bluuebunny/crossref_metadata_2025 huggingface dataset:
Skeletal muscle vasodilation at the onset of exercise
Authors: Buckwalter John B. , Ruble Stephen B. , Mueller Patrick J. , Clifford Philip S.
Published: December 2017

The purpose of this study was to determine whether β-adrenergic or muscarinic receptors are involved in skeletal muscle vasodilation at the onset of exercise. Mongrel dogs ( n = 7) were instrumented with flow probes on both external iliac arteries and a catheter in one femoral artery. Propranolol (1 mg), atropine (500 μg), both drugs, or saline was infused intra-arterially immediately before treadmill exercise at 3 miles/h, 0% grade. Immediate and rapid increases in iliac blood flow occurred with initiation of exercise under all conditions. Peak blood flows were not significantly different among conditions (682 ± 35, 646 ± 49, 637 ± 68, and 705 ± 50 ml/min, respectively). Although the doses of antagonists employed had no effect on heart rate or systemic blood pressure, they were adequate to abolish agonist-induced increases in iliac blood flow. Because neither propranolol nor atropine affected iliac blood flow, we conclude that activation of β-adrenergic and muscarinic receptors is not essential for the rapid vasodilation in active skeletal muscle at the onset of exercise in dogs.
Effect of crystalloid administration on oxygen extraction in endotoxemic pigs
Authors: Gow Kenneth W. , Phang P. Terry , Tebbutt-Speirs Susan M. , English John C. , Allard Michael F. , Goddard Christopher M. , Walley Keith R.
Published: December 2017

We asked whether crystalloid administration improves tissue oxygen extraction in endotoxicosis. Four groups of anesthetized pigs ( n = 8/group) received either normal saline infusion or no saline and either endotoxin or no endotoxin. We measured whole body (WB) and gut oxygen delivery and consumption during hemorrhage to determine the critical oxygen extraction ratio ([Formula: see text]). Just after onset of ischemia (critical oxygen delivery rate), gut was removed for determination of area fraction of interstitial edema and capillary hematocrit. Radiolabeled microspheres were used to determine erythrocyte transit time for the gut. Endotoxin decreased WB[Formula: see text](0.82 ± 0.06 to 0.55 ± 0.08, P < 0.05) and gut[Formula: see text](0.77 ± 0.07 to 0.52 ± 0.06, P< 0.05). Unexpectedly, saline administration also decreased WB[Formula: see text](0.82 ± 0.06 to 0.62 ± 0.08, P< 0.05) and gut[Formula: see text](0.77 ± 0.07 to 0.67 ± 0.06, P< 0.05) in nonendotoxin pigs. Saline administration increased the area fraction of interstitial space ( P< 0.05) and resulted in arterial hemodilution ( P < 0.05) but not capillary hemodilution ( P > 0.05). Saline increased the relative dispersion of erythrocyte transit times from 0.33 ± 0.08 to 0.72 ± 0.53 ( P< 0.05). Thus saline administration impairs tissue oxygen extraction possibly by increasing interstitial edema or increasing heterogeneity of microvascular erythrocyte transit times.
Dose-response relationship between plasma epinephrine concentration and alveolar liquid clearance in dogs
Authors: Maron Michael B.
Published: December 2017

Previously, alveolar liquid clearance (ALC) was observed to increase in a canine model of neurogenic pulmonary edema (NPE) by adrenal epinephrine (S. M. Lane, K. C. Maender, N. E. Awender, and M. B. Maron. Am. J. Respir. Crit. Care Med. 158: 760–768, 1998). In this study the dose-response relationship between plasma epinephrine concentration and ALC was determined in anesthetized dogs by infusing epinephrine to produce plasma concentrations of 256 ± 37, 1,387 ± 51, 15,737 ± 2,161, and 363,997 ± 66,984 (SE) pg/ml ( n = 6 for each concentration) for 4 h and measuring the resultant ALC. The latter was determined by mass balance after instillation of autologous plasma into a lower lung lobe. These plasma concentrations produced ALCs of 14.3 ± 1.2, 20.5 ± 1.9, 30.1 ± 1.5, and 37.9 ± 2.7% of the instilled volume, respectively. ALC after the lowest infusion rate was not different from that previously observed under baseline conditions (14.1 ± 2.1%), whereas in a previous study of NPE, plasma epinephrine concentration increased to 7,683 ± 687 pg/ml and ALC was 30.4 ± 1.6%. These data indicate that, during recovery from canine NPE, ALC is not maximally stimulated and suggest that it might be possible to pharmacologically produce further increases in the rate of resolution of this form of edema.
Role of insulin in antigen-induced airway eosinophilia and neuronal M2muscarinic receptor dysfunction
Authors: Belmonte K. E. , Fryer A. D. , Costello R. W.
Published: December 2017

