bluuebunny/crossref_metadata_2025 huggingface dataset:
Catchlike property of rat diaphragm: subsequent train frequency effects in variable-train stimulation
Authors: van Lunteren Erik , Sankey Christopher B.
Published: December 2017

A high-frequency burst of pulses at the onset of a subtetanic train of stimulation allows skeletal muscle to hold force at a higher level than expected from the extra pulses alone because of the catchlike property of muscle. The present study tested the hypothesis that the presence and degree of force increase induced by a high-frequency burst are strongly modulated by the subsequent train frequency. Rat diaphragm muscle strips (studied in vitro at 37°C) underwent two-, three-, or four-pulse bursts [interpulse interval (IPI) of 5 or 10 ms] at the onset of 10- to 50-Hz subtetanic trains. Force was quantified during the train with respect to its peak value (Fpeak), mean value (Fmean), and force-time integral (Farea), and it was compared with that produced during subtetanic trains of an equal number of pulses without preceding pulse bursts (Diff-Fpeak, Diff-Fmean, Diff-Farea). Fpeakand Fmeanincreased with two-, three-, and four-pulse bursts, and Diff-Fpeakand Diff-Fmeanincreased progressively with decreasing frequency of the subtetanic train. Farea, the best reflection of catchlike force augmentation, was increased mainly by the four-pulse bursts with an IPI of 10 ms, and Diff-Fareawas maximal at subsequent train frequencies of 15–25 Hz. The use of incorrect patterns of burst stimulation could also precipitate Fareadecreases, which were observed with the four-pulse, 5-ms IPI paradigm. The time required to reach 80% of maximal force (T80%) became shorter for each of the pulse burst stimulation patterns, with maximal reduction of Diff-T80%occurring at a subsequent train frequency of 20 Hz in all cases. These data indicate that extra-pulse burst stimulation paradigms need to incorporate the optimal combinations of extra-pulse number, IPI, and the frequency of the subsequent subtetanic train to take greatest advantage of the catchlike property of muscle.
Role of denervation in modulating IIb MHC gene expression in response to T3plus unloading state
Authors: di Maso Nick A. , Haddad Fadia , Zeng Ming , McCue Samuel A. , Baldwin Kenneth M.
Published: December 2017

Previously, we have reported that the combination of hindlimb suspension (HS) and thyroid hormone [triiodothyronine (T3)] treatment induces the de novo expression of the fast IIb myosin heavy chain (MHC) gene in the soleus. Thus we tested the hypotheses that the induction of IIb MHC expression with HS + T3is prevented with denervation and that this IIb induction is regulated by transcriptional processes. Adult female rats were subjected to 2 wk of combined HS + T3in which one side of the lower leg was simultaneously denervated. HS + T3caused decreased expression of the slow type I MHC and concomitant increases in both the fast type IIx and IIb MHC isoforms in the intact soleus muscle. Denervation prevented the endogenous expression of the IIb MHC gene at both the protein and mRNA levels. Although HS + T3intervention was able to markedly increase the expression of the 2.6-kb IIb MHC promoter-reporter construct using direct gene transfer, this induction, however, was not inhibited by denervation. These findings collectively suggest that normal innervation is essential for inducing the unique expression of the IIb MHC in a slow muscle in response to HS + T3; however, in the denervated muscle, there is a discordance between the regulation of the endogenous IIb MHC gene relative to the exogenous IIb MHC promoter-reporter construct.
Angiotensin-converting enzyme ID polymorphism and fitness phenotype in the HERITAGE Family Study
Authors: Rankinen Tuomo , Pérusse Louis , Gagnon Jaques , Chagnon Yvon C. , Leon Arthur S. , Skinner James S. , Wilmore Jack H. , Rao D. C. , Bouchard Claude
Published: December 2017

It has been suggested that genetic variation in the angiotensin-converting enzyme ( ACE) gene is associated with physical performance. We studied the association between the ACE insertion (I)/deletion (D) polymorphism and several fitness phenotypes measured before and after 20 wk of a standardized endurance training program in sedentary Caucasian ( n = 476) and black ( n = 248) subjects. Phenotypes measured were oxygen uptake (V˙o 2), work rate, heart rate, minute ventilation, tidal volume, and blood lactate levels during maximal and submaximal [50 W and at 60 and 80% of maximalV˙o 2(V˙o 2 max)] exercise and stroke volume and cardiac output during submaximal exercise (50 W and at 60%V˙o 2 max). The ACE ID polymorphism was typed with the three-primer PCR method. Out of 216 association tests performed on 54 phenotypes in 4 groups of participants, only 11 showed significant ( P values from 0.042 to 0.0001) associations with the ACE ID polymorphism. In contrast to previous claims, in Caucasian offspring, the DD homozygotes showed a 14–38% greater increase with training in V˙o 2 max,V˙o 2 at 80% ofV˙o 2 max, and all work rate phenotypes and a 36% greater decrease in heart rate at 50 W than did the II homozygotes. No associations were evident in Caucasian parents or black parents or offspring. Thus these data do not support the hypothesis that the ACE ID polymorphism plays a major role in cardiorespiratory endurance.
Eukaryotic initiation factors and protein synthesis after resistance exercise in rats
Authors: Farrell Peter A. , Hernandez Jazmir M. , Fedele Mark J. , Vary Thomas C. , Kimball Scot R. , Jefferson Leonard S.
Published: December 2017

