Lung water volume at rest and exercise in dogs.

Lung water volume was measured in dogs killed at rest and during maximal exercise. There was no significant difference between them. It is concluded that pulmonary interstitial edema does not occur during exercise.     

Vagal modulation of respiratory muscle activity in awake dogs during exercise and hypercapnia.

Using chronically instrumented awake tracheotomized dogs, we examined the contributions of vagal feedback to respiratory muscle activities, both electrical and mechanical, during normoxic hypercapnia (inspired CO2 fraction = 0.03, 0.04, 0.05, and 0.06) and during mild treadmill exercise (3, 4.3, and 6.4 km/h). Cooling exteriorized vagal loops eliminated both phasic and tonic mechanoreceptor input during either of these hyperpneas. At a given chemical or locomotor stimulus, vagal cooling caused a further increase in costal, crural, parasternal, and rib cage expiratory (triangularis sterni) muscles. No further change in abdominal expiratory muscle activity occurred secondary to vagal cooling during these hyperpneas. However, removal of mechanoreceptor input during hypercapnia was not associated with consistent changes in end-expiratory lung volume, as measured by the He-N2 rebreathe technique. We conclude that during these hyperpneas 1) vagal input is not essential for augmentation of expiratory muscle activity and 2) decrements in abdominal expiratory muscle activity may be offset by increments in rib cage expiratory muscle activity and contribute to the regulation of end-expiratory lung volume.     

Microdialysis and the measurement of muscle interstitial K+ during rest and exercise in humans.

The purpose of this study was to examine whether microdialysis and the internal reference thallium-201 ((201)Tl) could accurately measure muscle interstitial K+ (Ki+) before, during, and after exercise. The relative loss of (201)Tl and simultaneous relative recovery of K+ were measured in vitro for 12 microdialysis probes that were bathed in Ringer acetate medium and perfused at various flows (3-10 microl/min). (201)Tl loss was linearly related to K+ recovery, and their level of agreement was not different from zero. Microdialysis and (201)Tl were then used to measure Ki+ in the gastrocnemius medialis muscle of four humans during rest and static plantar flexion exercise. At rest, Ki+ was 3.9-4.3 mmol/l when the perfusate flow was 2 or 5 microl/min. During exercise, Ki+ increased from 6.9 +/- 0.4 to 7.5 +/- 0.3 mmol/l at low to high intensity and declined to 5.2 +/- 0.3 mmol/l after exercise. These results suggest that large changes in Ki+ in human skeletal muscle can be accurately measured by using microdialysis and (201)Tl.     

Long term bed rest with and without vibration exercise countermeasures: effects on human muscle protein dysregulation

The present investigation, the first in the field, was aimed at analyzing differentially, on individual samples, the effects of 55 days of horizontal bed rest, a model for microgravity, on myosin heavy and myosin light chain isoforms distribution (by SDS) and on the proteome (by 2-D DIGE and MS) in the vastus lateralis (VL), a mixed type II/I (～50:50%) head of the quadriceps and in the calf soleus (SOL), a predominantly slow (～35:65%) twitch muscle. Two separate studies were performed on six subjects without (BR) and six with resistive vibration exercise (RVE) countermeasures, respectively. Both VL and SOL underwent in BR decrements of ～15% in cross-sectional area and of ～22% in maximal torque that were prevented by RVE. Myosin heavy chain distribution showed increased type I and decreased type IIA in BR both in VL and in SOL, the opposite with RVE. A substantial downregulation of proteins involved in aerobic metabolism characterized both in SOL and VL in BR. RVE reversed the pattern more in VL than in SOL, whereas proteins involved in anaerobic glycolysis were upregulated. Proteins from the Z-disk region and from costamers were differently dysregulated during bed rest (both BR and RVE), particularly in VL.     

After effects of chronic hypoxia on cardiac output and muscle blood flow at rest and exercise

Cardiac output (Q, by N2-CO2 rebreathing) and limb muscle blood flow (qm, from 133Xe clearance) were determined in eight male subjects at rest and during cycloergometric loads immediately before and 12 days after return from the 1981 Swiss Lhotse Shar (8,398 m) Expedition. Compared to control conditions, after exposure to hypoxia: 1) Q was unchanged at rest and at 75 watts (W) but was 18% less (P less than 0.01) at 150 W with constant heart rate (approximately 140 beats X min-1); 2) qm in the vastus lateralis was identical at rest but 26% and 39% less (P less than 0.05 and P less than 0.001, respectively) at two submaximal leg work loads (75 and 125 W); 3) qm in the biceps at 50 W was 34% less (P less than 0.01); 4) hemoglobin flow (QHb and qmHb), similarly to blood flow (Q and qm), was significantly reduced; 5) the qm adjustment rate, measured from the time required to attain a new steady state upon a square wave change of work load starting from rest, was slower, particularly at the lower work loads. From the above results as well as from corresponding morphometric findings showing in the same subjects: 1) a decrease of the ratio between fiber section and number of capillaries and 2) a rise of the mitochondrial to fiber volume ratio, it is concluded that during altitude acclimatization peripheral O2 delivery becomes more efficient.     

