Angiotensin-converting enzyme inhibition delays pulmonary vascular neointimal formation

Primary pulmonary hypertension (PPH) is a disease characterized pathologically by pulmonary artery medial hypertrophy, adventitial thickening, and neointimal proliferation. Increasing recognition of the importance of remodeling to the pathogenesis of PPH suggests new therapeutic possibilities, but it will be necessary to (1) identify essential mediators of remodeling, and (2) demonstrate that inhibiting those mediators suppresses remodeling before new antiremodeling therapies can be considered feasible. The effect of angiotensin-converting enzyme (ACE) inhibition on pulmonary vascular remodeling was studied in a newly developed rat model in which neointimal lesions develop between 3 and 5 wk after monocrotaline injury is coupled with increased pulmonary artery blood flow after contralateral pneumonectomy. Neointimal formation was significantly suppressed at 5 wk by ACE inhibition whether it was started 10 d before or 3 wk after remodeling was initiated, although medial hypertrophy and adventitial thickening still developed. By 11 wk, the extent of neointimal formation in rats treated with ACE inhibition was similar to rats without ACE inhibition at 5 wk. Pulmonary artery pressures and right ventricular weights correlated with the extent of neointimal formation. Northern blot analysis and in situ hybridization demonstrated marked suppression of lung tropoelastin and type I procollagen gene expression in the presence of ACE inhibition. An angiotensin II type I receptor antagonist partially, but not completely, replicated the effects of ACE inhibition. These data suggest that the tissue angiotensin system may be a target for therapeutic efforts to suppress the vascular remodeling that is characteristic of primary pulmonary hypertension.     

Chronic pulmonary hypertension--the monocrotaline model and involvement of the hemostatic system

Monocrotaline (MCT) is a toxic pyrrolizidine alkaloid of plant origin. Administration of small doses of MCT or its active metabolite, monocrotaline pyrrole (MCTP), to rats causes delayed and progressive lung injury characterized by pulmonary vascular remodeling, pulmonary hypertension, and compensatory right heart hypertrophy. The lesions induced by MCT(P) administration in rats are similar to those observed in certain chronic pulmonary vascular diseases of people. This review begins with a synopsis of the hemostatic system, emphasizing the role of endothelium since endothelial cell dysfunction likely underlies the pathogenesis of MCT(P)-induced pneumotoxicity. MCT toxicology is discussed, focusing on morphologic, pulmonary mechanical, hemodynamic, and biochemical and molecular alterations that occur after toxicant exposure. Fibrin and platelet thrombosis of the pulmonary microvasculature occurs after administration of MCT(P) to rats, and several investigators have hypothesized that thrombi contribute to the lung injury and pulmonary hypertension. The evidence for involvement of the various components of the hemostatic system in MCT(P)-induced vascular injury and remodeling is reviewed. Current evidence is consistent with involvement of platelets and an altered fibrinolytic system, yet much remains to be learned about specific events and signals in the vascular pathogenesis.     

Etest for routine clinical antimicrobial susceptibility testing of rapid-growing mycobacteria isolates

Tumors depend on their blood supply for growth. The blood supply to metastatic neoplasia of lung is usually from the pulmonary circulation or both the pulmonary and systemic circulation. The antineoplastic effect of pulmonary artery occlusion was investigated in a rat model of methylcholanthrene-induced metastatic pulmonary sarcoma. Left pulmonary artery ligation was performed on day 7 after tumor inoculation, and animals were sacrificed on day 14. The tumor burden of the left lung decreased 44% when compared with the control group. The survival of non-tumor-bearing rats undergoing left pulmonary artery ligation for 24 hours followed by right pneumonectomy after 2 weeks was also studied. No significant lung damage after a period of left pulmonary artery ligation was seen, as evidenced by both survival after contralateral right pneumonectomy and histology. Balloon occlusion of pulmonary artery, together with regional chemotherapy for patients with lung metastases, may warrant investigation.     

