bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuropeptide Y release from human heart is enhanced during prolonged exercise in hypoxia
Authors: Kaijser L. , Pernow J. , Berglund B. , Grubbstrom J. , Lundberg J. M.
Published: December 2017

To evaluate the effect of hypoxemia on cardiac release of neuropeptide Y-like immunoreactivity (NPY-LI) and norepinephrine (NE), arterial and coronary sinus blood was sampled and coronary sinus blood flow was measured by thermodilution in nine healthy volunteers at rest and during supine cycle ergometer exercise while they breathed air and 12% O2, which reduced arterial O2 saturation to approximately 68%. Five subjects started to exercise for 30 min breathing air and continued for 30 min breathing 12% O2; four subjects breathed 12% O2 and air in the reverse order. The load was adjusted to give the same heart rate during O2 and air breathing. No significant cardiac net release of NPY-LI or NE was seen at rest. Exercise induced release of NPY-LI and NE. The net release of NPY-LI was 0.7 +/- 0.4 pmol/min during air breathing (average 12 and 30 min) and 2.8 +/- 0.6 pmol/min during 12% O2 breathing. The difference was not influenced by the order of the breathing periods. The NE coronary sinus-arterial difference was not significantly different between 12% O2 and air breathing, whereas the net release was significantly larger during 12% O2 breathing (0.6 +/- 0.1 vs. 0.4 +/- 0.1 nmol/min). Thus, NPY is released with NE from the heart during exercise. Arterial hypoxemia seems to be an additional stimulus of preferential NPY release.
Circumsinus branch: a convenient source of baro- and chemoreceptor activity in dogs
Authors: Vidruk E. H. , Sorkness R.
Published: December 2017

We found a branch of the carotid sinus nerve in 44 of 48 dogs. We propose that this branch be referred to as the “circumsinus” branch of the carotid sinus nerve. Both chemoreceptor and baroreceptor activity were detected in this branch during electrophysiological recording efforts utilizing classic nerve recording techniques. Its convenient location permits whole nerve or single unit recording without having to transect, dissect, or even expose the carotid sinus nerve. Carotid baroreceptor and chemoreceptor activity can be monitored with most of the carotid bifurcation's neural pathways intact.
Noninvasive measurement of forearm blood flow and oxygen consumption by near-infrared spectroscopy
Authors: De Blasi R. A. , Ferrari M. , Natali A. , Conti G. , Mega A. , Gasparetto A.
Published: December 2017

We applied near-infrared spectroscopy (NIRS) for the simultaneous measurement of forearm blood flow (FBF) and oxygen consumption (VO2) in the human by inducing a 50-mmHg venous occlusion. Eleven healthy subjects were studied both at rest and after hand exercise during vascular occlusion. FBF was also measured by strain-gauge plethysmography. FBF measured by NIRS was 1.9 +/- 0.8 ml.100 ml-1.min-1 at rest and 8.2 +/- 2.9 ml.100 ml-1.min-1 after hand exercise. These values showed a correlation (r = 0.94) with those obtained by the plethysmography. VO2 values were 4.6 +/- 1.3 microM O2 x 100 ml-1.min-1 at rest and 24.9 +/- 11.2 microM O2 x 100 ml-1.min-1 after hand exercise. The scatter of the FBF and VO2 values showed a good correlation between the two variables (r = 0.93). The results demonstrate that NIRS provides the particular advantage of obtaining the contemporary evaluation of blood flow and VO2, allowing correlation of these two variables by a single maneuver without discomfort for the subject.
Fura 2 determination of [Ca2+]i in isolated perfused heart using R wave-gated electromechanical shutters
Authors: Chen D. P. , Jimenez E. , Ataka K. , Levitsky S. , Feinberg H.
Published: December 2017

We describe a novel and relatively inexpensive spectrofluorescence system that supplies rapidly alternating wavelengths to either a standard cuvette or an isolated perfused heart. Its use is illustrated by determining changes in cytosolic intracellular Ca2+ concentration ([Ca2+]i) by using the Ca(2+)-sensitive fluorescent dye fura 2 in a rabbit heart preparation. The system uses two precision electromechanical shutters (capable of gating with respect to the electrocardiographic R wave for signal averaging) allowing alternate fura 2 excitation wavelengths (340 and 380 nm) without moving optical components and uses a fiber optic for conducting excitation and collecting epifluorescence. Sample recordings tracing the [Ca2+]i transient in an entire cardiac cycle and in capturing specific isolated regions (diastole and systole) of the cycle are presented. Limitations of this low-cost but easily implemented system are discussed.
Adrenergic vasoconstriction augments tissue O2 extraction during reductions in O2 delivery
Authors: Maginniss L. A. , Connolly H. , Samsel R. W. , Schumacker P. T.
Published: December 2017

When systemic O2 delivery is reduced, increases in systemic O2 extraction are facilitated by sympathetically mediated increases in vascular resistance that limit blood flow to regions with low metabolic demand. Local metabolic vasodilation competes with this vasoconstriction, thereby effecting a balance between tissue O2 supply and demand. This study examined the role of sympathetically mediated vasoconstriction on the critical level of O2 extraction in hindlimb and whole body during progressive reductions in O2 delivery. In anesthetized dogs, the left hindlimb was vascularly isolated and its O2 delivery was decreased in stages by reducing the speed of an occlusive pump. In a normovolemic group (n = 6), blood volume was maintained to minimize sympathetic tone while flow to the hindlimb was reduced. In a hypovolemic group (n = 6), blood volume was removed in stages to augment sympathetic tone progressively while flow to the limb was reduced simultaneously. A phenoxybenzamine group (n = 6) was identical to the hypovolemic group, except that alpha-adrenergic effects were inhibited with phenoxybenzamine (3 mg/kg). The systemic critical O2 extraction ratio in the phenoxybenzamine group (0.60 +/- 0.06) was less than for the hypovolemic group (0.71 +/- 0.04; P = 0.004). In the hindlimb, critical O2 extractions were significantly less in the normovolemic (0.46 +/- 0.17) and phenoxybenzamine (0.49 +/- 0.10) groups compared with the hypovolemic group (0.72 +/- 0.10; P < or = 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of mild hypocapnia on fetal breathing and behavior in unanesthetized normoxic fetal lambs
Authors: Kuipers I. M. , Maertzdorf W. J. , De Jong D. S. , Hanson M. A. , Blanco C. E.
Published: December 2017

