Otto Kamp

Netherlands Institute for Space Research, Utrecht, Utrecht, Utrecht, Netherlands

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Publications (230)1043.29 Total impact

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    ABSTRACT: MicroRNAs are involved in many pathologic processes and are a promising target for therapeutic intervention. However, successful, localized delivery of microRNA-based therapeutics is lacking. In this study, cationic ultrasound-responsive microbubbles (MBs) were used to deliver microRNA blockers and mimics in vitro and in vivo. Cationic MBs successfully delivered microRNA blockers to human endothelial cells on ultrasound (US) exposure in vitro. This in vitro US protocol did not successfully deliver microRNA mimics to skeletal muscle of mice, whereas an US protocol that is routinely used for contrast imaging did. Additionally, we used cationic MBs and US to locally deliver antimiR and antagomiR molecules with US causing inertial cavitation. Delivery of antimiR to the extracellular compartments of the muscle was only slightly increased, whereas delivery of antagomiR to the capillaries, myocytes and extracellular space was significantly increased. AntagomiR seems to be a more suitable microRNA blocker than antimiR for use in combination with MBs and US for local delivery.
    Ultrasound in Medicine & Biology. 11/2014;
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    ABSTRACT: Three-dimensional (3D) speckle tracking echocardiography (3DSTE) has been shown to be an accurate and reliable clinical tool for the evaluation of global and regional left ventricular (LV) function through strain analysis, but the absence of normal values has precluded its widespread use in clinical practice. The aim of this prospective multicentre study was to establish normal reference values of LV strain parameters using 3DSTE in a large healthy population.
    European Heart Journal – Cardiovascular Imaging 10/2014; · 3.67 Impact Factor
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    ABSTRACT: Viability seems to be important in preventing ventricular remodeling after acute myocardial infarction (AMI). We investigated the influence of viability, as demonstrated with low-dose dobutamine echocardiography, and the role of early revascularization on the process of left ventricular (LV) remodeling after AMI.
    Trials. 08/2014; 15(1):329.
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    IJC Heart & Vessels. 08/2014;
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    ABSTRACT: The use of stem cells for the repair of damaged cardiac tissue after a myocardial infarction holds great promise. However, a common finding in experimental studies is the low number of cells delivered at the area at risk. To improve the delivery, we are currently investigating a novel delivery platform in which stem cells are conjugated with targeted microbubbles, creating echogenic complexes dubbed StemBells. These StemBells vibrate in response to incoming ultrasound waves making them susceptible to acoustic radiation force. The acoustic force can then be employed to propel circulating StemBells from the centerline of the vessel to the wall, facilitating localized stem cell delivery. In this study we investigate the feasibility of manipulating StemBells acoustically in vivo after injection using a chicken embryo model. Bare stem cells or unsaturated stem cells (< 5 bubbles/cell) do not respond to ultrasound application (1 MHz, peak negative acoustical pressure P- = 200 kPa, 10% duty cycle). However, stem cells which are fully saturated with targeted microbubbles (> 30 bubbles/cell) can be propelled toward and arrested at the vessel wall. The mean translational velocities measured are 61 μgm/s and 177 μgm/s for P- = 200 kPa and P- = 450 kPa respectively. This technique therefore offers potential for enhanced and well-controlled stem cell delivery for improved cardiac repair after a myocardial infarction. Biotechnol. Bioeng. © 2014 Wiley Periodicals, Inc.
