Global deficiency of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), an enzyme that regenerates gl... more Global deficiency of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), an enzyme that regenerates glucocorticoids within cells, promotes angiogenesis and reduces acute infarct expansion following myocardial infarction (MI) suggesting that 11β-HSD1 activity has an adverse influence on wound healing in the heart after MI. The present study investigated whether 11β-HSD1 deficiency could prevent the development of heart failure following MI, and examined whether 11β-HSD1 deficiency in cardiomyocytes and vascular smooth muscle cells confers this protection. Male mice with global deficiency in 11β-HSD1, or with Hsd11b1 disruption in cardiac and vascular smooth muscle (via SM22α-Cre recombinase) underwent coronary artery ligation for induction of MI. Acute injury was equivalent in all groups. However, by 8 weeks after induction of MI, relative to C57Bl/6 wild type, globally 11β-HSD1 deficient mice had reduced infarct size (34.7±2.1%LV vs 44.0±3.3%LV, P=0.02), improved function (ejection fract...
Ca2+ paradox damage has been suggested to be determined by Na+ entry during Ca2+ depletion and ex... more Ca2+ paradox damage has been suggested to be determined by Na+ entry during Ca2+ depletion and exchange of Na+ for Ca2+ during Ca2+ repletion. With the use of 23Na nuclear magnetic resonance, we previously observed a Ca2+ paradox without a prior Na+ increase. We have now demonstrated a Na+ increase during Ca2+ and Mg2+ depletion without the occurrence of the Ca2+ paradox during Ca2+ repletion. Isolated rat hearts were perfused for 20 min with a Ca(2+)-free or a Ca(2+)- and Mg(2+)-free (Ca2+/Mg(2+)-free) solution under hypothermic conditions (20 and 25 degrees C). Intracellular Na+ concentration ([Na+]i) increased from 11.9 +/- 1.2 to 26.9 +/- 5.8 mM (P < 0.001) during Ca2+/Mg(2+)-free perfusion at 20 degrees C, whereas no significant change in [Na+]i occurred during 20 min of Ca(2+)-free perfusion at 20 degrees C. In addition, we confirmed that [Na+]i did not change significantly during 20 min of normothermic Ca(2+)-free perfusion. Creatine kinase release during normothermic Ca2+ repletion in the 20 degrees C groups was approximately 10% and in the 25 degrees C groups 75% of the release in the normothermia group. Recovery of rate-pressure product was approximately 50% in the 20 degrees C groups versus 0% in the normothermia group. In conclusion, hypothermic Ca2+/Mg(2+)-free perfusion results in a significant increase of [Na+]i, which does not contribute to the extent of the Ca2+ paradox on normothermic Ca2+ repletion.
Introduction While the embryonic zebrafish has been widely used for basic cardiac research the ad... more Introduction While the embryonic zebrafish has been widely used for basic cardiac research the adult zebrafish has been used less partly due to difficulties in evaluating the hearts structure and function in-vivo. Currently available cardiac imaging techniques are limited by the hearts small size and rapid rate. Successful development of cardiac MRI for the adult zebrafish could have significant scientific, ethical and economic benefits for cardiac research. Methods We have developed a novel magnetic resonance imaging (MRI) scanning system, designed to study cardiac structure and function in the live adult zebrafish. This has involved the development of an integrated zebrafish life support and monitoring system with an internal custom MRI solenoid microimaging coil – the ‘flow cell’ (Figure 1). Zebrafish are anesthetised (MS222) and held in position within a flow chamber that intersects the MRI coil for scanning (internal diameter 6.9 mm, SNR >130). Water flows through the system...
A functional MRI (fMRI) phantom was used to characterize the stability and behaviour of Echo Plan... more A functional MRI (fMRI) phantom was used to characterize the stability and behaviour of Echo Planar Imaging (EPI) on a number of preclinical MRI scanners. Large variations in functional Contrast to Noise Ratios (fCNR) were observed. Additionally a longitudinal study at a single site recorded significant changes in fCNR across time. A proportion of individual scans also displayed unusual behaviour. Given that a stable and reliable fCNR for a particular biological effect is the basis for current fMRI and resting state connectivity research, the results we report suggest that caution should be taken with those results. Further studies of factors affecting preclinical EPI stability should be undertaken as should similar checks on clinical systems.