We hypothesized that the level of arterial PCO2 (PaCO2) affects the incidence of fetal breathing movements and electrocorticographic (ECoG) states in chronically instrumented fetal sheep. Six fetuses of 128–132 days gestational age were instrumented for recording fetal behavior and for later connection to an extracorporeal membrane oxygenation (ECMO) system to change fetal blood gases. Before ECMO fetal arterial pH and blood gases were pH 7.40 +/- 0.01, PaCO2 42.9 +/- 1.5 Torr, and arterial PO2 (PaCO2) 19.2 +/- 1.7 Torr; during ECMO in normocapnia they were pH 7.37 +/- 0.01, PaCO2 46.1 +/- 0.7 Torr, and PaCO2 27.6 +/- 3.0 Torr; and during ECMO in mild hypocapnia they were pH 7.47 +/- 0.01, PaCO2 35.3 +/- 1.7 Torr, and PaCO2 26.6 +/- 1.7 Torr. The overall incidence of breathing movements, the incidence of breathing movements during low-voltage (LV) ECoG activity, and the mean duration of periods of breathing decreased significantly during hypocapnia. Fetal ECoG activity showed normal cycling during the periods of mild hypocapnia, and the mean duration of LV ECoG periods did not change. During mild hypocapnia, eye movements remained associated with LV ECoG activity and nuchal electromyographic activity remained associated with high-voltage ECoG activity. These results suggest that the presence of breathing movements in fetal life is not only dependent on the behavioral state but also on the level of fetal PaCO2.
Measurement of temporal changes in DLSBCO-3EQ from small alveolar samples in normal subjects
Authors: Soparkar G. R. , Mink J. T. , Graham B. L. , Cotton D. J.
Published: December 2017

The dynamic changes in CO concentration [CO] during a single breath could be influenced by topographic inhomogeneity in the lung or by peripheral inhomogeneity due to a gas mixing resistance in the gas phase of the lung or to serial gradients in gas diffusion. Ten healthy subjects performed single-breath maneuvers by slowly inhaling test gas from functional residual capacity to one-half inspiratory capacity and slowly exhaling to residual volume with target breath-hold times of 0, 1.5, 3, 6, and 9 s. We calculated the three-equation single-breath diffusing capacity of the lung for CO (DLSBCO-3EQ) from the mean [CO] in both the entire alveolar gas sample and in four successive equal alveolar gas samples. DLSBCO-3EQ from the entire alveolar gas sample was independent of breath-hold time. However, with 0 s of breath holding, from early alveolar gas samples DLSBCO-3EQ was reduced and from late alveolar gas samples it was increased. With increasing breath-hold time, DLSBCO-3EQ from the earliest alveolar gas sample rapidly increased, whereas from the last alveolar gas sample it rapidly decreased such that all values from the small alveolar gas samples approached DLSBCO-3EQ from the entire alveolar sample. These changes correlated with ventilation inhomogeneity, as measured by the phase III He concentration slope and the mixing efficiency, and were larger for maneuvers with inspired volumes to one-half inspiratory capacity vs. total lung capacity.(ABSTRACT TRUNCATED AT 250 WORDS)
Acoustically induced cortical arousal increases phasic pharyngeal muscle and diaphragmatic EMG in NREM sleep
Authors: Carlson D. M. , Carley D. W. , Onal E. , Lopata M. , Basner R. C.
Published: December 2017

Six healthy subjects (3 males, 3 females) were studied to assess phasic inspiratory responses of upper airway (UA) and diaphragm muscles to electrocortical arousal independent of other potential respiratory stimulation. Transient electroencephalographic (EEG) arousal (abrupt EEG frequency shift > or = 3 s without awakening) was induced during supine stage 2 non-rapid-eye-movement (NREM) sleep with binaural tone bursts (0.5 s, 4 kHz, 25–95 dB). Electromyograms (EMG) of levator veli palatini (EMGlvp) and genioglossus (EMGgg) were obtained with intramuscular electrodes, and EMG of diaphragm (EMGdi) was obtained with esophageal electrodes. EMG signals were processed as moving time-averaged inspiratory activity over 100-ms windows. For each arousal, each of five consecutive postarousal breaths (R1-R5) was scored for peak inspiratory phasic EMG and normalized as percent averaged EMG of the three prearousal breaths for all muscles. After arousal, EMGlvp was increased for R1-R5 and EMGgg and EMGdi were increased for R1-R4. The increase in EMGlvp was greater than those of EMGgg and EMGdi for all response breaths. There was a significant increase in EMGlvp in all subjects, and EMGgg and EMGdi were significantly increased in three and two subjects, respectively. These data indicate that isolated transient electrocortical arousal is generally associated with phasic inspiratory recruitment of UA and diaphragm muscles in normal humans during NREM sleep; velopharyngeal muscle recruitment appears to be more consistent and of greater magnitude and duration than that of oropharyngeal muscle or diaphragm. We speculate that transient arousal from sleep may contribute to UA patency independent of chemical and mechanical respiratory stimuli.
Precision and accuracy of a noninvasive inert gas washin method for determination of cardiac output in men
Authors: Nielsen O. W. , Hansen S. , Gronlund J.
Published: December 2017