Translational control of protein synthesis depends on numerous eukaryotic initiation factors (eIFs) and we have previously shown ( Am. J. Physiol. Endocrinol. Metab. 276: E721–E727, 1999) that increases in one factor, eIF2B, are associated with increases in rates of protein synthesis after resistance exercise in rats. In the present study we investigated whether the eIF4E family of initiation factors is also involved with an anabolic response to exercise. Male Sprague-Dawley rats either remained sedentary ( n = 6) or performed acute resistance exercise ( n = 6), and rates of protein synthesis were assessed in vivo 16 h after the last session of resistance exercise. eIF4E complexed to eIF4G (eIF4E ⋅ eIF4G), eIF4E binding protein 1 (4E-BP1) complexed to eIF4E, and phosphorylation state of eIF4E and 4E-BP1 (γ-form) were assessed in gastrocnemius. Rates of protein synthesis were higher in exercised rats compared with sedentary rats [205 ± 8 (SE) vs. 164 ± 5.5 nmol phenylalanine incorporated ⋅ g muscle−1⋅ h−1, respectively; P < 0.05]. Arterial plasma insulin concentrations were not different between the two groups. A trend ( P = 0.09) for an increase in eIF4E ⋅ eIF4G with exercise was noted; however, no statistically significant differences were observed in any of the components of the eIF4E family in response to resistance exercise. These new data, along with our previous report on eIF2B, suggest that the regulation of peptide chain initiation after exercise is more dependent on eIF2B than on the eIF4E system.
Effects of arousal and sleep state on systemic and pulmonary hemodynamics in obstructive apnea
Authors: Schneider H. , Schaub C. D. , Chen C. A. , Andreoni K. A. , Schwartz A. R. , Smith P. L. , Robotham J. L. , O'Donnell C. P.
Published: December 2017

During obstructive sleep apnea (OSA), systemic (Psa) and pulmonary (Ppa) arterial pressures acutely increase after apnea termination, whereas left and right ventricular stroke volumes (SV) reach a nadir. In a canine model ( n = 6), we examined the effects of arousal, parasympathetic blockade (atropine 1 mg/kg iv), and sleep state on cardiovascular responses to OSA. In the absence of arousal, SV remained constant after apnea termination, compared with a 4.4 ± 1.7% decrease after apnea with arousal ( P < 0.025). The rise in transmural Ppa was independent of arousal (4.5 ± 1.0 vs. 4.1 ± 1.2 mmHg with and without arousal, respectively), whereas Psa increased more after apnea termination in apneas with arousal compared with apneas without arousal. Parasympathetic blockade abolished the arousal-induced increase in Psa, indicating that arousal is associated with a vagal withdrawal of the parasympathetic tone to the heart. Rapid-eye-movement (REM) sleep blunted the increase in Psa (pre- to end-apnea: 5.6 ± 2.3 mmHg vs. 10.3 ± 1.6 mmHg, REM vs. non-REM, respectively, P< 0.025), but not transmural Ppa, during an obstructive apnea. We conclude that arousal and sleep state both have differential effects on the systemic and pulmonary circulation in OSA, indicating that, in patients with underlying cardiovascular disease, the hemodynamic consequences of OSA may be different for the right or the left side of the circulation.
Form follows function: how muscle shape is regulated by work
Authors: Russell Brenda , Motlagh Delara , Ashley William W.
Published: December 2017

What determines the shape, size, and force output of cardiac and skeletal muscle? Chicago architect Louis Sullivan (1856–1924), father of the skyscraper, observed that “form follows function.” This is as true for the structural elements of a striated muscle cell as it is for the architectural features of a building. Function is a critical evolutionary determinant, not form. To survive, the animal has evolved muscles with the capacity for dynamic responses to altered functional demand. For example, work against an increased load leads to increased mass and cross-sectional area (hypertrophy), which is directly proportional to an increased potential for force production. Thus a cell has the capacity to alter its shape as well as its volume in response to a need for altered force production. Muscle function relies primarily on an organized assembly of contractile and other sarcomeric proteins. From analysis of homogenized cells and molecular and biochemical assays, we have learned about transcription, translation, and posttranslational processes that underlie protein synthesis but still have done little in addressing the important questions of shape or regional cell growth. Skeletal muscles only grow in length as the bones grow; therefore, most studies of adult hypertrophy really only involve increased cross-sectional area. The heart chamber, however, can extend in both longitudinal and transverse directions, and cardiac cells can grow in length and width. We know little about the regulation of these directional processes that appear as a cell gets larger with hypertrophy or smaller with atrophy. This review gives a brief overview of the regulation of cell shape and the composition and aggregation of contractile proteins into filaments, the sarcomere, and myofibrils. We examine how mechanical activity regulates the turnover and exchange of contraction proteins. Finally, we suggest what kinds of experiments are needed to answer these fundamental questions about the regulation of muscle cell shape.
Time course evaluation of protein synthesis and glucose uptake after acute resistance exercise in rats
Authors: Hernandez Jazmir M. , Fedele Mark J. , Farrell Peter A.
Published: December 2017

