The Experts below are selected from a list of 14367 Experts worldwide ranked by ideXlab platform
Brian P Mullan - One of the best experts on this subject based on the ideXlab platform.
-
diuresis related weight loss reflects Interstitial compartment decongestion with minimal impact on intravascular Volume expansion or outcomes in post acute heart failure metrics of decongestion and Volume status
Journal of Cardiac Failure, 2021Co-Authors: Wayne L Miller, Ronstan Lobo, Diane E Grill, Brian P MullanAbstract:Abstract Background Findings from heart failure (HF) studies linking diuresis-related weight loss to clinical decongestion and outcomes are mixed. Differential responses of Interstitial and intravascular Volume compartments to diuretic therapy and heterogeneity in Volume profiles may confound the clinical interpretation of weight loss in patients with HF. Methods and Results Data were prospectively collected in hospitalized patients requiring diuresis. Plasma Volume (PV) was measured using I-131-labelled albumin indicator-dilution methodology. The cohort was stratified by tertiles of weight loss and analyzed for Interstitial fluid loss relative to changes in PV and HF-related morality or first rehospitalization. Among 92 patients, the admission PV was expanded +42% (4.7 ± 1.2 L) above normal with significant variability (14% normal PV, 18% mild-moderate expansion, and 68% with large PV expansion [>+25% above normal]). With diuresis there were proportional decreases in Interstitial Volume (–6.5 ± 4.4%) and PV (–7.5 ± 11%); however, absolute decreases in the PV (–254 mL, interquartile range –11 to –583 mL) were less than 10% of Interstitial Volume loss (–5040 mL, interquartile range –2800 to –7989 mL); greater Interstitial fluid loss did not translate into better outcomes (log-rank P = .430). Conclusions Diuresis-related decreases in weight reflect fluid loss from the Interstitial compartment with only minor changes in the PV and without an impact on outcomes. Further, the degree of PV expansion at hospital admission does not drive the magnitude of the diuresis response, even with a wide spectrum of body weights; Interstitial fluid overload is preferentially targeted and PV relatively preserved. Therefore, greater Interstitial fluid loss reflects clinical decongestion, but not better outcomes, and a limited association with intravascular Volume profiles potentially confounding weight loss as a prognostic metric in HF.
-
understanding the heterogeneity in Volume overload and fluid distribution in decompensated heart failure is key to optimal Volume management role for blood Volume quantitation
Jacc-Heart Failure, 2014Co-Authors: Wayne L Miller, Brian P MullanAbstract:OBJECTIVES: This study sought to quantitate total blood Volume (TBV) in patients hospitalized for decompensated chronic heart failure (DCHF) and to determine the extent of Volume overload, and the magnitude and distribution of blood Volume and body water changes following diuretic therapy. BACKGROUND: The accurate assessment and management of Volume overload in patients with DCHF remains problematic. METHODS: TBV was measured by a radiolabeled-albumin dilution technique with intravascular Volume, pre-to-post-diuretic therapy, evaluated at hospital admission and at discharge. Change in body weight in relation to quantitated TBV was used to determine Interstitial Volume contribution to total fluid loss. RESULTS: Twenty-six patients were prospectively evaluated. Two patients had normal TBV at admission. Twenty-four patients were hypervolemic with TBV (7.4 ± 1.6 liters) increased by +39 ± 22% (range, +9.5% to +107%) above the expected normal Volume. With diuresis, TBV decreased marginally (+30 ± 16%). Body weight declined by 6.9 ± 5.2 kg, and fluid intake/fluid output was a net negative 8.4 ± 5.2 liters. Interstitial compartment fluid loss was calculated at 6.2 ± 4.0 liters, accounting for 85 ± 15% of the total fluid reduction. CONCLUSIONS: TBV analysis demonstrated a wide range in the extent of intravascular overload. Dismissal measurements revealed marginally reduced intravascular Volume post-diuretic therapy despite large reductions in body weight. Mobilization of Interstitial fluid to the intravascular compartment with diuresis accounted for this disparity. Intravascular Volume, however, remained increased at dismissal. The extent, composition, and distribution of Volume overload are highly variable in DCHF, and this variability needs to be taken into account in the approach to individualized therapy. TBV quantitation, particularly serial measurements, can facilitate informed Volume management with respect to a goal of treating to euvolemia.