How the left lung is perfused after ligating the left pulmonary artery in the pig at birth: clinical implications for the hypoperfused lung

The left pulmonary artery and ductus arteriosus were ligated in 14 pigs at birth. Animals were sacrificed at intervals from 2 to 24 weeks of age. In the right lung the pulmonary artery and in the left, either the distal pulmonary artery, bronchial arteries or both were injected. The fixed lung specimens were studied by arteriography, dissection and microscopic examination of serial and random sections of lung tissue. The bronchial arterial circulation to, and within the right lung appeared normal and was similar to that described in the human lung. In the left lung, the bronchial arterial circulation hypertrophied rapidly during the first 2 weeks, and large anastomoses between pulmonary and systemic circulations were found at the same sites as in the normal pig lung. The position and structural characteristics of the anastomosing arteries is described in the different types of broncho-pulmonary connection. In most animals aged 16 weeks or more, peripheral bronchial arteries immediately proximal to the anastomotic sites, developed intimal and medial proliferation. The left lung continued to grow although in all animals it was small. The axial pulmonary artery and its branches became smaller with age. These findings help explain how the lung is perfused and grows in children with congenital heart disease and an acquired collateral pulmonary arterial circulation.     

Isolated lung perfusion with doxorubicin prolongs survival in a rodent model of pulmonary metastases

BACKGROUND: We developed a rodent model of unilateral pulmonary metastases to evaluate long-term survival after isolated lung perfusion with doxorubicin. METHODS: In the model development study, on day 0, two groups of F344 rats (n = 15) underwent transient right pulmonary artery occlusion for either 5 or 10 minutes at the time of intravenous injection of methylcholantrene-induced sarcoma cells. On day 14, all animals were sacrificed and lung nodules counted. In the survival study, on day 0, 21 rats received intravenous injection of sarcoma cells with concomitant 10-minute right pulmonary artery occlusion. On day 7, eight rats underwent left isolated lung perfusion with doxorubicin (6.4 mg/kg); five rats underwent perfusion with buffered Hespan; six untreated rats were studied as controls. RESULTS: Ten of fifteen animals (67%) in the model study with 5-minute pulmonary artery occlusion had right-sided tumor nodules. Ten-minute occlusion resulted in a tumor-free right lung in all animals. In the survival study, all animals in the Hespan and control groups died of massive tumor replacement of the left lung, with median survival times of 20 and 18 days, respectively. The median survival time of 36 days for the animals undergoing isolated lung perfusion with doxorubicin was significantly longer (p < 0.00001). The left lung of two of the doxorubicin perfused rats was tumor-free at 6 weeks. CONCLUSIONS: Isolated lung perfusion with doxorubicin results in a durable response and prolongs survival in the treatment of experimental sarcoma pulmonary metastases.     

Halasz syndrome revealed in the newborn infant by pulmonary arterial hypertension. Study of 4 cases

In the 4 studied patients presenting with an Halasz's syndrome, the disease was complicated since the neonatal period by pulmonary arterial hypertension and heart failure. Three out of the 4 infants rapidly died, one after pneumonectomy. The fourth is surviving and benefitted solely from medical cardiotonic treatment. The pathogenesis of early pulmonary arterial hypertension in Halasz's syndrome is complex. The possibly associated cardiac malformations, the persistance of fetal obstructive hypertension due to the increase of the flow in the left pulmonary artery, the left to right shunt induced by the abnormal venous return and predominantly by the systemic blood supply to the right lung, are responsible, at various degrees, for pulmonary hypertension. Among surgical procedures to be proposed, the simple ligation of abnormal arteries which take their origin from the aorta seems to be preferable to pneumonectomy.     

A cationic antimicrobial peptide enhances the infectivity of Coxiella burnetii

The pulmonary arteriole remodeling in Wistar rats with respiratory infection induced by mycoplasma pneumoniae was observed using light microscopy and morphometry. The pulmonary artery pressure (PAP) and index of right ventricular hypertrophy (RVHI) were measured. The intimal and medial hypertrophy can be seen in the pulmonary arterioles, leading to vessel wall thickening and narrowing of the lumina. The total number of the pulmonary arterioles decreased (P < 0.01), and both pulmonary hypertension (Ppa 4.11 +/- 0.19 kPa) and right ventricular hypertrophy (RVHI = 34.96 +/- 3.91%) occurred. In addition, an interstitial pulmonary fibrosis (IPF) was found, in which the content of collagen in the lung tissue changed, i. e., type I collagen increased whereas type III one decreased, and the ratio of type I collagen to type III one increased. It suggested that respiratory infection induced by repeated MP may result in remodeling of pulmonary arterioles and are closely related to pulmonary hypertension.     

