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George J. F. Heigenhauser - One of the best experts on this subject based on the ideXlab platform.
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Transvascular fluid flux from the Pulmonary Vasculature at rest and during exercise in horses.
The Journal of Physiology, 2006Co-Authors: Modest Vengust, Henry R. Staempfli, Laurent Viel, George J. F. HeigenhauserAbstract:Exercise causes changes in Pulmonary haemodynamics through redistribution of blood flow, increase in the Pulmonary surface area, and increase in Pulmonary vascular pressures. These changes contribute to the increase in fluid exchange across the alveolar–capillary barrier. To determine the extent of the fluid exchange across the alveolar–capillary barrier at rest and during exercise, six horses were exercised on a high-speed treadmill until fatigue. Arterial and mixed venous blood were sampled at rest and during exercise and recovery. Blood volume changes across the lung (ΔBV; measured in percentage) were calculated from changes in plasma protein and haemoglobin concentration, and haematocrit. Cardiac output (Q) was calculated using the Fick equation. Fluid flux (JV−A; measured in l min−1) across the alveolar–capillary barrier was then quantified based on Q and ΔBV. At rest, no fluid movement occurred across the Pulmonary Vasculature (0.6 ± 0.6 l min−1). During exercise, the amount of fluid moved from the Pulmonary circulation was 8.3 ± 1.3 l min−1 at 1 min, 6.4 ± 2.9 l min−1 at 2 min, 10.1 ± 1.0 l min−1 at 3 min, 12.9 ± 2.5 l min−1 at 4 and 9.6 ± 1.5 l min−1 at fatigue (all P < 0.0001). Erythrocyte volume decreased by 6% (P < 0.01) across the lungs, which decreased the colloid osmotic gradient in the Pulmonary Vasculature. Decrease colloid osmotic gradient along with increased hydrostatic forces in the Pulmonary Vasculature would enhance displacement of fluid into the Pulmonary interstitium. In conclusion, exercise caused large increases in transPulmonary fluid fluxes in horses. Here, we present a simple method to calculate transPulmonary fluid fluxes in different species, which can be used to elucidate mechanisms of lung fluid balance in vivo.
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Transvascular fluid flux from the Pulmonary Vasculature at rest and during exercise in horses.
The Journal of physiology, 2005Co-Authors: Modest Vengust, Henry R. Staempfli, Laurent Viel, George J. F. HeigenhauserAbstract:Exercise causes changes in Pulmonary haemodynamics through redistribution of blood flow, increase in the Pulmonary surface area, and increase in Pulmonary vascular pressures. These changes contribute to the increase in fluid exchange across the alveolar-capillary barrier. To determine the extent of the fluid exchange across the alveolar-capillary barrier at rest and during exercise, six horses were exercised on a high-speed treadmill until fatigue. Arterial and mixed venous blood were sampled at rest and during exercise and recovery. Blood volume changes across the lung (DeltaBV; measured in percentage) were calculated from changes in plasma protein and haemoglobin concentration, and haematocrit. Cardiac output (Q) was calculated using the Fick equation. Fluid flux (J(V-A); measured in l min(-1)) across the alveolar-capillary barrier was then quantified based on Q and DeltaBV. At rest, no fluid movement occurred across the Pulmonary Vasculature (0.6 +/- 0.6 l min(-1)). During exercise, the amount of fluid moved from the Pulmonary circulation was 8.3 +/- 1.3 l min(-1) at 1 min, 6.4 +/- 2.9 l min(-)(1) at 2 min, 10.1 +/- 1.0 l min(-1) at 3 min, 12.9 +/- 2.5 l min(-1) at 4 and 9.6 +/- 1.5 l min(-1) at fatigue (all P < 0.0001). Erythrocyte volume decreased by 6% (P < 0.01) across the lungs, which decreased the colloid osmotic gradient in the Pulmonary Vasculature. Decrease colloid osmotic gradient along with increased hydrostatic forces in the Pulmonary Vasculature would enhance displacement of fluid into the Pulmonary interstitium. In conclusion, exercise caused large increases in transPulmonary fluid fluxes in horses. Here, we present a simple method to calculate transPulmonary fluid fluxes in different species, which can be used to elucidate mechanisms of lung fluid balance in vivo.
