Work and oxygen consumption of isolated right ventricular papillary muscle in experimental pulmonary hypertension.

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 efficiency is reduced by mitochondrial dysfunction in addition to increased activation heat reported previously.

Increased MAO-A Activity Promotes Progression of Pulmonary Arterial Hypertension.

Monoamine oxidases (MAOs), 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 arterial hypertension (PAH) and right ventricular (RV) failure.

Single-cell analysis uncovers that metabolic reprogramming by ErbB2 signaling is essential for cardiomyocyte proliferation in the regenerating heart.

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 RNA-sequencing approach.

Metabolic Cost of Activation and Mechanical Efficiency of Mouse Soleus Muscle Fiber Bundles During Repetitive Concentric and Eccentric Contractions.

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) series of contractions. Bundles ( = 9) were subjected to sinusoidal length changes, while measuring force and oxygen consumption.

Meijer and Vloedman's histochemical demonstration of mitochondrial coupling obeys Lambert-Beer's law in the myocardium.

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 69:217-232, 1980, https://doi.

Muscle morphology of the vastus lateralis is strongly related to ergometer performance, sprint capacity and endurance capacity in Olympic rowers.

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 endurance capacity of Olympic rowers.

Critical determinants of combined sprint and endurance performance: an integrative analysis from muscle fiber to the human body.

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 levels.

Treatment strategies for the right heart in pulmonary hypertension.

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 main determinant of changes to the ventricle.

IGF-1 Attenuates Hypoxia-Induced Atrophy but Inhibits Myoglobin Expression in C2C12 Skeletal Muscle Myotubes.

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 enhance an eventual hypertrophic response to anabolic stimulation.

Oxygenation Threshold Derived from Near-Infrared Spectroscopy: Reliability and Its Relationship with the First Ventilatory Threshold.

Background: Near-infrared spectroscopy (NIRS) measurements of oxygenation reflect O2 delivery and utilization in exercising muscle and may improve detection of a critical exercise threshold.

Purpose: 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 training status. Second, to assess reproducibility of NIRS signals and exercise thresholds and investigate confounding effects of adipose tissue thickness on NIRS measurements.

Maximal oxygen uptake is proportional to muscle fiber oxidative capacity, from chronic heart failure patients to professional cyclists.

V̇o2 max 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 maximal oxygen uptake (V̇o2 max). However, ex vivo quantification of mitochondrial overcapacity is complicated by isolation or permeabilization procedures.

Intravenous iron therapy in patients with idiopathic pulmonary arterial hypertension and iron deficiency.

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 iPAH patients in terms of safety and effects on exercise capacity, and we studied whether altered exercise capacity resulted from changes in right ventricular (RV) function and skeletal muscle oxygen handling.

Increased in vivo mitochondrial oxygenation with right ventricular failure induced by pulmonary arterial hypertension: mitochondrial inhibition as driver of cardiac failure?

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 evaluation of oxygen tension levels within the in vivo right ventricle during PAH is currently lacking.

Increased oxidative metabolism and myoglobin expression in zebrafish muscle during chronic hypoxia.

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).

Development of an in vitro model to measure bioactivity of botulinum neurotoxin A in rat bladder muscle strips.

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.

Pulmonary 2-deoxy-2-[(18)F]-fluoro-d-glucose uptake is low in treated patients with idiopathic pulmonary arterial hypertension.

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, to determine whether the change is related to disease severity and survival. Sixteen IPAH patients who were treated with IPAH-specific therapy and 7 patients who had a myocardial infarction (MI) without pulmonary hypertension were included.

Intrinsic cardiac adrenergic (ICA) cell density and MAO-A activity in failing rat hearts.

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 monocrotaline-induced pulmonary hypertension.

Iron deficiency in systemic sclerosis patients with and without pulmonary hypertension.

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 systemic sclerosis patients with and without PH.

11C-Acetate clearance as an index of oxygen consumption of the right myocardium in idiopathic pulmonary arterial hypertension: a validation study using 15O-labeled tracers and PET.

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 routine clinical practice.