-
understanding the heterogeneity in Volume overload and fluid distribution in decompensated heart failure is key to optimal Volume management role for blood Volume quantitation
Jacc-Heart Failure, 2014Co-Authors: Wayne L Miller, Brian P MullanAbstract:OBJECTIVES: This study sought to quantitate total blood Volume (TBV) in patients hospitalized for decompensated chronic heart failure (DCHF) and to determine the extent of Volume overload, and the magnitude and distribution of blood Volume and body water changes following diuretic therapy. BACKGROUND: The accurate assessment and management of Volume overload in patients with DCHF remains problematic. METHODS: TBV was measured by a radiolabeled-albumin dilution technique with intravascular Volume, pre-to-post-diuretic therapy, evaluated at hospital admission and at discharge. Change in body weight in relation to quantitated TBV was used to determine Interstitial Volume contribution to total fluid loss. RESULTS: Twenty-six patients were prospectively evaluated. Two patients had normal TBV at admission. Twenty-four patients were hypervolemic with TBV (7.4 ± 1.6 liters) increased by +39 ± 22% (range, +9.5% to +107%) above the expected normal Volume. With diuresis, TBV decreased marginally (+30 ± 16%). Body weight declined by 6.9 ± 5.2 kg, and fluid intake/fluid output was a net negative 8.4 ± 5.2 liters. Interstitial compartment fluid loss was calculated at 6.2 ± 4.0 liters, accounting for 85 ± 15% of the total fluid reduction. CONCLUSIONS: TBV analysis demonstrated a wide range in the extent of intravascular overload. Dismissal measurements revealed marginally reduced intravascular Volume post-diuretic therapy despite large reductions in body weight. Mobilization of Interstitial fluid to the intravascular compartment with diuresis accounted for this disparity. Intravascular Volume, however, remained increased at dismissal. The extent, composition, and distribution of Volume overload are highly variable in DCHF, and this variability needs to be taken into account in the approach to individualized therapy. TBV quantitation, particularly serial measurements, can facilitate informed Volume management with respect to a goal of treating to euvolemia.
Volker Vielhauer - One of the best experts on this subject based on the ideXlab platform.
-
ccr1 blockade reduces Interstitial inflammation and fibrosis in mice with glomerulosclerosis and nephrotic syndrome
Kidney International, 2004Co-Authors: Volker Vielhauer, Stephan Segerer, Richard Horuk, Hermann Josef Gröne, Detlef Schlondorff, Frank Strutz, Matthias Kretzler, Elias Berning, Hans-joachim AndersAbstract:CCR1 blockade reduces Interstitial inflammation and fibrosis in mice with glomerulosclerosis and nephrotic syndrome. Background CC chemokines mediate leukocyte infiltration into inflamed tissue. We have recently shown that blockade of the CC chemokine receptor CCR1 reduces Interstitial inflammation and fibrosis in murine obstructive nephropathy. However, it is not known whether CCR 1 blockade is protective in progressive renal injury associated with severe proteinuria. We therefore studied the effect of the small-molecule CCR1 antagonist BX471 in a murine model of adriamycin-induced focal segmental glomerulosclerosis (FSGS) with nephrotic syndrome and progressive Interstitial inflammation and fibrosis. Methods Adriamycin nephropathy with persistent proteinuria was induced in male BALB/c mice by two intravenous injections of adriamycin (13 mg/kg) at day 0 and 14. BX471 treatment was started at day 14 when proteinuria and Interstitial inflammation had developed. At 6 weeks, renal histology was studied by morphometry and immunohistochemistry. Results At week 6, adriamycin-treated mice showed FSGS, associated with tubuloInterstitial injury consisting of tubular dilation and atrophy, Interstitial leukocyte infiltration, and fibrosis. The mRNA expression of CCR1 and CC chemokines, including the CCR1 ligands CCL3 (MIP-1α) and CCL5 (RANTES), was up-regulated in diseased kidneys, with a prominent Interstitial expression of CCL5. Compared to vehicle-treated controls BX471 significantly reduced the amount of macrophages and T lymphocytes in Interstitial lesions by 51% and 22%, respectively. Markers of renal fibrosis such as Interstitial fibroblasts (48%) and Interstitial Volume (23%) were significantly reduced by BX471 treatment. In contrast, the extent of proteinuria and glomerular sclerosis was not affected by BX471 treatment. Conclusion Blockade of CCR1 substantially reduced Interstitial leukocyte accumulation and the subsequent renal fibrosis in a murine model of nephrotic syndrome and FSGS. These findings support a role for CCR1 in Interstitial leukocyte recruitment and suggest that CCR1 blockade might be a new therapeutic strategy in progressive nephropathies such as FSGS.
