Venoarterial extracorporeal membrane oxygenation (ECMO) for support during whole lung lavage for pulmonary alveolar proteinosis.

INTRODUCTION ECMO as support during whole lung lavage (WLL) for pulmonary alveolar proteinosis is reserved for severe cases where oxygenation is inadequate to support the patient using the ventilator alone. While most publications describe a venovenous cannulation with variable results we present a successful case using venoarterial cannulation and discuss the potential benefits of this mode of ECMO support. CASE PRESENTATION We present the case of a 44 year old female with a past medical history of Behcets disease and a BMI of 37 who was diagnosed with pulmonary alveolar proteinosis (PAP) on a lung biopsy after presenting with dyspnea. As her supplemental oxygen needs escalated she was intubated and was difficult to oxygenate on a conventional ventilator. She was urgently taken to the operating room for venoarterial ECMO support and whole lung lavage. The patient was cannulated femorally using a 20 french venous catheter and an 18 french arterial catheter, with a retrograde arterial catheter to preserve distal perfusion to the right lower extremity. ECMO flow was satisfactory at 4L/min. The whole lung lavage was performed bilaterally using 12 liters of normal saline in one liter instillations with chest physiotherapy between liters. The character and color of the fluid was initially opaque and sero-sanguinous; at the conclusion of the 12 liter lavage the fluid was serous and transparent. Her oxygenation improved immediately post operatively and she was decannulated from ECMO on the fifth post-operative day without complications. DISCUSSION We propose that venoarterial ECMO is superior to venovenous ECMO during whole lung lavage because total cardiopulmonary support can be provided to the patient to maintain adequate oxygenation and hemodynamics. During whole lung lavage while the pulmonary vascular resistance increases, strain on the right ventricle increases and can be avoided with venoarterial ECMO. CONCLUSIONS Venoarterial ECMO for support during whole lung lavage for PAP may provide a superior alternative to venovenous ECMO in patients who are difficult to ventilate and/or oxygenate due to the severity of their disease. REFERENCES 1. Cohen ES, Elpern E, Silver MR. Pulmonary alveolar proteinosis causing severe hypoxemic respiratory failure treated with sequential whole-lung lavage utilizing venovenous extracorporeal membrane oxygenation: a case report and review. Chest. 2001 Sep;120(3):1024-6. 2. Centella T, Oliva E, Andrade IG, Epeldegui A. The use of a membrane oxygenator with extracorporeal circulation in bronchoalveolar lavage for alveolar proteinosis. Interact Cardiovasc Thorac Surg. 2005 Oct;4(5):447-9. Epub 2005 Jun 27. 3. Rogers RM, Szidon JP, Shelburne J, Neigh JL, Shuman JF, Tantum KR. Hemodynamic response of the pulmonary circulation to bronchopulmonary lavage in man. N Engl J Med. 1972 Jun 8;286(23):1230-3

Aberrant Lymphatic Endothelial Progenitors in Lymphatic Malformation Development

Lymphatic malformations (LMs) are vascular anomalies thought to arise from dysregulated lymphangiogenesis. These lesions impose a significant burden of disease on affected individuals. LM pathobiology is poorly understood, hindering the development of effective treatments. In the present studies, immunostaining of LM tissues revealed that endothelial cells lining aberrant lymphatic vessels and cells in the surrounding stroma expressed the stem cell marker, CD133, and the lymphatic endothelial protein, podoplanin. Isolated patient-derived CD133+ LM cells expressed stem cell genes (NANOG, Oct4), circulating endothelial cell precursor proteins (CD90, CD146, c-Kit, VEGFR-2), and lymphatic endothelial proteins (podoplanin, VEGFR-3). Consistent with a progenitor cell identity, CD133+ LM cells were multipotent and could be differentiated into fat, bone, smooth muscle, and lymphatic endothelial cells in vitro. CD133+ cells were compared to CD133− cells isolated from LM fluids. CD133− LM cells had lower expression of stem cell genes, but expressed circulating endothelial precursor proteins and high levels of lymphatic endothelial proteins, VE-cadherin, CD31, podoplanin, VEGFR-3 and Prox1. CD133− LM cells were not multipotent, consistent with a differentiated lymphatic endothelial cell phenotype. In a mouse xenograft model, CD133+ LM cells differentiated into lymphatic endothelial cells that formed irregularly dilated lymphatic channels, phenocopying human LMs. In vivo, CD133+ LM cells acquired expression of differentiated lymphatic endothelial cell proteins, podoplanin, LYVE1, Prox1, and VEGFR-3, comparable to expression found in LM patient tissues. Taken together, these data identify a novel LM progenitor cell population that differentiates to form the abnormal lymphatic structures characteristic of these lesions, recapitulating the human LM phenotype. This LM progenitor cell population may contribute to the clinically refractory behavior of LMs