The temporal pattern for changes in rates of protein synthesis and glucose uptake after resistance exercise, especially relative to each other, is not known. Male Sprague-Dawley rats performed acute resistance exercise ( n = 7) or remained sedentary ( n = 7 per group), and the following were assessed in vivo 1, 3, 6, 12 and 24 h later: rates of protein synthesis, rates of glucose uptake, phosphatidylinositol 3-kinase (PI3-kinase) activity, and p70S6kactivity. Rates of protein synthesis in mixed gastrocnemius muscle did not increase until 12 h after exercise (e.g., at 12 h, sedentary = 138 ± 4 vs. exercised = 178 ± 6 nmol phenylalanine incorporated ⋅ g muscle−1⋅ h−1, mean ± SE, P < 0.05), whereas at 6 h after exercise rates of glucose uptake were significantly elevated (sedentary = 0.18 ± 0.020 vs. exercised = 0.38 ± 0.024 μmol glucose 6-phosphate incorporated ⋅ kg muscle−1⋅ min−1, P < 0.05). At 24 h after exercise, rates of protein synthesis were still elevated, whereas glucose uptake had returned to basal levels. Arterial insulin concentrations were not different between groups at any time. Non-insulin-stimulated activities of PI3-kinase and p70S6kwere higher at 6, 12, and 24 h after exercise ( P < 0.05), and, generally, these occurred when rates of protein synthesis (12 and 24 h) and glucose uptake were elevated (6 and 12 but not 24 h) by exercise. These data suggest that regulators of protein synthesis and glucose uptake may respond to the same contraction-generated signals with different kinetics or that they respond to different intra- or extracellular signals that are generated by exercise.
Revealing deterministic structures in click-evoked otoacoustic emissions
Authors: Zimatore Giovanna , Giuliani Alessandro , Parlapiano Calogero , Grisanti Giorgio , Colosimo Alfredo
Published: December 2017

Click-evoked otoacoustic emissions (CEOAEs) were studied by means of recurrence quantification analysis (RQA) and were found to be endowed with a relevant amount of deterministic structuring. Such a structure showed highly significant correlation with the clinical evaluation of the signal over a data set including 56 signals. Moreover, 1) one of the RQA variables, Trend, was very sensitive to phase transitions in the dynamical regime of CEOAEs, and 2) appropriate use of principal component analysis proved able to isolate the individual character of the studied signals. These results are of general interest for the study of auditory signal transduction and generation mechanisms.
Impact of muscle injury and accompanying inflammatory response on thermoregulation during exercise in the heat
Authors: Montain Scott J. , Latzka William A. , Sawka Michael N.
Published: December 2017

This study examined whether muscle injury and the accompanying inflammatory responses alter thermoregulation during subsequent exercise-heat stress. Sixteen subjects performed 50 min of treadmill exercise (45–50% maximal O2 consumption) in a hot room (40°C, 20% relative humidity) before and at select times after eccentric upper body (UBE) and/or eccentric lower body (LBE) exercise. In experiment 1, eight subjects performed treadmill exercise before and 6, 25, and 30 h after UBE and then 6, 25, and 30 h after LBE. In experiment 2, eight subjects performed treadmill exercise before and 2, 7, and 26 h after LBE only. UBE and LBE produced marked soreness and significantly elevated creatine kinase levels ( P < 0.05), but only LBE increased ( P < 0.05) interleukin-6 levels. In experiment 1, core temperatures before and during exercise-heat stress were similar for control and after UBE, but some evidence for higher core temperatures was found after LBE. In experiment 2, core temperatures during exercise-heat stress were 0.2–0.3°C ( P < 0.05) above control values at 2 and 7 h after LBE. The added thermal strain after LBE ( P < 0.05) was associated with higher metabolic rate ( r = 0.70 and 0.68 at 2 and 6–7 h, respectively) but was not related ( P > 0.05) to muscle soreness ( r = 0.47 at 6–7 h), plasma interleukin-6 ( r = 0.35 at 6–7 h), or peak creatine kinase levels ( r = 0.22). Local sweating responses (threshold core temperature and slope) were not altered by UBE or LBE. The results suggest that profuse muscle injury can increase body core temperature during exercise-heat stress and that the added heat storage cannot be attributed solely to increased heat production.
Collagen gene expression in rat left ventricle: interactive effect of age and exercise training
Authors: Thomas D. Paul , Zimmerman Scott D. , Hansen Thomas R. , Martin David T. , McCormick Richard J.
Published: December 2017

Whether or not exercise training of sufficient intensity and duration to produce left ventricle (LV) hypertrophy also regulates deposition of interstitial collagen and cross-linking at the pretranslational level is unknown. Therefore, the effects of exercise training on gene expression for the two principal fibrillar collagens in LV, types I and III, were assessed in young adult (5 mo), middle-aged (15 mo), and old (26 mo) rats. We also evaluated the potential interaction of changes in mRNA for these procollagens with alterations in LV extracellular matrix characteristics by simultaneously measuring collagen concentration (hydroxyproline) and extent of mature collagen cross-linking (hydroxylysylpyridinoline, HP). Ten weeks of treadmill running resulted in LV hypertrophy and an increased maximal oxygen uptake in all three age groups of trained rats compared with sedentary controls. Percent collagen in rat LV almost doubled ( P < 0.0001) from 5 to 26 mo of age, an increase unaffected by exercise training. With aging, a significant decline in expression of mRNAs for both collagen type I ( P < 0.005) and type III ( P < 0.001) was observed in LV free wall (LVF) but not septum (LVS). Training prevented this decline in LVF mRNAs for the two principal fibrillar collagens in middle-aged rats whereas it attenuated the decline in senescent animals. HP concentration increased significantly with aging in both LVF ( P < 0.005) and LVS ( P < 0.01). Training modulated this effect, but again only in LVF, so that HP was significantly lower ( P < 0.05) in this region of the LV in old trained rats compared with sedentary counterparts. We conclude that exercise training modulates the effects of aging on collagen gene mRNAs and HP cross-linking regionally within the LV.
Submandibular secretory and vascular responses to stimulation of the parasympathetic innervation in anesthetized cats
Authors: Rourke K. , Edwards A. V.
Published: December 2017

