Willem van der laarse

Amsterdam University Medical Center | VUmc · Department of Physiology

Myoglobin is essential for oxygen transport to the muscle fibers. However, measurements of myoglobin (Mb) protein concentrations within individual human muscle fibers are scarce. Recent observations have revealed surprisingly low Mb concentrations in elite cyclists, however it remains unclear whether this relates to Mb translation, transcription an...

Right‐sided myocardial mechanical efficiency (work output/metabolic energy input) in pulmonary hypertension can be severely reduced. We determined the contribution of intrinsic myocardial determinants of efficiency using papillary muscle preparations from monocrotaline‐induced pulmonary hypertensive (MCT‐PH) rats. The hypothesis tested was that eff...

Right-sided myocardial mechanical efficiency (work output/metabolic energy input) in pulmonary hypertension can be severely reduced. We determined the contribution of intrinsic myocardial determinants of efficiency using papillary muscle preparations from monocrotaline-induced pulmonary hypertensive (MCT-PH) rats. The hypothesis was tested that eff...

Monoamine oxidases (MAO), a class of enzymes bound to the outer mitochondrial membrane, are important sources of reactive oxygen species. Increased MAO-A activity in endothelial cells and cardiomyocytes contributes to vascular dysfunction and progression of left heart failure. We hypothesized that inhibition of MAO-A can be used to treat pulmonary...

While the heart regenerates poorly in mammals, efficient heart regeneration occurs in zebrafish. Studies in zebrafish have resulted in a model in which preexisting cardiomyocytes dedifferentiate and reinitiate proliferation to replace the lost myocardium. To identify which processes occur in proliferating cardiomyocytes we have used a single-cell R...

Currently available data on the energetics of isolated muscle preparations are based on bouts of less than 10 muscle contractions, whereas metabolic energy consumption is mostly relevant during steady state tasks such as locomotion. In this study we quantified the energetics of small fiber bundles of mouse soleus muscle during prolonged (2 min) ser...

The capacity to regenerate damaged tissues, such as the heart, various enormously amongst species. While heart regeneration is generally very low in mammals, it can regenerate efficiently in certain amphibian and fish species. Zebrafish has been used extensively to study heart regeneration, resulting in the identification of proliferating cardiomyo...

A comparison with the mitochondrial oxidative capacity. TO THE EDITOR: With great interest we read Green and Askew’s Viewpoint (1) on validity of VO2peak, mode-specific VO2max, and VO2max. Exercise testing is generally performed to identify upper limits in cardiorespiratory fitness. However, VO2peak measurements could lead to inaccurate estimation...

Uncoupling of mitochondrial proton pumping and adenosine triphosphate (ATP) production lowers mitochondrial efficiency. Current methods to determine mitochondrial efficiency require substantial amounts of tissue and permeabilization or isolation procedures. A simple histochemical method has been described by Meijer and Vloedman (Histochemistry 69:2...

Optimizing physical performance is a major goal in current physiology. However, basic understanding of combining high sprint and endurance performance is currently lacking. This study identifies critical determinants of combined sprint and endurance performance using multiple regression analyses of physiologic determinants at different biologic lev...

Rowers need to combine high sprint and endurance capacities. Muscle morphology largely explains muscle power generating capacity, however, little is known on how muscle morphology relates to rowing performance measures. The aim was to determine how muscle morphology of the vastus lateralis relates to rowing ergometer performance, sprint and enduran...

The function of the right ventricle (RV) determines the prognosis of patients with pulmonary hypertension. While much progress has been made in the treatment of pulmonary hypertension, therapies for the RV are less well established. In this review of treatment strategies for the RV, first we focus on ways to reduce wall stress since this is the mai...

Abstract: Chronic hypoxia is associated with muscle wasting and decreased oxidative capacity. By contrast, training under hypoxia may enhance hypertrophy and increase oxidative capacity as well as oxygen transport to the mitochondria, by increasing myoglobin (Mb) expression. The latter may be a feasible strategy to prevent atrophy under hypoxia and...

BACKGROUND: Rowing races challenge rowers to combine high sprint and endurance capacity. Muscle morphology is an important determinant of sprint and endurance capacities and as such may also be a critical determinant of rowing performance. PURPOSE: To determine how much of the rowing performance of Olympic rowers is explained by sprint and enduranc...

The human heart requires a considerable amount of energy (10 W at rest to 100 W during exercise) for basal metabolism, activation processes and work to circulate blood (heart rate × stroke volume × arterial blood pressure). This article is protected by copyright. All rights reserved.

to the editor: We thank Gifford and colleagues for their comment ([3][1]) and agree that the correlation between mitochondrial oxidative capacity and V̇o2 max among our chronic heart failure (CHF) patients is not significant [ r = 0.47, P = 0.11 ([5][2])]. However, we disagree with their conclusion

A major problem in chronic heart failure is the inability of hypertrophied cardiomyocytes to maintain the required power output. A Hill-type oxygen diffusion model predicts that oxygen supply is limiting in hypertrophied cardiomyocytes at maximal rates of oxygen consumption and that this limitation can be reduced by increasing the myoglobin (Mb) co...