A clinical study of resected adenoid cystic carcinoma of the tracheobronchial tree

From 1973 to 1990, 7 patients presented with a adenoid cystic carcinoma of tracheobronchial tree that was treated surgically. The locations were larger airways; 4 in the trachea, 1 in the carina, 2 in the basal bronchus. Surgical treatments were performed in all cases. The following resections were done: trachea only 3; carina 1; trachea plus larynx 1; left lower lobe (sleeve lobectomy) 1; left lung (pneumonectomy) 1. Except for tracheolaryngectomy and left pneumonectomy, all cases were undergone primary anastomosis. Operative death was only one patient who died of anastomotic separation. Irradiation was performed in 6 patients before or after operation. Two patients were died due to lung metastases or leukemia. According to the Kaplan-Meier's method, the 5 years survival rate of all patients was 68.6%. Our experience suggests that surgical treatment and adjunctive radiotherapy is beneficial in patients with adenoid cystic carcinoma.     

Changes of vasoactive peptides and effects of inhaled nitric oxide after pneumonectomy

To clarify the role of vasoactive peptides in the physiologic response to pneumonectomy, we investigated the changes of atrial (A-type) natriuretic peptide (ANP). C-type natriuretic peptide (CNP), and endothelin-1 (ET-1) levels in the lung and blood after pneumonectomy and the effects of inhaled nitric oxide (NO; 5 ppm) after pneumonectomy in beagle dogs. The concentrations of these peptides in the lung and blood were measured by radioimmunoassay. The dogs in group A (n = 10) were observed without NO inhaling after right pneumonectomy, and the dogs in group B (n = 5) were observed with NO inhaling from 120 to 180 min after right pneumonectomy. After the thoracotomy, right lung tissue was resected for the pre-operative histological control. Tissue from the left lung was obtained at 120 min (5 dogs in group A), at 180 min (5 dogs in group A), and after 60 min of NO inhalation (group B) for the post-operative histological material. Peripheral blood was collected from the femoral artery. The pulmonary arterial pressure (PAP) was significantly increased after pneumonectomy, but rapidly decreased to the same level as the pre-operative stage after NO inhalation. Increases of plasma ANP, lung ANP and lung CNP levels occurred after pneumonectomy, while the ET-1 level was unchanged. Inhaled NO rapidly reduced the plasma ANP, lung ANP and lung CNP. These results indicate that both ANP and CNP act to maintain normotensive homeostatic balance in the pulmonary circulation.     

The orally active nonpeptide endothelin A-receptor antagonist A-127722 prevents and reverses hypoxia-induced pulmonary hypertension and pulmonary vascular remodeling in Sprague-Dawley rats

Exposure to hypoxia is associated with increased pulmonary artery pressure and plasma endothelin (ET-1) levels and with selective enhancement of ET-1 peptide and messenger RNA (mRNA) and endothelin-A (ET-A) receptor mRNA in rat lung. Our study tested the hypothesis that A-127722, an orally active antagonist of the ET-A receptor, can prevent hypoxia-induced pulmonary hypertension and vascular remodeling in the rat. Pretreatment with A-127722 (3, 10, and 30 mg/kg/day in drinking water for 2 days) caused dose-dependent inhibition of the pulmonary vasoconstrictor response to short-term hypoxia (10% O2, 90 min). Long-term A-127722 treatment (10 mg/kg/day in drinking water for 2 weeks) instituted 48 h before hypoxic exposure attenuated the subsequent development of pulmonary hypertension, the associated right atrial hypertrophy, and pulmonary vascular remodeling. Institution of A-127722 treatment (10 mg/kg/day in drinking water for 4 weeks) after 2 weeks of hypoxia retarded the progression of established hypoxia-induced pulmonary hypertension and right atrial hypertrophy and reversed the pulmonary vascular remodeling despite continuing hypoxic exposure. These findings support the hypothesis that endogenous ET-1 plays a major role in hypoxic pulmonary vasoconstriction/hypertension, right heart hypertrophy, and pulmonary vascular remodeling and suggest that ET-A receptor blockers may be useful in the treatment and prevention of hypoxic pulmonary hypertension in humans.     