Stout et al. (J. Appl. Physiol. 38:913–918, 1975) suggested an open-circuit multibreath (MB) inert gas method for determining pulmonary capillary blood flow (Qc) in anesthetized dogs receiving artificial ventilation. In the present work we investigated the accuracy and reproducibility of the MB method in nine healthy human subjects at spontaneous ventilation, and we compared the MB method with the inert gas rebreathing (RB) method. Qc was calculated at rest and during exercise at 50 or 100 W, and experimental errors were evaluated in computer simulations of a two-alveoli lung model. The calculated mean Qc values of the MB method were 5.56 +/- 1.23 (SD), 10.02 +/- 0.78, and 13.2 +/- 0.84 l/min, and the mean difference (MB Qc - RB Qc) was not significantly different (P > 0.05). The variation in Qc of the MB method was found to be significantly larger than that in Qc of the RB method (P < 0.01). Random measurement errors and uneven distribution of ventilation contributed to the experimental errors. We conclude that the MB method is inferior to the RB method but that the MB method may be useful under exercise conditions.
Vitamin E effects on indexes of lipid peroxidation in muscle from DHEA-treated and exercised rats
Authors: Goldfarb A. H. , McIntosh M. K. , Boyer B. T. , Fatouros J.
Published: December 2017

Sixty-four male Sprague-Dawley rats were randomly assigned to one of eight treatment groups to determine the effects of vitamin E (VitE), dehydroepiandrosterone (DHEA), and exercise on antioxidant status in plasma and skeletal muscle. Indexes of oxidative stress were determined by measuring two markers of lipid peroxidation and the activity of two free radical scavenging enzymes. One-half of the rats had their diets supplemented with 250 IU VitE/kg of diet. One-half of the rats were injected with 0.35 mol/kg body wt ip of DHEA-acetate, whereas the others were injected with vehicle. All treatments lasted 5 wk. Before being killed, one-half of each treatments group of rats was randomly assigned to run for 1 h on a motorized rodent treadmill at 21 m/min up a 12% grade. The other rats remained rested before being killed. Exercise increased thiobarbituric acid-reactive substances (TBARS) and lipid hydroperoxides in plasma and TBARS in red slow-twitch and white fast-twitch muscles. VitE reduced the amount of lipid hydroperoxides and TBARS in plasma and TBARS in all three muscle fiber types. VitE also reduced glutathione peroxidase (GPX) activity in plasma and red fast-twitch muscle. DHEA increased indexes of oxidative stress in plasma and white fast-twitch muscle. DHEA reduced GPX activity in plasma but increased GPX activity in all three muscle fiber types. These results indicate that aerobic exercise is a mild oxidative stressor with DHEA exacerbating this response and that VitE helps diminish this effect in certain muscle fiber types.
L-carnitine combined with minimal electrical stimulation promotes type transformation of canine latissimus dorsi
Authors: Dubelaar M. L. , Glatz J. F. , De Jong Y. F. , Van der Veen F. H. , Hulsmann W. C.
Published: December 2017

In the first part of this study, in four dogs the left latissimus dorsi was equipped to perform in vivo contraction measurements and the right latissimus dorsi served as control. After a control period, the dogs received L-carnitine intravenously for 8 wk. We found that carnitine caused the percentage of type I fibers to increase from 30 to 55% in the left latissimus dorsi but no change in the right latissimus dorsi. In the left latissimus dorsi, the contraction speed (percentage ripple) decreased from 75 to 30% and cytochrome-c oxidase activity increased 1.6-fold. No changes occurred in the right latissimus dorsi. To verify these observations, we performed a second study with placebo control for 8 wk, and only the left latissimus dorsi was subjected to weekly electrical stimulation. In the carnitine-treated dogs, the stimulated muscle showed an increase in the percentage of type I fibers from 16 to 35% and the ripple decreased from 92 to 77%. These measures did not change in the placebo-treated dogs. We concluded that weekly short-term stimulation does not lead to a change in fiber type; however, carnitine combined with minimal stimulation of the muscle leads to a significant shift in muscle fiber type composition toward a muscle with an increased content of type I fibers.
Effect of hypoxia and hyperoxia on human +Gz duration tolerance
Authors: Besch E. L. , Werchan P. M. , Wiegman J. F. , Nesthus T. E. , Shahed A. R.
Published: December 2017

To determine the effects of varying inspired O2 on positive radial acceleration (+Gz; i.e., head-to-foot inertial load) duration tolerance, seven men were exposed to the +4.5- to +7.0-Gz simulated aerial combat maneuver (SACM) by use of the Armstrong Laboratory (Brooks Air Force Base) centrifuge. Exposures were repeated on different days while subjects breathed gas mixtures of fractional concentration of O2 in inspired air (FIO2) between 0.12 and 0.6. SACM duration tolerance was positively related to inspired O2 of FIO2 between 0.12 and 0.2 but was unchanged at FIO2 between 0.2 and 0.6. SACM exposure decreased arterial O2 saturation and increased heart rates; SACM-induced changes were additive to FIO2 effects. The positive relationship between blood lactate and SACM duration tolerance at all FIO2 indicated an anaerobic component. It is concluded that SACM duration tolerance is limited by reduced FIO2 but not enhanced by hyperoxia. Thus the aerobic component of +4.5- to +7.0-Gz SACM duration tolerance is much greater than previously believed.
Effects of exercise and glycogen depletion on glyconeogenesis in muscle
Authors: Bonen A. , Homonko D. A.
Published: December 2017