Modest Vengust - One of the best experts on this subject based on the ideXlab platform.
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Transvascular fluid dynamics in the Pulmonary Vasculature in horses at rest and during exercise
2010Co-Authors: Modest VengustAbstract:Maximal exercise results in a marked increase in cardiac output (Q) with consequent adaptations in Pulmonary macro- and microVasculature. These adaptations change Pulmonary hemodynamics and increase fluid and solute movement between the Pulmonary circulation and the Pulmonary interstitium (across the lung). The purpose of this study was to determine Pulmonary circulation transvascular fluid fluxes in a quantitative manner during exercise in horses. This was determined during exercise at 80% VO2max on a high-speed treadmill until fatigue without any medication, with acetazolamide (Acz) treatment, and with furosemide (Fur) treatment. Acetazolamide, a carbonic anhydrase (CA) inhibitor, has several effects on Pulmonary Vasculature and erythrocytes, which influence Pulmonary circulation transvascular fluid fluxes and electrolyte changes across the lung. These mechanisms are expressed through its ability to reduce vascular smooth muscle tone and contractility, and to attenuate hydration/dehydration of CO2 via the CA, Jacobs-Stewart cycle and chloride shift (Hamburger shift) inhibition. Furosemide causes diuresis. The consequence of diuresis is a decrease in plasma volume, right ventricular preload, and Q, which results in reduction in transmural hydrostatic pressures in Pulmonary Vasculature. Reduction of transmural hydrostatic forces is the mechanism by which Fur is believed to attenuate exercise induced Pulmonary hemorrhage. Furosemide has also a dilatory effect on the Pulmonary Vasculature, and it may affect the chloride shift across the erythrocyte membrane. Resting, exercise, and recovery arterial and mixed venous blood were sampled from race fit standarbred horses. Blood (BV) and erythrocyte volume (EV) changes across the lung were calculated from changes in plasma protein, hemoglobin and hematocrit. Cardiac output was calculated using Fick equation. Fluid flux across the lung was quantified based on changes in BV and EV across the lung. Integrative physicochemical systems approach was used to describe acid base changes across the lung. The overall findings of these studies showed that approximately 12 L/min or 4 % of Q moves from the Pulmonary circulation into the Pulmonary interstitium during exertion in horses. This volume, which left the Pulmonary circulation, was derived primarily from the reduction of erythrocytes’ volume across the lung. Acetazolamide attenuated transvascular fluid fluxes in the Pulmonary circulation through attenuation of the erythrocyte volume changes. It did not change Q. Furosemide did not affect erythrocyte volume changes and transvascular fluid fluxes in the Pulmonary circulation, but reduced Q. Cardiac output during exercise is indicative of Pulmonary capillary recruitment and/or dilatation coupled with the increase in the Pulmonary surface area. From the results of our studies we conclude that Pulmonary circulation transvascular fluid fluxes are regulated by erythrocyte volume regulation. Hydrostatic transmural gradients across the Pulmonary Vasculature have a minor effect on Pulmonary circulation transvascular fluid fluxes during exercise in horses.
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Transvascular fluid flux from the Pulmonary Vasculature at rest and during exercise in horses.