    Biotechnology and Bioengineering 08/2014; · 4.16 Impact Factor
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    ABSTRACT: The addition of local ultrasound (US) with a contrast agent to standard intra-arterial thrombolysis can accelerate the thrombolytic treatment of stroke and myocardial infarction. The contrast agent consists of microsized gas-filled bubbles that collapse when exposed to US, causing destabilization of the clot and making the clot surface more susceptible to fibrinolytics. In this study, we investigated the effect of additional US and microbubbles on standard low-dose intra-arterial thrombolysis in a porcine model of extensive peripheral arterial occlusion. Extensive arterial thrombosis was induced in 10 pigs in the 4-cm external iliac artery by clamping and injection of 100 IU of bovine thrombin. A transcutaneous laser Doppler flow probe and an ultrasonic perivascular flow probe assessed microcirculation and arterial flow respectively. The urokinase-only (UK) group (n = 4) received standard thrombolytic therapy: intra-arterial bolus injection of 500,000 IU, followed by a continuous low-dose urokinase (50,000 IU/h) infusion through an intra-arterial catheter and local intermittent application of US, 1 second on, 5 seconds off, to visualize vascular patency during the first hour of therapy and to ensure microbubbles replenished the proximal portion of the occluded artery. The urokinase plus microbubbles (UK+) group (n = 6) received the same urokinase therapy with a concomitant intravenous infusion of microbubbles and local intermittent application of US. The contrast infusion protocol consisted of a bolus of two vials of 5 mL in the first 15 minutes and then three times 5 mL slowly hand-injected continuously during the next 45 min. After 3 hours of therapy, the animals were euthanized, and thrombi were harvested and weighed. All organs were cut in thin slices and macroscopically inspected for potential (hemorrhagic) adverse events, and tissue samples were taken. Median thrombus weights were 1.1 g (range, 0.8-1.3 g) in the UK+ group vs 1.6 g (range, 1.3-1.9 g) in the UK group (P = .01). Arterial blood flow increased in four of six pigs in the UK+ group by a mean 61% vs in one of four in the UK group, with 1%. Microcirculation and lower limb arterial pressure levels improved after the start of therapy in the UK+ group, contrary to a trend of decline in the UK group. No signs of bleeding complications were observed in either group. In this experimental pilot study, the addition of contrast-enhanced US accelerated the thrombolytic effect of low-dose intra-arterial thrombolysis in peripheral arterial occlusions. Further clinical studies are warranted.
    Journal of vascular surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter 04/2014; · 3.52 Impact Factor
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    ABSTRACT: Stem cells can be conjugated with targeted microbubbles to form highly echogenic complexes, dubbed StemBells. The complexes can improve stem cell delivery for the local repair of damaged cardiac tissue after a myocardial infarction through propulsion by acoustic radiation forces. While the first in-vivo tests hold great promise, the system would greatly benefit from a mapping of the acoustic parameter space. Here, we develop the theoretical background based on a modified Rayleigh-Plesset type equation to describe the dynamics of the StemBells in response to ultrasound. The complex is shown to resonate as a whole entity and resonance curves are constructed from numerical simulations resembling single bubble responses at a size that relates to the effective complex radius ~10 μm. Ultra high-speed optical imaging of single StemBell complexes at different frequencies using the microbubble spectroscopy method allows for a full characterization with excellent agreement with the developed model. Moreover, from the experimental resonance curves, we obtain values for the effective viscoelastic shell parameters of the StemBell complexes. These results have enabled the demonstration of the feasibility of manipulating StemBells inside chicken embryo microvasculature in an accompanying paper.
    The Journal of the Acoustical Society of America 04/2014; 135(4):2310. · 1.65 Impact Factor
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    ABSTRACT: The use of stem cells for regenerative tissue repair is hampered by the low number of cells delivered to the site of injury. To increase the delivery, we developed a new technique in which stem cells are coated with functionalized microbubbles, creating echogenic complexes dubbed StemBells. StemBells are highly susceptible to acoustic radiation force; this acoustic force can then be used after injection to deliver the StemBells locally at the treatment site. The dynamics of StemBells during ultrasound insonification was characterized using high-speed optical imaging and is described in an accompanying paper. Here, we investigate the feasibility of manipulating StemBells acoustically after injection employing a chicken embryo model, allowing for the real-time optical observation of the effects of acoustic radiation force in vivo. StemBells were infused by placing a custom-made catheter into one of the vitelline veins. Acoustic radiation force (1 MHz, P = 200-450 kPa, 10% duty cycle) was observed to propel StemBells from the centerline of the microvessels (200-500 μm) to the wall distal from the transducer. Peak translational velocities increased with pressure and varied between 50 μm/s to 300 μm/s. The acoustic radiation force had no effect on the trajectory of bare stem cells.