-
chemokine receptor ccr1 but not ccr5 mediates leukocyte recruitment and subsequent renal fibrosis after unilateral ureteral obstruction
Journal of The American Society of Nephrology, 2004Co-Authors: Vaclav Eis, Yvonne Linde, Jens T Siveke, Stephan Segerer, Guillermo Perez De Lema, Volker Vielhauer, Clemens D Cohen, Bruno Luckow, Matthias Kretzler, Matthias MackAbstract:As chemokine receptor CCR1 and CCR5 expression on circulating leukocytes is thought to contribute to leukocyte recruitment during renal fibrosis, the authors examined the effects of unilateral ureteral obstruction (UUO) in mice deficient for CCR1 or CCR5. Analysis of UUO kidneys from CCR1-deficient mice revealed a reduction of Interstitial macrophages and lymphocytes (35% and 55%, respectively) compared with wild-type controls. CCR1-deficient mice had reduced CCR5 mRNA levels in UUO kidneys, which correlated with a reduction of CCR5+ T cell infiltrate as determined by flow cytometry. Interstitial fibroblasts, renal TGF-beta1 mRNA expression, Interstitial Volume, and collagen I deposits were all significantly reduced in CCR1-deficient mice. In contrast, renal leukocytes and fibrosis were unaffected in CCR5-deficient mice with UUO. However, if treated with the CCR1 antagonist BX471, CCR5-deficient mice showed a similar reduction of renal leukocytes and fibrosis as CCR1-deficient mice. To determine the underlying mechanism labeled macrophages and T cells isolated from either wild-type, CCR1-deficient, or CCR5-deficient mice were injected into wild-type mice with UUO. Three hours later, renal cell recruitment was reduced for CCR1-deficient cells or cells pretreated with BX471 compared with CCR5-deficient or wild-type cells. Thus, CCR1 but not CCR5 is required for leukocyte recruitment and fibrosis after UUO in mice. Therefore, CCR1 is a promising target for therapeutic intervention in leukocyte-mediated fibrotic tissue injury, e.g. progressive renal fibrosis.
-
chemokine receptor ccr1 but not ccr5 mediates leukocyte recruitment and subsequent renal fibrosis after unilateral ureteral obstruction
Journal of The American Society of Nephrology, 2004Co-Authors: Bruno Luckow, Yvonne Linde, Jens T Siveke, Stephan Segerer, Guillermo Perez De Lema, Volker Vielhauer, Clemens D Cohen, Matthias Mack, Matthias Kretzler, Richard HorukAbstract:ABSTRACT. As chemokine receptor CCR1 and CCR5 expression on circulating leukocytes is thought to contribute to leukocyte recruitment during renal fibrosis, the authors examined the effects of unilateral ureteral obstruction (UUO) in mice deficient for CCR1 or CCR5. Analysis of UUO kidneys from CCR1-deficient mice revealed a reduction of Interstitial macrophages and lymphocytes (35% and 55%, respectively) compared with wild-type controls. CCR1-deficient mice had reduced CCR5 mRNA levels in UUO kidneys, which correlated with a reduction of CCR5+ T cell infiltrate as determined by flow cytometry. Interstitial fibroblasts, renal TGF-β1 mRNA expression, Interstitial Volume, and collagen I deposits were all significantly reduced in CCR1-deficient mice. In contrast, renal leukocytes and fibrosis were unaffected in CCR5-deficient mice with UUO. However, if treated with the CCR1 antagonist BX471, CCR5-deficient mice showed a similar reduction of renal leukocytes and fibrosis as CCR1-deficient mice. To determine the underlying mechanism labeled macrophages and T cells isolated from either wild-type, CCR1-deficient, or CCR5-deficient mice were injected into wild-type mice with UUO. Three hours later, renal cell recruitment was reduced for CCR1-deficient cells or cells pretreated with BX471 compared with CCR5-deficient or wild-type cells. Thus, CCR1 but not CCR5 is required for leukocyte recruitment and fibrosis after UUO in mice. Therefore, CCR1 is a promising target for therapeutic intervention in leukocyte-mediated fibrotic tissue injury, e.g. progressive renal fibrosis.