In the present study, we investigated the hypotheses that 1) skeletal muscle glyconeogenesis will increase after exercise, 2) greater changes in glyconeogenesis will be observed after exercise in fast-twitch muscles than in slow-twitch muscles, and 3) glycogen repletion will reduce the rates of glyconeogenesis. Mouse soleus and extensor digitorum longus (EDL) glycogen depots were reduced to the same levels by treadmill exercise (60 min) or epinephrine injection (75 micrograms/100 g body wt ip). Untreated animals were used as controls. We were able to prevent glycogen repletion by incubating muscles in vitro with sorbitol (75 mM) and to increase glycogen concentrations in vitro by incubating muscles with glucose (75 mM). The experimental results showed that glyconeogenesis was increased by exercise (EDL, +51%; soleus, +82%) when glycogen levels were kept low. When glycogen depots were increased, the rate of glyconeogenesis was lowered in the exercised EDL (P < 0.05) but not in the soleus (P > 0.05). Reductions in muscle glycogen by epinephrine did not change the rate of glyconeogenesis in EDL, either when glycogen depots were kept low or were repleted (P > 0.05). In contrast, in the soleus, epinephrine-induced reductions in glycogen did stimulate glyconeogenesis (P < 0.05). Analyses in EDL showed that in nonexercised muscles glycogen concentrations were minimally effective in altering the rates of glyconeogenesis. A 30% decrement in glycogen increased glyconeogenesis by 5% in resting muscles, whereas the same decrement increased glyconeogenesis by 51% in exercised muscles.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparison of diaphragmatic EMG power spectra: spontaneous contractions vs. evoked compound action potentials
Authors: Doud J. R. , Dornseif S. E. , Walsh J. M.
Published: December 2017

The electromyogram (EMG) power spectrum from spontaneous diaphragm contractions has been used to identify the development of fatigue. However, power spectral analysis of the spontaneous diaphragmatic EMG signal is limited and subject to error. In contrast, power spectral analysis of the compound diaphragm action potential (CDAP) may be superior. The aim of the present study was to determine whether the EMG power spectra of evoked CDAPs correlate with those of spontaneous diaphragm contractions. Four anesthetized mechanically ventilated dogs with spontaneous isometric diaphragm contractions were studied using a mechanically isolated in situ diaphragm preparation. CDAPs were elicited via phrenic nerve stimulation, and intramuscular wire electrodes recorded EMG. Diaphragm temperature was changed from 40 to 30 degrees C to elicit changes in the EMG power spectra. The EMG signal from 10 spontaneous contractions and 10 CDAPs were acquired at 1 degrees C intervals. Fast Fourier transform was applied to both spontaneous and CDAP data yielding the power spectra, which were represented by their center frequencies (fc). The CDAP fc correlated well with the EMG fc obtained from spontaneous contractions (r = 0.99). We conclude that evoked CDAPs may provide an accurate alternative to spontaneous contractions for EMG power spectral analysis of the diaphragm.
Superresistance against hypoxia after preliminary adaptation to repeated stress
Authors: Meerson F. , Pozharov V. , Minyailenko T.
Published: December 2017

The study investigated the influence of adaptation to stress on resistance to hypoxia. After rats were adaptated to moderate restraint stress, they were anesthetized and exposed to 6% O2. Adaptation increased tidal volume by 2.6-fold, lung and alveolar ventilation by 1.6- and 1.8-fold, respectively, and O2 consumption by 1.6-fold; limited lactate accumulation in the liver by 2-fold, in the heart by 34%, in the lung by 36%, and in the blood by 36%; and elevated pH. At the same time, preliminary adaptation to stress inhibited the hypoxic activation of lipolysis and peroxidation in all tissues. The concentration of lipid peroxides decreased after adaptation by 1.3- to 1.5-fold in different organs, whereas the content of free fatty acids diminished by 1.7- to 2.3-fold. Finally, after adaptation, mortality decreased under severe hypoxia by 6.5-fold. Thus, the data suggest that the cross-protective effect of adaptation was achieved by the economization of respiration and circulation, by marked augmentation in the ability of tissue to utilize blood O2, and by the limitation of processes that are able to damage tissue membranes, namely, acidosis, lipolysis, and lipid peroxidation.
Early alterations in soleus GLUT-4, glucose transport, and glycogen in voluntary running rats
Authors: Henriksen E. J. , Halseth A. E.
Published: December 2017

Voluntary wheel running (WR) by juvenile female rats was used as a noninterventional model of soleus muscle functional overload to study the regulation of insulin-stimulated glucose transport activity by the glucose transporter (GLUT-4 isoform) protein level and glycogen concentration. Soleus total protein content was significantly greater (+18%; P < 0.05) than in age-matched controls after 1 wk of WR, and this hypertrophic response continued in weeks 2–4 (+24–32%). GLUT-4 protein was 39% greater than in controls in 1-wk WR soleus, and this adaptation was accompanied by a similar increase in in vitro insulin-stimulated glucose transport activity (+29%). After 2 and 4 wk of WR, however, insulin-stimulated glucose transport activity had returned to control levels, despite a continued elevation (+25–28%) of GLUT-4 protein. At these two time points, glycogen concentration was significantly enhanced in WR soleus (+21–42%), which coincided with significant reductions in glycogen synthase activity ratios (-23 to -41%). These results indicate that, in this model of soleus muscle functional overload, the GLUT-4 protein level may initially regulate insulin-stimulated glucose transport activity in the absence of changes in other modifying factors. However, this regulation of glucose transport activity by GLUT-4 protein may be subsequently overridden by elevated glycogen concentration.
Estimation of extravascular lung water in humans with use of 2H2O: effect of blood flow and central blood volume
Authors: Wallin C. J. , Leksell L. G.
Published: December 2017

In the present human study we evaluated a newly developed double-indicator-dilution densitometric system for the estimation of cardiac output (Q), central blood volume (CBV), and extravascular lung water (EVLW) by using indocyanine green and heavy water (2H2O) as indicators. Eighteen cardiopulmonary healthy patients scheduled for abdominal surgery were studied. A routine anesthesia procedure was used [thiopental (3–5 mg/kg), N2O (inspired fraction of O2 = 0.4), and isoflurane (end tidal 0.5–1.5%)]. Q, CBV, and EVLW were measured at seven defined data collection points: awake, anesthetized spontaneously breathing, apneic, mechanically ventilated with and without positive end-expiratory pressure, post-operatively anesthetized, and postoperatively awake. During the whole study EVLW (3.8 +/- 0.9 ml/kg) was stable in the presence of large fluctuations in Q (2.5–10.1 l/min) and CBV (0.8–2.4 l). We concluded that the method is versatile and of low invasiveness, allowing reliable on-line Q and EVLW data for repeated measurements in the clinical setting.
Right atrial pressure and ANP release during prolonged exercise in a hot environment
Authors: Nose H. , Takamata A. , Mack G. W. , Kawabata T. , Oda Y. , Hashimoto S. , Hirose M. , Chihara E. , Morimoto T.
Published: December 2017

