Microvascular Corrosion Casting of the Lung. A State-of-the-Art Review

Corrosion casting and viewing of replicas with the scanning electron microscope is an excellent way to study the microvascular structure of the lung. This method can demonstrate aspects of the three-dimensional relationships, branching patterns, maximum diameters, arterio-venous connections, unusual sized and shaped capillaries, development and growth, neovascular structures and changes in development and disease better than any other means. Comparisons can be made in many experimental conditions and fundamental information obtained to answer physiologic questions. This paper reviews how the lung microvasculature has been studied by corrosion casting and scanning electron microscopy and indicates new areas where investigation might be pursued in humans and laboratory mammals. Although this technique has already greatly expanded our perception of the microcirculation, it should continue to be developed and become an even more valuable tool to study questions about the pulmonary vascular system

Microvascular Casting of the Lung: Bronchial Versus Pulmonary Artery Filling

To determine the importance of the pulmonary or bronchial arteries as the site of injection to cast the lung vasculature of rats, we retrospectively compared a group of normal Sprague-Dawley rats that were cast through either the caudal vena cava and right ventricle leading to the pulmonary arteries or through the aorta and bronchial arteries. There was no difference in the appearance of the whole casts or cast-to-lung weight ratios between the two groups, although an incompletely cast lung that was injected through the aorta showed preferential filling of the pleural and peribronchial regions. Nuclear impressions, a sign of good filling, were more frequent and the grade of the images was higher in the group filled through the vena cava. The microvascular density index was not different between the two groups, and a multivariate analysis of variance showed the injection site was not important in determining vascular density. The pulmonary vessels fill nearly as well when injected from the bronchial circulation indicating that the bronchial circulation can immediately perfuse the lung if the pulmonary arteries are obstructed, and casting can be carried out from either side with nearly the same results

Ranking Corrosion Efficiency: A Latin Square Study on Rat Lung Microvascular Corrosion Casts

Scanning electron microscopy of corrosion casts is an important tool for the study of microvascular structure but few systematic studies on methods of specimen preparation have been reported. This study sought to determine the relative importance of factors involved in corrosion. It compared potassium hydroxide, sodium hydroxide and water as major corrosive agents. It tested the size of the tissue sample, and the use of prealkali autolysis, detergent, and proteolytic enzymes in a Latin square designed study. The main findings were that sodium and potassium hydroxide were better than water (P \u3c 0.0001) and the longer the corrosion time the better corroded the samples were (P \u3c 0.0001 ). Although not a controlled factor, higher room temperature was also associated with better corrosion. The use of proteolytic enzymes, detergent, and warm tap water alone before the alkali treatment did not significantly improve the corrosion in this study, although this does not preclude an effect with another experimental design

Microvascular Casting of the Lung: Vascular Lavage

Corrosion casting is an important tool for the study of microvascular structure, but unlike tissue preparation for light and electron microscopy, few controlled studies of the methods for preparation of microvascular casts for scanning electron microscopy have been reported. Most vascular casting begins with rinsing cells from the lumen of the blood vessels, but the necessity of this has not been shown. Because of a report of successful casting without rinsing and light microscopic evidence of edema with complete rinsing prior to casting, this preparation procedure was examined. Casts of lung vasculature that were thoroughly rinsed were compared to those that were not. Of the six rats that were not lavaged, only one gave a completely filled cast, but of the six animals that were well rinsed, only one did not fill. Except for the filling and mild periarterial edema, no significant difference in cast quality or features was detected. Rinsing improves the frequency of obtaining completely filled casts. The edema does not greatly interfere with the capillary image and its location gives insight into this process in the lung

Risk factors for death in 632 patients with sickle cell disease in the United States and United Kingdom