-
chemokines and chemokine receptors are involved in the resolution or progression of renal disease
Kidney International, 2003Co-Authors: Hans-joachim Anders, Volker Vielhauer, Detlef SchlondorffAbstract:Locally secreted chemokines mediate leukocyte recruitment during the initiation and amplification phase of renal inflammation. In turn, the infiltrating leukocytes contribute to renal damage by releasing inflammatory and profibrotic factors. Rapid down modulation of the chemokine signal will support resolution of acute inflammation, whereas progression occurs if ongoing or repeated renal injury maintains continuous local chemokine secretion and leukocyte influx into the glomerulus or the Interstitial space. In glomerular injury proteinuria itself as well as glomerular secreted cytokines stimulate downstream tubular epithelial cells to also secrete chemokines. During primary tubular injury, tubular epithelial cells directly become a major site of chemokine production. This in turn supports leukocyte infiltration and activation. Infiltrating leukocytes stimulate fibroblast proliferation and matrix synthesis, leading to widening of the Interstitial space. The specific and intricate renal vascular architecture renders the organ susceptible to ischemic damage as Interstitial Volume increases. Ischemia in turn serves as a stimulus for chemokine and cytokine production and matrix synthesis. The mutual stimulation between fibroblasts and infiltrating leukocytes supports progressive tubular damage, renal fibrosis, and glomerulosclerosis. Potentially this vicious circle leading to progression of chronic nephropathies offers the opportunity for therapeutic intervention. Interfering with the chemokine network that mediates leukocyte recruitment may represent a promising therapeutic option for progressive renal disorders and renal fibrosis. This article summarizes the present data on the role of chemokines in acute and chronic renal disease with special emphasis on their potential role in mediating resolution or progression of renal disease as well as on therapeutic options.
-
a chemokine receptor ccr 1 antagonist reduces renal fibrosis after unilateral ureter ligation
Journal of Clinical Investigation, 2002Co-Authors: Hans-joachim Anders, Yvonne Linde, Simone M Blattner, Volker Vielhauer, Clemens D Cohen, Frank Strutz, Matthias Mack, Michael Frink, Matthias Kretzler, Hermann Josef GröneAbstract:The expression of chemokines and their receptors is thought to contribute to leukocyte infiltration and progressive renal fibrosis after unilateral ureter obstruction (UUO). We hypothesized that blocking the chemokine receptor CCR1 using the nonpeptide antagonist BX471 could reduce leukocyte infiltration and renal fibrosis after UUO. UUO kidneys from BX471-treated mice (day 0–10 and day 6–10) revealed a 40–60% reduction of Interstitial macrophage and lymphocyte infiltrate compared with controls. Treated mice also showed a marked reduction of CCR1 and CCR5 mRNA levels, and FACS analysis showed a comparable reduction of CD8+/CCR5+ T cells. Markers of renal fibrosis, such as Interstitial fibroblasts, Interstitial Volume, mRNA and protein expression for collagen I, were all significantly reduced by BX471-treatment compared with vehicle controls. By contrast treatment was ineffective when the drug was supplied only from days 0 to 5. In summary, blockade of CCR1 substantially reduces cell accumulation and renal fibrosis after UUO. Most interestingly, late onset of treatment is also effective. We therefore conclude that CCR1 blockade may represent a new therapeutic strategy for reducing cellular infiltration and renal fibrosis as major factors in the progression to end-stage renal failure.
Hans-joachim Anders - One of the best experts on this subject based on the ideXlab platform.