In the lungs, neuronal M2muscarinic receptors limit ACh release from parasympathetic nerves. In antigen-challenged animals, eosinophil proteins block these receptors, resulting in increased ACh release and vagally mediated hyperresponsiveness. In contrast, diabetic rats are hyporesponsive and have increased M2receptor function. Because there is a low incidence of asthma among diabetic patients, we investigated whether diabetes protects neuronal M2receptor function in antigen-challenged rats. Antigen challenge of sensitized rats decreased M2receptor function, increased vagally mediated hyperreactivity by 75%, and caused a 10-fold increase in eosinophil accumulation around airway nerves. In antigen-challenged diabetic rats, neuronal M2receptor function was preserved and there was no eosinophil accumulation around airway nerves. Insulin treatment of diabetic rats completely restored loss of M2receptor function, vagally mediated hyperresponsiveness, and eosinophilia after antigen challenge. These data demonstrate that insulin is required for development of airway inflammation, loss of neuronal M2muscarinic receptor function, and subsequent hyperresponsiveness in antigen-challenged rats and may explain decreased incidence of asthma among diabetic humans.
Maintained exercise pressor response in heart failure
Authors: Shoemaker J. Kevin , Kunselman Allen R. , Silber David H. , Sinoway Lawrence I.
Published: December 2017

The impact of forearm blood flow limitation on muscle reflex (metaboreflex) activation during exercise was examined in 10 heart failure (HF) (NYHA class III and IV) and 9 control (Ctl) subjects. Rhythmic handgrip contractions (25% maximal voluntary contraction, 30 contractions/min) were performed over 5 min under conditions of ambient pressure or with +50 mmHg positive pressure about the exercising forearm. Mean arterial blood pressure (MAP) and venous effluent hemoglobin (Hb) O2saturation, lactate and H+concentrations ([La] and [H+], respectively) were measured at baseline and during exercise. For ambient contractions, the increase (Δ) in MAP by end exercise (ΔMAP; i.e., the exercise pressor response) was the same in both groups (10.1 ± 1.2 vs. 7.33 ± 1.3 mmHg, HF vs. Ctl, respectively) despite larger Δ[La] and Δ[H+] for the HF group ( P < 0.05). With ischemic exercise, the ΔMAP for HF (21.7 ± 2.7 mmHg) exceeded that of Ctl subjects (12.2 ± 2.8 mmHg) ( P < 0.0001). Also, for HF, Δ[La] (2.94 ± 0.4 mmol) and Δ[H+] (24.8 ± 2.7 nmol) in the ischemic trial were greater than in Ctl (1.63 ± 0.4 mmol and 15.3 ± 2.8 nmol; [La] and [H+], respectively) ( P < 0.02). Hb O2saturation was reduced in Ctl from ∼43% in the ambient trial to ∼27% with ischemia ( P < 0.0001). O2extraction was maximized under ambient exercise conditions for HF but not for Ctl. Despite progressive increases in blood perfusion pressure over the course of ischemic exercise, no improvement in Hb O2saturation or muscle metabolism was observed in either group. These data suggest that muscle reflex activation of the pressor response is intact in HF subjects but the resulting improvement in perfusion pressure does not appear to enhance muscle oxidative metabolism or muscle blood flow, possibly because of associated increases in sympathetic vasoconstriction of active skeletal muscle.
Kinetics of oxygen uptake at the onset of exercise in boys and men
Authors: Hebestreit H. , Kriemler S. , Hughson R. L. , Bar-Or O.
Published: December 2017

