bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction of thyroid hormone and functional overload on skeletal muscle isomyosin expression
Authors: Swoap S. J. , Haddad F. , Caiozzo V. J. , Herrick R. E. , McCue S. A. , Baldwin K. M.
Published: December 2017

This study examined the interaction of exogenous thyroid hormone 3,5,3′-triiodothyronine (T3) and functional overload on skeletal muscle myosin heavy chain (MHC) expression, studied at both the protein and mRNA level of analysis. Animals were allocated to the following groups: 1) normal control, 2) overload control, 3) hyperthyroid control, and 4) hyperthyroid+overload. Overload of the rat plantaris was accomplished by surgical removal of its synergists (soleus and gastrocnemius), and the animals were made hyperthyroid by injections of T3 (350 micrograms/kg every other day). After overload of 8 wk, muscle enlargement occurred by 53% for both overload groups (P < 0.05). This was accompanied by a 330 and 82% increase in the relative content of type I and IIa MHC, respectively, and a corresponding decrease by 16 and 44% in type IIx and IIb MHC, respectively, in the overload control group (P < 0.05 vs. normal control). Changes in the relative and absolute content of mRNA for these MHCs paralleled the protein response. Exogenous T3 completely reversed the upregulation of type I MHC and the downregulation of type IIx associated with overload at both the protein and mRNA level (P < 0.05). However, T3 was only partially effective in blunting the downregulation of IIb MHC and the upregulation of IIa MHC (protein and mRNA) accompanying the overload.(ABSTRACT TRUNCATED AT 250 WORDS)
Contribution of body composition and physical activity to age-related decline in peak VO2 in men and women
Authors: Toth M. J. , Gardner A. W. , Ades P. A. , Poehlman E. T.
Published: December 2017

We examined the contribution of variations in body composition and leisure time physical activity to the age-related decline in peak oxygen consumption (VO2) in men and women. Healthy males 17–80 yr old (n = 378) and females 18–81 yr old (n = 224) were characterized for peak VO2 from a treadmill test to exhaustion, fat-free mass and fat mass by underwater weighing, and leisure time physical activity. Peak VO2 showed a greater absolute decline (P < 0.05) with age in males (r = -0.70, slope = -0.034 l.min-1.yr-1; P < 0.01) than in females (r = -0.78, slope = -0.028 l.min-1.yr-1; P < 0.01). After statistically controlling for differences in fat-free mass and fat mass, the decline in peak VO2 was diminished in both sexes, although a greater rate of decline persisted in males (r = -0.47, slope = -0.016 l.min-1.yr-1; P < 0.01) than in females (r = -0.39, slope = -0.009 l.min-1.yr-1; P < 0.01). We found that the addition of leisure time physical activity (independent of body composition) to the regression model further attenuated the rate of decline in males (r = -0.40, slope = -0.013 l.min-1.yr-1; P < 0.01) but did not alter the age-related decline in peak VO2 in females (r = -0.39, slope = -0.009 l.min-1.yr-1; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of hyperoxia at 1 and 2 ATA on hypoxia and hypercapnia in human skin during experimental inflammation
Authors: Abbot N. C. , Beck J. S. , Carnochan F. M. , Gibbs J. H. , Harrison D. K. , James P. B. , Lowe J. G.
Published: December 2017

Transcutaneous PO2 and PCO2 measurements and estimates of skin respiration were monitored at different levels of inspired PO2 in 20 healthy adults during the first 4 days of the tuberculin reaction, a convenient model of acute inflammation. Hyperoxia at 1 and 2 ATA significantly increased transcutaneous PO2 levels in undisturbed and in inflamed skin but did not fully correct the relative hypoxia at the site of inflammation. Hypercapnia was reduced with O2 breathing at 2 ATA. The apparent rate of O2 consumption at the reaction site was raised during hyperoxia, most prominently at 2 ATA. The most intense reactions showed a central relative slowing of laser-Doppler blood flow indicative of microcirculatory impairment. The extent of the relative hypoxia and hypercapnia was greatest in these strongest reactions. The density of lymphocytes and monocytes in biopsies of 48-h reactions was loosely related to the corresponding transcutaneous PO2 measurements. The present study provides evidence that diffusion barriers, in addition to increased local respiration, can contribute to the apparent hypoxia and hypercapnia of this inflammatory model.
Detection of free radicals by electron spin resonance in rat diaphragm after resistive loading
Authors: Borzone G. , Zhao B. , Merola A. J. , Berliner L. , Clanton T. L.
Published: December 2017

Indirect evidence supports free radical production in the diaphragm under excessive mechanical loads in both in vitro and in situ preparations. We hypothesized that free radicals are produced in the diaphragm with loads in vivo at a sufficient concentration to be detected by electron spin resonance (ESR) spectroscopy. Anesthetized rats underwent severe inspiratory resistive loading for 2.5–3 h with maintenance of blood oxygenation and arterial blood pressure by breathing 70% oxygen. The ESR spectra of four samples (freeze-clamped at liquid nitrogen temperature) from each experimental animal were compared with the spectra from a control animal breathing air and a control animal breathing 70% oxygen. We observed 1) an approximately 30% increase in intensity of free radical signal in experimental animals (n = 10) compared with control animals breathing oxygen (n = 10; P < 0.01) and control animals breathing air (n = 10; P < 0.05), 2) that oxygen alone had no effect on the ESR spectrum, and 3) the intensity of the ESR signal decreased approximately 25% in the experimental group when samples were taken 10 min postmortem, whereas no difference in signal was observed for control animals. We conclude that the diaphragm shows an increased production of free radicals associated with respiratory failure induced by resistive breathing.
Pulmonary hypertension and arterial changes in calves with a systemic-to-left pulmonary artery connection
Authors: Fasules J. W. , Tryka F. , Chipman C. W. , Van Devanter S. H.
Published: December 2017