    The Journal of the Acoustical Society of America 04/2014; 135(4):2310. · 1.65 Impact Factor
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    ABSTRACT: The majority of patients survive an acute myocardial infarction (AMI). Their outcome is negatively influenced by post-AMI events, such as loss of viable cardiomyocytes due to a post-AMI inflammatory response, eventually resulting in heart failure and/or death. Recent pre-clinical animal studies indicate that mesenchymal stem cells derived from adipose tissue (ASC) are new promising candidates that may facilitate cardiovascular regeneration in the infarcted myocardium. In this review we have compared all animal studies in which ASC were used as a therapy post-AMI and have focused on aspects that might be important for future successful clinical application of ASC.
    Stem cell reviews 03/2014; · 5.08 Impact Factor
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    ABSTRACT: Current stroke risk schemes need improvement of predictive value in patients with atrial fibrillation. Transoesophageal echocardiography (TEE) may facilitate stroke risk assessment in such patients and guide antithrombotic treatment. We randomised 238 patients with non-valvular atrial fibrillation and a moderate stroke risk to aspirin or adjusted vitamin K antagonist therapy after TEE had ruled out thrombogenic features in the atria and aorta. The primary outcome was a composite of stroke, major bleeding, peripheral embolism and all-cause mortality. Mean CHA2DS2-VASc score was 2.1±1.1. The incidences of the composite primary outcome at a mean follow-up of 1.6 years were 3.2% (2.02% per year) in the aspirin group compared to 6.1% (3.84% per year) in the vitamin K antagonists group with an absolute advantage of 2.9 percentage points. Aspirin was non-inferior to vitamin K antagonists (p<0.0001) because the upper limit of the 90% CI did not exceed the 7% absolute difference in event rate between the two treatment arms. This hypothesis-generating pilot trial has found that TEE may be used for refinement of stroke risk in paroxysmal atrial fibrillation patients. A larger trial is needed to confirm these data. ( number NTC00224757).
    Heart (British Cardiac Society) 01/2014; · 5.01 Impact Factor
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    ABSTRACT: The aim is to detect early changes in myocardial mechanics in hypertrophic cardiomyopathy (HCM) mutation carriers, three-dimensional speckle tracking echocardiography (3DSTE) was used for screening of family members in the HCM population. Eighty subjects were divided as: HCM mutation carriers (n = 23), manifest HCM patients (n = 28), and normal controls (n = 29). They prospectively underwent 3DSTE for left atrial (LA) and left ventricle (LV) strain analysis. HCM mutation carriers showed significantly higher LA minimum volume (ml/m(2)) (17 ± 6 vs. 14 ± 4, respectively, P = 0.03) and a significantly lower peak atrial longitudinal strain (PALS) (%), (27 ± 5 vs. 31 ± 7, respectively, P = 0.02) when compared to controls. However, no differences were found in global or regional LV systolic myocardial deformation between both groups. Manifest HCM patients, compared to carriers showed significantly higher LA minimum (27 ± 10 vs. 17 ± 6, respectively, P < 0.001) and maximum volume (42 ± 14 vs. 32 ± 8, respectively, P = 0.007) as well as lower LA ejection fraction (%) (35 ± 8 vs. 47 ± 9, respectively, P < 0.001) and PALS (17 ± 5 vs. 27 ± 5, respectively, P < 0.001). Comparing LV strain, HCM patients showed reduced global longitudinal (-11 ± 4 vs. -16 ± 3, respectively, P < 0.001) and area strain (-35 ± 6 vs. -40 ± 5, respectively, P = 0.005). HCM mutation carriers may be distinguished from healthy subjects using 3DSTE through detection of LA dysfunction that may indicate LV diastolic dysfunction. Further research in a larger study population with gene-specific analysis is warranted for potential clinical usefulness of 3DSTE in family screening for HCM.