The Journal of Physiology, 2006Co-Authors: Modest Vengust, Henry R. Staempfli, Laurent Viel, George J. F. HeigenhauserAbstract:Exercise causes changes in Pulmonary haemodynamics through redistribution of blood flow, increase in the Pulmonary surface area, and increase in Pulmonary vascular pressures. These changes contribute to the increase in fluid exchange across the alveolar–capillary barrier. To determine the extent of the fluid exchange across the alveolar–capillary barrier at rest and during exercise, six horses were exercised on a high-speed treadmill until fatigue. Arterial and mixed venous blood were sampled at rest and during exercise and recovery. Blood volume changes across the lung (ΔBV; measured in percentage) were calculated from changes in plasma protein and haemoglobin concentration, and haematocrit. Cardiac output (Q) was calculated using the Fick equation. Fluid flux (JV−A; measured in l min−1) across the alveolar–capillary barrier was then quantified based on Q and ΔBV. At rest, no fluid movement occurred across the Pulmonary Vasculature (0.6 ± 0.6 l min−1). During exercise, the amount of fluid moved from the Pulmonary circulation was 8.3 ± 1.3 l min−1 at 1 min, 6.4 ± 2.9 l min−1 at 2 min, 10.1 ± 1.0 l min−1 at 3 min, 12.9 ± 2.5 l min−1 at 4 and 9.6 ± 1.5 l min−1 at fatigue (all P < 0.0001). Erythrocyte volume decreased by 6% (P < 0.01) across the lungs, which decreased the colloid osmotic gradient in the Pulmonary Vasculature. Decrease colloid osmotic gradient along with increased hydrostatic forces in the Pulmonary Vasculature would enhance displacement of fluid into the Pulmonary interstitium. In conclusion, exercise caused large increases in transPulmonary fluid fluxes in horses. Here, we present a simple method to calculate transPulmonary fluid fluxes in different species, which can be used to elucidate mechanisms of lung fluid balance in vivo.
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Transvascular fluid flux from the Pulmonary Vasculature at rest and during exercise in horses.
The Journal of physiology, 2005Co-Authors: Modest Vengust, Henry R. Staempfli, Laurent Viel, George J. F. HeigenhauserAbstract:Exercise causes changes in Pulmonary haemodynamics through redistribution of blood flow, increase in the Pulmonary surface area, and increase in Pulmonary vascular pressures. These changes contribute to the increase in fluid exchange across the alveolar-capillary barrier. To determine the extent of the fluid exchange across the alveolar-capillary barrier at rest and during exercise, six horses were exercised on a high-speed treadmill until fatigue. Arterial and mixed venous blood were sampled at rest and during exercise and recovery. Blood volume changes across the lung (DeltaBV; measured in percentage) were calculated from changes in plasma protein and haemoglobin concentration, and haematocrit. Cardiac output (Q) was calculated using the Fick equation. Fluid flux (J(V-A); measured in l min(-1)) across the alveolar-capillary barrier was then quantified based on Q and DeltaBV. At rest, no fluid movement occurred across the Pulmonary Vasculature (0.6 +/- 0.6 l min(-1)). During exercise, the amount of fluid moved from the Pulmonary circulation was 8.3 +/- 1.3 l min(-1) at 1 min, 6.4 +/- 2.9 l min(-)(1) at 2 min, 10.1 +/- 1.0 l min(-1) at 3 min, 12.9 +/- 2.5 l min(-1) at 4 and 9.6 +/- 1.5 l min(-1) at fatigue (all P < 0.0001). Erythrocyte volume decreased by 6% (P < 0.01) across the lungs, which decreased the colloid osmotic gradient in the Pulmonary Vasculature. Decrease colloid osmotic gradient along with increased hydrostatic forces in the Pulmonary Vasculature would enhance displacement of fluid into the Pulmonary interstitium. In conclusion, exercise caused large increases in transPulmonary fluid fluxes in horses. Here, we present a simple method to calculate transPulmonary fluid fluxes in different species, which can be used to elucidate mechanisms of lung fluid balance in vivo.
Kazuhiro Yasufuku - One of the best experts on this subject based on the ideXlab platform.