The pathogenic mechanisms by which increased pressure and flow lead to pulmonary vascular disease are poorly understood, especially in newborns. To study the pathophysiological correlations and timing of the development of structural changes in response to high flow in nonhypoxic neonates, a model of high pulmonary flow was developed in newborn calves by anastomosis of the isolated left pulmonary artery (LPA) to the aorta. LPA pressure and flow increased acutely. LPA pressure reached near-systemic levels by 10 wk, whereas LPA flow was maximally increased at 1 mo before decreasing in several calves. Right pulmonary arterial pressure remained normal, and ventricular hypertrophy did not develop. Morphometric evaluation of the left lung demonstrated decreased arteriolar diameter, increased medial thickness, muscularization of arterioles at the bronchoalveolar junction, luminal obliteration of small arteries, and dilation lesions. The LPA pressure and vascular changes were greater and developed over a shorter time period than did prior models of nonhypoxic flow-induced pulmonary vascular changes. Lesser degrees of decreased arteriolar diameter and muscularization of small vessels were seen in the right lung, indicating a difference in the vascular response to moderately increased flow vs. increased pressure and flow. Thus, calves with an isolated LPA-to-aortic anastomosis simulate the hemodynamic and pulmonary vascular changes seen in newborns with congenital heart defects. Such calves may serve as models to assess effects of mechanical stresses on a newborn's vasculature.
Cyclooxygenase and lipoxygenase inhibition by BW-755C reduces acrolein smoke-induced acute lung injury
Authors: Janssens S. P. , Musto S. W. , Hutchison W. G. , Spence C. , Witten M. , Jung W. , Hales C. A.
Published: December 2017

Inhalation of smoke containing acrolein, the most common toxin in urban fires after carbon monoxide, causes vascular injury with non-cardiogenic pulmonary edema containing potentially edematogenic eicosanoids such as thromboxane (Tx) B2, leukotriene (LT) B4, and the sulfidopeptide LTs (LTC4, LTD4, and LTE4). To determine which eicosanoids are important in the acute lung injury, we pretreated sheep with BW-755C (a combined cyclooxygenase and lipoxygenase inhibitor), U-63557A (a specific Tx synthetase inhibitor), or indomethacin (a cyclooxygenase inhibitor) before a 10-min exposure to a synthetic smoke containing carbon particles (4 microns) with acrolein and compared the results with those from control sheep that received only carbon smoke. Acrolein smoke induced a fall in arterial PO2 and rises in peak inspiratory pressure, main pulmonary arterial pressure, pulmonary vascular resistance, lung lymph flow, and the blood-free wet-to-dry weight ratio. BW-755C delayed the rise in peak inspiratory pressure and prevented the fall in arterial PO2, the rise in lymph flow, and the rise in wet-to-dry weight ratio. Neither indomethacin nor U-63557A prevented the increase in lymph flow or wet-to-dry weight ratio, although they did blunt and delay the rise in airway pressure and did prevent the rises in pulmonary arterial pressure and pulmonary vascular resistance. Thus, cyclooxygenase products, probably Tx, are responsible for the pulmonary hypertension after acrolein smoke and to some extent for the increased airway resistance but not the pulmonary edema. Prevention of high-permeability pulmonary edema after smoke with BW-755C suggests that LTB4, may be etiologic, as previous work has eliminated LTC4, LTD4, and LTE4.
Hyperbaric oxygenation increases arousal and breathing movements in fetal lambs
Authors: Tiktinsky-Rupp M. H. , Hasan S. U. , Bishop B. , Morin F. C.
Published: December 2017

Oxygenation produced by distending the lungs with 100% O2 increases the occurrence of arousal and fetal breathing movements (FBM), particularly during non-rapid-eye-movement (NREM) sleep, in fetal sheep of > or = 135 days of gestation. We studied the breathing and behavioral responses to a rise in arterial PO2 (PaO2) without lung distension in fetuses between 128 and 132 days of gestation. Twelve fetuses were chronically instrumented to record FBM, behavioral state, blood pressure, arterial blood gas tensions, and pH. Fetal PaO2 was raised by having the ewe breathe 100% O2 at 3 atmosphere absolute pressure spontaneously (group 1, n = 5, 129 +/- 1 days of gestation) or with mechanical ventilation to control fetal arterial PCO2 (group 2, n = 7, 131 +/- 1 days of gestation). Hyperbaric oxygenation raised fetal PaO2 by 20 Torr in both groups. During hyperbaric oxygenation, the occurrence of arousal increased severalfold in both groups. The occurrence of FBM increased during arousal in both groups, during rapid-eye-movement sleep in group 1, and during NREM sleep in group 2. The timing of diaphragmatic activity during arousal and the variability of diaphragmatic activity during NREM sleep were different than those in rapid-eye-movement sleep. We conclude that oxygenation without lung distension increases the occurrence of arousal and of FBM, principally during arousal and NREM sleep, in fetuses of > or = 135 days of gestation.
Alveolar septal structure in different species
Authors: Mercer R. R. , Russell M. L. , Crapo J. D.
Published: December 2017