-
ccr1 blockade reduces Interstitial inflammation and fibrosis in mice with glomerulosclerosis and nephrotic syndrome
Kidney International, 2004Co-Authors: Volker Vielhauer, Stephan Segerer, Richard Horuk, Hermann Josef Gröne, Detlef Schlondorff, Frank Strutz, Matthias Kretzler, Elias Berning, Hans-joachim AndersAbstract:CCR1 blockade reduces Interstitial inflammation and fibrosis in mice with glomerulosclerosis and nephrotic syndrome. Background CC chemokines mediate leukocyte infiltration into inflamed tissue. We have recently shown that blockade of the CC chemokine receptor CCR1 reduces Interstitial inflammation and fibrosis in murine obstructive nephropathy. However, it is not known whether CCR 1 blockade is protective in progressive renal injury associated with severe proteinuria. We therefore studied the effect of the small-molecule CCR1 antagonist BX471 in a murine model of adriamycin-induced focal segmental glomerulosclerosis (FSGS) with nephrotic syndrome and progressive Interstitial inflammation and fibrosis. Methods Adriamycin nephropathy with persistent proteinuria was induced in male BALB/c mice by two intravenous injections of adriamycin (13 mg/kg) at day 0 and 14. BX471 treatment was started at day 14 when proteinuria and Interstitial inflammation had developed. At 6 weeks, renal histology was studied by morphometry and immunohistochemistry. Results At week 6, adriamycin-treated mice showed FSGS, associated with tubuloInterstitial injury consisting of tubular dilation and atrophy, Interstitial leukocyte infiltration, and fibrosis. The mRNA expression of CCR1 and CC chemokines, including the CCR1 ligands CCL3 (MIP-1α) and CCL5 (RANTES), was up-regulated in diseased kidneys, with a prominent Interstitial expression of CCL5. Compared to vehicle-treated controls BX471 significantly reduced the amount of macrophages and T lymphocytes in Interstitial lesions by 51% and 22%, respectively. Markers of renal fibrosis such as Interstitial fibroblasts (48%) and Interstitial Volume (23%) were significantly reduced by BX471 treatment. In contrast, the extent of proteinuria and glomerular sclerosis was not affected by BX471 treatment. Conclusion Blockade of CCR1 substantially reduced Interstitial leukocyte accumulation and the subsequent renal fibrosis in a murine model of nephrotic syndrome and FSGS. These findings support a role for CCR1 in Interstitial leukocyte recruitment and suggest that CCR1 blockade might be a new therapeutic strategy in progressive nephropathies such as FSGS.
-
chemokines and chemokine receptors are involved in the resolution or progression of renal disease
Kidney International, 2003Co-Authors: Hans-joachim Anders, Volker Vielhauer, Detlef SchlondorffAbstract:Locally secreted chemokines mediate leukocyte recruitment during the initiation and amplification phase of renal inflammation. In turn, the infiltrating leukocytes contribute to renal damage by releasing inflammatory and profibrotic factors. Rapid down modulation of the chemokine signal will support resolution of acute inflammation, whereas progression occurs if ongoing or repeated renal injury maintains continuous local chemokine secretion and leukocyte influx into the glomerulus or the Interstitial space. In glomerular injury proteinuria itself as well as glomerular secreted cytokines stimulate downstream tubular epithelial cells to also secrete chemokines. During primary tubular injury, tubular epithelial cells directly become a major site of chemokine production. This in turn supports leukocyte infiltration and activation. Infiltrating leukocytes stimulate fibroblast proliferation and matrix synthesis, leading to widening of the Interstitial space. The specific and intricate renal vascular architecture renders the organ susceptible to ischemic damage as Interstitial Volume increases. Ischemia in turn serves as a stimulus for chemokine and cytokine production and matrix synthesis. The mutual stimulation between fibroblasts and infiltrating leukocytes supports progressive tubular damage, renal fibrosis, and glomerulosclerosis. Potentially this vicious circle leading to progression of chronic nephropathies offers the opportunity for therapeutic intervention. Interfering with the chemokine network that mediates leukocyte recruitment may represent a promising therapeutic option for progressive renal disorders and renal fibrosis. This article summarizes the present data on the role of chemokines in acute and chronic renal disease with special emphasis on their potential role in mediating resolution or progression of renal disease as well as on therapeutic options.