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nanoparticle based ct visualization of Pulmonary Vasculature for minimally invasive thoracic surgery planning
PLOS ONE, 2019Co-Authors: Harley Chan, Hideki Ujiie, Nicholas Bernards, Kosuke Fujino, Jonathan C. Irish, Jinzi Zheng, Kazuhiro YasufukuAbstract:PURPOSE To evaluate CF800, a novel lipid-based liposomal nanoparticle that co-encapsulates indocyanine green (ICG) and iohexol, for CT imaging of Pulmonary Vasculature in minimally-invasive thoracic surgery planning. METHODS CF800 was intravenously administered to 7 healthy rabbits. In vivo CT imaging was performed 15 min post-injection, with a subset of animals imaged at 24h, 48h, and 72h post injection. Signal-to-background ratios (SBR) were calculated at the inferior vena cava and compared across time-points. A similar protocol was applied to 2 healthy pigs to evaluate the feasibility and efficacy in a large animal model. To evaluate the feasibility of clinical application, a survey was completed by 7 surgical trainees to assess pre- and post-injection CT images of rabbits and pigs. Responses on the discernibility of Pulmonary Vasculature sub-branches and comfort level to use the images for pre-operative planning were collected and analyzed. RESULTS CF800 injection improved visualization of Pulmonary vessels in both rabbit and pig models. The SBR of rabbit Pulmonary Vasculature was significantly higher after CF800 injection (range 3.7-4.4) compared to pre-injection (range 3.3-3.8, n = 7; p<0.05). SBR remained significantly different up to 24 hours after injection (range 3.7-4.3, n = 4; p<0.05). Trainees' evaluation found the post-injection CT images had significantly higher discernibility at the second vessel branch generation in both rabbit and pig models. Trainees identified smaller Vasculature branch generations in the post-injection images compared to the pre-treatment images in both rabbit (mean 6.7±1.8 vs 5.4±2.1; p<0.05) and pig (mean 6.7±1.8 vs 5.4±2.1; p<0.05). Trainees were significantly more comfortable using post-injection images for surgical planning compared to the pre-injection images (rabbit: 8.1±1.1 vs. 4.7±2.1; pig: 7.6±2.1 vs. 4.9±2.2; p<0.05). CONCLUSION CF800 provides SBR and contrast enhancement of Pulmonary Vasculature which may assist in pre-surgical CT planning of minimally invasive thoracic surgery.
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Nanoparticle-based CT visualization of Pulmonary Vasculature for minimally-invasive thoracic surgery planning
PloS one, 2019Co-Authors: Harley Chan, Hideki Ujiie, Nicholas Bernards, Kosuke Fujino, Jonathan C. Irish, Jinzi Zheng, Kazuhiro YasufukuAbstract:PURPOSE To evaluate CF800, a novel lipid-based liposomal nanoparticle that co-encapsulates indocyanine green (ICG) and iohexol, for CT imaging of Pulmonary Vasculature in minimally-invasive thoracic surgery planning. METHODS CF800 was intravenously administered to 7 healthy rabbits. In vivo CT imaging was performed 15 min post-injection, with a subset of animals imaged at 24h, 48h, and 72h post injection. Signal-to-background ratios (SBR) were calculated at the inferior vena cava and compared across time-points. A similar protocol was applied to 2 healthy pigs to evaluate the feasibility and efficacy in a large animal model. To evaluate the feasibility of clinical application, a survey was completed by 7 surgical trainees to assess pre- and post-injection CT images of rabbits and pigs. Responses on the discernibility of Pulmonary Vasculature sub-branches and comfort level to use the images for pre-operative planning were collected and analyzed. RESULTS CF800 injection improved visualization of Pulmonary vessels in both rabbit and pig models. The SBR of rabbit Pulmonary Vasculature was significantly higher after CF800 injection (range 3.7-4.4) compared to pre-injection (range 3.3-3.8, n = 7; p
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Representative 3D reconstruction of rabbit Pulmonary Vasculature shows increased vascular branch visualization following CF800 injection.
2019Co-Authors: Harley Chan, Hideki Ujiie, Nicholas Bernards, Kosuke Fujino, Jonathan C. Irish, Jinzi Zheng, Kazuhiro YasufukuAbstract:(A) Pulmonary Vasculature in the CT image acquired before CF800 injection. (B) Pulmonary Vasculature in the CT image acquired 5 minutes after CF800 injection. Images are depicted using a thresholding-based method with lower and upper threshold values set at 25–40% of maximum intensity within the segmented lungs (values on top-right). Small Pulmonary Vasculature branches at the distal branch generations can be segmented in the post-injection image due to increased attenuation (arrowheads).