    The international journal of cardiovascular imaging 01/2014; · 2.15 Impact Factor
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    ABSTRACT: To assess whether cardiac abnormalities after aneurysmal subarachnoid hemorrhage (aSAH) are associated with delayed cerebral ischemia (DCI) and clinical outcome, independent from known clinical risk factors for these outcomes. In a prospective, multicenter cohort study, we performed echocardiography and ECG and measured biochemical markers for myocardial damage in patients with aSAH. Outcomes were DCI, death, and poor clinical outcome (death or dependency for activities of daily living) at 3 months. With multivariable Poisson regression analysis, we calculated risk ratios (RRs) with corresponding 95% confidence intervals. We used survival analysis to assess cumulative percentage of death in patients with and without echocardiographic wall motion abnormalities (WMAs). We included 301 patients with a mean age of 57 years; 70% were women. A wall motion score index ≥1.2 had an adjusted RR of 1.2 (0.9-1.6) for DCI, 1.9 (1.1-3.3) for death, and 1.8 (1.1-3.0) for poor outcome. Midventricular WMAs had adjusted RRs of 1.1 (0.8-1.4) for DCI, 2.3 (1.4-3.8) for death, and 2.2 (1.4-3.5) for poor outcome. For apical WMAs, adjusted RRs were 1.3 (1.1-1.7) for DCI, 1.5 (0.8-2.7) for death, and 1.4 (0.8-2.5) for poor outcome. Elevated troponin T levels, ST-segment changes, and low voltage on the admission ECGs had a univariable association with death but were not independent predictors for outcome. WMAs are independent risk factors for clinical outcome after aSAH. This relation is partly explained by a higher risk of DCI. Further study should aim at treatment strategies for these aSAH-related cardiac abnormalities to improve clinical outcome.
    Neurology 01/2014; 82(4):351-8. · 8.30 Impact Factor
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    ABSTRACT: Increased left ventricular mass (LVM), low ventricular ejection fraction (EF), and high pulse-wave velocity (PWV) relate to overall and cardiovascular mortality in patients with ESRD. The aim of this study was to determine the effect of online hemodiafiltration (HDF) versus low-flux hemodialysis (HD) on LVM, EF, and PWV. Echocardiography was used to assess LVM and EF in 342 patients in the CONvective TRAnsport STudy followed for up to 4 years. PWV was measured in 189 patients for up to 3 years. Effect of HDF versus HD on LVM, EF, and PWV was evaluated using linear mixed models. Patients had a mean age of 63 years, and 61% were male. At baseline, median LVM was 227 g (interquartile range [IQR], 183-279 g), and median EF was 65% (IQR, 55%-72%). Median PWV was 9.8 m/s (IQR, 7.5-12.0 m/s). There was no significant difference between the HDF and HD treatment groups in rate of change in LVM (HDF: change, -0.9 g/yr [95% confidence interval (95% CI), -8.9 to 7.7 g]; HD: change, 12.5 g/yr [95% CI, -3.0 to 27.5 g]; P for difference=0.13), EF (HDF: change, -0.3%/yr [95% CI, -2.3% to 1.8%]; HD: change, -3.4%/yr [95% CI, -5.9% to -0.9%]; P=0.17), or PWV (HDF: change, -0.0 m/s per year [95% CI, -0.4 to 0.4 m/s); HD: change, 0.0 m/s per year [95% CI, -0.3 to 0.2 m/s]; P=0.89). No differences in rate of change between treatment groups were observed for subgroups of age, sex, residual kidney function, dialysis vintage, history of cardiovascular disease, diabetes, or convection volume. Treatment with online HDF did not affect changes in LVM, EF, or PWV over time compared with HD.