Because the retractive forces due to surface tension decrease with increasing radius of curvature, there should be a greater contribution to lung recoil attributable to the stress-bearing role of elastic elements in the lung parenchyma of species with larger alveoli. To examine alterations in lung structure that may relate to this stress-bearing role, the lungs of mice, hamsters, rats, rabbits, rhesus monkeys, baboons, and humans were preserved by vascular perfusion of fixative. The number of alveoli per lung, alveolar radius of curvature, surface area, and volume were measured by serial section reconstruction. Electron-microscopic determinations were made of the volume fraction and thickness of the epithelium, interstitium, and endothelium and of the connective tissue fibers of the alveolar septa and the portions of alveolar septa that form the alveolar ducts. The thickness of the alveolar septal interstitium increased linearly with the increase in radius of curvature of alveoli. The increase in interstitial thickness in lungs with larger alveoli was paralleled by large increases in the volume of collagen and elastin fibers present in this space. Comparable changes in the thickness of connective tissue fibers in alveolar duct walls were also found. This study demonstrates species-related changes in the structure of alveolar septa and in lung collagen and elastin fibers that are consistent with connective tissue fibers having a greater stress-bearing role in both the alveolar septa and alveolar ducts of species with larger alveoli.
Strength training increases insulin action in healthy 50- to 65-yr-old men
Authors: Miller J. P. , Pratley R. E. , Goldberg A. P. , Gordon P. , Rubin M. , Treuth M. S. , Ryan A. S. , Hurley B. F.
Published: December 2017

The insulin resistance associated with aging may be due, in part, to reduced levels of physical activity in the elderly. We hypothesized that strength training increases insulin action in older individuals. To test this hypothesis, 11 healthy men 50–63 yr old [mean 58 +/- 1 (SE) yr] underwent a two-step hyperinsulinemic-euglycemic glucose clamp with concurrent indirect calorimetry and an oral glucose tolerance test (OGTT) before and after 16 wk of strength training. The training program increased overall strength by 47% (P < 0.001). Fat-free mass (FFM; measured by hydrodensitometry) increased (62.4 +/- 2.1 vs. 63.6 +/- 2.1 kg; P < 0.05) and body fat decreased (27.2 +/- 1.8 vs. 25.6 +/- 1.9%; P < 0.001) with training. Fasting plasma glucose levels and glucose levels during the OGTT were not significantly lower after training. In contrast, fasting plasma insulin levels decreased (85 +/- 25 vs. 55 +/- 10 pmol/l; P < 0.05) and insulin levels decreased (P < 0.05, analysis of variance) during the OGTT. Glucose infusion rates during the hyperinsulinemic-euglycemic glucose clamp increased 24% (13.5 +/- 1.7 vs. 16.7 +/- 2.2 mumol.kg FFM-1.min-1; P < 0.05) during the low (20 mU.m-2.min-1) insulin infusion and increased 22% (55.7 +/- 3.3 vs. 67.7 +/- 3.9 mumol.kg FFM-1.min-1; P < 0.05) during the high (100 mU.m-2.min-1) insulin infusion. These increases were accompanied by a 40% increase (n = 7; P < 0.08) in nonoxidative glucose metabolism during the high insulin infusion. These results demonstrate that strength training increases insulin action and lowers plasma insulin levels in middle-aged and older men.
Differential effects of nitrovasodilators and nitric oxide on porcine tracheal and bronchial muscle in vitro
Authors: Stuart-Smith K. , Bynoe T. C. , Lindeman K. S. , Hirshman C. A.
Published: December 2017

Nitrovasodilators and nitric oxide relax airway smooth muscle. The mechanism by which nitrovasodilators are thought to act is by release of nitric oxide, but the importance of nitric oxide in nitrovasodilator-induced airway smooth muscle relaxation is unclear. The aim of this study was to compare the relaxing effects of nitric oxide itself with those of nitrovasodilators in porcine tracheal muscle and intrapulmonary airways and to investigate the mechanisms involved. Strips of porcine tracheal smooth muscle, rings of bronchi, and strips of bronchi from the same animal were suspended in organ chambers in modified Krebs Ringer solution (95% O2–5% CO2, 37 degrees C). Tissues were contracted with carbachol, and concentration-response curves to nitric oxide, sodium nitroprusside, and SIN-1 (an active metabolite of molsidomine) were obtained. All tissues relaxed to sodium nitroprusside, SIN-1, and nitric oxide. The relaxation to nitric oxide but not to SIN-1 or sodium nitroprusside was inhibited by methylene blue. Tissues pretreated with methylene blue that failed to relax to nitric oxide were, however, relaxed by sodium nitroprusside. These results demonstrate that nitrovasodilators relax airways by a mechanism other than by or in addition to the release of nitric oxide.
Effects of length and stimulation frequency on fatigue of the human tibialis anterior muscle
Authors: Sacco P. , McIntyre D. B. , Jones D. A.
Published: December 2017

It has been suggested that the reduced fatigability of muscles exercised at short length may result from a decrease in the metabolic cost of contractions in the shortened position. We compared the fatigue properties and metabolic cost of stimulated isometric tetanic contractions in the tibialis anterior of 10 normal subjects at the optimum length (Lo) for force production and when the muscle was shortened (Ls). Six 15-s ischemic contractions at Ls caused force to decline to 53% of the fresh value when tested at Lo, whereas muscles exercised and tested at Lo declined to 40% of fresh force. However, the extent of fatigue was proportionately greater if the muscle was exercised and tested at Ls. The apparent fatigue resistance of short muscles was found to be a consequence of recovery occurring under ischemic conditions while the muscle was changed from Ls to Lo-. 31P-nuclear magnetic resonance spectroscopy showed similar metabolic changes associated with 5-s stimulated contractions at Lo and Ls, indicating that any differences in fatigability at the two lengths were not caused by altered metabolic costs. The similarity between the force profiles of muscles fatigued at Ls and those fatigued by high-frequency stimulation supports the hypothesis that an enhanced activation failure occurs at Ls, possibly resulting from failure of sarcolemmal action potential propagation in the transverse tubules.
Effects of solution osmolality on absorption of select fluid replacement solutions in human duodenojejunum
Authors: Shi X. , Summers R. W. , Schedl H. P. , Chang R. T. , Lambert G. P. , Gisolfi C. V.
Published: December 2017