American Journal of Physiology - Heart and Circulatory Physiology, 2015
The extent of infarct injury is a key determinant of structural and functional remodeling followi... more The extent of infarct injury is a key determinant of structural and functional remodeling following myocardial infarction (MI). Infarct volume in experimental models of MI can be determined accurately by in vivo magnetic resonance imaging (MRI), but this is costly and not widely available. Experimental studies therefore commonly assess injury by histological analysis of sections sampled from the infarcted heart, an approach that is labor intensive, can be subjective and does not fully assess the extent of injury. The present study aimed to assess the suitability of optical projection tomography (OPT) for identification of injured myocardium and for accurate and efficient assessment of infarct volume. Intact, perfusion fixed, optically cleared hearts, collected from mice 7 days after induction of MI by coronary artery occlusion, were scanned by a tomograph for autofluorescence emission after UV excitation, generating >400 transaxial sections for reconstruction. Differential autofluorescence permitted discrimination between viable and injured myocardium and highlighted the heterogeneity within the infarct zone. 2D infarct areas derived from OPT imaging and Masson's trichrome staining of slices from the same heart were highly correlated (r2=0.99, P<0.0001). Infarct volume derived from reconstructed OPT sections correlated with volume derived from in vivo late gadolinium enhancement MRI (LGE-MRI) (r2=0.7608, P<0.005). Tissue processing for OPT did not compromise subsequent immunohistochemical detection of endothelial cell and inflammatory cell markers. OPT is thus a non-destructive, efficient and accurate approach for routine in vitro assessment of murine myocardial infarct volume.
In the current study, we have developed a magnetic resonance imaging-based method for non-invasiv... more In the current study, we have developed a magnetic resonance imaging-based method for non-invasive detection of complement activation in placenta and foetal brain in vivo in utero. Using this method, we found that anti-complement C3-targeted ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles bind within the inflamed placenta and foetal brain cortical tissue, causing a shortening of the T2* relaxation time. We used two mouse models of pregnancy complications: a mouse model of obstetrics antiphospholipid syndrome (APS) and a mouse model of preterm birth (PTB). We found that detection of C3 deposition in the placenta in the APS model was associated with placental insufficiency characterised by increased oxidative stress, decreased vascular endothelial growth factor and placental growth factor levels and intrauterine growth restriction. We also found that foetal brain C3 deposition was associated with cortical axonal cytoarchitecture disruption and increased neurodegeneration...
American journal of physiology. Heart and circulatory physiology, 2003
This study tests the hypothesis that a decrease of the free energy of ATP hydrolysis (Delta GATP)... more This study tests the hypothesis that a decrease of the free energy of ATP hydrolysis (Delta GATP) below a threshold value will inhibit Na+-K+-ATPase (Na+ pump) activity and result in an increase of intracellular Na+ concentration ([Na+]i) in the heart. Conditions were designed in which hearts were solely dependent on ATP derived from oxidative phosphorylation. The only substrate supplied was the fatty acid butyrate (Bu) at either low, 0.1 mM (LowBu), or high, 4 mM (HighBu), concentrations. Escalating work demand reduced the Delta GATP of the LowBu hearts. 31P, 23Na, and 87Rb NMR spectroscopy measured high-energy phosphate metabolites, [Na+]i, and Rb+ uptake. Rb+ uptake was used to estimate Na+ pump activity. To measure [Na+]i using a shift reagent for cations, extracellular Ca2+ was reduced to 0.85 mM, which eliminated work demand Delta GATP reductions. Increasing extracellular Na+ (Nae+) to 200 mM restored work demand Delta GATP reductions. In response to higher [Na+]e, [Na+]i incr...
Ca2+ paradox damage has been suggested to be determined by Na+ entry during Ca2+ depletion and ex... more Ca2+ paradox damage has been suggested to be determined by Na+ entry during Ca2+ depletion and exchange of Na+ for Ca2+ during Ca2+ repletion. With the use of 23Na nuclear magnetic resonance, we previously observed a Ca2+ paradox without a prior Na+ increase. We have now demonstrated a Na+ increase during Ca2+ and Mg2+ depletion without the occurrence of the Ca2+ paradox during Ca2+ repletion. Isolated rat hearts were perfused for 20 min with a Ca(2+)-free or a Ca(2+)- and Mg(2+)-free (Ca2+/Mg(2+)-free) solution under hypothermic conditions (20 and 25 degrees C). Intracellular Na+ concentration ([Na+]i) increased from 11.9 +/- 1.2 to 26.9 +/- 5.8 mM (P < 0.001) during Ca2+/Mg(2+)-free perfusion at 20 degrees C, whereas no significant change in [Na+]i occurred during 20 min of Ca(2+)-free perfusion at 20 degrees C. In addition, we confirmed that [Na+]i did not change significantly during 20 min of normothermic Ca(2+)-free perfusion. Creatine kinase release during normothermic Ca2+...