David T. Curiel - One of the best experts on this subject based on the ideXlab platform.
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Selective induction of tumor-associated antigens in murine Pulmonary Vasculature using double-targeted adenoviral vectors
Gene Therapy, 2005Co-Authors: Maaike Everts, Sangae Kim-park, Meredith A. Preuss, Michael J. Passineau, Joel N. Glasgow, Alexander Pereboev, Parameshwar J. Mahasreshti, William E. Grizzle, Paul N. Reynolds, David T. CurielAbstract:Targeted therapies directed to tumor-associated antigens are being investigated for the treatment of cancer. However, there are few suitable animal models for testing the ability to target these tumor markers. Therefore, we have exploited mice transgenic for the human coxsackie and adenovirus receptor (hCAR) to establish a new model for transient expression of human tumor-associated antigens in the Pulmonary Vasculature. Systemic administration of Ad in hCAR mice resulted in an increase in transgene expression in the lungs compared to wild-type mice, as determined using a luciferase reporter gene. To reduce transgene expression in the liver, the predominant organ of ectopic Ad localization and transgene expression following systemic administration, we utilized the endothelial-specific flt-1 promoter, which resulted in a further increased lung-to-liver ratio of luciferase expression. Administration of an adenoviral vector encoding the tumor-associated antigen carcinoembryonic antigen (CEA) under transcriptional control of the flt-1 promoter resulted in selective expression of this antigen in the Pulmonary Vasculature of hCAR mice. Feasibility of targeting to expressed CEA was subsequently demonstrated using adenoviral vectors preincubated with a bifunctional adapter molecule recognizing this tumor-associated antigen, thus demonstrating utility of this transient transgenic animal model.
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1017. Selective Induction of Tumor-Associated Antigens in Murine Pulmonary Vasculature Using Double-Targeted Adenoviral Vectors
Molecular Therapy, 2005Co-Authors: Maaike Everts, Sangae Kim-park, Meredith A. Preuss, Michael J. Passineau, Joel N. Glasgow, Alexander Pereboev, Parameshwar J. Mahasreshti, William E. Grizzle, Paul N. Reynolds, David T. CurielAbstract:Targeted therapies directed to tumor-associated antigens are being investigated for the treatment of cancer. However, there are few suitable animal models for testing the ability to target these tumor markers. Therefore, we have exploited mice transgenic for the human coxsackie and adenovirus receptor (hCAR) to establish a new model for transient expression of human tumor-associated antigens in the Pulmonary Vasculature. Systemic administration of Ad in hCAR mice resulted in an increase in transgene expression in the lungs compared to wild type mice, as determined using a luciferase reporter gene. To reduce transgene expression in the liver, the predominant organ of ectopic Ad localization and transgene expression following systemic administration, we utilized the endothelial-specific flt-1 promoter, which resulted in a further increased lung-to-liver ratio of luciferase expression. Administration of an adenoviral vector encoding the tumor-associated antigen carcinoembryonic antigen (CEA) under transcriptional control of the flt-1 promoter resulted in selective expression of this antigen in the Pulmonary Vasculature of hCAR mice. Feasibility of targeting to expressed CEA was subsequently demonstrated using adenoviral vectors pre-incubated with a bifunctional adapter molecule recognizing this tumor-associated antigen, thus demonstrating utility of this transient transgenic animal model.
Harley Chan - One of the best experts on this subject based on the ideXlab platform.