    Clinical Journal of the American Society of Nephrology 01/2014; · 5.07 Impact Factor
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    ABSTRACT: The Wistar rat is a commonly used strain for experimental animal models. Recently it was shown that results vary between studies using Wistar rats of different suppliers. Therefore we studied whether Wistar rats obtained from Harlan Laboratories (Ha, n=24) and Charles River (CR, n=22) had a different outcome in an acute myocardial infarction (AMI) model. AMI was induced in both Ha and CR Wistar rats by one operator. This resulted in a significantly higher survival rate for Ha (79.2±10.2%) compared with CR rats (54.2±10.2%, p<0.05). Furthermore, CR rats had lost significantly more weight after 7days (-5.9±3.1%) compared with Ha rats (-0.8±1.7%; p<0.001), indicating a worse health status of the CR rats. Paradoxically, the induced infarct was smaller in CR rats (7.3±3.6% of the heart) compared with Ha rats (12.1±4.7%, p<0.05). This indicates that CR rats were less sensitive for the cardiomyocyte damage subsequent to AMI induction, but remarkably showed more clinical side effects indicating that Wistar rats from two suppliers had a different response within the same AMI model.
    Research in Veterinary Science 01/2014; · 1.77 Impact Factor
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    ABSTRACT: Purpose The aim of this study was to prospectively investigate the association of retinopathy with changes in left ventricular (LV) function. Methods Within the Hoorn Study, a population-based cohort study of diabetes in The Netherlands, retinal photography and echocardiography were performed in the year 2000 (baseline) and 2008 (follow-up). Retinopathy was graded according to the Eurodiab classification and further defined as absent or present retinopathy. LV systolic and diastolic function were assessed by LV ejection fraction (%), LV mass (g/m2.7) and left atrial (LA) volume indices and the ratio of LV inflow (E) and early diastolic lengthening (e’) velocities. Linear regression analyses stratified for sex were completed to investigate associations of retinopathy with changes in LV function in participants with impaired glucose metabolism and type 2 diabetes. Results 147 participants (58% men, mean age 66) were included in the study, of whom 13.6% were present with retinopathy at baseline. LV ejection fraction was similar among participants with and without retinopathy (60.2% versus 60.7%) at baseline. Eight years later, retinopathy was significantly associated with a lower LV ejection fraction (β 8.0 95% CI -15.37 to -0.68) in men , independent of risk factors. Microvascular endothelial dysfunction ([ED] β 4.87 95% CI -13.40 to 3.67) and low-grade inflammation ([LGI] β -5.30 95% CI -13.72 to 3.12) both diminished the association. No significant associations between retinopathy and other LV function parameters were observed. Conclusion Retinopathy was significantly associated with a lower LV ejection fraction in men but not in women. LGI and ED might explain the observed association.
    Journal of Diabetes and its Complications 01/2014; · 2.06 Impact Factor
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    ABSTRACT: Objectives To assess the prognostic value of absolute NT-proBNP concentration in combination with changes during admission and early after discharge because of acute heart failure (AHF). Background In AHF, readmission and mortality rates are high. Identifying those at highest risk for events early after hospital discharge might help to select patients in need of intensive outpatient monitoring. Methods and results We evaluated the prognostic value of NT-proBNP concentration on admission, at discharge, 1 month after hospital discharge and change over time in 309 patients included in the PRIMA-study. In a multivariate cox regression analysis, change in NT-proBNP concentration during admission, change from discharge to 1 month after discharge, and the absolute NT-proBNP concentration at one month after discharge were of independent prognostic value for both endpoints (HR for HF-hospital free survival 1.71, 95% CI 1.13 - 2.60, Wald 6.4, P = 0.011 versus 2.71, 95% CI 1.76-4.17, Wald 20.5, P < 0.001 versus 1.81, 95% CI 1.13 – 2.89, Wald 6.1, P=0.014). Conclusion Knowledge of change in NT-proBNP concentration during admission because of AHF in combination with change early after discharge and the absolute NT-proBNP concentration at one month after discharge allows accurate risk stratification.