Global deficiency of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), an enzyme that regenerates gl... more Global deficiency of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), an enzyme that regenerates glucocorticoids within cells, promotes angiogenesis and reduces acute infarct expansion following myocardial infarction (MI) suggesting that 11β-HSD1 activity has an adverse influence on wound healing in the heart after MI. The present study investigated whether 11β-HSD1 deficiency could prevent the development of heart failure following MI, and examined whether 11β-HSD1 deficiency in cardiomyocytes and vascular smooth muscle cells confers this protection. Male mice with global deficiency in 11β-HSD1, or with Hsd11b1 disruption in cardiac and vascular smooth muscle (via SM22α-Cre recombinase) underwent coronary artery ligation for induction of MI. Acute injury was equivalent in all groups. However, by 8 weeks after induction of MI, relative to C57Bl/6 wild type, globally 11β-HSD1 deficient mice had reduced infarct size (34.7±2.1%LV vs 44.0±3.3%LV, P=0.02), improved function (ejection fract...
Ca2+ paradox damage has been suggested to be determined by Na+ entry during Ca2+ depletion and ex... more Ca2+ paradox damage has been suggested to be determined by Na+ entry during Ca2+ depletion and exchange of Na+ for Ca2+ during Ca2+ repletion. With the use of 23Na nuclear magnetic resonance, we previously observed a Ca2+ paradox without a prior Na+ increase. We have now demonstrated a Na+ increase during Ca2+ and Mg2+ depletion without the occurrence of the Ca2+ paradox during Ca2+ repletion. Isolated rat hearts were perfused for 20 min with a Ca(2+)-free or a Ca(2+)- and Mg(2+)-free (Ca2+/Mg(2+)-free) solution under hypothermic conditions (20 and 25 degrees C). Intracellular Na+ concentration ([Na+]i) increased from 11.9 +/- 1.2 to 26.9 +/- 5.8 mM (P &lt; 0.001) during Ca2+/Mg(2+)-free perfusion at 20 degrees C, whereas no significant change in [Na+]i occurred during 20 min of Ca(2+)-free perfusion at 20 degrees C. In addition, we confirmed that [Na+]i did not change significantly during 20 min of normothermic Ca(2+)-free perfusion. Creatine kinase release during normothermic Ca2+ repletion in the 20 degrees C groups was approximately 10% and in the 25 degrees C groups 75% of the release in the normothermia group. Recovery of rate-pressure product was approximately 50% in the 20 degrees C groups versus 0% in the normothermia group. In conclusion, hypothermic Ca2+/Mg(2+)-free perfusion results in a significant increase of [Na+]i, which does not contribute to the extent of the Ca2+ paradox on normothermic Ca2+ repletion.
Introduction While the embryonic zebrafish has been widely used for basic cardiac research the ad... more Introduction While the embryonic zebrafish has been widely used for basic cardiac research the adult zebrafish has been used less partly due to difficulties in evaluating the hearts structure and function in-vivo. Currently available cardiac imaging techniques are limited by the hearts small size and rapid rate. Successful development of cardiac MRI for the adult zebrafish could have significant scientific, ethical and economic benefits for cardiac research. Methods We have developed a novel magnetic resonance imaging (MRI) scanning system, designed to study cardiac structure and function in the live adult zebrafish. This has involved the development of an integrated zebrafish life support and monitoring system with an internal custom MRI solenoid microimaging coil – the ‘flow cell’ (Figure 1). Zebrafish are anesthetised (MS222) and held in position within a flow chamber that intersects the MRI coil for scanning (internal diameter 6.9 mm, SNR >130). Water flows through the system...
A functional MRI (fMRI) phantom was used to characterize the stability and behaviour of Echo Plan... more A functional MRI (fMRI) phantom was used to characterize the stability and behaviour of Echo Planar Imaging (EPI) on a number of preclinical MRI scanners. Large variations in functional Contrast to Noise Ratios (fCNR) were observed. Additionally a longitudinal study at a single site recorded significant changes in fCNR across time. A proportion of individual scans also displayed unusual behaviour. Given that a stable and reliable fCNR for a particular biological effect is the basis for current fMRI and resting state connectivity research, the results we report suggest that caution should be taken with those results. Further studies of factors affecting preclinical EPI stability should be undertaken as should similar checks on clinical systems.