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nanoparticle based ct visualization of Pulmonary Vasculature for minimally invasive thoracic surgery planning
PLOS ONE, 2019Co-Authors: Harley Chan, Hideki Ujiie, Nicholas Bernards, Kosuke Fujino, Jonathan C. Irish, Jinzi Zheng, Kazuhiro YasufukuAbstract:PURPOSE To evaluate CF800, a novel lipid-based liposomal nanoparticle that co-encapsulates indocyanine green (ICG) and iohexol, for CT imaging of Pulmonary Vasculature in minimally-invasive thoracic surgery planning. METHODS CF800 was intravenously administered to 7 healthy rabbits. In vivo CT imaging was performed 15 min post-injection, with a subset of animals imaged at 24h, 48h, and 72h post injection. Signal-to-background ratios (SBR) were calculated at the inferior vena cava and compared across time-points. A similar protocol was applied to 2 healthy pigs to evaluate the feasibility and efficacy in a large animal model. To evaluate the feasibility of clinical application, a survey was completed by 7 surgical trainees to assess pre- and post-injection CT images of rabbits and pigs. Responses on the discernibility of Pulmonary Vasculature sub-branches and comfort level to use the images for pre-operative planning were collected and analyzed. RESULTS CF800 injection improved visualization of Pulmonary vessels in both rabbit and pig models. The SBR of rabbit Pulmonary Vasculature was significantly higher after CF800 injection (range 3.7-4.4) compared to pre-injection (range 3.3-3.8, n = 7; p<0.05). SBR remained significantly different up to 24 hours after injection (range 3.7-4.3, n = 4; p<0.05). Trainees' evaluation found the post-injection CT images had significantly higher discernibility at the second vessel branch generation in both rabbit and pig models. Trainees identified smaller Vasculature branch generations in the post-injection images compared to the pre-treatment images in both rabbit (mean 6.7±1.8 vs 5.4±2.1; p<0.05) and pig (mean 6.7±1.8 vs 5.4±2.1; p<0.05). Trainees were significantly more comfortable using post-injection images for surgical planning compared to the pre-injection images (rabbit: 8.1±1.1 vs. 4.7±2.1; pig: 7.6±2.1 vs. 4.9±2.2; p<0.05). CONCLUSION CF800 provides SBR and contrast enhancement of Pulmonary Vasculature which may assist in pre-surgical CT planning of minimally invasive thoracic surgery.
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Nanoparticle-based CT visualization of Pulmonary Vasculature for minimally-invasive thoracic surgery planning
PloS one, 2019Co-Authors: Harley Chan, Hideki Ujiie, Nicholas Bernards, Kosuke Fujino, Jonathan C. Irish, Jinzi Zheng, Kazuhiro YasufukuAbstract:PURPOSE To evaluate CF800, a novel lipid-based liposomal nanoparticle that co-encapsulates indocyanine green (ICG) and iohexol, for CT imaging of Pulmonary Vasculature in minimally-invasive thoracic surgery planning. METHODS CF800 was intravenously administered to 7 healthy rabbits. In vivo CT imaging was performed 15 min post-injection, with a subset of animals imaged at 24h, 48h, and 72h post injection. Signal-to-background ratios (SBR) were calculated at the inferior vena cava and compared across time-points. A similar protocol was applied to 2 healthy pigs to evaluate the feasibility and efficacy in a large animal model. To evaluate the feasibility of clinical application, a survey was completed by 7 surgical trainees to assess pre- and post-injection CT images of rabbits and pigs. Responses on the discernibility of Pulmonary Vasculature sub-branches and comfort level to use the images for pre-operative planning were collected and analyzed. RESULTS CF800 injection improved visualization of Pulmonary vessels in both rabbit and pig models. The SBR of rabbit Pulmonary Vasculature was significantly higher after CF800 injection (range 3.7-4.4) compared to pre-injection (range 3.3-3.8, n = 7; p
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Representative 3D reconstruction of rabbit Pulmonary Vasculature shows increased vascular branch visualization following CF800 injection.
2019Co-Authors: Harley Chan, Hideki Ujiie, Nicholas Bernards, Kosuke Fujino, Jonathan C. Irish, Jinzi Zheng, Kazuhiro YasufukuAbstract:(A) Pulmonary Vasculature in the CT image acquired before CF800 injection. (B) Pulmonary Vasculature in the CT image acquired 5 minutes after CF800 injection. Images are depicted using a thresholding-based method with lower and upper threshold values set at 25–40% of maximum intensity within the segmented lungs (values on top-right). Small Pulmonary Vasculature branches at the distal branch generations can be segmented in the post-injection image due to increased attenuation (arrowheads).