The objective of this study was to compare the O2 uptake (V˙o 2) kinetics at the onset of heavy exercise in boys and men. Nine boys, aged 9–12 yr, and 8 men, aged 19–27 yr, performed a continuous incremental cycling task to determine peak V˙o 2(V˙o 2 peak). On 2 other days, subjects performed each day four cycling tasks at 80 rpm, each consisting of 2 min of unloaded cycling followed twice by cycling at 50%V˙o 2 peak for 3.5 min, once by cycling at 100%V˙o 2 peak for 2 min, and once by cycling at 130%V˙o 2 peak for 75 s. O2 deficit was not significantly different between boys and men (respectively, 50%V˙o 2 peak task: 6.6 ± 11.1 vs. 5.5 ± 7.3 ml ⋅ min−1 ⋅ kg−1; 100% V˙o 2 peak task: 28.5 ± 8.1 vs. 31.8 ± 6.3 ml ⋅ min−1 ⋅ kg−1; and 130%V˙o 2 peaktask: 30.1 ± 5.7 vs. 35.8 ± 5.3 ml ⋅ min−1 ⋅ kg−1). To assess the kinetics, phase I was excluded from analysis. Phase IIV˙o 2 kinetics could be described in all cases by a monoexponential function. ANOVA revealed no differences in time constants between boys and men (respectively, 50%V˙o 2 peaktask: 22.8 ± 5.1 vs. 26.4 ± 4.1 s; 100%V˙o 2 peak task: 28.0 ± 6.0 vs. 28.1 ± 4.4 s; and 130%V˙o 2 peak task: 19.8 ± 4.1 vs. 20.7 ± 5.7 s). In conclusion, O2 deficit and fast-componentV˙o 2 on-transients are similar in boys and men, even at high exercise intensities, which is in contrast to the findings of other studies employing simpler methods of analysis. The previous interpretation that children rely less on nonoxidative energy pathways at the onset of heavy exercise is not supported by our findings.
Influence of malonyl-CoA and palmitate concentration on rate of palmitate oxidation in rat muscle
Authors: Merrill G. F. , Kurth E. J. , Rasmussen B. B. , Winder W. W.
Published: December 2017

5-Aminoimidazole-4-carboxamide 1-β-d-ribofuranoside (AICAR) is taken up by perfused skeletal muscle and phosphorylated to form 5-aminoimidazole-4-carboxamide-1-β-d-ribofuraosyl-5′-monophosphate (analog of 5′-AMP) with consequent activation of AMP-activated protein kinase, phosphorylation of acetyl-CoA carboxylase, decrease in malonyl-CoA, and increase in fatty acid oxidation. This study was designed to determine the effect of increasing levels of palmitate on the rate of fatty acid oxidation. Malonyl-CoA concentration was manipulated with AICAR at different palmitate concentrations. Rat hindlimbs were perfused with Krebs-Henseleit bicarbonate containing 4% bovine serum albumin, washed bovine red cells, 200 μU/ml insulin, 10 mM glucose, and different concentrations of palmitate (0.1–1.0 mM) without or with AICAR (2.0 mM). Perfusion with medium containing AICAR was found to activate AMP-activated protein kinase in skeletal muscle, inactivate acetyl-CoA carboxylase, and decrease malonyl-CoA at all concentrations of palmitate. The rate of palmitate oxidation increased as a function of palmitate concentration in both the presence and absence of AICAR but was always higher in the presence of AICAR. These results provide additional evidence that malonyl-CoA is an important regulator of the rate of fatty acid oxidation at palmitate concentrations in the physiological range.
Recovery of free ADP, Pi, and free energy of ATP hydrolysis in human skeletal muscle
Authors: Wackerhage Henning , Hoffmann Uwe , Essfeld Dieter , Leyk Dieter , Mueller Klaus , Zange Jochen
Published: December 2017

We measured significant undershoots of the concentrations of free ADP ([ADP]) and Pi([Pi]) and the free energy of ATP hydrolysis (Δ GATP) below initial resting levels during recovery from severe ischemic exercise with31P-nuclear magnetic resonance spectroscopy in 11 healthy sports students. Undershoots of the rate of oxidative phosphorylation would be predicted if the rate of oxidative phosphorylation would depend solely on free [ADP], [Pi], or Δ GATP. However, undershoots of the rate of oxidative phosphorylation have not been reported in the literature. Furthermore, undershoots of the rate of oxidative phosphorylation are unlikely because there is evidence that a balance between ATP production and consumption cannot be achieved if an undershoot of the rate of oxidative phosphorylation actually occurs. Therefore, oxidative phosphorylation seems to depend not only on free [ADP], [Pi], or Δ GATP. An explanation is that acidosis-related or other factors control oxidative phosphorylation additionally, at least under some conditions.
Respiratory changes associated with rapid eye movements in normo- and hypercapnia during sleep
Authors: Schäfer Thorsten , Schläfke Marianne E.
Published: December 2017