To investigate the relationship between right atrial pressure (RAP) and atrial natriuretic peptide (ANP) release during prolonged exercise in a hot environment (30 degrees C, 20% relative humidity), we studied with a Swan-Ganz catheter five male volunteers exercising on a cycle ergometer at 60% of peak aerobic power for 50 min. The ANP level increased from 14 +/- 3 (SE) to 69 +/- 10 pg/ml (P < 0.001) during the first 10 min of exercise as RAP rose from 4.3 +/- 0.8 to 6.9 +/- 1.1 mmHg (P < 0.001). The 10-min ANP level was significantly correlated with RAP (r = 0.88, P < 0.05) but not with heart rate, pulmonary arterial blood temperature, plasma norepinephrine, or plasma epinephrine. The 10-min RAP value was inversely correlated with blood volume (r = -0.98, P < 0.01) and also with stroke volume (r = -0.96, P < 0.01). In the next 20 min of exercise, ANP continued to increase to 101 +/- 12 pg/ml (P < 0.02 vs. 10 min) and remained at this level until 50 min of exercise, whereas RAP decreased and reached a level not significantly different from baseline at 50 min (5.7 +/- 1.0 mmHg; P < 0.01 vs. 10 min). This dissociation of ANP and RAP may have been related to the significant increases from the 10-min values of heart rate, blood temperature, norepinephrine (all P < 0.01), and epinephrine (P < 0.02) during the same period. These results suggest that ANP release is primarily controlled by atrial distension at the onset of exercise but that other stimulators may be involved thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)
Intestinal carbohydrate absorption and permeability at high altitude (5,730 m)
Authors: Dinmore A. J. , Edwards J. S. , Menzies I. S. , Travis S. P.
Published: December 2017

To investigate the effects of high altitude on intestinal function, the absorption and permeation of nonmetabolizable carbohydrates were measured in 14 volunteers (median age 21 yr, range 19–37 yr) at sea level in Oxford, UK; at 1,050 m in Nepal; at 5,570 m after 5 days at > 5,500 m; and at 5,730 m after 11 days at > 5,500 m. Body weight decreased 5.7 +/- 1.19 kg from sea level to 5,570 m (P < 0.001 by paired t test) despite 72-h dietary records showing no change in energy intake. Absorption of carbohydrates by mediated transport was measured by urinary xylose and 3-O-methyl-D-glucose excretion. Xylose excretion (%oral dose) decreased from 31.4 +/- 4.5% to 20.7 +/- 4.5% (P < 0.001) and 3-O-methyl-D-glucose excretion decreased from 39.7 +/- 6.1 to 33.7 +/- 7.0% (P = 0.003) from sea level to 5,730 m. Monosaccharide permeation measured by L-rhamnose excretion decreased from 11.3 +/- 2.5 to 6.2 +/- 2.0% (P = 0.001). Intestinal permeability, a measure of barrier function (ratio of lactulose to L-rhamnose), increased from 0.036 +/- 0.014 at sea level to 0.084 +/- 0.042 at 1,050 m (P = 0.006), possibly due to infective enteropathy after arrival in Nepal, but reverted to normal (0.045 +/- 0.013; P = 0.062) at 5,730 m. Absorption of all carbohydrates returned to normal after return to the UK. This study showed that a decrease in mediated (D-xylose or 3-O-methyl-D-glucose) and diffusional (L-rhamnose) monosaccharide absorption occurs at high altitude but that intestinal permeability at 5,730 m is unchanged.
Respiratory-related blood pressure variability in patients after heart transplantation
Authors: Macor F. , Fagard R. , Vanhaecke J. , Amery A.
Published: December 2017

Our objective was to study whether the variations of blood pressure synchronous with respiration depend on the simultaneous changes of heart rate. Power spectral analysis of the heart period or R-R interval, blood pressure, and respiratory activity was performed by fast Fourier transform during 30 min of supine rest in 12 patients between 16 and 23 days after orthotopic heart transplantation and in 12 age- and sex-matched normal control subjects. The components of the variations of the R-R interval and blood pressure associated with respiration [high-frequency (HF) components] were derived from the power spectra. The HF component of the power spectrum of the R-R interval was almost absent in the transplanted patients compared with the control subjects (2.9 vs. 104 ms2; P < 0.001), whereas the HF component of the power spectrum of blood pressure was not significantly different between the two groups (1.72 vs. 1.65 mmHg2 for systolic and 0.35 vs. 0.60 mmHg2 for diastolic blood pressure). Respiratory variations of both systolic and diastolic blood pressure in humans can depend only slightly on the respiratory heart rate variations.
Endothelin receptor subtypes in human versus rabbit pulmonary arteries
Authors: Fukuroda T. , Kobayashi M. , Ozaki S. , Yano M. , Miyauchi T. , Onizuka M. , Sugishita Y. , Goto K. , Nishikibe M.
Published: December 2017