Submandibular secretory responses to stimulation of the parasympathetic chorda-lingual nerve in anaesthetized cats have been investigated before, during, and after intracarotid infusion of endothelin-1 (ET-1), which reduced blood flow through the gland by 64 ± 7%. Stimulation at different frequencies (2, 4, 8, and 16 Hz) evoked a frequency-dependent increase in the flow of submandibular saliva, sodium concentration and output, and output of both potassium and protein. The reduction in submandibular blood flow, which occurred in response to the infusion of ET-1, was associated with a decreased flow of saliva and a diminished output of both sodium and protein. The flow of saliva was linearly related to submandibular blood flow both in the presence and absence of ET-1. It is concluded that submandibular secretory responses to electrical stimulation of the parasympathetic innervation can be significantly attenuated by reducing the blood flow through the gland by ET-1 infusion, just as it is when the blood flow is reduced by hypotension.
Effect of expiratory resistive loading on the noninvasive tension-time index in COPD
Authors: Thompson William H. , Carvalho Paula , Souza James P. , Charan Nirmal B.
Published: December 2017

Expiratory resistive loading (ERL) is used by chronic obstructive pulmonary disease (COPD) patients to improve respiratory function. We, therefore, used a noninvasive tension-time index of the inspiratory muscles (TTmus =P̄i/Pi max × Ti/Tt, where P̄i is mean inspiratory pressure estimated from the mouth occlusion pressure, Pi max is maximal inspiratory pressure, Ti is inspiratory time, and Tt is total respiratory cycle time) to better define the effect of ERL on COPD patients. To accomplish this, we measured airway pressures, mouth occlusion pressure, respiratory cycle flow rates, and functional residual capacity (FRC) in 14 COPD patients and 10 normal subjects with and without the application of ERL. TTmus was then calculated and found to drop in both COPD and normal subjects ( P < 0.05). The decline in TTmus in both groups resulted solely from a prolongation of expiratory time with ERL ( P < 0.001 for COPD, P < 0.05 for normal subjects). In contrast to the COPD patients, normal subjects had an elevation in P̄i and FRC, thus minimizing the decline in TTmus. In conclusion, ERL reduces the potential for inspiratory muscle fatigue in COPD by reducing Ti/Tt without affecting FRC andP̄i.
Ventilation-perfusion matching in long-term microgravity
Authors: Verbandt Y. , Wantier M. , Prisk G. K. , Paiva M.
Published: December 2017

We studied the ventilation-perfusion matching pattern in normal gravity (1 G) and short- and long-duration microgravity (μG) using the cardiogenic oscillations in the sulfur hexaflouride (SF6) and CO2 concentration signals during the phase III portion of vital capacity single-breath washout experiments. The signal power of the cardiogenic concentration variations was assessed by spectral analysis, and the phase angle between the oscillations of the two simultaneously expired gases was obtained through cross-correlation. For CO2, a significant reduction of cardiogenic power was observed in μG, with respect to 1 G, but the reduction was smaller and more variable in the case of SF6. A shift from an in-phase condition in 1 G to an out-of-phase condition was found for both short- and long-duration μG. We conclude that, although the distribution of ventilation and perfusion becomes more homogeneous in μG, significant inhomogeneities persist and that areas of high perfusion become associated with areas of relatively lower ventilation. In addition, these modifications seem to remain constant during long-term exposure to μG.
Effects of 2 G on adiposity, leptin, lipoprotein lipase, and uncoupling protein-1 in lean and obese Zucker rats
Authors: Warren L. Elisabeth , Horwitz Barbara A. , Hamilton Jock S. , Fuller Charles A.
Published: December 2017

Male Zucker rats were exposed to 2 G for 8 wk to test the hypothesis that the leptin regulatory pathway contributes to recovery from effects of 2 G on feeding, growth, and nutrient partitioning. After initial hypophagia, body mass-independent food intake of the lean rats exposed to 2 G surpassed that of the lean rats maintained at 1 G, but food intake of the obese rats exposed to 2 G remained low. After 8 wk at 2 G, body mass and carcass fat were less in both genotypes. Leptin and percent fat were lower in lean rats exposed to 2 G vs. 1 G but did not differ in obese rats exposed to 2 G vs. 1 G. Although exposure to 2 G did not alter uncoupling protein-1 levels, it did elicit white fat pad-specific changes in lipoprotein lipase activity in obese but not lean rats. We conclude that 2 G affects both genotypes but that the lean Zucker rats recover their food intake and growth rate and retain “normal” lipoprotein lipase activity to a greater degree than do the obese rats, emphasizing the importance of a functional leptin regulatory pathway in this acclimation.
Depression of ventilatory responses after daily, cyclic hypercapnic hypoxia in piglets
Authors: Waters Karen A. , Tinworth Kellie D.
Published: December 2017

Ventilatory responses (VRs) were measured via a sealed face mask and pneumotachograph in 30 unsedated, mixed-breed miniature piglets at 12.6 ± 2.3 days of age ( day 1) and then repeated after seven daily 24-min exposures to 10% O2-6% CO2 [hypercapnic hypoxia (HH)]. Arterial blood was sampled at baseline, after 10 min of exposure, and after 10 min of recovery. VRs included hypoxia (10% O2 in N2), hypercapnia (6% CO2 in air), and HH (10% O2-6% CO2-balance N2). Treatment groups ( n = 10 each) were exposed to 24 min of HH from day 2 to 8 as sustained HH (24 min of HH and then 24 min of air) or cyclic HH (4 min of HH alternating with 4 min of air). Day 1 and 9data were compared in treatment and control groups. After cyclic HH, respiratory responses to CO2 were reduced during hypercapnia and during HH ( P < 0.001 vs. control for minute ventilation in both). In both treatment groups, time to peak minute ventilation was delayed in hypoxia ( P = 0.02, ANOVA), and response amplitude was increased ( P < 0.001 and P = 0.003, sustained and cyclic HH, respectively, vs. control). Respiratory pattern was also altered during the VRs and among treatment groups. Stimulus presentation characteristics exert effects on VRs that are independent of those elicited by daily HH.
Respiratory control in humans after 8 h of lowered arterial Po 2, hemodilution, or carboxyhemoglobinemia
Authors: Ren Xiaohui , Dorrington Keith L. , Robbins Peter A.
Published: December 2017