Rapid eye movements during rapid-eye-movement (REM) sleep are associated with rapid, shallow breathing. We wanted to know whether this effect persisted during increased respiratory drive by CO2. In eight healthy subjects, we recorded electroencephalographic, electrooculographic, and electromyographic signals, ventilation, and end-tidal[Formula: see text] during the night. Inspiratory[Formula: see text] was changed to increase end-tidal [Formula: see text] by 3 and 6 Torr. During normocapnia, rapid eye movements were associated with a decrease in total breath time by −0.71 ± 0.19 (SE) s ( P < 0.05) because of shortened expiratory time (−0.52 ± 0.08 s, P < 0.001) and with a reduced tidal volume (−89 ± 27 ml, P < 0.05) because of decreased rib cage contribution (−75 ± 18 ml, P < 0.05). Abdominal (−11 ± 16 ml, P = 0.52) and minute ventilation (−0.09 ± 0.21 ml/min, P = 0.66) did not change. In hypercapnia, however, rapid eye movements were associated with a further shortening of total breath time. Abdominal breathing was also inhibited (−79 ± 23 ml, P< 0.05), leading to a stronger inhibition of tidal volume and minute ventilation (−1.84 ± 0.54 l/min, P < 0.05). We conclude that REM-associated respiratory changes are even more pronounced during hypercapnia because of additional inhibition of abdominal breathing. This may contribute to the reduction of the hypercapnic ventilatory response during REM sleep.
Effects of acetylcholine and nitric oxide on forearm blood flow at rest and after a single muscle contraction
Authors: Brock R. W. , Tschakovsky M. E. , Shoemaker J. K. , Halliwill J. R. , Joyner M. J. , Hughson R. L.
Published: December 2017

We tested the hypothesis that ACh or nitric oxide (NO) might be involved in the vasodilation that accompanies a single contraction of the forearm. Eight adults (3 women and 5 men) completed single 1-s-duration contractions of the forearm to raise and lower a weight equivalent to ∼20% maximal voluntary contraction through a distance of 5 cm. In a second protocol, each subject had a cuff, placed completely about the forearm, inflated to 120 mmHg for a 1-s period, then released as a simulation of the mechanical effect of muscle contraction. Three conditions were studied, always in this order: 1) control, with intra-arterial infusion of saline; 2) after muscarinic blockade with atropine; and 3) after NO synthase inhibition with N G-monomethyl-l-arginine (l-NMMA) plus atropine. Forearm blood flow (FBF), measured by combined pulsed and echo Doppler ultrasound, was reduced at rest with l-NMMA-atropine compared with the other two conditions. After the single contraction, there were no effects of atropine, butl-NMMA reduced the peak FBF and the total postcontraction hyperemia. After the single cuff inflation, atropine had no effects, whereasl-NMMA caused changes similar to those seen after contraction, reducing the peak FBF and the total hyperemia. The observation thatl-NMMA reduced FBF in response to both cuff inflation and a brief contraction indicates that NO from the vascular endothelium might modulate the basal level of vascular tone and the mechanical component of the hyperemia with exercise. It is unlikely that ACh and NO from the endothelium are involved in the dilator response to a single muscle contraction.
Ambulatory impedance cardiography: a feasibility study
Authors: Sherwood Andrew , McFetridge Judy , Hutcheson J. Stanford
Published: December 2017

A wearable, ambulatory impedance monitor (AIM) has been developed to permit impedance cardiographic measurements while patients and volunteers engage in normal daily activities. The AIM system was developed for use with a new hybrid tetrapolar spot-band electrode configuration and was designed to be comfortable and inconspicuous. The objective of the present study was to provide a preliminary evaluation of AIM comparability with the widely validated Minnesota model 304B impedance cardiograph with standard tetrapolar band electrodes. Orthostatic challenge was used to systematically alter cardiac function in a laboratory setting in 11 healthy men and women. Both while the subjects were sitting and while they were standing, the AIM yielded measures of cardiac function, including heart rate, preejection period, left ventricular ejection time, and stroke volume, that were similar to those acquired by using the reference Minnesota 304B system (all Pearson R correlations > +0.87, all P < 0.001). Cardiac responses to postural shift, expressed as change measures from sitting to standing, were also comparable for the AIM and Minnesota reference monitoring systems. Potential applications, including the assessment of 24-h hemodynamic profiles, are illustrated and discussed.
Serum response factor mRNA induction in the hypertrophying chicken patagialis muscle
Authors: Carson James A. , Booth Frank W.
Published: December 2017