Pattern of injury and the role of neutrophils in reperfusion injury of rat lung

Using a rat lung model, we sought to characterize the time course for ischemia-reperfusion injury and the role of neutrophils in the development of injury. Adult male Long-Evans rats underwent left thoracotomy with dissection and clamping of the left pulmonary artery, bronchus, and vein for 90 min, resulting in complete left lung ischemia. The lungs were then ventilated and reperfused for up to 4 hr. Time-matched sham animals underwent the identical thoracotomy and hilar dissection, but the lungs were not rendered ischemic. Using vascular permeability of 125I-labeled bovine serum albumin as a measure of reperfusion injury, a bimodal pattern of injury was observed. Compared to sham controls, animals undergoing ischemia-reperfusion demonstrated a significant early phase of lung injury at 30 min of reperfusion (P < 0.0001), followed by partial recovery. A second peak of lung injury was noted after 4 hr of reperfusion (P < 0.001). Myeloperoxidase activity in reperfused lung tissue, a measure of neutrophil sequestration, increased during the reperfusion time course. To determine the role of neutrophils in the development of lung reperfusion injury, additional animals undergoing the identical ischemia-reperfusion protocol received either rabbit anti-rat neutrophil serum or preimmune serum the day prior to operation. Profound neutropenia (< 75/mm3 blood) was confirmed by differential leukocyte counts. Neutropenia had no protective effect against microvascular permeability at 30 min of reperfusion, but there was a significant reduction in lung injury at 4 hr (P < 0.005). We conclude that, during lung ischemia-reperfusion, there is a bimodal pattern of injury, consisting of both neutrophil-independent and neutrophil-mediated events.     

Epidural and intrathecal n-butyl-p-aminobenzoate solution in the rat. Comparison with bupivacaine

Lipoprotein(a) [Lp(a)] has been proposed as a restenosis risk factor, but it is not known if Lp(a) is present in the injured arterial wall during the initial neointimal growth. The purpose of this study was to determine if Lp(a) is incorporated into the vessel wall during rapid neointimal formation after arterial injury in primates. In this model, distention of the iliac artery with an angioplasty catheter caused focal breaks in the internal elastic lamina (IEL) in 80% of the vessels and extensive IEL fragmentation with medial disruption in 20% of the vessels. Neointimal growth was noted in all injured arteries; thrombus formation was noted in 40% of the vessels. Based on morphometric measurements, injured arteries had neointimal areas of 0.41 +/- 0.05 (n = 4) and 0.83 +/- 0.23 (n = 6) mm2 at 14 and 28 days after injury, respectively. Control arteries had an intact IEL and a monolayer of intimal cells. Lp(a) localization was examined histologically by using a mouse monoclonal anti-Lp(a) antibody. Lp(a), found in all injured arteries, was localized primarily in the neointima in 50% of the vessels. In the subset of vessels with evidence of thrombus formation, intense Lp(a) immunostaining was associated with the thrombus. Lp(a) was specific to injured arteries as uninjured vessels did not stain. In addition, staining was not seen with a negative control, a nonspecific mouse IgG1 antibody. The presence of Lp(a) at the site of rapid neointimal growth supports a role for this lipoprotein in the response to vascular injury after balloon angioplasty.     