In humans exposed to 8 h of isocapnic hypoxia, there is a progressive increase in ventilation that is associated with an increase in the ventilatory sensitivity to acute hypoxia. To determine the relative roles of lowered arterial Po 2 and oxygen content in generating these changes, the acute hypoxic ventilatory response was determined in 11 subjects after four 8-h exposures: 1) protocol IH (isocapnic hypoxia), in which end-tidal Po 2 was held at 55 Torr and end-tidal Pco 2 was maintained at the preexposure value; 2) protocol PB (phlebotomy), in which 500 ml of venous blood were withdrawn; 3) protocol CO, in which carboxyhemoglobin was maintained at 10% by controlled carbon monoxide inhalation; and 4) protocol C as a control. Both hypoxic sensitivity and ventilation in the absence of hypoxia increased significantly after protocol IH ( P < 0.001 and P < 0.005, respectively, ANOVA) but not after the other three protocols. This indicates that it is the reduction in arterial Po 2 that is primarily important in generating the increase in the acute hypoxic ventilatory response in prolonged hypoxia. The associated reduction in arterial oxygen content is unlikely to play an important role.
c-Fos expression in the central nervous system elicited by phrenic nerve stimulation
Authors: Malakhova O. E. , Davenport P. W.
Published: December 2017

Phrenic nerve afferents (PNa) have been shown to activate neurons in the spinal cord, brain stem, and forebrain regions. The c-Fos technique has been widely used as a method to identify neuronal regions activated by afferent stimulation. This technique was used to identify central neural areas activated by PNa. The right phrenic nerve of urethane-anesthetized rats was stimulated in the thorax. The spinal cord and brain were sectioned and stained for c-Fos expression. Labeled neurons were found in the dorsal horn laminae I and II of the C3–C5 spinal cord ipsilateral to the site of PNa stimulation. c-Fos-labeled neurons were found bilaterally in the medial subnuclei of the nucleus of the solitary tract, rostral ventral respiratory group, and ventrolateral medullary reticular formation. c-Fos-labeled neurons were found bilaterally in the paraventricular and supraoptic hypothalamic nuclei, in the paraventricular thalamic nucleus, and in the central nucleus of the amygdala. The presence of c-Fos suggests that these neurons are involved in PNa information processing and a component of the central mechanisms regulating respiratory function.
Invited Review: Physiological consequences of intermittent hypoxia: systemic blood pressure
Authors: Fletcher Eugene C.
Published: December 2017

One of the major manifestations of obstructive sleep apnea is profound and repeated hypoxia during sleep. Acute hypoxia leads to stimulation of the peripheral chemoreceptors, which in turn increases sympathetic outflow, acutely increasing blood pressure. The chronic effect of these repeated episodic or intermittent periods of hypoxia in humans is difficult to study because chronic cardiovascular changes may take many years to manifest. Rodents have been a tremendous source of information in short- and long-term studies of hypertension and other cardiovascular diseases. Recurrent short cycles of normoxia-hypoxia, when administered to rats for 35 days, allows examination of the chronic cardiovascular response to intermittent hypoxia patterned after the episodic desaturation seen in humans with sleep apnea. The result of this type of intermittent hypoxia in rats is a 10- to 14-mmHg increase in resting (unstimulated) mean blood pressure that lasts for several weeks after cessation of the daily cyclic hypoxia. Carotid body denervation, sympathetic nerve ablation, renal sympathectomy, adrenal medullectomy, and angiotensin II receptor blockade block the blood pressure increase. It appears that adrenergic and renin-angiotensin system overactivity contributes to the early chronic elevated blood pressure in rat intermittent hypoxia and perhaps to human hypertension associated with obstructive sleep apnea.
Living and training in moderate hypoxia does not improveV˙o 2 max more than living and training in normoxia
Authors: Henderson Kyle K. , Clancy Richard L. , Gonzalez Norberto C.
Published: December 2017

The objective of these experiments was to determine whether living and training in moderate hypoxia (MHx) confers an advantage on maximal normoxic exercise capacity compared with living and training in normoxia. Rats were acclimatized to and trained in MHx [inspired Po 2(Pi O2 ) = 110 Torr] for 10 wk (HTH). Rats living in normoxia trained under normoxic conditions (NTN) at the same absolute work rate: 30 m/min on a 10° incline, 1 h/day, 5 days/wk. At the end of training, rats exercised maximally in normoxia. Training increased maximal O2 consumption (V˙o 2 max) in NTN and HTH above normoxic (NS) and hypoxic (HS) sedentary controls. However,V˙o 2 max and O2 transport variables were not significantly different between NTN and HTH:V˙o 2 max 86.6 ± 1.5 vs. 86.8 ± 1.1 ml · min−1 · kg−1; maximal cardiac output 456 ± 7 vs. 443 ± 12 ml · min−1 · kg−1; tissue blood O2 delivery (cardiac output × arterial O2 content) 95 ± 2 vs. 96 ± 2 ml · min−1 · kg−1; and O2 extraction ratio (arteriovenous O2 content difference/arterial O2 content) 0.91 ± 0.01 vs. 0.90 ± 0.01. Mean pulmonary arterial pressure (Ppa, mmHg) was significantly higher in HS vs. NS ( P < 0.05) at rest (24.5 ± 0.8 vs. 18.1 ± 0.8) and during maximal exercise (32.0 ± 0.9 vs. 23.8 ± 0.6). Training in MHx significantly attenuated the degree of pulmonary hypertension, with Ppa being significantly lower at rest (19.3 ± 0.8) and during maximal exercise (29.2 ± 0.5) in HTH vs. HS. These data indicate that, despite maintaining equal absolute training intensity levels, acclimatization to and training in MHx does not confer significant advantages over normoxic training. On the other hand, the pulmonary hypertension associated with acclimatization to hypoxia is reduced with hypoxic exercise training.
Respiratory effects of transient axial acceleration
Authors: Loring Stephen H. , Lee Hsueh-Tze , Butler James P.
Published: December 2017