    Journal of Cardiac Failure. 01/2014;
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    ABSTRACT: Left ventricular mass (LVM) is known to be related to overall and cardiovascular mortality in end stage kidney disease (ESKD) patients. The aims of the present study are 1) to determine whether LVM is associated with mortality and various cardiovascular events and 2) to identify determinants of LVM including biomarkers of inflammation and fibrosis. Analysis was performed with data of 327 ESKD patients, a subset from the CONvective TRAnsport STudy (CONTRAST). Echocardiography was performed at baseline. Cox regression analysis was used to assess the relation of LVM tertiles with clinical events. Multivariable linear regression models were used to identify factors associated with LVM. Median age was 65 (IQR: 54-73) years, 203 (61%) were male and median LVM was 227 (IQR: 183-279) grams. The risk of all-cause mortality (hazard ratio (HR) = 1.73, 95% CI: 1.11-2.99), cardiovascular death (HR = 3.66, 95% CI: 1.35-10.05) and sudden death (HR = 13.06; 95% CI: 6.60-107) was increased in the highest tertile (>260grams) of LVM. In the multivariable analysis positive relations with LVM were found for male gender (B = 38.8±10.3), residual renal function (B = 17.9±8.0), phosphate binder therapy (B = 16.9±8.5), and an inverse relation for a previous kidney transplantation (B = -41.1±7.6) and albumin (B = -2.9±1.1). Interleukin-6 (Il-6), high-sensitivity C-reactive protein (hsCRP), hepcidin-25 and connective tissue growth factor (CTGF) were not related to LVM. We confirm the relation between a high LVM and outcome and expand the evidence for increased risk of sudden death. No relationship was found between LVM and markers of inflammation and fibrosis. ISRCTN38365125.
    PLoS ONE 01/2014; 9(2):e84587. · 3.53 Impact Factor
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    ABSTRACT: The use of stem cells for the repair of damaged cardiac tissue after a myocardial infarction holds great promise. However, a common finding in experimental studies is that only a small fraction of the transplanted cells engraft in the infarcted area of the heart. In this study we investigated the use of stem cells conjugated with targeted microbubbles, creating echogenic complexes dubbed StemBells, to achieve increased stem cell delivery. The dynamics of the constructs in response to an ultrasound wave was characterized using high speed optical imaging. A modified Rayleigh-Plesset equation was developed to corroborate our experimental findings. We show that acoustic radiation force can be used to propel StemBells to the wall of a 200 μm vessel in a chicken embryo. This technique therefore facilitates the possibility to localize stem cell delivery to increase the engraftment and improve the clinical outcome of stem cell therapy.
    2013 IEEE International Ultrasonics Symposium (IUS); 07/2013
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    ABSTRACT: BACKGROUND:Preservation of myocardial perfusion during general anesthesia is likely important in patients at risk for perioperative cardiac complications. Data related to the influence of general anesthesia on the normal myocardial circulation are limited. In this study, we investigated myocardial microcirculatory responses to pharmacological vasodilation and sympathetic stimulation during general anesthesia with sevoflurane in healthy humans immediately before surgical stimulation.METHODS:Six female and 7 male subjects (mean age 43 years, range 28-61) were studied at baseline while awake and during the administration of 1 minimum alveolar concentration sevoflurane. Using myocardial contrast echocardiography, myocardial blood flow (MBF) and microcirculatory variables were assessed at rest, during adenosine-induced hyperemia, and after cold pressor test-induced sympathetic stimulation. MBF was calculated from the relative myocardial blood volume multiplied by its exchange frequency (β) divided by myocardial tissue density (ρT), which was set at 1.05 g·mL(-1).RESULTS:During sevoflurane anesthesia, MBF at rest was similar to baseline values (1.05 ± 0.28 vs 1.05 ± 0.32 mL·min(-1)·g(-1); P = 0.98; 95% confidence interval [CI], -0.18 to 0.18). Myocardial blood volume decreased (P = 0.0044; 95% CI, 0.01-0.04) while its exchange frequency (β) increased under sevoflurane anesthesia when compared with baseline. In contrast, hyperemic MBF was reduced during anesthesia compared with baseline (2.25 ± 0.5 vs 3.53 ± 0.7 mL·min(-1)·g(-1); P = 0.0003; 95% CI, 0.72-1.84). Sympathetic stimulation during sevoflurane anesthesia resulted in a similar MBF compared to baseline (1.53 ± 0.53 and 1.55 ± 0.49 mL·min(-1)·g(-1); P = 0.74; 95% CI, -0.47 to 0.35).CONCLUSIONS:In otherwise healthy subjects who are not subjected to surgical stimulation, MBF at rest and after sympathetic stimulation is preserved during sevoflurane anesthesia despite a decrease in myocardial blood volume. However, sevoflurane anesthesia reduces hyperemic MBF, and thus MBF reserve, in these subjects.