These experiments examined relationships between initial osmolality and carbohydrate (CHO) composition of an infused solution and osmolality and water and CHO absorption in a test segment. A triple-lumen tube with a 10-cm mixing segment and a 40-cm test segment was passed into the duodenojejunum. The infusion port was approximately 10 cm beyond the pyloric sphincter. Perfusion solutions were hypotonic (186 mosmol/kg; solution A), isotonic (283 mosmol/kg; solution B), and hypertonic (403 mosmol/kg; solution C). All solutions contained 18 meq Na+ and 3 meq K+. In the mixing segment, osmolality increased 83 mosmol/kg and decreased 90 mosmol/kg for solutions A and C, respectively. Corresponding changes in the test segment were an increase of 60 mosmol/kg and a decrease of 34 mosmol/kg. The osmolality of solution B did not change. In the test segment, mean osmolality and water and total solute fluxes were not significantly different among solutions, but solution C produced 27% greater fluid absorption than did solution A. When net fluid movement from mixing and test segments was determined, solution A produced 17% greater fluid absorption than did solution C. The mean increases in plasma and urine volumes over the 80-min test period were not significantly different. In the test segment, water flux correlated with CHO and Na+ fluxes but not with osmolality. In conclusion, 1) significant differences in solution osmolality were eliminated within the proximal duodenum and 2) perfusing 6% CHO solutions with osmolalities ranging from 186 to 403 mosmol/kg did not produce significant differences in fluid homeostasis (plasma volume) at the end of an 80-min test period.
Interaction of chronic creatine depletion and muscle unloading: effects on postural locomotor muscles
Authors: Adams G. R. , Haddad F. , Baldwin K. M.
Published: December 2017

In some rodent skeletal muscles, hindlimb non-weight-bearing activity induces a shift in the expression of myosin heavy chains (MHCs) that favors the type II isoforms at the expense of type I. Chemically induced chronic creatine depletion results in isomyosin shifts favoring expression of type I MHCs. In this study, creatine depletion was induced separately and in combination with non-weight-bearing activity to determine if the response to lowering this metabolite would counter the MHC transitions expected from non-weight bearing. Creatine depletion was induced by feeding rats a diet supplemented with the creatine analogue beta-guanidinopropionic acid (beta-GPA). Female Sprague-Dawley rats weighing 247 +/- 8 g were randomly assigned to four groups: 1) normal diet control, 2) beta-GPA control (BC), 3) normal diet suspended (NS), and 4) beta-GPA suspended (BS). BC and BS animals were fed a diet containing the creatine analogue for 68 days. Hindlimb non-weight bearing in BS and NS animals was accomplished by tail suspension for the final 30 days of this period. beta-GPA feeding lowered the creatine content of muscles sampled by 65%. Creatine depletion resulted in a 16% increase in citrate synthase activity in the soleus (SOL) and a 24% increase in the plantaris (PLN). In two postural muscles, the SOL and vastus intermedius (VI), tail suspension resulted in large decreases in the type I MHC expression and increases in type IIx and IIb MHCs. In two locomotor muscles, the PLN and medial gastrocnemius, type I MHC declined and type IIb increased with suspension.(ABSTRACT TRUNCATED AT 250 WORDS)
Eccentric contraction-induced injury in normal and hindlimb-suspended mouse soleus and EDL muscles
Authors: Warren G. L. , Hayes D. A. , Lowe D. A. , Williams J. H. , Armstrong R. B.
Published: December 2017

The primary objective of this study was to compare the magnitude of injury in mouse extensor digitorum longus (EDL) and soleus muscles induced by high-force eccentric contractions. A second objective was to study the effect of altering the daily loading of the muscles through hindlimb suspension (HS) on the injury. One of two protocols was performed in vitro: 1) 15 eccentric contractions (n = 20: 10 EDL and 10 soleus muscles) or 2) 15 isometric contractions (n = 20: 10 EDL and 10 soleus muscles). After the protocol, the decrements in contractile performance and lactate dehydrogenase (LDH) release were measured at 15-min intervals over 1 h. Immediately after the eccentric contraction protocol, markedly greater decrements in maximal isometric tetanic force (Po) occurred in the normal EDL than in the normal soleus muscles (60.7 +/- 4.2 vs. 7.6 +/- 2.1%, P < or = 0.0001). LDH release immediately after the eccentric contraction protocol was 2.7-fold greater in the normal EDL than in the normal soleus muscles. To investigate the role of recent loading of the muscles in the injury, EDL (n = 9) and soleus (n = 10) muscles from mice subjected to HS for 14 days performed the eccentric contraction protocol. HS resulted in greater decrements in contractile performance for the soleus muscles (decreases in Po immediately after the protocol for HS and normal soleus muscles were 31.0 +/- 1.8 and 7.6 +/- 2.1%, respectively; P < or = 0.0001) but not for the EDL muscles.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiovascular responses to exhaustive upright cycle exercise in highly trained older men
Authors: Fleg J. L. , Schulman S. P. , O'Connor F. C. , Gerstenblith G. , Becker L. C. , Fortney S. , Goldberg A. P. , Lakatta E. G.
Published: December 2017