-
a chemokine receptor ccr 1 antagonist reduces renal fibrosis after unilateral ureter ligation
Journal of Clinical Investigation, 2002Co-Authors: Hans-joachim Anders, Yvonne Linde, Simone M Blattner, Volker Vielhauer, Clemens D Cohen, Frank Strutz, Matthias Mack, Michael Frink, Matthias Kretzler, Hermann Josef GröneAbstract:The expression of chemokines and their receptors is thought to contribute to leukocyte infiltration and progressive renal fibrosis after unilateral ureter obstruction (UUO). We hypothesized that blocking the chemokine receptor CCR1 using the nonpeptide antagonist BX471 could reduce leukocyte infiltration and renal fibrosis after UUO. UUO kidneys from BX471-treated mice (day 0–10 and day 6–10) revealed a 40–60% reduction of Interstitial macrophage and lymphocyte infiltrate compared with controls. Treated mice also showed a marked reduction of CCR1 and CCR5 mRNA levels, and FACS analysis showed a comparable reduction of CD8+/CCR5+ T cells. Markers of renal fibrosis, such as Interstitial fibroblasts, Interstitial Volume, mRNA and protein expression for collagen I, were all significantly reduced by BX471-treatment compared with vehicle controls. By contrast treatment was ineffective when the drug was supplied only from days 0 to 5. In summary, blockade of CCR1 substantially reduces cell accumulation and renal fibrosis after UUO. Most interestingly, late onset of treatment is also effective. We therefore conclude that CCR1 blockade may represent a new therapeutic strategy for reducing cellular infiltration and renal fibrosis as major factors in the progression to end-stage renal failure.
Wayne L Miller - One of the best experts on this subject based on the ideXlab platform.
-
diuresis related weight loss reflects Interstitial compartment decongestion with minimal impact on intravascular Volume expansion or outcomes in post acute heart failure metrics of decongestion and Volume status
Journal of Cardiac Failure, 2021Co-Authors: Wayne L Miller, Ronstan Lobo, Diane E Grill, Brian P MullanAbstract:Abstract Background Findings from heart failure (HF) studies linking diuresis-related weight loss to clinical decongestion and outcomes are mixed. Differential responses of Interstitial and intravascular Volume compartments to diuretic therapy and heterogeneity in Volume profiles may confound the clinical interpretation of weight loss in patients with HF. Methods and Results Data were prospectively collected in hospitalized patients requiring diuresis. Plasma Volume (PV) was measured using I-131-labelled albumin indicator-dilution methodology. The cohort was stratified by tertiles of weight loss and analyzed for Interstitial fluid loss relative to changes in PV and HF-related morality or first rehospitalization. Among 92 patients, the admission PV was expanded +42% (4.7 ± 1.2 L) above normal with significant variability (14% normal PV, 18% mild-moderate expansion, and 68% with large PV expansion [>+25% above normal]). With diuresis there were proportional decreases in Interstitial Volume (–6.5 ± 4.4%) and PV (–7.5 ± 11%); however, absolute decreases in the PV (–254 mL, interquartile range –11 to –583 mL) were less than 10% of Interstitial Volume loss (–5040 mL, interquartile range –2800 to –7989 mL); greater Interstitial fluid loss did not translate into better outcomes (log-rank P = .430). Conclusions Diuresis-related decreases in weight reflect fluid loss from the Interstitial compartment with only minor changes in the PV and without an impact on outcomes. Further, the degree of PV expansion at hospital admission does not drive the magnitude of the diuresis response, even with a wide spectrum of body weights; Interstitial fluid overload is preferentially targeted and PV relatively preserved. Therefore, greater Interstitial fluid loss reflects clinical decongestion, but not better outcomes, and a limited association with intravascular Volume profiles potentially confounding weight loss as a prognostic metric in HF.