Ventilatory responses to partial cardiopulmonary bypass at rest and exercise in dogs

We determined the role of blood flow-induced changes in CO2 load to the lungs on ventilatory control, at rest and in the steady-state of electrically induced exercise, in the anesthetized dog. A portion of the vena caval blood was diverted to the descending aorta following "arterialization" through an extracorporeal gas exchanger. Ventilation typically decreased, both at rest and during exercise (i.e., at 2 different levels of mixed venous CO2), in proportion to the CO2 loss; arterial PCO2 was consequently regulated. There were concomitant increases of the pulmonary and peripheral vascular resistance. Bilateral cervical vagosympathectomy markedly attenuated the ventilatory response at rest, thus disrupting arterial PCO2 homeostasis, but not so during exercise. The results therefore provide evidence for and support the suggestion of CO2 flow-related hyperpnea both at rest and during muscular exercise.     

Effects of respiratory muscle work on exercise performance.

The normal respiratory muscle effort at maximal exercise requires a significant fraction of cardiac output and causes leg blood flow to fall. We questioned whether the high levels of respiratory muscle work experienced in heavy exercise would affect performance. Seven male cyclists [maximal O(2) consumption (VO(2)) 63 +/- 5 ml. kg(-1). min(-1)] each completed 11 randomized trials on a cycle ergometer at a workload requiring 90% maximal VO(2). Respiratory muscle work was either decreased (unloading), increased (loading), or unchanged (control). Time to exhaustion was increased with unloading in 76% of the trials by an average of 1.3 +/- 0.4 min or 14 +/- 5% and decreased with loading in 83% of the trials by an average of 1.0 +/- 0.6 min or 15 +/- 3% compared with control (P < 0.05). Respiratory muscle unloading during exercise reduced VO(2), caused hyperventilation, and reduced the rate of change in perceptions of respiratory and limb discomfort throughout the duration of exercise. These findings demonstrate that the work of breathing normally incurred during sustained, heavy-intensity exercise (90% VO(2)) has a significant influence on exercise performance. We speculate that this effect of the normal respiratory muscle load on performance in trained male cyclists is due to the associated reduction in leg blood flow, which enhances both the onset of leg fatigue and the intensity with which both leg and respiratory muscle efforts are perceived.     

Effect of obesity on respiratory mechanics during rest and exercise in COPD

The presence of obesity in COPD appears not to be a disadvantage with respect to dyspnea and weight-supported cycle exercise performance. We hypothesized that one explanation for this might be that the volume-reducing effects of obesity convey mechanical and respiratory muscle function advantages. Twelve obese chronic obstructive pulmonary disease (COPD) (OB) [forced expiratory volume in 1 s (FEV(1)) = 60%predicted; body mass index (BMI) = 32 ± 1 kg/m(2); mean ± SD] and 12 age-matched, normal-weight COPD (NW) (FEV(1) = 59%predicted; BMI = 23 ± 2 kg/m(2)) subjects were compared at rest and during symptom-limited constant-work-rate exercise at 75% of their maximum. Measurements included pulmonary function tests, operating lung volumes, esophageal pressure, and gastric pressure. OB vs. NW had a reduced total lung capacity (109 vs. 124%predicted; P < 0.05) and resting end-expiratory lung volume (130 vs. 158%predicted; P < 0.05). At rest, there was no difference in respiratory muscle strength but OB had greater (P < 0.05) static recoil and intra-abdominal pressures than NW. Peak ventilation, oxygen consumption, and exercise endurance times were similar in OB and NW. Pulmonary resistance fell (P < 0.05) at the onset of exercise in OB but not in NW. Resting inspiratory capacity, dyspnea/ventilation plots, and the ratio of respiratory muscle effort to tidal volume displacement were similar, as was the dynamic performance of the respiratory muscles including the diaphragm. In conclusion, the lack of increase in dyspnea and exercise intolerance in OB vs. NW could not be attributed to improvement in respiratory muscle function. Potential contributory factors included alterations in the elastic properties of the lungs, raised intra-abdominal pressures, reduced lung hyperinflation, and preserved inspiratory capacity.     