It is unclear whether the markedly enhanced aerobic exercise capacity of older endurance-trained men relative to their sedentary age peers is mediated primarily by central or peripheral cardiovascular mechanisms. To address this question, we performed radionuclide ventriculography with respiratory gas exchange measurements during exhaustive upright cycle ergometry in 16 endurance-trained men aged 63 +/- 7 yr and in 35 untrained men of similar age. As expected, maximal O2 consumption during treadmill exercise was much higher in athletes than in controls. At rest and during fixed submaximal cycle work rates through 100 W, athletes demonstrated lower heart rates and greater stroke volume indexes than controls while maintaining similar cardiac indexes and O2 uptake (VO2). At exhaustion, athletes achieved 53% higher work rates and peak VO2 per kilogram body weight than the sedentary men. The higher peak VO2 in athletes was achieved by a 22.5% larger cardiac index and a 15.6% greater arteriovenous O2 difference. The larger peak cardiac index in the athletes than in sedentary controls was mediated entirely by a greater stroke volume index; peak heart rates were virtually identical. The athletes' greater stroke volume index was achieved through an 11% larger end-diastolic volume index and a 7% higher ejection fraction, both of borderline significance. At exhaustion, athletes demonstrated a lower systemic vascular resistance than controls, despite a higher value at rest. Athletes also showed greater exercise-induced increments in heart rate, stroke volume index, and cardiac index and a greater reduction in systemic vascular resistance from rest to maximal workload.(ABSTRACT TRUNCATED AT 250 WORDS)
Peripheral vasoconstriction shortly after onset of moderate exercise in humans
Authors: Toska K. , Eriksen M.
Published: December 2017

The immediate cardiovascular responses at the onset of supine dynamic leg exercise were studied by noninvasive methods in healthy humans. Total peripheral conductance (TPC), heart rate, and cardiac output increased very rapidly at the onset of exercise. Mean arterial pressure (MAP) showed a moderate anticipatory increase during a 10-s countdown to exercise and then decreased (but not below resting level) during the first 10 s of exercise. The TPC response was biphasic, and TPC started to fall from its peak value approximately 12 s after onset of exercise. This peripheral vasoconstriction increased MAP. After 25 s, the cardiovascular variables were stable for the rest of the 2-min exercise period. In the same subjects, cholinergic blockade was induced by atropine sulfate (0.035 mg/kg) and resting cardiac output, MAP, and TPC increased considerably. The exercise protocol was repeated after atropine, and the increase in heart rate at onset of exercise was slower and smaller. MAP decreased and remained depressed throughout the exercise period. A monophasic increase in TPC was seen. We suggest that, in the normal situation, the biphasic response in TPC reflects a baroreflex sympathetic vasoconstriction very shortly after onset of exercise and that this response is due to a rapid increase in set point for arterial pressure control at the onset of exercise. After cholinergic blockade, MAP was probably continuously well above the set point for arterial pressure control both before and during exercise and no reflex vasoconstriction was observed in this situation.
Effect of carbohydrate ingestion on glucose kinetics during exercise
Authors: McConell G. , Fabris S. , Proietto J. , Hargreaves M.
Published: December 2017

Six well-trained men (peak pulmonary oxygen uptake = 5.03 +/- 0.11 l/min) were studied during 2 h of exercise at 69 +/- 1% peak pulmonary oxygen uptake to examine the effect of carbohydrate (CHO) ingestion on glucose kinetics. Subjects ingested 250 ml of either a 10% glucose solution containing 6-[3H]glucose (CHO) or a sweet placebo every 15 min during exercise. Glucose kinetics were assessed by 6,6-[2H]glucose infusion corrected for gut-derived glucose in CHO. Plasma glucose was higher (P < 0.05) in CHO from 20 min. Total glucose appearance was higher in CHO due to glucose delivery from the gut (68 +/- 7 g), since hepatic glucose production was reduced by 51% (29 +/- 5 vs. 59 +/- 5 g). Glucose uptake was higher in CHO (96 +/- 7 vs. 60 +/- 6 g) with the ingested glucose supplying 67 +/- 4 g and, with the assumption that it was fully oxidized, accounted for 14 +/- 1% of total energy expenditure. In conclusion, CHO ingestion during prolonged exercise results in suppression of hepatic glucose production and increased glucose uptake. These effects appear to be mediated mainly by increased plasma glucose and insulin levels.
Directionally opposite left atrial and ventricular volume changes during lower body suction
Authors: Eckberg D. L.
Published: December 2017

In animals, sympathetic responses to orthostasis are regulated in part by cardiopulmonary afferents arising from atrial and ventricular baroreceptors. To determine the relative importance of these baroreceptor regions in the cardiopulmonary baroreflex of normal humans, simultaneous measurements of left atrial and right and left ventricular volumes (cine computed tomography), invasive hemodynamics, forearm vascular resistance (plethysmography), and efferent sympathetic nerve activity to muscle (microneurography) were obtained under control conditions and with nonhypotensive lower body negative pressure (-10 mmHg, LBNP-10) in nine normal human subjects. LBNP-10 did not alter heart rate or mean systemic arterial pressure, but it did produce significant decreases in pulmonary artery diastolic and right atrial pressures. This reduction in cardiac filling pressures resulted in efferent sympathoexcitation evidenced by increases in forearm vascular resistance and efferent sympathetic nerve activity to the muscle. LBNP-10 did not alter end-diastolic volume of the left or the right ventricle. Similarly, ventricular stroke volume was unchanged during LBNP-10, as assessed by cine computed tomography or thermodilution techniques. In contrast, LBNP-10 resulted in a significant decrease in left atrial volume. Thus, LBNP produced a significant decrease in cardiac filling pressures and left atrial volumes with resultant reflex sympathoexcitation, whereas ventricular volumes were unchanged. These observations suggest an important role for left atrial (nonventricular) baroreceptor afferents in the cardiopulmonary baroreflex of normal humans.
Effects of hypercapnia and hypoxia on inspiratory and expiratory diaphragmatic activity in conscious cats
Authors: Bonora M. , Boule M.
Published: December 2017