-
understanding the heterogeneity in Volume overload and fluid distribution in decompensated heart failure is key to optimal Volume management role for blood Volume quantitation
Jacc-Heart Failure, 2014Co-Authors: Wayne L Miller, Brian P MullanAbstract:OBJECTIVES: This study sought to quantitate total blood Volume (TBV) in patients hospitalized for decompensated chronic heart failure (DCHF) and to determine the extent of Volume overload, and the magnitude and distribution of blood Volume and body water changes following diuretic therapy. BACKGROUND: The accurate assessment and management of Volume overload in patients with DCHF remains problematic. METHODS: TBV was measured by a radiolabeled-albumin dilution technique with intravascular Volume, pre-to-post-diuretic therapy, evaluated at hospital admission and at discharge. Change in body weight in relation to quantitated TBV was used to determine Interstitial Volume contribution to total fluid loss. RESULTS: Twenty-six patients were prospectively evaluated. Two patients had normal TBV at admission. Twenty-four patients were hypervolemic with TBV (7.4 ± 1.6 liters) increased by +39 ± 22% (range, +9.5% to +107%) above the expected normal Volume. With diuresis, TBV decreased marginally (+30 ± 16%). Body weight declined by 6.9 ± 5.2 kg, and fluid intake/fluid output was a net negative 8.4 ± 5.2 liters. Interstitial compartment fluid loss was calculated at 6.2 ± 4.0 liters, accounting for 85 ± 15% of the total fluid reduction. CONCLUSIONS: TBV analysis demonstrated a wide range in the extent of intravascular overload. Dismissal measurements revealed marginally reduced intravascular Volume post-diuretic therapy despite large reductions in body weight. Mobilization of Interstitial fluid to the intravascular compartment with diuresis accounted for this disparity. Intravascular Volume, however, remained increased at dismissal. The extent, composition, and distribution of Volume overload are highly variable in DCHF, and this variability needs to be taken into account in the approach to individualized therapy. TBV quantitation, particularly serial measurements, can facilitate informed Volume management with respect to a goal of treating to euvolemia.
-
understanding the heterogeneity in Volume overload and fluid distribution in decompensated heart failure is key to optimal Volume management role for blood Volume quantitation
Jacc-Heart Failure, 2014Co-Authors: Wayne L Miller, Brian P MullanAbstract:OBJECTIVES: This study sought to quantitate total blood Volume (TBV) in patients hospitalized for decompensated chronic heart failure (DCHF) and to determine the extent of Volume overload, and the magnitude and distribution of blood Volume and body water changes following diuretic therapy. BACKGROUND: The accurate assessment and management of Volume overload in patients with DCHF remains problematic. METHODS: TBV was measured by a radiolabeled-albumin dilution technique with intravascular Volume, pre-to-post-diuretic therapy, evaluated at hospital admission and at discharge. Change in body weight in relation to quantitated TBV was used to determine Interstitial Volume contribution to total fluid loss. RESULTS: Twenty-six patients were prospectively evaluated. Two patients had normal TBV at admission. Twenty-four patients were hypervolemic with TBV (7.4 ± 1.6 liters) increased by +39 ± 22% (range, +9.5% to +107%) above the expected normal Volume. With diuresis, TBV decreased marginally (+30 ± 16%). Body weight declined by 6.9 ± 5.2 kg, and fluid intake/fluid output was a net negative 8.4 ± 5.2 liters. Interstitial compartment fluid loss was calculated at 6.2 ± 4.0 liters, accounting for 85 ± 15% of the total fluid reduction. CONCLUSIONS: TBV analysis demonstrated a wide range in the extent of intravascular overload. Dismissal measurements revealed marginally reduced intravascular Volume post-diuretic therapy despite large reductions in body weight. Mobilization of Interstitial fluid to the intravascular compartment with diuresis accounted for this disparity. Intravascular Volume, however, remained increased at dismissal. The extent, composition, and distribution of Volume overload are highly variable in DCHF, and this variability needs to be taken into account in the approach to individualized therapy. TBV quantitation, particularly serial measurements, can facilitate informed Volume management with respect to a goal of treating to euvolemia.
Hassan Bagherebadian - One of the best experts on this subject based on the ideXlab platform.
