Acute and chronic exercise in patients with heart failure with reduced ejection fraction: evidence of structural and functional plasticity and intact angiogenic signalling in skeletal muscle.

Key Points: The vascular endothelial growth factor (VEGF) responses to acute submaximal exercise and training effects in patients with heart failure with reduced ejection fraction (HFrEF) were investigated. Six patients and six healthy matched controls performed knee-extensor exercise (KE) at 50% of maximum work rate before and after (only patients) KE training. Muscle biopsies were taken to assess skeletal muscle structure and the angiogenic response.

Sedentary aging increases resting and exercise-induced intramuscular free radical formation.

Mitochondrial free radical formation has been implicated as a potential mechanism underlying degenerative senescence, although human data are lacking. Therefore, the present study was designed to examine if resting and exercise-induced intramuscular free radical-mediated lipid peroxidation is indeed increased across the spectrum of sedentary aging. Biopsies were obtained from the vastus lateralis in six young (26 + or - 6 yr) and six aged (71 + or - 6 yr) sedentary males at rest and after maximal knee extensor exercise.

Limited maximal exercise capacity in patients with chronic heart failure: partitioning the contributors.

Objectives: This study aimed to assess the factors limiting maximal exercise capacity in patients with chronic heart failure (CHF).

Background: Maximal exercise capacity, an important index of health in CHF, might be limited by central and/or peripheral factors; however, their contributions remain poorly understood.

Methods: We studied oxygen (O2) transport and metabolism at maximal cycle (centrally taxing) and knee-extensor (KE) (peripherally taxing) exercise in 12 patients with CHF and 8 healthy control subjects in normoxia and hyperoxia (100% O2).

The skeletal muscle VEGF mRNA response to acute exercise in patients with chronic heart failure.

In seven patients with chronic heart failure (CHF) and six controls, we examined (a) resting and post-exercise muscle vascular endothelial growth factor (VEGF) mRNA levels and (b) their relationship with muscle structure and function. Muscle biopsies were taken after 30 min of single-leg knee-extensor exercise at 50% of maximum work rate (50% WR(max)) from both the exercised and rested legs. Muscle blood flow (.

Electron paramagnetic spectroscopic evidence of exercise-induced free radical accumulation in human skeletal muscle.

The present study determined if acute exercise increased free radical formation in human skeletal muscle. Vastus lateralis biopsies were obtained in a randomized balanced order from six males at rest and following single-leg knee extensor exercise performed for 2 min at 50% of maximal work rate (WR(MAX)) and 3 min at 100% WR(MAX). EPR spectroscopy revealed an exercise-induced increase in mitochondrial ubisemiquinone (UQ*-) [0.

Control of mitochondrial gene expression in the aging rat myocardium.

Aging induces complex changes in myocardium bioenergetic and contractile properties. Using F344BNF(1) rats, we examined age-dependent changes in myocardial bioenergetic enzymes (catalytic activities and transcript levels) and mRNA levels of putative transcriptional regulators of bioenergetic genes. Very old rats (35 months) showed a 22% increase in ventricular mass with no changes in DNA or RNA per gram.

Regulation of skeletal muscle mitochondrial content during aging.

Mitochondrial content of skeletal muscle varies among fiber types, and changes in complex ways during aging. We evaluated the regulatory origins of differences in mitochondrial content among muscles of varied fiber type in F344xBNF1 rats, and how these regulatory patterns are altered with aging. In adult (12 month) animals we found that units citrate synthase (CS)/g tissue, a marker for mitochondrial content, varied approximately 3-fold among 10 skeletal muscles.

The effect of fixation and histological preparation on coronary artery dimensions.

Histometric data are necessary for quantifying the cellular and tissue structure which serves as a basis for the construction of mathematical and integrative models. However, fixation and histological processing of tissues such as dehydration, embedding, sectioning and staining can cause dimensional changes and tissue distortion. The present study was designed to analyze the effects of one widely used fixation and histological preparation protocol for muscle tissue on several morphometric parameters of the coronary arteries.