The influence of steady-state changes in chemical stimuli on ventilation and electromyographic activity of the diaphragm during both inspiration (total DI) and expiration (total DE) was studied in unanesthetized intact adult cats before and after carotid denervation. In intact animals, during hypercapnia (2 4, and 6% CO2), tidal volume (VT) and total DI increase, whereas total DE did not consistently change. During ambient hypocapnic hypoxia (14, 12, and 10% O2), VT increased only at 10% O2, whereas total DI increased at all levels studied. Total DE increased substantially at 14% O2, persisting up to the end of expiration with 12 and 10% O2. This effect was markedly attenuated during normocapnic hypoxia. During CO hypoxemia (1,700 ppm in air), VT as well as total DI and total DE decreased because of a large reduction in inspiratory and expiratory time elicited by tachypneic breathing. The effects of hypercapnia and hypoxia persisted after carotid denervation. Therefore, 1) in contrast to hypercapnia, hypoxia markedly enhances the expiratory diaphragmatic activity, 1) this expiratory braking mechanism depends on the severity of hypoxia and is partly due to hypocapnia secondary to hypoxia; and 3) because this effect was observed after carotid denervation and during CO hypoxemia, it may arise in the central nervous system, possibly in bulbopontine structures.
Effects of strength training on bone mineral density: hormonal and bone turnover relationships
Authors: Ryan A. S. , Treuth M. S. , Rubin M. A. , Miller J. P. , Nicklas B. J. , Landis D. M. , Pratley R. E. , Libanati C. R. , Gundberg C. M. , Hurley B. F.
Published: December 2017

The effects of a 16-wk strength-training program on bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry in 21 men [age 61 +/- 1 (SE) yr]. Sixteen men (age 59 +/- 2 yr) served as control subjects. To investigate the possible hormonal relationships underlying the effects on BMD, serum concentrations of growth hormone, insulin-like growth factor I, and testosterone were determined before and after training. In addition, osteocalcin and skeletal alkaline phosphatase (markers of bone formation) and tartrate-resistant acid phosphatase (a marker of bone resorption) were measured before and after training to assess bone turnover. The training program resulted in a 2.8 +/- 0.6% increase in femoral neck BMD (1.004 +/- 0.037 vs. 1.031 +/- 0.037 g/cm2; P < 0.001). However, there were no significant changes in total body, anterioposterior spine, lateral spine, Ward's triangle, or greater trochanter BMD. Moreover, there were no significant changes in growth hormone, insulin-like growth factor I, testosterone, osteocalcin, or skeletal alkaline phosphatase. There were no changes in the control group. Thus, strength training can increase femoral neck BMD, and this effect does not appear to be accompanied by changes in anabolic hormones or markers of bone formation and resorption.
Maximal aerobic capacity and total blood volume in highly trained middle-aged and older female endurance athletes
Authors: Stevenson E. T. , Davy K. P. , Seals D. R.
Published: December 2017

The primary aim of this study was to test the hypothesis that, relative to age-matched sedentary controls, middle-aged and older female endurance athletes exhibit levels of maximal rate of O2 consumption (VO2max) similar to those previously reported in male endurance athletes in the same age group and, furthermore, that these high levels of VO2max are associated with elevated and total blood volume in 13 highly trained female runners and 17 healthy untrained women 50–70 yr of age. The runners had lower (P < 0.001) body mass index and estimated body fat relative to the controls. They also had higher levels of VO2max (2.70 +/- 0.08 vs. 1.74 +/- 0.06 l/min, 48.6 +/- 1.9 vs. 26.5 +/- 0.8 ml.kg-1.min-1, 58.0 +/- 1.8 vs. 38.8 +/- 1.2 ml.kg fat-free mass-1.min-1; all P < 0.001) and total blood volume (4,964 +/- 226 vs. 4,336 +/- 130 ml, P < 0.02; 89 +/- 4 vs. 64 +/- 2 ml/kg, P < 0.001; 106 +/- 4 vs. 96 +/- 3 ml/kg fat-free mass, P < 0.05). The elevated total blood volumes in the runners were due to both higher plasma and erythrocyte volumes. In addition, hematocrit and hemoglobin concentrations were higher in the runners (P < 0.007). VO2max was strongly (P < 0.001) related to total blood volume (r = 0.79), plasma volume (r = 0.76), and erythrocyte volume (r = 0.78) when all were expressed relative to body weight.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of sleep deprivation on responses to airway obstruction in the sleeping dog
Authors: O'Donnell C. P. , King E. D. , Schwartz A. R. , Smith P. L. , Robotham J. L.
Published: December 2017

The effect of sleep deprivation on sleep architecture and respiratory responses to repetitive airway obstruction during sleep was investigated in four chronically instrumented tracheostomized dogs during 12-h nocturnal experiments. A 24-h period of prior sleep deprivation increased (P < 0.05) the rate at which airway obstruction could be induced from 20 +/- 3 (SE) to 37 +/- 10 times/h compared with non-sleep-deprived dogs. During non-rapid-eye-movement sleep the duration of obstruction, minimum arterial hemoglobin saturation, and peak negative inspiratory effort at arousal were 20.5 +/- 1.0 s, 91.7 +/- 0.5%, and 28.4 +/- 1.8 mmHg, respectively, in non-sleep-deprived dogs. Sleep deprivation increased (P < 0.01) the duration of obstruction to 28.0 +/- 0.9 s, worsened (P < 0.05) the minimal arterial hemoglobin desaturation to 85.4 + 3.1%, and increased (P < 0.025) the peak negative inspiratory effort at arousal to 36.1 +/- 1.6 mmHg. Sleep deprivation also caused increases (P < 0.025) in total sleep time, rapid-eye-movement (REM) sleep time, and percentage of time in REM sleep in a 2-h recovery period without airway obstruction at the end of the study. We conclude that airway obstruction in the sleeping dog can reproduce the disturbances in sleep architecture and respiration that occur in obstructive sleep apnea and that prior sleep deprivation will increase apnea severity, degree of somnolence, and REM sleep rebound independent of change in upper airway collapsibility.
Exogenous surfactant improves lung compliance and oxygenation in adult rats with meconium aspiration
Authors: Sun B. , Herting E. , Curstedt T. , Robertson B.
Published: December 2017

