relaxation in the veins by activation of the EP(1)-receptor.

Plexogenic angiopathy in pulmonary intralobar sequestrations: pathogenetic mechanisms.

Vascular remodeling to form plexiform (glomoid) lesions is a little-known manifestation of intralobar pulmonary sequestration. We describe histologic and immunohistochemical features of these lesions in resected specimens from three subjects aged 3, 19, and 28 years. The vascular changes, which included medial and intimal thickening, angioblastic proliferation, plexiform lesions, and dilation lesions, occurred in a setting of hypoxia, chronic inflammation, and high pressure and flow via a systemic arterial supply. We demonstrated strong immunoreactivity of the angioblastic tissue and the plexiform lesions with antibodies to muscle actin, alpha-smooth muscle actin, and vimentin, and weak to absent reactivity with antibody to desmin. We suggest that in these sequestrations plexiform lesions develop via angioblastic proliferation at arterial branch points and that dilation lesions develop from subsequent expansion of distal anastomoses.

Partial pressure of oxygen is lower in the left upper pulmonary vein than in the right in adults with atrial septal defect: difference in P(O2) between the right and left pulmonary veins.

BACKGROUND: The right-to-left shunt at the atrial level is responsible for arterial hypoxemia in patients with atrial septal defect. OBJECTIVES: This study investigated the mechanism of arterial hypoxemia in patients with atrial septal defect by measuring the P(O2) in both the right and left upper pulmonary veins. SUBJECTS AND METHOD: We prospectively measured the P(O2) in the femoral artery and the right and left upper pulmonary veins during cardiac catheterization in 13 adults (median age, 53 years) and 7 children (median age, 7 years) with secundum atrial septal defect. The adults and children were studied consecutively. Contrast echocardiography was performed to evaluate right-to-left shunt in all adults. RESULTS: Among the children, there were no patients showing arterial hypoxemia, and there was no difference in the P(O2) (+/-SD) between the right and left upper pulmonary veins (right, 100+/-3.8 mm Hg vs left, 100+/-7.8 mm Hg; p = 0.92). However, arterial hypoxemia was present in 11 of the 13 adult patients, although contrast echocardiography showed more than a moderate degree of right-to-left shunt in only four adults. The P(O2) was lower in the left upper pulmonary vein than it was in the right upper pulmonary vein in all adult patients (right, 91.6+/-13.8 mm Hg vs left, 73.0+/-11.5 mm Hg; p < 0.0001). CONCLUSION: The P(O2) was lower in the left upper pulmonary vein than it was in the right upper pulmonary vein in adults with atrial septal defect. Care must be taken in measuring pulmonary blood flow if the P(O2) in the left upper pulmonary vein is low enough to influence oxygen content. The decreased P(O2) in the left upper pulmonary vein may contribute to arterial hypoxemia in addition to right-to-left shunt at the atrial level in adults with atrial septal defect.

Regulatory peptides in the heart and major vessels of man and mammals.

Studies on the distribution of peptides in human tissues have been made either by measuring responses to localized stimuli or by subjecting extracts of different regions to radioimmunoassay (RIA). Attempts at isolating regulatory peptides from the mammalian tissues have resulted in the isolation of many bioactive fragments. Later, modification of initial isolation methods led to the identification of the native molecules in various tissues and body fluids. The present study examined atrial natriuretic peptide (ANP) and several other peptides in cardiac tissues of several species of laboratory mammal and human beings; using a sensitive and highly specific radioimmunoassays. In all the species studied, ANP-like immunoreactivity appeared to be highest in the heart tissue of rat. The peptide was highest in the right atrium (RA) of rat and lowest in the RA of guinea pig (P< 0.002). Neuropeptide Y (NPY) another abundant cardiac peptide was present in the cardiac tissues of all species but was more in the left atrium (LA) than the RA of all species (P<0.05). Calcitonin gene-related peptide (CGRP) was present throughout the cardiovascular system of the rat and guinea pig. Small but detectable amount of Neurotensin (NT) immunoreactivity was found in the rat but was consistently negative in the guinea pig cardiac tissues (P< 0.05). Substance P (SP) immunoreactivity was detected in the rat and higher quantities being in the Aorta but no trace of the peptide was detected in the left ventricle, aorta nor the pulmonary vein of post mortem human. Though the structure of most of the species studied has been elucidated, the primary structure of guinea pig ANP has not been fully generated. Thus the data obtained may suggest that in keeping with these mammalian peptides, the primary structures may be variant. With most of the peptides studied (e.g. ANP, Neuropepdide Y), immunoreactivity occurs predominantly in the atrial tissues, but is also present in vessels outside the heart, a finding which may be of functional significance.