Gene expression in the stretched chicken patagialis (Pat) muscle has not been extensively examined. This study’s purpose was to determine the Pat muscle’s expression pattern of serum response factor (SRF), skeletal α-actin, and MyoD mRNAs after 3 days (onset of stretch), 6 days (end of first week of rapid growth), and 14 days (slowed rate of stretch-induced growth) of stretch. SRF mRNA demonstrated two species (B1 and B2), with B2 being more prevalent in the predominantly fast-twitch Pat muscle, compared with the slow-tonic muscle. Stretch overload increased B1 and B2 SRF mRNA concentrations, and the increase in B1 SRF mRNA concentration was greater at day 6compared with days 3 or 14. MyoD mRNA concentration was greater in 3-day-stretched Pat muscles, compared with days 6 or 14 . Skeletal α-actin mRNA concentration was not changed during the study. Gel mobility shift assays demonstrated that SRF binding with serum response element 1 of the skeletal α-actin promoter had no altered binding patterns from 6-day-stretched Pat nuclear extracts. It appears that SRF and MyoD mRNAs are induced in the stretch-overloaded Pat muscle but at different time points.
A method for isolating adult and neonatal airway smooth muscle cells and measuring shortening velocity
Authors: Driska S. P. , Laudadio R. E. , Wolfson M. R. , Shaffer T. H.
Published: December 2017

Methods are described for isolating smooth muscle cells from the tracheae of adult and neonatal sheep and measuring the single-cell shortening velocity. Isolated cells were elongated, Ca2+ tolerant, and contracted rapidly and substantially when exposed to cholinergic agonists, KCl, serotonin, or caffeine. Adult cells were longer and wider than preterm cells. Mean cell length in 1.6 mM CaCl2 was 194 ± 57 (SD) μm ( n = 66) for adult cells and 93 ± 32 μm ( n = 20) for preterm cells ( P < 0.05). Mean cell width at the widest point of the adult cells was 8.2 ± 1.8 μm ( n = 66) and 5.2 ± 1.5 μm ( n = 20) for preterm cells ( P < 0.05). Cells were loaded into a perfusion dish maintained at 35°C and exposed to agonists, and contractions were videotaped. Cell lengths were measured from 30 video frames and plotted as a function of time. Nonlinear fitting of cell length to an exponential model gave shortening velocities faster than most of those reported for airway smooth muscle tissues. For a sample of 10 adult and 10 preterm cells stimulated with 100 μM carbachol, mean (± SD) shortening velocity of the preterm cells was not different from that of the adult cells (0.64 ± 0.30 vs. 0.54 ± 0.27 s−1, respectively), but preterm cells shortened more than adult cells (68 ± 12 vs. 55 ± 11% of starting length, respectively; P < 0.05). The preparative and analytic methods described here are widely applicable to other smooth muscles and will allow contraction to be studied quantitatively at the single-cell level.
Effects of microgravity on maximal power of lower limbs during very short efforts in humans
Authors: Antonutto G. , Capelli C. , Girardis M. , Zamparo P. , di Prampero P. E.
Published: December 2017

The maximal power of the lower limbs was determined in four astronauts (age 37–53 yr) 1) during maximal pushes of ∼250 ms on force platforms [“maximal explosive power” (MEP)] or 2) during all-out bouts of 6–7 s on an isokinetic cycloergometer [pedal frequency 1 Hz: maximal cycling power (MCP)]. The measurements were done before and immediately after spaceflights of 31–180 days. Before flight, peak and mean values were 3.18 ± 0.38 and 1.5 ± 0.13 (SD) kW for MEP and 1.17 ± 0.12 and 0.68 ± 0.08 kW for MCP, respectively. After reentry, MEP was reduced to 67% after 31 days and to 45% after 180 days. MCP decreased less, attaining ∼75% of preflight level, regardless of the flight duration. The recovery of MCP was essentially complete 2 wk after reentry, whereas that of MEP was slower, a complete recovery occurring after an estimated time close to that spent in flight. In the same subjects, the muscle mass of the lower limbs, as assessed by NMR, decreased by 9–13%, irrespective of flight duration (J. Zange, K. Müller, M. Schuber, H. Wackerhage, U. Hoffmann, R. W. Günther, G. Adam, J. M. Neuerburg, V. E. Sinitsyn, A. O. Bacharev, and O. I. Belichenko. Int. J. Sports Med. 18, Suppl. 4: S308–S309, 1997). The larger fall in maximal power, compared with that in muscle mass, suggests that a fraction of the former (especially relevant for MEP) is due to the effects of weightlessness on the motor unit recruitment pattern.
Effect of short-term training on mitochondrial ATP production rate in human skeletal muscle
Authors: Starritt Emma C. , Angus Damien , Hargreaves Mark
Published: December 2017