Background: The role of pulmonary hypertension as a cause of mortality in sickle cell disease (SCD) is controversial. Methods and Results: We evaluated the relationship between an elevated estimated pulmonary artery systolic pressure and mortality in patients with SCD. We followed patients from the walk-PHaSST screening cohort for a median of 29 months. A tricuspid regurgitation velocity (TRV)≥3.0 m/s cuttof, which has a 67-75% positive predictive value for mean pulmonary artery pressure ≥25 mm Hg was used. Among 572 subjects, 11.2% had TRV≥3.0 m/sec. Among 582 with a measured NT-proBNP, 24.1% had values ≥160 pg/mL. Of 22 deaths during follow-up, 50% had a TRV≥3.0 m/sec. At 24 months the cumulative survival was 83% with TRV≥3.0 m/sec and 98% with TRV47 years, male gender, chronic transfusions, WHO class III-IV, increased hemolytic markers, ferritin and creatinine were also associated with increased risk of death. Conclusions: A TRV≥ 3.0 m/sec occurs in approximately 10% of individuals and has the highest risk for death of any measured variable. The study is registered in ClinicalTrials.gov with identifier: NCT00492531

Impact of oral cyclophosphamide on health-related quality of life in patients with active scleroderma lung disease: Results from the scleroderma lung study

Objective To assess the impact of cyclophosphamide (CYC) on the health-related quality of life (HRQOL) of patients with scleroderma after 12 months of treatment. Methods One hundred fifty-eight subjects participated in the Scleroderma Lung Study, with 79 each randomized to CYC and placebo arms. The study evaluated the results of 3 measures of health status: the Short Form 36 (SF-36), the Health Assessment Questionnaire (HAQ) disability index (DI), and Mahler's dyspnea index, and the results of 1 preference-based measure, the SF-6D. The differences in the HRQOL between the 2 groups at 12 months were calculated using a linear mixed model. Responsiveness was evaluated using the effect size. The proportion of subjects in each treatment group whose scores improved at least as much as or more than the minimum clinically important difference (MCID) in HRQOL measures was assessed. Results After adjustment for baseline scores, differences in the HAQ DI, SF-36 role physical, general health, vitality, role emotional, mental health scales, and SF-36 mental component summary (MCS) score were statistically significant for CYC versus placebo ( P < 0.05). Effect sizes were negligible (<0.20) for all of the scales of the SF-36, HAQ DI, and SF-6D at 12 months. In contrast, a higher proportion of patients who received CYC achieved the MCID compared with placebo in the HAQ DI score (30.9% versus 14.8%), transitional dyspnea index score (46.4% versus 12.7%), SF-36 MCS score (33.3% versus 18.5%), and SF-6D score (21.3% versus 3.8%). Conclusion One year of treatment with CYC leads to an improvement in HRQOL in patients with scleroderma lung disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56039/1/22580_ftp.pd

Capillary Proliferation in Systemic-Sclerosis-Related Pulmonary Fibrosis: Association with Pulmonary Hypertension

We sought to determine if any histopathologic component of the pulmonary microcirculation can distinguish systemic sclerosis (SSc)-related pulmonary fibrosis (PF) with and without pulmonary hypertension (PH)

Helsinki by nature : The Nature Step to Respiratory Health

Background: The Nature Step to Respiratory Health was the overarching theme of the 12th General Meeting of the Global Alliance against Chronic Respiratory Diseases (GARD) in Helsinki, August 2018. New approaches are needed to improve respiratory health and reduce premature mortality of chronic diseases by 30% till 2030 (UN Sustainable Development Goals, SDGs). Planetary health is defined as the health of human civilization and the state of the natural systems on which it depends. Planetary health and human health are interconnected, and both need to be considered by individuals and governments while addressing several SDGs. Results: The concept of the Nature Step has evolved from innovative research indicating, how changed lifestyle in urban surroundings reduces contact with biodiverse environments, impoverishes microbiota, affects immune regulation and increases risk of NCDs. The Nature Step calls for strengthening connections to nature. Physical activity in natural environments should be promoted, use of fresh vegetables, fruits and water increased, and consumption of sugary drinks, tobacco and alcohol restricted. Nature relatedness should be part of everyday life and especially emphasized in the care of children and the elderly. Taking "nature" to modern cities in a controlled way is possible but a challenge for urban planning, nature conservation, housing, traffic arrangements, energy production, and importantly for supplying and distributing food. Actions against the well-known respiratory risk factors, air pollution and smoking, should be taken simultaneously. Conclusions: In Finland and elsewhere in Europe, successful programmes have been implemented to reduce the burden of respiratory disorders and other NCDs. Unhealthy behaviour can be changed by well-coordinated actions involving all stakeholders. The growing public health concern caused by NCDs in urban surroundings cannot be solved by health care alone; a multidisciplinary approach is mandatory.peerReviewe