Near-infrared spectroscopy (NIRS) measurements of oxygenation reflect O2 delivery and utilization in exercising muscle and may improve detection of a critical exercise threshold.First, to detect an oxygenation breakpoint (Δ[O2HbMb-HHbMb]-BP) and compare this breakpoint to ventilatory thresholds during a maximal incremental test across sexes and tra...

VO2max during whole-body exercise is presumably constrained by oxygen delivery to mitochondria rather than by mitochondria's ability to consume oxygen. Humans and animals have been reported to exploit only 60-80% of their mitochondrial oxidative capacity at VO2max However, ex vivo quantification of mitochondrial overcapacity is complicated by isola...

Background: Maximal oxygen uptake (VO2max) is presumably constrained by oxygen delivery rather than mitochondria’s ability to consume oxygen. It has been suggested that animals exploit only 60-80% of their in vitro oxidative capacity when they exercise at VO2max. In humans, however, the quantification of mitochondrial overcapacity remains unclear....

Sporters als schaatsers, wielrenners en roeiers moeten beschikken over een goed uithoudingsvermogen, maar moeten ook kunnen sprinten. Hoe train je zowel het sprint- als het duurvermogen zonder dat dit ten koste gaat van elkaar? Ons onderzoek richt zich op de vraag of en hoe elite wielrenners, schaatsers en roeiers tegelijkertijd hun sprint- en duur...

Unlabelled: In patients with idiopathic pulmonary arterial hypertension (iPAH), iron deficiency is common and has been associated with reduced exercise capacity and worse survival. Previous studies have shown beneficial effects of intravenous iron administration. In this study, we investigated the use of intravenous iron therapy in iron-deficient...

Background The leading cause of mortality due to pulmonary arterial hypertension (PAH) is failure of the cardiac right ventricle. It has long been hypothesized that during the development of chronic cardiac failure the heart becomes energy deprived, possibly due to shortage of oxygen at the level of cardiomyocyte mitochondria. However, direct evalu...

Fish may be extremely hypoxia resistant. We investigated how muscle fibre size and oxidative capacity in zebrafish (Danio rerio) adapt during severe chronic hypoxia. Zebrafish were kept for either 3 or 6 weeks under chronic constant hypoxia (CCH) (10% air/90%N2 saturated water). We analyzed cross-sectional area (CSA), succinate dehydrogenase (SDH)...

Myocardial efficiency of pulmonary hypertensive (PH) patients and isolated right ventricular papillary muscles from PH rats can be severely reduced. We aimed to determine the causes of the efficiency reduction in isolated papillary muscles of monocrotaline-injected PH rats (MCT, 60mg/kg; 8 control and 16 MCT male Wistar rats). After 3 weeks PH was...

Background Botulinum toxin A (BoNT-A) is a new treatment modality in various causes of bladder dysfunction; like neurogenic detrusor overactivity and overactive bladder. The best technique of administrating BoNT-A in patients is unknown. A validated in vitro model could be used to investigate newer intravesical administration techniques of BoNT-A....

The efficiency (work/oxygen consumption) of isolated papillary muscles from failing hearts is reduced. We investigated whether this can be due to an increase of intrinsic cardiac adrenergic (ICA) cell density. The number of ICA cells in the septum and both ventricular walls was determined by tyrosine hydroxylase immunohistochemistry in rats with mo...

Objectives: SSc-associated pulmonary hypertension (SSc-PH) has a worse prognosis compared with SSc without PH (SSc-nonPH). Iron deficiency (ID) was previously associated with worse clinical outcome and survival in other types of PH, but ID effects in SSc-PH are unknown. Therefore we investigated the prevalence and clinical significance of ID in sy...

Abstract Glucose metabolism measurement using 2-deoxy-2-[(18)F]-fluoro-d-glucose ((18)FDG) positron emission tomography (PET) could provide in vivo information about pulmonary vascular remodeling. The purpose of this study was to assess whether pulmonary (18)FDG uptake in idiopathic pulmonary arterial hypertension (IPAH) patients changes and, if so...

Unlabelled: Idiopathic pulmonary arterial hypertension (IPAH) results in increased right ventricular (RV) workload and oxygen demand. It has been shown that myocardial oxygen consumption (MVO2) of the hypertrophied right ventricle of IPAH patients can be measured using PET and (15)O-labeled tracers. This method is, however, not very suitable for r...