Seven untrained volunteers [3 men, 4 women, 20.1 ± 2.0 (SD) yr, 66.0 ± 11.0 kg, 171 ± 13 cm] participated in a 10-day cycle exercise training program. Resting muscle samples were obtained from vastus lateralis before and after 5 and 10 days of training. Mitochondrial ATP production rate (MAPR) was assayed in isolated mitochondria by using a bioluminescence technique and referenced to the activity of glutamate dehydrogenase in the muscle sample. MAPR increased 136 and 161% after 10 days of training for the mitochondrial substrate combinations pyruvate + palmitoyl-l-carnitine + α-ketoglutarate + malate and palmitoyl-l-carnitine + malate, respectively. Total muscle glutamate dehydrogenase and citrate synthase activity increased 53 and 16%, respectively, after 5 days but did not significantly increase further after 10 days. The results from the present study indicate that MAPR, measured by using the substrate combinations pyruvate + palmitoyl-l-carnitine + α-ketoglutarate + malate and palmitoyl-l-carnitine + malate, can rapidly increase in response to endurance training.
Muscle glycogen accumulation after a marathon: roles of fiber type and pro- and macroglycogen
Authors: Asp Sven , Daugaard Jens R. , Rohde Thomas , Adamo Kristi , Graham Terry
Published: December 2017

Muscle glycogen remains subnormal several days after muscle damaging exercise. The aims of this study were to investigate how muscle acid-soluble macroglycogen (MG) and acid-insoluble proglycogen (PG) pools are restored after a competitive marathon and also to determine whether glycogen accumulates differently in the various muscle fiber types. Six well-trained marathon runners participated in the study, and muscle biopsies were obtained from the vastus lateralis of the quadriceps muscle before, immediately after, and 1, 2, and 7 days ( days 1, 2, and 7, respectively) after the marathon. During the race, 56 ± 3.8% of muscle glycogen was utilized, and a greater fraction of MG (72 ± 3.7%) was utilized compared with PG (34 ± 6.5%). On day 2, muscle glycogen and MG values remained lower than prerace values, despite a carbohydrate-rich diet, but they had both returned to prerace levels on day 7. The PG concentration was lower on day 1 compared with before the race, whereas there were no significant differences between the prerace PG concentration and the concentrations on days 2 and 7. On day 2 the glycogen concentration was particularly low in the type I fibers, indicating that local processes are important for the accumulation pattern. We conclude that a greater fraction of human muscle MG than of PG is utilized during a marathon and that accumulation of MG is particularly delayed after the prolonged exercise bout. Furthermore, factors produced locally appear important for the glycogen accumulation pattern.
Radiographic evidence of interstitial pulmonary edema after exercise at altitude
Authors: Anholm James D. , Milne Eric N. C. , Stark Paul , Bourne Jonathan C. , Friedman Paul
Published: December 2017

Pulmonary function abnormalities after exercise are suggestive of pulmonary edema; however, radiographic evidence is lacking. Well-trained cyclists were studied to determine whether there is radiographic evidence of pulmonary edema after endurance exercise (cycling distance 5.3–131.5 km) at altitude. Chest radiographs obtained before exercise were coded for later interpretation. Films obtained after exercise were coded with a different number. A total of 74 sets of posteroanterior and lateral films were analyzed by three radiologists for signs of pulmonary edema. Radiographic changes were graded on a three-point scale. An edema score was calculated by summing the score for each individual radiographic finding for each radiologist and an overall edema score representing the mean scores from all three radiologists. The overall edema score increased from 0.8 ± 1.2 before exercise to 1.8 ± 1.6 after exercise ( P < 0.01). These results suggest that, after prolonged high-intensity exercise at moderate altitude, there is radiographic evidence of early pulmonary edema in some cyclists.
NO-cGMP pathway accentuates the decrease in heart rate caused by cardiac vagal nerve stimulation
Authors: Sears Claire E. , Choate Julia K. , Paterson David J.
Published: December 2017

The role of the cardiac muscarinic-receptor-coupled nitric oxide (NO) pathway in the cholinergic control of heart rate (HR) is controversial. We investigated whether adding excessive NO or its intracellular messenger cGMP could significantly modulate the HR response to vagal nerve stimulation (VNS) in the anesthetized rabbit and isolated guinea pig atria. The NO donor molsidomine (0.2 mg/kg iv) significantly enhanced the decrease in HR seen with right VNS (5 Hz, 5 V, 30 s) in vivo. A qualitatively similar effect was seen with the NO donor sodium nitroprusside (SNP; 10 and 100 μM) during VNS in vitro. This effect was still present when the baseline shift in HR caused by SNP was eliminated by using the specific hyperpolarization-activated current antagonist 4-( N-ethyl- N-phenylamino)-1,2-dimethyl-6-(methylamino)-pyrimidinium chloride (ZD-7288, 1 μM). The accentuated decrease in HR with SNP during VNS was mimicked by the stable analog of cyclic GMP, 8-bromoguanosine 3′,5′-cyclic monophosphate (0.5 mM). This, however, was not seen with bath application of the stable analog of acetylcholine, carbamylcholine chloride (100 nM). We conclude that excessive NO enhances the magnitude of the decrease in HR caused by VNS. This effect appears to involve a presynaptic action via a cGMP-dependent pathway because it was not mimicked by bath-applied carbamylcholine chloride.
Liver AMP-activated protein kinase and acetyl-CoA carboxylase during and after exercise
Authors: Carlson C. L. , Winder W. W.
Published: December 2017