Greater capillary-fiber interface per fiber mitochondrial volume in skeletal muscles of old rats.

The objective was to examine whether muscle structural capacity for O2 flux (i.e., capillary-to-fiber surface ratio) relative to fiber mitochondrial volume deteriorates with the muscle atrophy of aging in predominantly slow- (soleus, S) and fast-twitch (extensor digitorum longus, EDL) muscles of old (24 mo) and very old (35 mo) F344BN rats compared with adult (12 mo old).

Oxygen consumption during maximal exercise in Fischer 344 x Brown Norway F1 hybrid rats.

We characterized O2 consumption (VO2) during treadmill exercise in 12-, 24-, and 35-month-old Fischer 344 x Brown Norway F1 hybrid (F344BNF1) rats. When accounting for differences in body mass (Mb), (O2)peak decreased by 10% and 33% in 24- and 35-month-old rats, respectively, compared with rats at 12 months (analysis of covariance, p < .01).

Resistance to fatigue of individual Xenopus single skeletal muscle fibres is correlated with mitochondrial volume density.

The purpose of the present study was to compare the individual fatigue characteristics of isolated single skeletal muscle fibres with their mitochondrial volume density (MVD), using direct histological morphometry. Single muscle fibres (n= 14) were microdissected from lumbrical muscle of adult female Xenopus laevis, and force was measured while fibres were stimulated (tetanic contractions of 200 ms trains with 70 Hz stimuli at 9 V) at progressively increasing frequencies (2 min each at 0.25, 0.

Reduced mechanical efficiency in chronic obstructive pulmonary disease but normal peak VO2 with small muscle mass exercise.

We studied six patients with chronic obstructive pulmonary disease (COPD) (FEV1 = 1.1 +/- 0.2 L, 32% of predicted) and six age- and activity level-matched control subjects while performing both maximal bicycle exercise and single leg knee-extensor exercise.

Comparative studies of high performance swimming in sharks I. Red muscle morphometrics, vascularization and ultrastructure.

Tunas (family Scombridae) and sharks in the family Lamnidae are highly convergent for features commonly related to efficient and high-performance (i.e. sustained, aerobic) swimming.

Regulation of skeletal muscle morphology in type 2 diabetic subjects by troglitazone and metformin: relationship to glucose disposal.

The goal of this work was to compare the effects of different antidiabetic therapies on the phenotype of skeletal muscle in type 2 diabetic subjects failing sulfonylurea therapy. Subjects were treated with a thiazolidinedione (troglitazone, TGZ) or a biguanide (metformin, MET) in addition to glyburide for 3 to 4 months. Insulin action was determined with a hyperinsulinemic (300 mU.

Aerobic capacities in the skeletal muscles of Weddell seals: key to longer dive durations?

In contrast to terrestrial animals that function under hypoxic conditions but display the typical exercise response of increasing ventilation and cardiac output, marine mammals exercise under a different form of hypoxic stress. They function for the duration of a dive under progressive asphyxia, which is the combination of increasing hypoxia, hypercapnia and acidosis. Our previous studies on short-duration, shallow divers found marked adaptations in their skeletal muscles, which culminated in enhanced aerobic capacities that are similar to those of athletic terrestrial mammals.

Regional differences in expression of VEGF mRNA in rat gastrocnemius following 1 hr exercise or electrical stimulation.

Background: Vascular endothelial growth factor (VEGF) mRNA levels increase in rat skeletal muscle after a single bout of acute exercise. We assessed regional differences in VEGF165 mRNA levels in rat gastrocnemius muscle using in situ hybridization after inducing upregulation of VEGF by treadmill running (1 hr) or electrical stimulation (1 hr). Muscle functional regions were defined as oxidative (primarily oxidative fibers, I and IIa), or glycolytic (entirely IIb or IId/x fibers).

Fiber capillarization relative to mitochondrial volume in diaphragm of shrew.