We studied which endothelin (ET) receptor subtypes mediate ET-1-induced vasocontraction in the human pulmonary artery (PA) compared with the rabbit PA. ET-1 produced potent contraction in both human and rabbit isolated PAs. In human PA, ET-1-induced contraction was competitively antagonized by BQ-123 (an ETA receptor antagonist) with a pA2 value of 7.68. In rabbit PA, however, even a high concentration of BQ-123 (1 microM) did not affect the contraction. BQ-3020 (an ETB receptor agonist) produced potent contraction in rabbit PA but not in human PA. Binding assays of the membrane preparations showed that human and rabbit PAs contained ETA and ETB receptors in ratios of 93:7 and 23:77, respectively. These results suggest interspecies differences in the ET receptor subtypes that mediate ET-1-induced vasocontraction; ETA receptors are dominant in the human PA, whereas ETB receptors are dominant in the rabbit PA. Furthermore, the predominance of ETA receptors in human PA was supported by autoradiographical studies. If ET-1 acts as a physiological and/or pathophysiological vasocontractor in the human pulmonary circulation, an ETA receptor antagonist would function as a pulmonary vasodilator in humans.
Mechanistic differences in NK cell cytolytic activity in treadmill-trained and chronic ethanol-consuming mice
Authors: Blank S. E. , Johansson J. O. , Pfister L. J. , Gallucci R. M. , Lee E. G. , Meadows G. G.
Published: December 2017

The present study was undertaken to investigate mechanisms contributing to differences in natural killer (NK) cell activity in moderately endurance-trained and ethanol-consuming mice. Independent of ethanol exposure, NK cell activity in nylon wool-nonadherent (NWNA) splenocytes is lower in trained than in sedentary control mice (Blank et al. J. Appl. Physiol. 72: 8–14, 1992). Reduced activity may result from a generalized loss of cytolytically active cells, redistribution of NK cells from the spleen to other body compartments, or disruption of paracrine regulation of NK cells after removal of nylon wool-adherent cells. To examine these possibilities, NK cell cytolytic activity was determined in nonenriched splenocytes from treadmill-trained and ethanol-consuming mice. Lymphocyte subpopulations in nonenriched splenocytes and NWNA splenocytes were also compared. Peripheral blood lymphocyte subpopulations were determined to examine combined effects of training and ethanol intake on regional distribution of lymphocytes in blood and spleen. NK cell activity in nonenriched splenocytes from trained water-drinking mice was not reduced compared with that in sedentary mice; rather, cytolytic activity was moderately enhanced (17% increase in lytic units, P < 0.05). Training did not change percentages of T-cells, B-cells, and NK [NK1.1+ and large granular lymphocytes (LGL-1+)] cells or the LGL/NK ratio in the spleen and blood. NK cell cytolytic activity was significantly reduced in nonenriched splenocytes from ethanol-consuming mice, independent of training. These findings support the hypothesis that moderate-intensity endurance training influences splenic NK cell function by modulating paracrine regulation of NK cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Is nitric oxide involved in cutaneous vasodilation during body heating in humans?
Authors: Dietz N. M. , Rivera J. M. , Warner D. O. , Joyner M. J.
Published: December 2017

The neurotransmitter responsible for neurogenic vasodilation in human skin during body heating is unknown. We sought to determine whether the vasodilating substance nitric oxide (NO) is involved in this phenomenon. Six subjects were heated for 50 min by use of a water-perfused suit while forearm blood flow (FBF) was measured with plethysmography and skin blood flow (SkBF) was measured by the laser-Doppler method in both arms. In one forearm, NG-monomethyl-L-arginine (L-NMMA), an NO synthase blocker, was infused into the brachial artery. Bolus doses of L-NMMA (< or = 4 mg/min) for 5 min were given to blunt NO-mediated vasodilator responses to acetylcholine (ACh, 64 micrograms/min). A continuous infusion of L-NMMA (< or = 1.0 mg/min) was used during body heating to maintain NO synthase blockade. In the forearm receiving L-NMMA, FBF was 1.8 +/- 0.3 ml.100 ml-1.min-1 before drug infusion and rose to 9.5 +/- 1.3 ml.100 ml-1.min-1 with ACh. After L-NMMA infusion, FBF was 1.3 +/- 0.2 ml.100 ml-1.min-1 and rose to 2.6 +/- 0.4 ml.100 ml-1.min-1 with ACh (both P < 0.05 vs. pre-L-NMMA). Similar changes in SkBF were seen with ACh and L-NMMA, confirming that the drugs reached cutaneous vessels. With body heating, oral temperature increased by 1.2 degrees C, heart rate increased by 34 beats/min, and mean arterial pressure remained constant at approximately 75 mmHg. FBF in the treated forearm rose to 11.5 +/- 2.1 vs. 12.6 +/- 1.7 ml.100 ml-1.min-1 in the control forearm (P > 0.05, control vs. treated response).(ABSTRACT TRUNCATED AT 250 WORDS)
Localization of putative neural respiratory regions in the human by functional magnetic resonance imaging
Authors: Gozal D. , Hathout G. M. , Kirlew K. A. , Tang H. , Woo M. S. , Zhang J. , Lufkin R. B. , Harper R. M.
Published: December 2017

In humans, the location of brain regions responsible for mediating the ventilatory response to CO2 remains unknown. Most of the available knowledge has been derived from animal studies or from pathophysiological correlations in patients presenting altered control of breathing. Magnetic resonance imaging at a specific pulse sequence designed to assess changes in brain tissue microcirculation was performed in 11 healthy volunteers, during steady-state conditions, while breathing 100% O2 or 5% CO2-95% O2. In one subject, 10% CO2-90% O2 was employed to examine a dose-response effect. Significant changes in image signal intensity consistently occurred in ventral and dorsal regions of medullary structures as well as in the midline pons and ventral cerebellum. These responses appeared to be dose dependent and reproducible. Magnetic resonance imaging revealed patterns of activation in brain stem and cerebellar regions during hypercapnic ventilatory challenge. These areas may underlie mechanisms for mediating the response to chemoreceptor activation.
Response of human cerebral blood flow to +Gz accelerations
Authors: Ossard G. , Clere J. M. , Kerguelen M. , Melchior F. , Seylaz J.
Published: December 2017