    Anesthesia and analgesia 02/2013; · 3.08 Impact Factor
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    ABSTRACT: In this study, we investigated the effect of secondary Bjerknes forces on targeted microbubbles using high-speed optical imaging. We observed that targeted microbubbles attached to an underlying surface and subject to secondary Bjerknes forces deform in the direction of their neighboring bubble, thereby tending toward a prolate shape. The deformation induces an elastic restoring force, causing the bubbles to recoil back to their equilibrium position; typically within 100 μs after low-intensity ultrasound application. The temporal dynamics of the recoil was modeled as a simple mass-spring system, from which a value for the effective spring constant k of the order 10(-3) Nm(-1) was obtained. Moreover, the translational dynamics of interacting targeted microbubbles was predicted by a hydrodynamic point particle model, including a value of the spring stiffness k of the very same order as derived experimentally from the recoiling curves. For higher acoustic pressures, secondary Bjerknes forces rupture the molecular adhesion of the bubbles to the surface. We used this mutual attraction to quantify the binding force between a single biotinylated microbubble and an avidin-coated surface, which was found to be between 0.9 and 2 nanonewtons (nN). The observation of patches of lipids left at the initial binding site suggests that lipid anchors are pulled out of the microbubble shell, rather than biotin molecules unbinding from avidin. Understanding the effect of ultrasound application on targeted microbubbles is crucial for further advances in the realm of molecular imaging.
    Ultrasound in medicine & biology 01/2013; · 2.46 Impact Factor

Publication Stats

4k Citations
1,043.29 Total Impact Points


  • 2013–2014
    • Netherlands Institute for Space Research, Utrecht
      Utrecht, Utrecht, Netherlands
    • Erasmus MC
      Rotterdam, South Holland, Netherlands
  • 2001–2014
    • VU University Medical Center
      • Department of Cardiology
      Amsterdamo, North Holland, Netherlands
  • 1992–2014
    • VU University Amsterdam
      • • Department of Cardiology
      • • Institute for Cardiovascular Research VU
      Amsterdamo, North Holland, Netherlands
  • 2011
    • Maastricht University
      • Cardiologie
      Maastricht, Provincie Limburg, Netherlands
    • University of Antwerp
      Antwerpen, Flanders, Belgium
  • 2004–2009
    • University of Groningen
      • • Department of Clinical Pharmacology
      • • Department of Cardiology
      Groningen, Province of Groningen, Netherlands
  • 2006–2007
    • Pavol Jozef Šafárik University in Košice
      • Department of Internal Medicine
      Kassa, Košický, Slovakia
  • 2003–2005
    • St. Antonius Ziekenhuis
      • Department of Cardiology
      Nieuwegein, Provincie Utrecht, Netherlands
  • 1993–2004
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • • Department of Cardiology and Cardio-thoracic Surgery
      • • Academic Medical Center
      Amsterdamo, North Holland, Netherlands
  • 1997–2002
    • Leiden University Medical Centre
      • • Department of Radiology
      • • Department of Cardiology
      Leiden, South Holland, Netherlands
  • 1998
    • Cleveland Clinic
      Cleveland, Ohio, United States
  • 1996
    • Catharina Hospital
      Eindhoven, North Brabant, Netherlands
  • 1995
    • University of Amsterdam
      • Department of Cardiology
      Amsterdam, North Holland, Netherlands