Distribution of Lys-gamma 2-melanocyte-stimulating hormone- (Lys-gamma 2-MSH)-like immunoreactivity in neuronal elements in the brain and peripheral tissues of the rat.

Using an antiserum raised against Lys- gamma 2-melanocyte-stimulating hormone (Lys- gamma 2-MSH), with a high specificity for this peptide and its des-Lys derivative, gamma 2-MSH, we found Lys- gamma 2-MSH-like immunoreactivity to have a widespread distribution in the rat brain. In colchicine-treated rats, groups of immunopositive cell bodies were found in the intermediate and anterior lobes of the pituitary gland, in the hypothalamic arcuate nucleus and in the commissural part of the nucleus of the solitary tract (NTS). Immunopositive fibers were found to originate from the latter two cell body regions. The distribution of these fibers was similar to that of the pro-opiomelanocortin containing cell bodies and projections as it has been described previously. Immunopositive terminals were found in brain region containing neurons which have been shown to express mRNA for melanocortin receptors, though the distribution of Lys-gamma 2-MSH-like immunoreactivity is considerably more widespread than that of mRNA for the 'gamma-MSH receptor' (the melanocortin MC3 receptor), which has been reported to be mainly expressed in the hypothalamus. In the periphery Lys-gamma 2-MSH immunoreactivity was localized in the adrenal medulla and in neuronal fibers and varicosities in the heart. The vascular system, the bronchi and kidney were immunonegative. The occurrence of Lys-gamma 2-MSH immunoreactivity in many of the brain regions which are involved in cardiovascular regulation offers leads for further studies on the putative role of gamma-MSHs in cardiovascular control. The occurrence in the rat heart of Lys-gamma 2-MSH-containing fibers suggests a role of the gamma-MSHs in cardiac function.

Markers of activated hemostasis and fibrinolysis in patients with pulmonary malignancies: comparison of plasma levels in central venous and pulmonary venous blood.

Malignancy frequently is accompanied by activated coagulation and fibrinolysis indicating a hypercoagulable state. The purpose of our study was to estimate the contribution of local tumor-induced mechanisms to the activation of hemostasis and fibrinolysis. In a prospective study, we compared the plasma levels of thrombin-antithrombin complexes, prothrombin fragment 1+2, and D-dimers in blood samples that simultaneously were drawn from the superior vena cava and the pulmonary vein of a tumor-bearing pulmonary lobe. Samples from the superior vena cava were drawn before operation and served as controls. After thoracotomy, a second group of samples was simultaneously taken from the pulmonary veins of the tumor-bearing lobe and the superior vena cava. Forty-five patients with pulmonary malignancies were included (25 adenocarcinomas and 20 squamous cell carcinomas). There were no significant differences of thrombin-antithrombin complexes, prothrombin fragment 1+2, and D-dimers levels in patients suffering from adenocarcinoma and from squamous cell carcinoma. Intraoperatively, prothrombin fragment 1+2 and D-dimers levels were markedly increased when compared with the preoperative values (p<0.0001). There was no increase of thrombin-antithrombin complexes levels due to the operative traumatization. Prothrombin fragment 1+2, thrombin-antithrombin complexes, and D-dimers plasma levels were significantly higher in the pulmonary venous blood than in the blood simultaneously drawn from the superior vena cava (p<0.0001). Our findings indicate that malignant lung tumors directly contribute to the activation of hemostasis and fibrinolysis in these clinical settings.

Expression of angiostatin, integrin alphavbeta3, and vitronectin in human lungs in sepsis.

Angiostatin, integrin alphavbeta3, and vitronectin play important roles in inflammation. However, there is very little information on expression of these molecules in the lungs of humans with sepsis. Therefore, as a first step to eventually study the function of these molecules, the authors conducted an immunohistochemical study to evaluate their expression in lungs of normal (N = 8) and sepsis patients (N = 8). In normal lungs, angiostatin expression was minimal in the alveolar septa and alveolar macrophages, and absent in large blood vessels, bronchioles, and interstitium. In sepsis patients, the staining was intense in the septa, neutrophils, alveolar macrophages, and large blood vessels. Integrin alphavbeta3 staining was observed in occasional bronchiolar epithelial cells and a few alveolar macrophages in the normal lungs. The integrin was expressed extensively and intensely in bronchiolar epithelium and alveolar macrophages, and with lesser intensity in large blood vessels in inflamed lungs. Compared to the normal lung, vitronectin expression was increased in alveolar macrophages and in vascular smooth muscles in inflamed lungs. These data show cell-specific increase in the expression of integrin alphavbeta3, angiostatin, and vitronectin in inflamed lungs of sepsis patients. Because all these molecules can have significant influence on inflammation, the data reported in this manuscript create a need for further investigation.

Postmortem diffusion of alcohol from the stomach.