-
dynamic contrast enhanced mri parameters and tumor cellularity in a rat model of cerebral glioma at 7 t
Magnetic Resonance in Medicine, 2014Co-Authors: Stephen L Brown, Tavarekere N Nagaraja, Madhava P Aryal, Hassan Bagherebadian, Swayamprava Panda, Kelly A Keenan, Glauber Cabral, Joseph D FenstermacherAbstract:Purpose To test the hypothesis that a noninvasive dynamic contrast enhanced MRI (DCE-MRI) derived Interstitial Volume fraction (ve) and/or distribution Volume (VD) were correlated with tumor cellularity in cerebral tumor. Methods T1-weighted DCE-MRI studies were performed in 18 athymic rats implanted with U251 xenografts. After DCE-MRI, sectioned brain tissues were stained with Hematoxylin and Eosin for cell counting. Using a Standard Model analysis and Logan graphical plot, DCE-MRI image sets during and after the injection of a gadolinium contrast agent were used to estimate the parameters plasma Volume (vp), forward transfer constant (Ktrans), ve, and VD. Results Parameter values in regions where the standard model was selected as the best model were: (mean ± S.D.): vp = (0.81 ± 0.40)%, Ktrans = (2.09 ± 0.65) × 10−2 min−1, ve = (6.65 ± 1.86)%, and VD = (7.21 ± 1.98)%. The Logan-estimated VD was strongly correlated with the standard model's vp + ve (r = 0.91, P < 0.001). The parameters, ve and/or VD, were significantly correlated with tumor cellularity (r ≥ −0.75, P < 0.001 for both). Conclusion These data suggest that tumor cellularity can be estimated noninvasively by DCE-MRI, thus supporting its utility in assessing tumor pathophysiology. Magn Reson Med 71:2206–2214, 2014. © 2013 Wiley Periodicals, Inc.
-
cilengitide induced temporal variations in transvascular transfer parameters of tumor vasculature in a rat glioma model identifying potential mri biomarkers of acute effects
PLOS ONE, 2013Co-Authors: Tavarekere N Nagaraja, Tom Mikkelsen, Stephen L Brown, Madhava P Aryal, Hassan Bagherebadian, James Yang, Swayamprava Panda, Kelly A KeenanAbstract:Increased efficacy of radiotherapy (RT) 4-8 h after Cilengitide treatment has been reported. We hypothesized that the effects of Cilengitide on tumor transvascular transfer parameters might underlie, and thus predict, this potentiation. Athymic rats with orthotopic U251 glioma were studied at ~21 days after implantation using dynamic contrast-enhanced (DCE)-MRI. Vascular parameters, viz: plasma Volume fraction (vp), forward Volume transfer constant (Ktrans) and Interstitial Volume fraction (ve) of a contrast agent, were determined in tumor vasculature once before, and again in cohorts 2, 4, 8, 12 and 24 h after Cilengitide administration (4 mg/kg; N = 31; 6-7 per cohort). Perfusion-fixed brain sections were stained for von Willebrand factor to visualize vascular segments. A comparison of pre- and post-treatment parameters showed that the differences between MR indices before and after Cilengitide treatment pivoted around the 8 h time point, with 2 and 4 h groups showing increases, 12 and 24 h groups showing decreases, and values at the 8 h time point close to the baseline. The vascular parameter differences between group of 2 and 4 h and group of 12 and 24 h were significant for Ktrans (p = 0.0001 and ve (p = 0,0271). Vascular staining showed little variation with time after Cilengitide. The vascular normalization occurring 8 h after Cilengitide treatment coincided with similar previous reports of increased treatment efficacy when RT followed Cilengitide by 8 h. Pharmacological normalization of vasculature has the potential to increase sensitivity to RT. Evaluating acute temporal responses of tumor vasculature to putative anti-angiogenic drugs may help in optimizing their combination with other treatment modalities.
-
model selection in measures of vascular parameters using dynamic contrast enhanced mri experimental and clinical applications
NMR in Biomedicine, 2013Co-Authors: Hassan Bagherebadian, James R EwingAbstract:A review of the selection of models in dynamic contrast-enhanced MRI (DCE-MRI) is conducted, with emphasis on the balance between the bias and variance required to produce stable and accurate estimates of vascular parameters. The vascular parameters considered as a first-order model are the forward Volume transfer constant K(trans) , the plasma Volume fraction vp and the Interstitial Volume fraction ve . To illustrate the critical issues in model selection, a data-driven selection of models in an animal model of cerebral glioma is followed. Systematic errors and extended models are considered. Studies with nested and non-nested pharmacokinetic models are reviewed; models considering water exchange are considered.