Intolerance symptoms associated with high sustained +Gz (head to foot) accelerations are attributed to lack of cerebral perfusion. To determine the response of cerebral circulation to +Gz stress, cerebral blood flow (CBF) was measured in humans with the transcranial Doppler method while cephalic arterial blood pressure was calculated simultaneously using a photoplethysmographic technique. Nine volunteers performed four randomized centrifuge runs at +2 to +5 Gz with a 0.4-G/s onset rate for 30 s. Compared with the control values, for +2-, +3-, +4-, and +5-Gz profiles, CBF was reduced by 19 +/- 7, 26 +/- 8, 49 +/- 26, and 61 +/- 29% (SD), respectively, at the end of the onset and by 18 +/- 4, 21 +/- 11, 27 +/- 7, and 47 +/- 29%, respectively, in the last 20 s of the plateau of acceleration. At the end of the onset and during the plateau of +Gz acceleration, CBF was less reduced than cephalic arterial blood pressure, suggesting that some mechanisms would occur to maintain cerebral perfusion under +Gz stress. These protective mechanisms are likely due to a siphon effect and/or an autoregulatory compensation.
Human and rodent muscle Na(+)-K(+)-ATPase in diabetes related to insulin, starvation, and training
Authors: Schmidt T. A. , Hasselbalch S. , Farrell P. A. , Vestergaard H. , Kjeldsen K.
Published: December 2017

As determined by vanadate-facilitated [3H]ouabain binding to intact samples, semistarvation and untreated streptozotocin- or partial pancreatectomy-induced diabetes reduced rat soleus muscle Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) concentration by 12–21% (P < 0.05). Conversely, insulin treatment of rats with streptozotocin-induced diabetes induced an increase of 18-26% above control (P < 0.05). Treadmill training diminished the reduction in muscle [3H]ouabain binding site concentration induced by untreated diabetes to only 2–5%. No significant variation was observed in rat cerebral cortex Na(+)-K(+)-ATPase concentration as a result of diabetes, semistarvation, or insulin treatment. In human subjects, Na(+)-K(+)-ATPase concentration in vastus lateralis muscle biopsies was 17 and 22% greater (P < 0.05), respectively, in patients with treated non-insulin-dependent diabetes mellitus (n = 24) and insulin-dependent diabetes mellitus (n = 7) than in control subjects (n = 8). A positive linear correlation between muscle Na(+)-K(+)-ATPase and plasma insulin concentrations was observed (r = 0.50, P = 0.006; n = 29). Thus, insulin seems a regulator of muscle Na(+)-K(+)-ATPase concentration, reduction of muscle Na(+)-K(+)-ATPase concentration with untreated diabetes bears similarities with undernourishment, and physical conditioning may ameliorate the muscle Na(+)-K(+)-ATPase concentration decrease induced by diabetes.
Adrenomedullin dilates the pulmonary vascular bed in vivo
Authors: Lippton H. , Chang J. K. , Hao Q. , Summer W. , Hyman A. L.
Published: December 2017

The present study was undertaken to investigate the effects of adrenomedullin (ADM), a newly discovered peptide in normal human plasma, in the pulmonary and systemic vascular bed of the intact cat. Because pulmonary blood flow and left atrial pressure were held constant, changes in lobar arterial pressure directly reflected changes in pulmonary vascular resistance. Under conditions of resting (low) pulmonary vasomotor tone, intralobar arterial bolus injections of ADM-(1–52) and two truncated ADM sequences, ADM-(13–52) and ADM-(1–12), had little effect on baseline lobar arterial pressure. In contrast, when pulmonary vasomotor tone was actively increased by intralobar arterial infusion of U-46619, intralobar arterial bolus injections of ADM-(1–52) (10–3,000 ng) and ADM-(13–52) (10–3,000 ng) decreased lobar arterial pressure in a dose-dependent manner, whereas only the highest doses of ADM-(1–52) and ADM-(13–52) (1,000–3,000 ng) mildly decreased systemic arterial pressure. Under the same experimental conditions, injections of ADM-(1–12) had no effect on lobar arterial and systemic arterial pressures. The present data suggest that ADM-(13–52) or a similar ADM fragment is responsible for the marked pulmonary vasodilator activity of ADM-(1–52) in vivo.
Role of sarcolemma action potentials and excitability in muscle fatigue
Authors: Balog E. M. , Thompson L. V. , Fitts R. H.
Published: December 2017

The purposes of this study were to characterize the alterations in the sarcolemma action potential (AP) waveform and sarcolemma excitability as a result of fatiguing stimulation of the frog semitendinosus muscle and to relate these changes to the decrease in the force-generating ability of the muscle. Trains of APs were recorded before and after stimulation (100-ms trains, 150 Hz, 1/s for 5 min). The resting membrane potential (RMP), AP overshoot (OS), and duration at 50% of peak magnitude (DUR) were -84.3 +/- 2.0 mV, 19.5 +/- 1.9 mV, and 1.3 +/- 0.1 ms, respectively, before stimulation. The stimulation protocol caused RMP to depolarize to -75.1 +/- 2.0 mV, OS to fall to 7.3 +/- 1.9 mV, and DUR to increase to 2.5 +/- 0.4 ms. RMP and OS recovered fully in 5 min after the cessation of stimulation, whereas DUR was still prolonged. Before the stimulation protocol, AP frequency matched the stimulation frequency at all stimulation rates < or = 150 Hz. At 200-Hz stimulation, AP frequency was 192 +/- 6 Hz. After 5 min of stimulation, AP frequency matched the stimulation frequency only at < or = 60 Hz. At 100-, 150-, and 200-Hz stimulation, AP frequencies were 89 +/- 8, 84 +/- 17, and 79 +/- 15 Hz, respectively. Because of a decreased fusion frequency at fatigue, the fall in the sarcolemma AP frequency did not contribute to the decreased force. The stimulation-induced alterations in the AP waveform were moderate and unlikely to have caused fatigue. However, the alterations in AP may have been more extreme in the depths of the transverse tubules.
Exercise-induced changes in immune function: effects of zinc supplementation
Authors: Singh A. , Failla M. L. , Deuster P. A.
Published: December 2017