We explored postmortem ethanol diffusion from the stomach using a human cadaver model with multiple blood site sampling. In all, 400 ml of alcohol solution (5%, 10%, 20%, or 40% methanol and ethanol weight/volume in water) was introduced into the stomach by oesophageal tube. Blood methanol concentrations correlated with ethanol concentrations (methanol range, 1-676 mg%; ethanol range, 1-531 mg%; r = 0.9973). The pattern of ethanol diffusion showed marked between-case variability. Typically, concentrations were highest in pericardial fluid and, in decreasing order, in left pulmonary vein, aorta, left heart, pulmonary artery, superior vena cava, inferior vena cava, right heart, right pulmonary vein, and femoral vein. Diffusional flux was broadly proportional to the concentration of ethanol used. It was time-dependent (as assessed by 24-h and 48-h sampling) and markedly inhibited by refrigeration at 4 degrees C. After gastric instillation of 400 ml of 5% solution for 48 h at room temperature in paired cadavers, ethanol concentrations (mg%) were as follows: pericardial fluid 135, 222; aorta 50, 68; left heart 77, 26; right heart 41, 28; femoral vein 0. Using a 10% solution, ethanol concentrations (mg%) were as follows: pericardial fluid 401, 255; aorta 129, 134; left heart 61, 93; right heart 31, 41; femoral vein 5, 7. Introducing 50 ml of 10% alcohol solution into the oesophagus after oesophagogastric junction ligation produced similar aortic blood ethanol concentrations. This suggests that postmortem gastrooesophageal reflux and diffusion from the oesophagus is the mechanism of artefactual elevation of aortic blood ethanol.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein AI-derived pulmonary vascular amyloid in aged dogs.

Our studies confirm the common occurrence of a unique form of apolipoprotein AI (apoAI)-derived vascular amyloidosis in dogs that appears to be unrelated to other disease conditions, but is associated with aging. Vascular amyloid deposits were most frequently located within the intima and media of medium-sized pulmonary arteries, and were not confirmed in any other tissues. Pulmonary vascular amyloid immunoreactive with antiserum to purified N-terminal (1-71) canine apoAI amyloid protein was demonstrated retrospectively in 12.8% of necropsied dogs (N = 243) 10 years of age or older. In a subsequent expanded 1-year prospective study of necropsied dogs (N = 231) of all ages, apoAI-derived pulmonary vascular amyloid deposits were demonstrated in 0.7% of dogs < 10 years of age and in 22% of dogs 10 years of age or older. The incidence of this form of amyloid in dogs 10 years of age or older was significantly associated with advancing age (P < 0.00001). However, significant differences regarding gender, breed, or the frequency of selected common disease conditions were not observed when the dogs with apoAI-derived amyloid were compared with control dogs. The possibility that this new form of senile apoAI-derived amyloidosis is a manifestation of an age-associated aberration in apoAI metabolism or is related to a mutant form of apoAI is the subject of ongoing investigations.

Culture and characterization of pulmonary microvascular endothelial cells.

Surface proteins were compared in endothelial cells (EC) obtained from bovine peripheral lung, pulmonary artery and vein, and dorsal aorta using sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis. Galactose-containing glycoproteins [molecular weight (M(r)) 160-220 and 40 kDa] binding to the Ricinus communis agglutinin (RCA) and peanut agglutinin (PNA) were selectively observed on pulmonary microvessel EC as compared to EC from pulmonary artery, pulmonary vein, and dorsal aorta. The unique RCA- and PNA-binding profiles of EC from the pulmonary artery and microvessels may be important in characterizing EC from different sites in the pulmonary circulation. The pulmonary microvessel EC monolayer was also 15-fold more restrictive to transendothelial flux of [14C]sucrose (M(r) = 342 Da) than the pulmonary artery EC monolayer. In contrast, the microvessel EC were only six- and twofold more restrictive to the flux of larger tracer molecules, ovalbumin (M(r) 43 kDa) and albumin (M(r) = 69 kDa) than pulmonary artery EC. The greater restrictiveness of pulmonary microvessel EC monolayer indicates a major phenotypic difference in the cultured pulmonary microvessel EC barrier function.

Leiomyosarcoma of the pulmonary vein: case report with immunohistochemical and ultrastructural findings.

We report a case of neoplasia of pulmonary vein in a 45-year-old woman who presented with increasing dyspnea. As a consequence, the neoplasia filled the entire left atrium and appeared to be attached to the left superior pulmonary vein on surgical excision. Histologically, it was composed of a proliferation of sarcomatous cells, with a high mitotic rate and diffuse immunohistochemical positivity for smooth muscle actin, consistent with a leiomyosarcoma. The microscopic, immunohistochemical, and ultrastructural findings are discussed.