Completion right lower lobectomy for recurrence after left pneumonectomy for metastases

Resection of pulmonary recurrences on the residual lung after pneumonectomy for metastases is exceptional. A 37-year-old woman was submitted to left extended pleuro-pneumonectomy after left leg amputation for fibrosarcoma. At 43 months later, a wedge resection on the right lower lobe was performed followed 32 months later by a further wedge resection in the same lobe. A completion right lower lobectomy for a new recurrence was performed 17 months after the last pulmonary resection. The patient did not develop postoperative complications. She is still alive and free of disease 10 years and 9 months after pneumonectomy and 36 months after completion lobectomy on the residual lung. In highly selected patients, aggressive surgery for metastases on the residual lung can be successfully performed and it can improve survival.     

Asymmetric distribution of the pulmonary blood flow between the right and left lungs in d-transposition of the great arteries

Pulmonary angiograms, radionuclide lung images and chest roentgenograms were evaluated regarding the incidence, magnitude and natural evolution of maldistribution of the pulmonary blood flow between the lungs in 63 patients with dextrotransposition of the great arteries. Approximately half of these patients had some degree of greater perfusion of the right relative to the left lung. A significant correlation was demonstrated between the incidence of this maldistribution of blood flow and the angulation between the main and the right pulmonary arteries. For any given angulation between these vessels, additional pulmonary stenosis increased the incidence of disparity in perfusion. Our observations suggest the following developmental mechanisms: The maldistribution in flow results from the abnormal rightward inclination of the main pulmonary artery in the transposition malformation which straightens the flow axis from the main to the right pulmonary artery. Under these circumstances the momentum of the blood in the main pulmonary artery carries the blood preferentially into the right pulmonary artery. This momentum is increased when there is stenosis of the left ventricular outflow tract. Consequent differences in the mechanical properties of the two pulmonary vascular beds can increase this maldistribution. The disparity in perfusion between the lungs is not present in newborns with d-transposition, appears to be progressive in severity and in time may result in almost complete cessation of effective perfusion of the left lung. The effect of the Mustard operation on this abnormality of flow is discussed.     

Fetal branch pulmonary arterial vascular impedance during the second half of pregnancy

OBJECTIVE: Our purpose was to establish normal physiologic parameters in the fetal proximal and distal branch pulmonary arterial vascular impedance during the second half of pregnancy and to analyze relationships between proximal and distal pulmonary arterial blood velocity waveforms. STUDY DESIGN: In this cross-sectional study 100 uncomplicated singleton pregnancies were studied by pulsed color Doppler techniques between 18 and 41 weeks of gestation (median 30 weeks). Both right and left proximal (immediately after the bifurcation of the main pulmonary artery) and distal (beyond the first bifurcation of the branch pulmonary artery) pulmonary artery blood velocity waveforms were recorded and pulsatility index values were calculated. Peak systolic velocities and time-to-peak-velocity intervals were measured. Time-to-peak-velocity intervals were also analyzed at the level of aortic and pulmonary valves and at the ductus arteriosus. Right and left pulmonary artery diameters and right lung length were measured. RESULTS: In both right and left proximal and distal pulmonary arteries pulsatility index values decreased (p < 0.0001) and the peak systolic velocities (p < 0.003) and time-to-peak-velocity intervals (p < 0.0001) increased during the second half of pregnancy. In the proximal pulmonary arteries the pulsatility index values decreased linearly until 34 to 35 weeks of gestation and in the distal pulmonary arteries until 31 weeks of gestation. Thereafter they remained unchanged. In pulmonary arteries time-to-peak-velocity intervals were shorter (p < 0.01) than at the pulmonary valve level. There were no significant differences between the right or left pulmonary arteries in the pulsatility index values, peak systolic velocities, time-to-peak-velocity intervals, or pulmonary artery diameters. In the proximal pulmonary arteries the pulsatility index values (p < 0.02) and peak systolic velocities (p < 0.0001) were higher and time-to-peak-velocity intervals (p < 0.0001) were longer than in the distal pulmonary arteries. There was a 2.5-fold increase in pulmonary artery diameters and right lung length. CONCLUSIONS: Fetal branch pulmonary arterial vascular impedance decreases significantly during the second half of pregnancy. The linear decrease in vascular impedance during the second trimester and in the beginning of the third trimester may be related to the growth of the lung and the increase in the number of resistance vessels. During the latter part of the third trimester pulmonary vascular impedance does not decrease further.     