The objective was to examine fiber capillarization in relation to fiber mitochondrial volume in the highly aerobic diaphragm of the shrew, the smallest mammal. The diaphragms of four common shrews [Sorex araneus; body mass, 8.2 +/- 1.

Muscle structural capacity for oxygen flux from capillary to fiber mitochondria.

The concept of major functional resistance to O2 flux at the capillary-fiber interface implies that muscle structural capacity for O2 flux from capillary to fiber mitochondria needs to be assessed in terms of capillary surface per fiber surface. Morphological data support this notion and show the importance of assessing the size of the capillary-fiber interface relative to muscle fiber O2 demand.

Muscle adaptation to altitude: tissue capillarity and capacity for aerobic metabolism.

Prolonged exposure to high altitude leads to reduced muscle mass and performance. The fall in muscle mass follows a reduction in fiber size, which at first was believed to be accompanied by increased fiber capillarization and aerobic enzymes. Subsequent studies showed that hypoxia alone does not alter capillary number and geometry in skeletal muscles of mammals at altitude.

Estimating the size of the capillary-to-fiber interface in skeletal muscle: a comparison of methods.

Current evidence suggests that the size of the capillary-to-fiber (C/F) interface is a major determinant of O2 flux into muscle fibers, and methods have been developed for estimating the size of this region via the C/F perimeter ratio in perfusion-fixed material (Mathieu-Costello O, Ellis CG, Potter RF, MacDonald IC, and Groom AC. Am J Physiol Heart Circ Physiol 261: H1617-H1625, 1991) and the quotient of the individual, fiber-based C/F number ratio and fiber perimeter (C/F perimeter exchange index) in muscle biopsies (Hepple RT. Can J Appl Physiol 22: 11-22, 1997).

Skeletal muscle capillarity and angiogenic mRNA levels after exercise training in normoxia and chronic hypoxia.

Gene expression of vascular endothelial growth factor (VEGF), and to a lesser extent of transforming growth factor-beta(1) (TGF-beta(1)) and basic fibroblast growth factor (bFGF), has been found to increase in rat skeletal muscle after a single exercise bout. In addition, acute hypoxia augments the VEGF mRNA response to exercise, which suggests that, if VEGF is important in muscle angiogenesis, hypoxic training might produce greater capillary growth than normoxic training. Therefore, we examined the effects of exercise training (treadmill running at the same absolute intensity) in normoxia and hypoxia (inspired O(2) fraction = 0.

Muscle capillary supply in harbor seals.

The purpose of this study was to examine muscle capillary supply in harbor seals. Locomotory and nonlocomotory muscles of four harbor seals (mass = 17.5-41 kg) were glutaraldehyde-perfusion fixed and samples processed for electron microscopy and analyzed by morphometry.

Chronic hypoxia attenuates resting and exercise-induced VEGF, flt-1, and flk-1 mRNA levels in skeletal muscle.

Vascular endothelial growth factor (VEGF) is a hypoxia-inducible angiogenic mitogen. However, chronic hypoxia is generally not found to increase mammalian skeletal muscle capillarity. We sought to determine the effect of chronic hypoxia (8 wk, inspired O2 fraction = 0.

Effect of acute exercise on citrate synthase activity in untrained and trained human skeletal muscle.

Maximal citrate synthase activity (CS) is routinely used as a marker of aerobic capacity and mitochondrial density in skeletal muscle. However, reported CS has been notoriously variable, even with similar experimental protocols and sampling from the same muscles. Exercise training has resulted in increases in CS ranging from 0 to 100%.

Effect of high transcapillary pressures on capillary ultrastructure and permeability coefficients in dog lung.

To determine the correlation between ultrastructural and physiological changes in blood-gas barrier function in lungs transiently exposed to very high vascular pressures, we increased capillary transmural pressure (Ptm) of 6 canine isolated perfused left lower lung lobe preparations (high-pressure group) to 80.3 Torr for 3.8 min and then determined the capillary filtration (K(fc)) and osmotic reflection (sigma(d)) coefficients at a Ptm of 19.