Aberrant Lymphatic Endothelial Progenitors in Lymphatic Malformation Development

Lymphatic malformations (LMs) are vascular anomalies thought to arise from dysregulated lymphangiogenesis. These lesions impose a significant burden of disease on affected individuals. LM pathobiology is poorly understood, hindering the development of effective treatments. In the present studies, immunostaining of LM tissues revealed that endothelial cells lining aberrant lymphatic vessels and cells in the surrounding stroma expressed the stem cell marker, CD133, and the lymphatic endothelial protein, podoplanin. Isolated patient-derived CD133+ LM cells expressed stem cell genes (NANOG, Oct4), circulating endothelial cell precursor proteins (CD90, CD146, c-Kit, VEGFR-2), and lymphatic endothelial proteins (podoplanin, VEGFR-3). Consistent with a progenitor cell identity, CD133+ LM cells were multipotent and could be differentiated into fat, bone, smooth muscle, and lymphatic endothelial cells in vitro. CD133+ cells were compared to CD133− cells isolated from LM fluids. CD133− LM cells had lower expression of stem cell genes, but expressed circulating endothelial precursor proteins and high levels of lymphatic endothelial proteins, VE-cadherin, CD31, podoplanin, VEGFR-3 and Prox1. CD133− LM cells were not multipotent, consistent with a differentiated lymphatic endothelial cell phenotype. In a mouse xenograft model, CD133+ LM cells differentiated into lymphatic endothelial cells that formed irregularly dilated lymphatic channels, phenocopying human LMs. In vivo, CD133+ LM cells acquired expression of differentiated lymphatic endothelial cell proteins, podoplanin, LYVE1, Prox1, and VEGFR-3, comparable to expression found in LM patient tissues. Taken together, these data identify a novel LM progenitor cell population that differentiates to form the abnormal lymphatic structures characteristic of these lesions, recapitulating the human LM phenotype. This LM progenitor cell population may contribute to the clinically refractory behavior of LMs.</p

Hyperdominance in Amazonian Forest Carbon Cycling

While Amazonian forests are extraordinarily diverse, the abundance of trees is skewed strongly towards relatively few ‘hyperdominant’ species. In addition to their diversity, Amazonian trees are a key component of the global carbon cycle, assimilating and storing more carbon than any other ecosystem on Earth. Here we ask, using a unique data set of 530 forest plots, if the functions of storing and producing woody carbon are concentrated in a small number of tree species, whether the most abundant species also dominate carbon cycling, and whether dominant species are characterized by specific functional traits. We find that dominance of forest function is even more concentrated in a few species than is dominance of tree abundance, with only ≈1% of Amazon tree species responsible for 50% of carbon storage and productivity. Although those species that contribute most to biomass and productivity are often abundant, species maximum size is also influential, while the identity and ranking of dominant species varies by function and by region

Long-term thermal sensitivity of Earth’s tropical forests

The sensitivity of tropical forest carbon to climate is a key uncertainty in predicting global climate change. Although short-term drying and warming are known to affect forests, it is unknown if such effects translate into long-term responses. Here, we analyze 590 permanent plots measured across the tropics to derive the equilibrium climate controls on forest carbon. Maximum temperature is the most important predictor of aboveground biomass (−9.1 megagrams of carbon per hectare per degree Celsius), primarily by reducing woody productivity, and has a greater impact per °C in the hottest forests (>32.2°C). Our results nevertheless reveal greater thermal resilience than observations of short-term variation imply. To realize the long-term climate adaptation potential of tropical forests requires both protecting them and stabilizing Earth’s climate

Basin-wide variations in Amazon forest structure and function are mediated by both soils and climate

Forest structure and dynamics vary across the Amazon Basin in an east-west gradient coincident with variations in soil fertility and geology. This has resulted in the hypothesis that soil fertility may play an important role in explaining Basin-wide variations in forest biomass, growth and stem turnover rates. Soil samples were collected in a total of 59 different forest plots across the Amazon Basin and analysed for exchangeable cations, carbon, nitrogen and pH, with several phosphorus fractions of likely different plant availability also quantified. Physical properties were additionally examined and an index of soil physical quality developed. Bivariate relationships of soil and climatic properties with above-ground wood productivity, stand-level tree turnover rates, above-ground wood biomass and wood density were first examined with multivariate regression models then applied. Both forms of analysis were undertaken with and without considerations regarding the underlying spatial structure of the dataset. Despite the presence of autocorrelated spatial structures complicating many analyses, forest structure and dynamics were found to be strongly and quantitatively related to edaphic as well as climatic conditions. Basin-wide differences in stand-level turnover rates are mostly influenced by soil physical properties with variations in rates of coarse wood production mostly related to soil phosphorus status. Total soil P was a better predictor of wood production rates than any of the fractionated organic- or inorganic-P pools. This suggests that it is not only the immediately available P forms, but probably the entire soil phosphorus pool that is interacting with forest growth on longer timescales. A role for soil potassium in modulating Amazon forest dynamics through its effects on stand-level wood density was also detected. Taking this into account, otherwise enigmatic variations in stand-level biomass across the Basin were then accounted for through the interacting effects of soil physical and chemical properties with climate. A hypothesis of self-maintaining forest dynamic feedback mechanisms initiated by edaphic conditions is proposed. It is further suggested that this is a major factor determining endogenous disturbance levels, species composition, and forest productivity across the Amazon Basin. © 2012 Author(s). CC Attribution 3.0 License

Lymphatic Malformations and Oxygenators: Basic Research and Clinical Experience as the Research/ECMO Fellow at Columbia and Cannulation Instead of Intubation: VV ECMO for Respiratory Failure in a Patient with Idiopathic Pulmonary Arterial Hypertension

Presentation: 14 minute

Identification of CD133⁺ cells in LMs of different subtypes and anatomical locations.

<p>(A) LYVE1 and podoplanin staining of cervicofacial mixed LM tissue and patient-matched uninvolved tissue. White arrowheads mark normal lymphatics. (B) Podoplanin and CD133 staining of neonatal foreskin (postnatal day 1), uninvolved tissue, mixed cervicofacial (Mixed CF) LM tissues (2x), and Gorham’s dermal tissue. White arrowheads mark CD133⁺/podoplanin⁺ lymphatic endothelium. Red arrowheads mark CD133^low/podoplanin⁺ lymphatic endothelium. Yellow arrowheads mark CD133⁺/podoplanin⁺ stromal cells. Blue asterisks mark blood vessels with autofluorescing red blood cells. Scale bars: 50μm. lymphatic channel (lc)</p