Whereas gravity has an inspiratory effect in upright subjects, transient upward acceleration is reported to have an expiratory effect. To explore the respiratory effects of transient axial accelerations, we measured axial acceleration at the head and transrespiratory pressure or airflow in five subjects as they were dropped or lifted on a platform. For the first 100 ms, upward acceleration caused a decrease in mouth pressure and inspiratory flow, and downward acceleration caused the opposite. We also simulated these experimental observations by using a computational model of a passive respiratory system based on anatomical data and normal respiratory characteristics. After 100 ms, respiratory airflow in our subjects became highly variable, no longer varying with acceleration. Electromyograms of thoracic and abdominal respiratory muscles showed bursts of activity beginning 40–125 ms after acceleration, suggesting reflex responses responsible for subsequent flow variability. We conclude that, in relaxed subjects, transient upward axial acceleration causes inspiratory airflow and downward acceleration causes expiratory airflow, but that after ∼100 ms, reflex activation of respiratory musculature largely determines airflow.
Effects of testosterone and exercise on muscle leanness in eugonadal men with AIDS wasting
Authors: Fairfield Wesley P. , Treat Michael , Rosenthal Daniel I. , Frontera Walter , Stanley Takara , Corcoran Colleen , Costello Madeline , Parlman Kristin , Schoenfeld David , Klibanski Anne , Grinspoon Steven
Published: December 2017

Loss of lean body and muscle mass characterizes the acquired immunodeficiency syndrome (AIDS) wasting syndrome (AWS). Testosterone and exercise increase muscle mass in men with AWS, with unclear effects on muscle composition. We examined muscle composition in 54 eugonadal men with AWS who were randomized to 1) testosterone (200 mg im weekly) or placebo and simultaneously to 2) resistance training or no training in a 2 × 2 factorial design. At baseline and after 12 wk, we performed assessments of whole body composition by dual-energy X-ray absorptiometry and single-slice computed tomography for midthigh cross-sectional area and muscle composition. Leaner muscle has greater attenuation. Baseline muscle attenuation correlated inversely with whole body fat mass ( r = −0.52, P = 0.0001). This relationship persisted in a model including age, body mass index, testosterone level, viral load, lean body mass, and thigh muscle cross-sectional area ( P = 0.02). Testosterone ( P = 0.03) and training ( P = 0.03) increased muscle attenuation. These data demonstrate that thigh muscle attenuation by computed tomography varies inversely with whole body fat and increases with testosterone and training. Anabolic therapy in these patients increases muscle leanness.
Delayed partial liquid ventilation shows no efficacy in the treatment of smoke inhalation injury in swine
Authors: Harrington D. T. , Jordan B. S. , Dubick M. A. , Cancio L. C. , Brinkley W. , Kim S. , Burleson D. G. , Delgado A. , Goodwin C. W.
Published: December 2017

In an earlier neonatal porcine model of smoke inhalation injury (SII), immediate postinjury application of partial liquid ventilation (PLV) had dramatic beneficial effects on lung compliance, oxygenation, and survival over a 24-h period. To explore the efficacy of PLV following SII, we treated animals at 2 and 6 h after SII and followed them for 72 h. Pigs weighing 8–12 kg were sedated and pharmacologically paralyzed, given a SII, and placed on volume-cycled, pressure-limited ventilation. Animals were randomized to three groups: group I (+SII, no PLV, n = 8), group II(+SII, PLV at 2 h, n = 6), and group III (+SII, PLV at 6 h, n = 7). Ventilatory parameters and arterial blood gasses were obtained at scheduled intervals. The PLV animals ( groups II and III) followed a worse course than group I (no PLV); PLV groups had higher peak and mean airway pressures, oxygenation index, and rate-pressure product (a barotrauma index) and lower lung compliance and arterial partial pressure of oxygen-to-inspired oxygen fraction ratio (all P < 0.05). PLV conferred no survival advantage. The reported beneficial effects of PLV with other models of acute lung injury do not appear to extend to the treatment of SII when PLV is instituted in a delayed manner. This study was not able to validate the previously reported beneficial effects of PLV in SII and actually found deleterious effects, perhaps reflecting the predominance of airway over alveolar disease in SII.
Selected Contribution: Regulation of sleep-wake states in response to intermittent hypoxic stimuli applied only in sleep
Authors: Hamrahi Hedieh , Stephenson Richard , Mahamed Safraaz , Liao Kiong Sen , Horner Richard L.
Published: December 2017