To examine the effect of zinc (Zn) supplementation on exercise-induced changes in immune function, five male runners were randomly assigned in a double-blind crossover design to take a supplement (S; 25 mg of Zn and 1.5 mg of copper) or placebo (P) twice daily for 6 days. On morning 4 of each phase, 1 h after taking S or P, subjects ran on a treadmill at 70–75% of maximal oxygen uptake until exhaustion (approximately 2 h). Blood samples were obtained before (Pre), immediately after (Post), and 1 (Rec1) and 2 (Rec2) days after the run. [3H]thymidine incorporation by mitogen-treated mononuclear cell cultures was significantly lower (P < 0.05) Post than Pre, Rec1, or Rec2 for both S and P. Respiratory burst activity of isolated neutrophils was enhanced after exercise with P but not with S (P: Pre 12.0 +/- 1.1 vs. Post 17.6 +/- 2.3 nmol O2-/10(6) cells; S: Pre 11.7 +/- 0.3 vs. Post 12.1 +/- 1.2 nmol O2-/10(6) cells). Thus supplemental Zn blocked the exercise-induced increase in reactive oxygen species. Whether this antioxidant effect of Zn will benefit individuals exposed to chronic physical stress remains to be determined.
Beat-by-beat changes of viscoelastic and inertial properties of the pulmonary arteries
Authors: Lieber B. B. , Li Z. , Grant B. J.
Published: December 2017

We tested the hypothesis that pulmonary arterial input impedance varies during the ventilatory cycle due to alterations not only of the viscoelastic components of the pulmonary vasculature but also due to changes of the inertial components. A four-element lumped-parameter model was used to fit the pulmonary arterial pressure-flow recordings in the time domain in 10 anesthetized dogs. The four elements consisted of a resistor (R) that represents input resistance, a second resistor (R1) and a capacitor (C1) that represent the viscoelastic properties of the pulmonary vasculature, and an inductor (L1) that represents inertial properties of blood within the pulmonary vasculature. The parameters were evaluated at each heartbeat throughout the ventilatory cycle at three levels of positive end-expiratory pressure. All four parameters varied significantly during the ventilatory cycle. R, C1, L1, and R1 varied by up to 97, 33, 13, and 17%, respectively. Changes in parameter values were most apparent at the start of expiration when the most rapid changes of lung volume occur. This pattern of the results is consistent with the hypothesis that the time variation of pulmonary arterial impedance is due to dynamic shifts of blood volume between the extra-alveolar and alveolar arteries.
Effect of hypoxia on metabolic rate in awake ponies
Authors: Korducki M. J. , Forster H. V. , Lowry T. F. , Forster M. M.
Published: December 2017

To determine the effect of hypoxia on metabolic rate (VO2) of ponies, on 2 days we studied ponies that were breathing room air for 1 h followed by 5 h of either hypoxic hypoxia (fractional concn of inspired O2 = 0.126) or 5 h of CO hypoxia. Control arterial PO2 was 103 +/- 1.2 Torr, and at 5 min and 5 h of hypoxic hypoxia, arterial PO2 was 53.1 +/- 1.8 and 41.0 +/- 1.8 Torr, respectively. There was a time-dependent hypocapnia and alkalosis during hypoxic hypoxia. During CO hypoxia, carboxyhemoglobin increased to 25% after 30 min and remained constant thereafter. With increased carboxyhemoglobin, arterial PCO2 was 1.3 Torr above (P < 0.05) and 1.5 Torr (P < 0.05) below control levels after 30 min and 3 h, respectively. There were no significant (P > 0.10) changes in VO2 during either hypoxic or CO hypoxia. However, in 50% of the ponies, VO2, pulmonary ventilation, and rectal temperature increased and shivering was evident after 30 min of hypoxia. Peak values of pulmonary ventilation, VO2, and shivering occurred at approximately 2 h with a subsequent return toward control levels. We conclude that, in contrast to smaller mammals, acute hypoxia does not depress VO2 of ponies. The hypermetabolism and hyperthermia during chronic hypoxia in some ponies may reflect a transient failure in thermoregulation.
Ventilatory response to spontaneous resistive load variations during sleep
Authors: Cibella F. , Cuttitta G. , Romano S. , Grassino A. , Bellia V.
Published: December 2017

We investigated the ventilatory response to spontaneous changes in resistive load during sleep in nine adult asthmatic patients, four of whom were snorers. All patients had a history of nocturnal worsening of respiratory symptoms and were submitted to a nocturnal polysomnographic study in a sleep laboratory. During the night, all patients showed spontaneous increases in pulmonary resistance due to bronchoconstriction. A temporary additional increase in inspiratory resistance (RI) was observed as a result of snoring. In all patients, a highly significant inverse linear relationship was found between ventilation (VE) and RI, but the slopes of the regressions varied considerably among patients; the decrease in VE was due to a reduced mean inspiratory flow. The most effective ventilatory compensation to increasing resistive load (lowest absolute values in the VE/RI slopes) was observed in two patients: one nonsnorer and one snorer. Effective VE compensation appeared to be dependent on the individual's combined adjustments of transpulmonary pressure (Ptp) and duty cycle (TI/TT). In fact, an increase in Ptp, linearly related to RI, was observed in all patients except one (a snorer during nonsnoring breathing); however, the Ptp increase was able to compensate VE only when TI/TT increased. We conclude that, in sleeping asthmatic patients, VE adaptation to increased spontaneous load is highly variable among patients and its effectiveness is related to individual strategies on the basis of adequate adjustments of neuromuscular output and timing of the breathing cycle.