Exercise induces a decline in liver malonyl-CoA, an inhibitor of carnitine palmitoyltransferase-1. The purpose of these experiments was to determine whether this decrease in malonyl-CoA is accompanied by an activation of AMP-activated protein kinase (AMPK) and inactivation of acetyl-CoA carboxylase (ACC). Rats were killed at rest, after 10 min of running at 32 m/min up a 15% grade or at 0, 15, or 60 min postexercise after 120 min of running at 16 m/min. There was no significant difference in AMPK and ACC activities after 120 min of exercise, although a trend toward a decrease in ACC and an increase in AMPK was noted 15 min postexercise. After 10 min at 32 m/min, however, maximal ACC activity decreased from 487 ± 27 to 280 ± 39 nmol ⋅ g−1⋅ min−1, and the activation constant for citrate activation of ACC increased from 5.9 to 12.5 mM. AMPK activity increased from a resting value of 4.7 ± 0.4 to 9.8 ± 2.0 pmol ⋅ mg−1⋅ min−1after exercise. These data provide indirect evidence of phosphorylation and inactivation of liver ACC during heavy exercise. In contrast, the decrease in malonyl-CoA during long-term, low-intensity exercise may occur by mechanisms other than phosphorylation of ACC.
Critical closing pressure explains cerebral hemodynamics during the Valsalva maneuver
Authors: Dawson Suzanne L. , Panerai Ronney B. , Potter John F.
Published: December 2017

The Valsalva maneuver (VM), a voluntary increase in intrathoracic pressure of ∼40 mmHg, has been used to examine cerebral autoregulation (CA). During phase IV of the VM there are pronounced changes in mean arterial blood pressure (MABP), pulse interval, and cerebral blood flow (CBF), but the changes in CBF are of a much greater magnitude than those seen in MABP, a finding to date attributed to either a delay in activation of the CA mechanism or the inability of this mechanism to cope with the size and speed of the blood pressure changes involved. These changes in CBF also precede those in MABP, a pattern of events not explained by the physiological process of CA. Measurements of CBF velocity (transcranial Doppler) and MABP (Finapres) were performed in 53 healthy volunteers (aged 31–80 yr). By calculating beat-to-beat values of critical closing pressure (CCP) during the VM, we have found that this parameter suddenly drops at the start of phase IV, providing a coherent explanation for the large increase in CBF. If CCP is included in the estimation of cerebrovascular resistance, a temporal pattern more consistent with an autoregulatory response to the MABP overshoot is also found. CCP is intricately involved in the control of CBF during the VM and should be considered in the assessment of CA.
A source of experimental underestimation of aerosol bolus deposition
Authors: Verbanck S. , Darquenne C. , Prisk G. K. , Vincken W. , Paiva M.
Published: December 2017

We examined the measurement error in inhaled and exhaled aerosol concentration resulting from the bolus delivery system when small volumes of monodisperse aerosols are inspired to different lung depths. A laser photometer that illuminated ∼75% of the breathing path cross section recorded low inhaled bolus half-widths (42 ml) and negative deposition values for shallow bolus inhalation when the inhalation path of a 60-ml aerosol was straight and unobstructed. We attributed these results to incomplete mixing of the inhaled aerosol bolus over the breathing path cross section, on the basis of simultaneous recordings of the photometer with a particle-counter sampling from either the center or the edge of the breathing path. Inserting a 90° bend into the inhaled bolus path increased the photometer measurement of inhaled bolus half-width to 57 ml and yielded positive deposition values. Dispersion, which is predominantly affected by exhaled bolus half-width, was not significantly altered by the 90° bend. We conclude that aerosol bolus-delivery systems should ensure adequate mixing of the inhaled bolus to avoid error in measurement of bolus deposition.
An overview of phrenic nerve and diaphragm muscle development in the perinatal rat
Authors: Greer John J. , Allan Douglas W. , Martin-Caraballo Miguel , Lemke Robert P.
Published: December 2017