Key points Skeletal muscles increase oxygen consumption to produce energy during exercise; however, the processes controlling the rate of adaptation (its kinetics) at exercise onset and offset are not well understood. Here we measure kinetics in single frog skeletal muscle fibres using a unique experimental system that allows features of intracellu...

BACKGROUND: In pulmonary arterial hypertension (PAH), high right ventricular (RV) power output requires increased myocardial oxygen consumption. Oxygen supply, however, does not increase in proportion. It is unknown what cellular mechanisms underlie this lack of adaptation. We therefore determined oxygen supply parameters in RV tissue slices of dec...

Injurious mechanical ventilation (MV) may augment organ injury remote from the lungs. During sepsis, myocardial dysfunction is common and increased endothelial activation and permeability can cause myocardial edema, which may, among other factors, hamper myocardial function. We investigated the effects of MV with injuriously high tidal volumes on t...

Increased afterload in idiopathic pulmonary arterial hypertension (IPAH) causes right ventricular (RV) hypertrophy and failure. Since RV remodelling occurs with alterations in RV oxygen metabolism, increasing our understanding in the factors determining RV O(2) consumption in IPAH is necessary. In the left ventricle, it is known that heart rate and...

During normal brain development, axons are myelinated by mature oligodendrocytes (OLGs). Under pathological, demyelinating conditions within the central nervous system (CNS), axonal remyelination is only partially successful because oligodendrocyte precursor cells (OPCs) largely remain in an undifferentiated state resulting in a failure to generate...

In idiopathic pulmonary arterial hypertension (IPAH), increased right ventricular (RV) power is required to maintain cardiac output. For this, RV O2 consumption (MVO2) must increase by augmentation of O2 supply and/or improvement of mechanical efficiency-ratio of power output to MVO2. In IPAH with overt RV failure, however, there is evidence that O...

BackgrOUND: Impaired right ventricular (RV) myocardial blood flow (MBF) has been associated with RV dysfunction and fatal RV failure in idiopathic pulmonary hypertension during stress. MBF and O(2) extraction from myocardial capillaries (O(2) extraction fraction (OEF)) influence myocardial O(2) supply. To determine how the baseline RV OEF affects t...

Patients with complicated intra-abdominal infections are prone to develop multiple organ failure, including myocardial dysfunction. We hypothesized that early dysfunction during sepsis is associated with inflammation, mitochondrial injury, impaired mitochondrial function, and activation of mitochondrial biogenesis. Rats received lipopolysaccharide...

Recently it was suggested that patients with pulmonary hypertension (PH) suffer from inspiratory muscle dysfunction. However, the nature of inspiratory muscle weakness in PH remains unclear. To assess whether alterations in contractile performance and in morphology of the diaphragm underlie inspiratory muscle weakness in PH. PH was induced in Wista...

An inverse relationship exists between striated muscle fiber size and its oxidative capacity. This relationship implies that muscle fibers, which are triggered to simultaneously increase their mass/strength (hypertrophy) and fatigue resistance (oxidative capacity), increase these properties (strength or fatigue resistance) to a lesser extent compar...

fibrosis is associated with various cardiac pathologies and dysfunction. Current quantification methods are time-consuming and laborious. We describe a semi-automated quantification technique for myocardial fibrosis and validated this using traditional methods. pulmonary Hypertension (PH) was induced in adult Wistar rats by subcutaneous monocrotali...

The aims of this study were to assess the prevalence of iron deficiency in idiopathic pulmonary arterial hypertension (IPAH) and investigate whether oral iron supplementation has effects in iron-deficient patients. Iron parameters were measure for all IPAH patients attending our centre (VU University Medical Center, Amsterdam, the Netherlands) betw...

Isolated rat papillary muscles of the right ventricle were used to discover the origin of reduced myocardial efficiency in chronic heart failure. Right ventricular hypertrophy was induced by monocrotaline injection, causing pulmonary hypertension. Control (n = 7) and hypertrophied (n = 11) papillary muscles were subjected to sinusoidal length chang...

Pulmonary arterial hypertension (PAH) still cannot be cured, warranting the search for novel treatments. Fasudil (a Rho kinase inhibitor) was compared with bosentan (an endothelin receptor blocker) and sildenafil (a phosphodiesterase 5 inhibitor), with emphasis on right ventricular (RV) function, in a reversal rat model of monocrotaline (MCT)-induc...

Background : Fibrosis is associated with various cardiac pathologies and dysfunction. Current quantification methods are time-consuming and laborious. We describe a semi-automated quantification technique for myocardial fibrosis and validated this using traditional methods. Methods : Pulmonary Hypertension (PH) was induced in adult Wistar rats by s...