We studied the effects of exogenous surfactant on lung function and morphology in an adult rat model of severe meconium aspiration syndrome. Animals ventilated with 100% oxygen received 4–6 ml of human meconium (25 mg/ml) intratracheally. After 30 min, lung-thorax compliance had decreased by > 30% and arterial PO2 was < 10 kPa. Animals were then treated with no material (MECO group), 0.9% NaCl (MECO-saline group), natural porcine surfactant (NPS group) at a dose of 100 mg/kg, or modified porcine surfactant at a dose of either 100 (MPS100 group) or 200 mg/kg (MPS200 group) and were ventilated for another 180 min. Immediate and sustained improvement of arterial PO2 and compliance was observed in the MPS200 group, whereas the MPS100 and NPS groups showed less pronounced effects. There was a significant improvement of quasi-static lung volumes at maximum insufflation pressure and during deflation in the MPS200, MPS100, and NPS groups. Recordings with Wilhelmy balance showed that minimum surface tension of bronchoalveolar lavage fluid from animals receiving either type or dose of surfactant was significantly lower than in the MECO and MECO-saline groups. Meconium aspiration induced diffuse and prominent atelectasis, intra-alveolar edema, and hyaline membranes. These morphological abnormalities were reversed by exogenous surfactant, especially by the high-dose regimen.
Effect of sampling site on femoral venous blood gas values
Authors: Agusti A. G. , Roca J. , Barbera J. A. , Casademont J. , Rodriguez-Roisin R. , Wagner P. D.
Published: December 2017

To examine whether the tip of the femoral vein catheter used for sampling femoral venous PO2 during cycling exercise is contaminated by skin or saphenous vein blood, we studied 6 healthy volunteers [21.7 +/- 0.7 (SD) yr] during three identical incremental exercise tests while breathing room air on the same day. Femoral venous blood was sampled simultaneously from two catheters inserted into the femoral vein but advanced in opposite directions (7 cm distally and 5 cm proximally). Blood sampling for measurements of PO2, PCO2, pH, hemoglobin concentration, and oxyhemoglobin saturation was done simultaneously from both catheters in duplicate at rest, at 60% of maximum workload (60% W), and at maximum symptom-limited exercise (100% W). Temperature was measured with a thermistor probe placed in the proximal catheter. At rest, distal PO2 was significantly lower than that measured proximally (24.9 +/- 4.3 vs 30.8 +/- 6.1 mmHg, respectively; P < 0.004), but no differences were found during exercise (60% W, 23.6 +/- 3.4 vs. 24.5 +/- 3.6 mmHg; 100% W, 26.0 +/- 3.6 vs. 25.5 +/- 2.8 mmHg, respectively). Comparison of blood temperatures between proximal and distal sites of sampling in two subjects showed negligible differences. Intrasubject coefficient of variation of distal femoral venous PO2 over the three bouts of exercise was 11.5% (2.9 mmHg) at rest, 5.9% (1.4 mmHg) at 60% W, and 5.6% (1.5 mmHg) at 100% W. Mean differences in distal PO2 between duplicate samples were 0.5 +/- 1.4 mmHg at rest, 0.1 +/- 0.8 mmHg at 60% W, and 0.6 +/- 0.9 mmHg at 100% W.(ABSTRACT TRUNCATED AT 250 WORDS)
Aerosolized deferoxamine prevents lung and systemic injury caused by smoke inhalation
Authors: LaLonde C. , Ikegami K. , Demling R.
Published: December 2017

We assessed the role of oxidant release at the airway mucosal surface on airway injury and systemic response to a severe smoke insult. Adult sheep (n = 20) were insufflated with well-characterized smoke from burning cotton toweling. A standardized dose of 12 breaths of smoke with a tidal volume of 20 ml/kg was given under anesthesia. Sheep were awakened, monitored for 24 h, and killed; data were compared with control sheep. Sheep were given 1) humidified oxygen, 2) continuous aerosol of 10% deferoxamine (DFO)-pentastarch solution beginning after smoke, 3) DFO-alone aerosol, or 4) pentastarch-alone aerosol. DFO has antioxidant properties directly and chelates iron. Severe respiratory failure occurred in all but DFO-pentastarch group. Shunt fraction increased from a control of 4%. Histological assessment revealed severe airway mucosal edema, ulceration, bronchorrhea, and severe atelectasis but only moderate alveolar edema. Increased lipid peroxides were also noted in free airway fluid and in bronchoalveolar lavage fluid. In addition, oxygen consumption increased by 75%, fluid requirements increased threefold, and protein-rich systemic soft tissue lymph flow doubled, all significant increases compared with control sheep. No significant physiological or histological changes were noted in DFO-pentastarch aerosol group. We conclude that 1) oxidants possibly initiated through free iron release are involved in severe smoke-induced airway injury and resulting systemic inflammatory response, probably through an amplified oxidant injury and 2) an aerosol of a DFO-pentastarch complex prevents the injury process, whereas DFO alone is not effective as an aerosol.
Role of Ca2+ in protecting the heart from hyperkalemia and acidosis in the rabbit: implications for exercise
Authors: Leitch S. P. , Paterson D. J.
Published: December 2017