American Journal of Physiology - Heart and Circulatory Physiology, 2015
The extent of infarct injury is a key determinant of structural and functional remodeling followi... more The extent of infarct injury is a key determinant of structural and functional remodeling following myocardial infarction (MI). Infarct volume in experimental models of MI can be determined accurately by in vivo magnetic resonance imaging (MRI), but this is costly and not widely available. Experimental studies therefore commonly assess injury by histological analysis of sections sampled from the infarcted heart, an approach that is labor intensive, can be subjective and does not fully assess the extent of injury. The present study aimed to assess the suitability of optical projection tomography (OPT) for identification of injured myocardium and for accurate and efficient assessment of infarct volume. Intact, perfusion fixed, optically cleared hearts, collected from mice 7 days after induction of MI by coronary artery occlusion, were scanned by a tomograph for autofluorescence emission after UV excitation, generating &amp;amp;gt;400 transaxial sections for reconstruction. Differential autofluorescence permitted discrimination between viable and injured myocardium and highlighted the heterogeneity within the infarct zone. 2D infarct areas derived from OPT imaging and Masson&amp;amp;#39;s trichrome staining of slices from the same heart were highly correlated (r2=0.99, P&amp;amp;lt;0.0001). Infarct volume derived from reconstructed OPT sections correlated with volume derived from in vivo late gadolinium enhancement MRI (LGE-MRI) (r2=0.7608, P&amp;amp;lt;0.005). Tissue processing for OPT did not compromise subsequent immunohistochemical detection of endothelial cell and inflammatory cell markers. OPT is thus a non-destructive, efficient and accurate approach for routine in vitro assessment of murine myocardial infarct volume.
In the current study, we have developed a magnetic resonance imaging-based method for non-invasiv... more In the current study, we have developed a magnetic resonance imaging-based method for non-invasive detection of complement activation in placenta and foetal brain in vivo in utero. Using this method, we found that anti-complement C3-targeted ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles bind within the inflamed placenta and foetal brain cortical tissue, causing a shortening of the T2* relaxation time. We used two mouse models of pregnancy complications: a mouse model of obstetrics antiphospholipid syndrome (APS) and a mouse model of preterm birth (PTB). We found that detection of C3 deposition in the placenta in the APS model was associated with placental insufficiency characterised by increased oxidative stress, decreased vascular endothelial growth factor and placental growth factor levels and intrauterine growth restriction. We also found that foetal brain C3 deposition was associated with cortical axonal cytoarchitecture disruption and increased neurodegeneration...
American journal of physiology. Heart and circulatory physiology, 2003
This study tests the hypothesis that a decrease of the free energy of ATP hydrolysis (Delta GATP)... more This study tests the hypothesis that a decrease of the free energy of ATP hydrolysis (Delta GATP) below a threshold value will inhibit Na+-K+-ATPase (Na+ pump) activity and result in an increase of intracellular Na+ concentration ([Na+]i) in the heart. Conditions were designed in which hearts were solely dependent on ATP derived from oxidative phosphorylation. The only substrate supplied was the fatty acid butyrate (Bu) at either low, 0.1 mM (LowBu), or high, 4 mM (HighBu), concentrations. Escalating work demand reduced the Delta GATP of the LowBu hearts. 31P, 23Na, and 87Rb NMR spectroscopy measured high-energy phosphate metabolites, [Na+]i, and Rb+ uptake. Rb+ uptake was used to estimate Na+ pump activity. To measure [Na+]i using a shift reagent for cations, extracellular Ca2+ was reduced to 0.85 mM, which eliminated work demand Delta GATP reductions. Increasing extracellular Na+ (Nae+) to 200 mM restored work demand Delta GATP reductions. In response to higher [Na+]e, [Na+]i incr...
Ca2+ paradox damage has been suggested to be determined by Na+ entry during Ca2+ depletion and ex... more Ca2+ paradox damage has been suggested to be determined by Na+ entry during Ca2+ depletion and exchange of Na+ for Ca2+ during Ca2+ repletion. With the use of 23Na nuclear magnetic resonance, we previously observed a Ca2+ paradox without a prior Na+ increase. We have now demonstrated a Na+ increase during Ca2+ and Mg2+ depletion without the occurrence of the Ca2+ paradox during Ca2+ repletion. Isolated rat hearts were perfused for 20 min with a Ca(2+)-free or a Ca(2+)- and Mg(2+)-free (Ca2+/Mg(2+)-free) solution under hypothermic conditions (20 and 25 degrees C). Intracellular Na+ concentration ([Na+]i) increased from 11.9 +/- 1.2 to 26.9 +/- 5.8 mM (P < 0.001) during Ca2+/Mg(2+)-free perfusion at 20 degrees C, whereas no significant change in [Na+]i occurred during 20 min of Ca(2+)-free perfusion at 20 degrees C. In addition, we confirmed that [Na+]i did not change significantly during 20 min of normothermic Ca(2+)-free perfusion. Creatine kinase release during normothermic Ca2+...
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Papers by Maurits Jansen