Nonspecific endothelin-receptor antagonist blunts monocrotaline-induced pulmonary hypertension in rats

Endothelin-1 (ET-1), a potent vasoactive and mitogenic peptide, has been implicated in the pathogenesis of several forms of pulmonary hypertension. We hypothesized that nonspecific blockade of ET receptors would blunt the development of monocrotaline (MCT)-induced pulmonary hypertension in rats. A single dose of the nonspecific ET blocker bosentan (100 mg/kg) given to intact rats by gavage completely blocked the pulmonary vasoconstrictor actions of Big ET-1 and partially blunted hypoxic pulmonary vasoconstriction. After 3 wk, MCT-injected (105 mg/kg sc) rats gavaged once daily with bosentan (200 mg/kg) had lower right ventricular (RV) systolic pressure (RVSP), RV-to-body weight (RV/BW) and RV-to-left ventricular (LV) plus septal (S) weight [RV/(LV+S)] ratios and less percent medial thickness of small pulmonary arteries than control MCT-injected rats. Lower dose bosentan (100 mg/kg) had no effect on these parameters after MCT or saline injection. Bosentan raised plasma ET-1 levels but had no effect on lung ET-1 levels. Bosentan (200 mg/kg) also had no effect on wet-to-dry lung weight ratios 6 days after MCT injection. When given during the last 10 days, but not the first 11 days of a 3-wk period after MCT injection, bosentan reduced RV/(LV+S) compared with MCT-injected controls. We conclude that ET-1 contributes to the pathogenesis of MCT-induced pulmonary hypertension and acts mainly during the later inflammatory rather than the acute injury phase after injection.     

Ischemic preconditioning enhances donor lung preservation in the rat

BACKGROUND: Ischemic preconditioning achieved by brief periods of ischemia and reperfusion before a prolonged period of ischemia can significantly reduce the extent of cardiac damage in many mammalian species and human beings. In this study we used a rat model of single lung transplantation to show that ischemic preconditioning also occurs in the lung. METHODS: Rats randomly selected for ischemic preconditioning had their left main bronchus and pulmonary artery occluded for 5 minutes, followed by 10 minutes of reperfusion and ventilation. Lungs of control rats were ventilated for 15 minutes. The lungs were perfused with University of Wisconsin solution, then heart and lungs were excised en bloc and stored in University of Wisconsin solution at 0 degree C for 6 or 12 hours. After left pneumonectomy, the left lung of the donor was then implanted into the recipient via left thoracotomy. After 1 hour of ventilation and reperfusion, a right pneumonectomy was performed making the animal completely dependent on the transplanted lung. Samples of arterial blood from the left ventricle were then taken for arterial oxygen tension and arterial carbon dioxide tension determination. Water contents of the donor lungs were measured before and after reperfusion. Thiobarbituric acid reactive substances were measured in the right donor lung after storage. RESULTS: Lungs transplanted after 12 hours of storage had profoundly impaired gas exchange (arterial oxygen tension = 34 +/- 5; arterial carbon dioxide tension = 69 +/- 7 mm Hg) compared with the normal levels in the 6-hour storage group (arterial oxygen tension = 308 +/- 22; arterial carbon dioxide tension = 17 +/- 1 mm Hg). Ischemic preconditioning significantly improved gas exchange in the 12-hour storage group (arterial oxygen tension = 83 +/- 11; arterial carbon dioxide tension = 40 +/- 4 mm Hg). Ischemic preconditioning also significantly decreased thiobarbituric acid reactive substances formation at both 6- and 12-hour storage. CONCLUSIONS: These results show that the phenomenon of ischemic preconditioning occurs in the lung and that it may reduce injury to the donor lung during prolonged cold ischemic storage.     