Catecholamines can offset the negative effect of acidosis and raised extracellular K+ concentration in the isolated rabbit heart when these factors are changed with similar kinetics and concentrations as those observed in exercise. This effect appears to be mediated by changes in Ca2+ handling in the heart. To test the role of Ca2+ in vivo, we studied the interactive effects of infusions of KCl, lactic acid, norepinephrine (NE), and CaCl2 on cardiovascular performance in the anesthetized rabbit. After propranolol, CaCl2 was given during acidosis and hyperkalemia. Acidosis (arterial pH 7.17 +/- 0.3) markedly reduced cardiac performance, and its effects were exacerbated by hyperkalemia (7.3 +/- 0.4 mM). NE reversed the cardiac response to combined acidosis and hyperkalemia. After propranolol, arterial pH and arterial K+ concentration changed more rapidly with acidosis and hyperkalemia, combined with a faster fall in cardiac performance, but CaCl2 offset these negative hemodynamic effects. The rises in plasma Ca2+, NE, and sympathetic activity during exercise may therefore interact to ameliorate the harmful effects of acidosis and hyperkalemia.
Effects of infused epinephrine on slow phase of O2 uptake kinetics during heavy exercise in humans
Authors: Gaesser G. A. , Ward S. A. , Baum V. C. , Whipp B. J.
Published: December 2017

We tested the hypothesis that infused epinephrine (Epi) would augment the slow phase of oxygen uptake (VO2) during heavy exercise. Six normal healthy males initially performed a ramp test on a cycle ergometer to estimate the lactate threshold (LT) and determine peak VO2. Each subject then performed two 20-min constant-load tests at a power output calculated to elicit a VO2 equal to estimated LT + 0.2(peak VO2--estimated LT) under control conditions throughout and with an intravenous infusion of Epi from minutes 10 to 20 at a rate of 100 ng.kg-1.min-1. Pulmonary gas exchange variables were determined breath by breath. Arterialized venous blood was repeatedly sampled from the dorsum of the heated hand. Epi infusion elevated (P < 0.05) plasma Epi concentration (i.e., from 420 +/- 130 pg/ml at minute 10 to 2,190 +/- 410 pg/ml at minute 20) but had no effect on plasma norepinephrine or K+ concentrations. Concentrations of blood lactate and pyruvate were increased, pH was decreased, and base excess became more negative by infusion of Epi (P < 0.05). Epi infusion increased (P < 0.05) CO2 production and the respiratory exchange ratio but had no effect on ventilation or VO2. VO2 increased (P < 0.05) to the same extent in both control (3.14 +/- 0.12 l/min at minute 10, 3.28 +/- 0.12 l/min at minute 20) and Epi infusion (3.10 +/- 0.11 l/min at minute 10, 3.25 +/- 0.11 l/min at minute 20) trials. We therefore concluded that neither Epi nor its associated humoral consequences contribute significantly to the slow phase of VO2 kinetics during heavy exercise.
Symmetry, bifurcations, and chaos in a distributed respiratory control system
Authors: Sammon M.
Published: December 2017

A multivariate model is outlined for a distributed respiratory central pattern generator (RCPG) and its afferent control. Oscillatory behavior of the system depends on structure and symmetry of a matrix of phase-switching functions (F omega, phi) that control distribution of central excitation (CE) and inhibition (CI) within the circuit. The matrix diagonal (F omega) controls activation of CI variables as excitatory inputs are altered (e.g., central and afferent contributions to inspiratory off switch); off-diagonal terms (F phi) distribute excitations within the CI system and produce complex eigenvalues at the switching points between inspiration and expiration. For null F phi, phase switchings of saddle equilibria located at end expiration and end inspiration are overdamped all-or-nothing events; graded control of CI is seen for phi > 0. When coupling is significant (phi >> 0), CI dynamics become underdamped, admitting a domain of inputs where chaotic behavior is predictably observed. For the homogeneous RCPG (symmetric F omega, phi), CE oscillations are one-dimensional limit cycles (D = 1) or weakly chaotic (D approximately equal to 1). When perturbations from symmetry are significant, the distributed RCPG becomes partitioned where strongly chaotic oscillations (D > or = 2) and central apnea (D = 0) are seen more frequently. The equations provide means for mapping Silnikov bifurcations that alter the geometry and dimension of the breathing pattern and formalisms for discussing RCPG processing of afferent information.
Altered mechanical properties of lung parenchyma in postobstructive pulmonary vasculopathy
Authors: Kelly S. M. , Bates J. H. , Michel R. P.
Published: December 2017

Postobstructive pulmonary vasculopathy (POPV) produced by chronic unilateral ligation of one pulmonary artery, results in perfusion of the pulmonary capillaries with systemic arterial blood. As a consequence, gas exchange occurs primarily in the contralateral nonligated lung. To determine whether the mechanical properties of the lung parenchyma are changed in POPV, we compared five dogs with chronic ligation of the left main pulmonary artery with five control dogs. Separate measurements of left and right lung airway flows, tracheal pressures, and alveolar pressures were made during mechanical ventilation at frequencies between 5 and 40 breaths/min. We calculated pulmonary elastance (EL) and pulmonary (RL), airway (Raw), and tissue (Rti) resistances. At all frequencies, dogs with POPV had higher left (ligated) EL and Rti and lower right (normal) lung Rti but similar EL compared with the respective lungs from control animals. Raw was the same in both lungs. Histology showed visceral pleura thickening and encroachment of new bronchial collaterals and lymphatics on the parenchyma of the ligated lungs. The contralateral lungs were entirely normal. We conclude that in POPV 1) there is an increase, in the ligated lung, of both EL and RL, the latter likely due to histological changes of the lung parenchyma, and 2) there is a reduction of Rti in the contralateral lung.