Skeletal muscle VEGF gradients in peripheral arterial disease: simulations of rest and exercise

VEGF is a key promoter of angiogenesis and a major target of proangiogenic therapy for peripheral arterial disease (PAD). Greater understanding of VEGF angiogenic signaling and guidance by gradients for new capillaries will aid in developing new proangiogenic therapies and improving existing treatments. However, in vivo measurements of VEGF concentration gradients at the cell scale are currently impossible. We have developed a computational model to quantify VEGF distribution in extensor digitorum longus skeletal muscle using measurements of VEGF, VEGF receptor (VEGFR), and neuropilin-1 (NRP1) expression in an experimental model of rat PAD. VEGF is secreted by myocytes, diffuses through and interacts with extracellular matrix and basement membranes, and binds VEGFRs and NRP1 on endothelial cell surfaces of blood vessels. We simulate the effects of increased NRP1 expression and of therapeutic exercise training on VEGF gradients, receptor signaling, and angiogenesis. Our study predicts that angiogenic therapy for PAD may be achieved not only through VEGF upregulation but also through modulation of VEGFRs and NRP1. We predict that expression of 10(4) NRP1/cell can increase VEGF binding to receptors by 1.7-fold (vs. no NRP1); in nonexercise-trained muscle with PAD, angiogenesis is hindered due to limited VEGF upregulation, signaling, and gradients; in exercise-trained muscle, VEGF signaling is enhanced by upregulation of VEGFRs and NRP1, and VEGF signaling is strongest within the first week of exercise therapy; and hypoxia-induced VEGF release is important to direct angiogenesis towards unperfused tissue.     

Glutamate ingestion and its effects at rest and during exercise in humans.

Glutamate is central to several transamination reactions that affect the production of ammonia, alanine, glutamine, as well as TCA cycle intermediates during exercise. To further study glutamate metabolism, we administered 150 mg/kg body wt of monosodium glutamate (MSG) and placebo to seven male subjects who then either rested or exercised (15-min cycling at approximately 85% maximal oxygen consumption). MSG ingestion resulted in elevated plasma glutamate, aspartate, and taurine, both at rest and during exercise (P < 0.05), whereas most other amino acids were unchanged. Neither plasma alanine nor ammonia was altered at rest. During exercise and after glutamate ingestion, alanine was increased (P < 0.05) and ammonia was attenuated (P < 0.05). Glutamine was also elevated after glutamate ingestion during rest and exercise trials. MSG administration also resulted in elevated insulin levels (P < 0.05), which were parallel to the trend in C-peptide levels. Thus MSG can successfully elevate plasma glutamate, both at rest and during exercise. The plasma amino acid responses suggest that increased glutamate availability during exercise alters its distribution in transamination reactions within active muscle, which results in elevated alanine and decreased ammonia levels.     

Exercise-induced muscle damage: effects of light exercise on damaged muscle.

The effects of performing light eccentric exercise (LB) during the period of recovery from a heavy eccentric exercise bout (HB) were studied. An experimental and a control group, each consisting of nine college age volunteers (seven women, two men) performed two HB--HB1 and HB2--14 days apart, using the elbow flexor and extensor muscles of one arm. The experimental group performed an additional LB on the day following the first HB. HB1 resulted in muscle soreness, muscle weakness, changes in elbow joint flexibility, and large delayed increases in serum creatine kinase (CK) activity. The HB2 produced smaller changes in all parameters, indicating that adaptation to the effects of eccentric exercise had occurred in the muscle. The LB did not alter muscle soreness, strength or elbow flexibility, but did reduce or delay CK activity increase after HB1. The LB had no apparent effect on adaptation to HB2.     

Cardiovascular effects of static and dynamic exercise

The cardiovascular response to static exercise has often been quantified on the basis of a comparison between static handgrip and dynamic cycling exercise. It is then difficult to make precise comparisons because the physical units of work are not compatible. If the data from dynamic exercise can be used to predict the cardiovascular response to zero movement (static exercise) this would suggest that static exercise is not fundamentally different from dynamic exercise. Using leg extension exercise which lasted for 1 min, a set of weights was lifted repeatedly 50 times/min, through three different distances. On each occasion, the heart rate, systolic time intervals (STI) and systemic arterial blood pressure were monitored non-invasively. Regression analysis of heart rate (HR) or blood pressure (BP) against the distance moved by the weights was used to predict the heart rate or blood pressure that would be expected for static exercise. In addition the same responses were measured following 1 min of static exercise during which the weights were held up but not moved. Five subjects, trained in leg extension exercise, completed the four exercise sessions in a random order. A constant force was produced in each variant of the protocol and in the static exercise it amounted to 50% maximal voluntary contraction (MVC). The forces developed and the distance the weights were lifted were monitored. During this sustained static exercise at relatively low intensity the cardiovascular changes could be predicted from the responses induced by dynamic exercise. It is suggested that other factors are important in determining the cardiovascular response to exercise, not simply the mode.