Endoscopic mucosal resection for early esophageal cancer]

OBJECTIVES: We investigated the role of endogenous endothelin-1 in the development of cardiac hypertrophy in vivo under pressure overload conditions. BACKGROUND: Endothelin-1, a potent vasoconstrictor peptide, has recently been shown to act as a growth factor of myocardial cells in culture. METHODS: We examined the effect of an endothelin-A receptor antagonist (FR139317) on the development of right ventricular hypertrophy in rats with monocrotaline-induced pulmonary hypertension. Three groups of rats were studied: those given monocrotaline alone or monocrotaline plus FR139317 and those given vehicle alone (control group). RESULTS: The ratio of right ventricular systolic pressure to aortic systolic pressure was similarly elevated in rats treated with monocrotaline and monocrotaline plus FR139317. The right ventricular/left ventricular weight ratio was increased in monocrotaline-treated rats but lower in rats treated with monocrotaline plus FR139317 than in those treated with monocrotaline alone (p < 0.01). As a biochemical marker of hypertrophy, the isoform ratio of beta-myosin heavy chain protein was determined for the right ventricular tissue samples. This ratio was increased in all monocrotaline-treated rats but was lower (p < 0.01) in rats given monocrotaline plus FR139317 than in those given monocrotaline alone. The isoform ratio of beta-myosin heavy chain messenger ribonucleic acid quantitated by S1 nuclease mapping also was lower (p < 0.025) in rats receiving monocrotaline plus FR139317 than in those receiving monocrotaline alone. CONCLUSIONS: These data suggest that blocking the action of endothelin-1 with a receptor antagonist ameliorates cardiac hypertrophy in this model system, and that this action is not mediated by ameliorating hemodynamic changes.     

Moyamoya disease associated with pulmonary sarcoidosis--case report

A 61-year-old female presented with a unique case of moyamoya disease associated with pulmonary sarcoidosis. She was admitted for sudden onset of left temporalgia with episode of numbness on face, tongue, and upper extremity on the right side. The next morning, she had symptoms of Gerstmann syndrome and her ability to speak was disturbed. Her medical history included radical resection of lung cancer on the right side. She had no symptoms of pulmonary sarcoidosis. Neuroimaging showed an infarction in the left occipital lobe. Angiography showed occlusions of the bilateral internal carotid arteries at the supraclinoid portions. Subsequently, a left superficial temporal artery-middle cerebral artery anastomosis with encephalo-myo-synangiosis was performed. Ninety-three days after admission, she suddenly developed dyspnea which resulted in death 3 hours later. Autopsy findings showed typical epithelioid granulomas of sarcoid type in the lymph nodes of the peribronchus, lung, and liver. Thrombotic emboli were found in the bilateral pulmonary arteries, and marked fibrous intimal thickening in the bilateral internal carotid arteries. Immunological reaction with inflammatory events may cause pathological changes in patients with moyamoya disease or sarcoidosis. The co-incidence in this case suggests that some common inflammatory events may be involved in the pathogenesis of these diseases.     

Bilateral Krukenberg tumors due to appendiceal mucinous carcinoid

Three cases of congenital polyalveolar lobe (pulmonary hamartoma) were diagnosed in female Thoroughbred foals. Foal 1 was born at full term but died shortly afterwards. Foal 2 was aborted at the seventh month of gestation. Parturition was induced at the tenth month of gestation in foal 3 because it developed hydrops of the amnion and ascites. In all three foals, the polyalveolar lobe occurred on the right side and affected the entire right lung. In each case, the right lung formed a tumour-like mass, and expanded into the left chest cavity. The lung masses were pink to dark red and spongy to rubbery, with marked lobular patterns on the pleural and cut surfaces. The left lung was compressed and small. The right and left lungs weighed 0.9-6.3 kg and 80 g-0.3 kg, respectively. Microscopically, the polyalveolar lobe consisted of normal alveoli, bronchioli and blood vessels, but the alveolus:artery ratio was greater than normal. In the polyalveolar lobe of two foals the numbers of alveoli per artery were 65.2 and 52.5; in contrast, the corresponding values for three control lungs were 26.9, 26.5 and 27.6. Chronic passive congestion with generalized oedema was observed in foals 2 and 3.