Recurrent sleep-related hypoxia occurs in common disorders such as obstructive sleep apnea (OSA). The marked changes in sleep after treatment suggest that stimuli associated with OSA (e.g., intermittent hypoxia) may significantly modulate sleep regulation. However, no studies have investigated the independent effects of intermittent sleep-related hypoxia on sleep regulation and recovery sleep after removal of intermittent hypoxia. Ten rats were implanted with telemetry units to record the electroencephalogram (EEG), neck electromyogram, and body temperature. After >7 days recovery, a computer algorithm detected sleep-wake states and triggered hypoxic stimuli (10% O2) or room air stimuli only during sleep for a 3-h period. Sleep-wake states were also recorded for a 3-h recovery period after the stimuli. Each rat received an average of 69.0 ± 6.9 hypoxic stimuli during sleep. The non-rapid eye movement (non-REM) and rapid-eye-movement (REM) sleep episodes averaged 50.1 ± 3.2 and 58.9 ± 6.6 s, respectively, with the hypoxic stimuli, with 32.3 ± 3.2 and 58.6 ± 4.8 s of these periods being spent in hypoxia. Compared with results for room air controls, hypoxic stimuli led to increased wakefulness ( P < 0.005), nonsignificant changes in non-REM sleep, and reduced REM sleep ( P < 0.001). With hypoxic stimuli, wakefulness episodes were longer and more frequent, non-REM periods were shorter and more frequent, and REM episodes were shorter and less frequent ( P < 0.015). Hypoxic stimuli also increased faster frequencies in the EEG ( P < 0.005). These effects of hypoxic stimuli were reversed on return to room air. There was a rebound increase in REM sleep, increased slower non-REM EEG frequencies, and decreased wakefulness ( P < 0.001). The results show that sleep-specific hypoxia leads to significant modulation of sleep-wake regulation both during and after application of the intermittent hypoxic stimuli. This study is the first to determine the independent effects of sleep-related hypoxia on sleep regulation that approximates OSA before and after treatment.
Selected Contribution: Pulmonary hypertension in mice following intermittent hypoxia
Authors: Fagan Karen A.
Published: December 2017

Sleep apnea (intermittent periods of hypoxia with or without hypercapnia) is associated with systemic hypertension and increased mortality from cardiovascular disease, but the relationship to pulmonary hypertension is uncertain. Previous studies on intermittent hypoxia (IH) in rats that demonstrated pulmonary hypertension utilized relatively long periods of hypoxia. Recent studies that utilized brief periods of hypoxia have conflicting reports of right ventricular (RV) hypertrophy. In addition, many studies have not measured pulmonary hemodynamics to asses the severity of pulmonary hypertension in vivo. Given the increasing availability of genetically engineered mice and the need to establish a rodent model of IH-induced pulmonary hypertension, we studied the effect of IH (2-min cycles of 10% and 21% O2, 8 h/day, 4 wk) on wild-type mice, correlating in vivo measurements of pulmonary hypertension with RV mass and pulmonary vascular remodeling. RV systolic pressure was increased after IH (36 ± 0.9 mmHg) compared with normoxia (29.5 ± 0.6) but was lower than continuous hypoxia (44.2 ± 3.4). RV mass [RV-to-(left ventricle plus septum) ratio] correlated with pressure measurements (IH = 0.27 ± 0.02, normoxia = 0.22 ± 0.01, and continuous hypoxia = 0.34 ± 0.01). Hematocrits were also elevated after IH and continuous hypoxia (56 ± 1.6 and 54 ± 1.1 vs. 44.3 ± 0.5%). Evidence of neomuscularization of the distal pulmonary circulation was found after IH and continuous hypoxia. We conclude that mice develop pulmonary hypertension following IH, representing a possible animal model of pulmonary hypertension in response to the repetitive hypoxia-reoxygenation of sleep apnea.
Growth hormone pulsatility profile characteristics following acute heavy resistance exercise
Authors: Nindl Bradley C. , Hymer Wesley C. , Deaver Daniel R. , Kraemer William J.
Published: December 2017

This investigation examined the hypothesis that acute heavy resistance exercise (AHRE) would increase overnight concentrations of circulating human growth hormone (hGH). Ten men (22 ± 1 yr, 177 ± 2 cm, 79 ± 3 kg, 11 ± 1% body fat) underwent two overnight blood draws sampled every 10 min from 1700 to 0600: a control and an AHRE condition. The AHRE was conducted from 1500 to 1700 and was a high-volume, multiset exercise bout. Three different immunoassays measured hGH concentrations: the Nichols immunoradiometric assay (Nichols IRMA), National Institute of Diabetes and Digestive and Kidney Diseases radioimmunoassay (NIDDK RIA), and the Diagnostic Systems Laboratory immunofunctional assay (DSL IFA). The Pulsar peak detection system was used to evaluate the pulsatility profile characteristics of hGH. Maximum hGH was lower in the exercise (10.7 μg/l) vs. the control (15.4 μg/l) condition. Mean pulse amplitude was lower in the exercise vs. control condition when measured by the Nichols IRMA and the DSL IFA. A differential pattern of release was also observed after exercise in which hGH was lower in the first half of sleep but higher in the second half. We conclude that AHRE does influence the temporal pattern of overnight hGH pulsatility. Additionally, because of the unique molecular basis of the DSL IFA, this influence does have biological relevance because functionally intact molecules are affected.
Regulation of skeletal muscle ATP catabolism by AMPD1 genotype during sprint exercise in asymptomatic subjects
Authors: Norman Barbara , Sabina Richard L. , Jansson Eva
Published: December 2017

Deficiency of myoadenylate deaminase, the muscle isoform of AMP deaminase encoded by the AMPD1 gene, is a common myopathic condition associated with alterations in skeletal muscle energy metabolism. However, recent studies have demonstrated that most individuals harboring this genetic abnormality are asymptomatic. Therefore, 18 healthy subjects with different AMPD1 genotypes were studied during a 30-s Wingate test in order to evaluate the influence of this inherited defect in AMPD1 expression on skeletal muscle energy metabolism and exercise performance in the asymptomatic population. Exercise performances were similar across the AMPD1 genotypes, whereas significant differences in several descriptors of energy metabolism were observed. Normal homozygotes (NN) exhibited the highest levels of AMP deaminase activities, net ATP catabolism, and IMP accumulation, whereas intermediate values were observed in heterozygotes (MN). Conversely, mutant homozygotes (MM) had very low AMP deaminase activities and showed no significant net catabolism of ATP or IMP accumulation. Accordingly, MM also did not show any postexercise increase in plasma ammonia. Unexpectedly, MN consistently exhibited greater increases in plasma ammonia compared with NN despite the relatively lower accumulation of IMP in skeletal muscle. Moreover, time course profiles of postexercise plasma ammonia and blood lactate accumulation also differed across AMPD1 genotypes. Finally, analysis of adenosine in leftover biopsy material revealed a modest twofold increase in MN and a dramatic 25-fold increase in MM.
Role of speed vs. grade in relation to muscle pump function at locomotion onset
Authors: Sheriff Don D. , Hakeman Amy L.
Published: December 2017

We sought to clarify the roles of contraction frequency (speed) and contraction force (grade) in the rise in muscle blood flow at the onset of locomotion. Shoemaker et al. ( Can J Physiol Pharmacol 76: 418–427, 1998) explored this relationship in human handgrip exercise and found that the time course of the rise in muscle vascular conductance was similar when a light weight was lifted in a fast cadence and a heavy weight was lifted in a slow cadence (total work constant). This indicates that muscle pumping (contraction frequency) was of limited importance in governing the time course. Rather, vasodilator substances released in proportion to the total work performed appeared to determine the pattern and extent of the rise in conductance. We hypothesized that conductance would rise faster during locomotion at a high speed (frequency) and low grade (force) than at a low speed and high grade, despite similar total increases in conductance, owing to more effective muscle pumping at faster contraction rates. Seven male rats performed nine 1-min bouts of treadmill locomotion across a combination of three speeds (5, 10, and 20 m/min) and three grades (−10, 0, and +15°) in random order. Locomotion at 10 m/min and 0° grade and 20 m/min and −10° grade led to an equal rise in terminal aortic vascular conductance. However, the equal rise was achieved more quickly at the higher running speed, suggestive of more effective muscle pumping. Across the nine combinations of exercise, speed began to exert a statistically significant influence on conductance by the 3rd s of locomotion. Grade did not begin to exert an influence until the 12th s of locomotion (similar to the delays reported for arteriolar dilation to muscle contraction). Additional experiments in dogs provided similar results. Thus the muscle pump appears to initiate the increase in blood flow in proportion to contraction frequency at locomotion onset.
Ventilation-perfusion inhomogeneity increases gas uptake: theoretical modeling of gas exchange
Authors: Peyton Philip J. , Robinson Gavin J. B. , Thompson Bruce
Published: December 2017

Ventilation-perfusion (V˙a/Q˙) inhomogeneity was modeled to measure its effect on gas exchange in the presence of inspired mixtures of two soluble gases using a two-compartment computer model. Theoretical studies involving a mixture of hypothetical gases with equal solubility in blood showed that the effect of increasing inhomogeneity of distributions of either ventilation or blood flow is to paradoxically increase uptake of the gas with the lowest overall uptake in relation to its inspired concentration. This phenomenon is explained by the concentrating effects that uptake of soluble gases exert on each other in low V˙a/Q˙ compartments. Repeating this analysis for inspired mixtures of 30% O2and 70% nitrous oxide (N2O) confirmed that, during “steady-state” N2O anesthesia, uptake of N2O is predicted to paradoxically increase in the presence of worsening V˙a/Q˙ inhomogeneity.
Microvascular and interstitial Po2measurements in rat skeletal muscle by phosphorescence quenching
Authors: Shibata Masahiro , Ichioka Shigeru , Ando Joji , Kamiya Akira
Published: December 2017

To clarify the transport of O2across the microvessels in skeletal muscle, we designed an intravital laser microscope that utilizes a phosphorescence quenching technique to determine both the microvascular and tissue Po2. After we injected the phosphorescent probe into systemic blood, phosphorescence excited by a N2-dye pulse laser was detected with a photomultiplier over a 10 μm in diameter area. In vitro and in vivo calibrations confirmed that the present method is accurate for Po2measurements in the range of 7–90 Torr ( r= 0.958) and has a rapid response time. This method was then used to measure the Po2of microvessels with different diameters (40–130 μm) and of interstitial spaces in rat cremaster muscle. These measurements showed a significant drop in Po2in the arterioles after branching (from 74.6 to 46.6 Torr) and the presence of a large Po2gradient at the blood-tissue interface of arterioles (15–20 Torr). These findings suggest that capillaries are not the sole source of oxygen supply to surrounding tissue.
Periarticular cancellous bone changes following anterior cruciate ligament injury
Authors: Wohl Gregory R. , Shymkiw Roxane C. , Matyas John R. , Kloiber Reinhard , Zernicke Ronald F.
Published: December 2017

To understand more fully the early bone changes in an experimental model of osteoarthrosis, we quantified periarticular bone mineral density and bone mechanical properties in anterior cruciate ligament transected (ACLX) knee joints (4, 10, 32, and 39 wk post-ACLX) compared with contralateral joints and unoperated normal joints of skeletally mature animals. Maximal stress and energy were significantly reduced in ACLX cancellous bone from the medial femoral condyles at 4 wk postinjury. All mechanical properties (e.g., yield stress and elastic modulus) declined after 4 wk and were significantly reduced at 10 wk. ACLX bone mineral density was significantly reduced at all measured time points. Ash content was significantly reduced at 10 and 32 wk. Changes in the lateral condyles were similar but less pronounced than in the medial condyles. These bony changes accompanied the earliest articular cartilage molecular changes and preceded changes in the articular cartilage gross morphology. We suggest that these early changes in bone mechanical behavior contribute to the progression of osteoarthrosis and pathogenic changes in the joint.