In this overview, we outline what is known regarding the key developmental stages of phrenic nerve and diaphragm formation in perinatal rats. These developmental events include the following. Cervical axons emerge from the spinal cord during embryonic (E) day 11. At ∼E12.5, phrenic and brachial axons from the cervical segments merge at the brachial plexi. Subsequently, the two populations diverge as phrenic axons continue to grow ventrally toward the diaphragmatic primordium and brachial axons turn laterally to grow into the limb bud. A few pioneer axons extend ahead of the majority of the phrenic axonal population and migrate along a well-defined track toward the primordial diaphragm, which they reach by E13.5. The primordial diaphragmatic muscle arises from the pleuroperitoneal fold, a triangular protrusion of the body wall composed of the fusion of the primordial pleuroperitoneal and pleuropericardial tissues. The phrenic nerve initiates branching within the diaphragm at ∼E14, when myoblasts in the region of contact with the phrenic nerve begin to fuse and form distinct primary myotubes. As the nerve migrates through the various sectors of the diaphragm, myoblasts along the nerve’s path begin to fuse and form additional myotubes. The phrenic nerve intramuscular branching and concomitant diaphragmatic myotube formation continue to progress up until E17, at which time the mature pattern of innervation and muscle architecture are approximated. E17 is also the time of the commencement of inspiratory drive transmission to phrenic motoneurons (PMNs) and the arrival of phrenic afferents to the motoneuron pool. During the period spanning from E17 to birth (gestation period of ∼21 days), there is dramatic change in PMN morphology as the dendritic branching is rearranged into the rostrocaudal bundling characteristic of mature PMNs. This period is also a time of significant changes in PMN passive membrane properties, action-potential characteristics, and firing properties.
Effects of muscle perfusion pressure on fatigue and systemic arterial pressure in human subjects
Authors: Wright Julie R. , McCloskey D. I. , Fitzpatrick Richard C.
Published: December 2017

The effects of changes in arterial perfusion across the physiological range on the fatigue of a working human hand muscle were studied in seven normal subjects. With the hand above heart level, subjects made repeated isometric contractions of the adductor pollicis muscle at 50% of maximal voluntary contraction in a 6-s on, 4-s off cycle. To assess fatigue, a maximal isometric twitch was elicited in each “off” period by electrical stimulation of the ulnar nerve. The experiment was repeated at least 2 days later with the hand at heart level. Five subjects showed faster fatigue with the arm elevated, and two subjects showed little difference in fatigue for the two conditions. Central blood pressure rose in proportion to fatigue for the subjects overall and returned quickly to its initial level afterwards. We conclude that human muscle fatigue can be increased by physiological reductions in perfusion pressure. Central blood pressure increases as the muscle fatigues, a response that may partially offset declining muscle performance.
Mechanism for the posture-specific plasma volume increase after a single intense exercise protocol
Authors: Nagashima Kei , Mack Gary W. , Haskell Andrew , Nishiyasu Takeshi , Nadel Ethan R.
Published: December 2017

To test the hypothesis that exercise-induced hypervolemia is a posture-dependent process, we measured plasma volume, plasma albumin content, and renal function in seven healthy subjects for 22 h after single upright (Up) or supine (Sup) intense (85% peak oxygen consumption rate) exercise. This posture was maintained for 5 h after exercise. Plasma volume decreased during exercise but returned to control levels by 5 h of recovery in both postures. By 22 h of recovery, plasma volume increased 2.4 ± 0.8 ml/kg in Up but decreased 2.1 ± 0.8 ml/kg in Sup. The plasma volume expansion in Up was accompanied by an increase in plasma albumin content (0.11 ± 0.04 g/kg; P < 0.05). Plasma albumin content was unchanged in Sup. Urine volume and sodium clearance were lower in Up than Sup ( P < 0.05) by 5 h of recovery. These data suggest that increased plasma albumin content contributes to the acute phase of exercise-induced hypervolemia. More importantly, the mechanism by which exercise influences the distribution of albumin between extra- and intravascular stores after exercise is altered by posture and is unknown. We speculate that factors associated with postural changes (e.g., central venous pressure) modify the increase in plasma albumin content and the plasma volume expansion after exercise.
Hindlimb immobilization applied to 21-day-oldmdx mice prevents the occurrence of muscle degeneration
Authors: Mokhtarian Asghar , Lefaucheur Jean Pascal , Even Patrick C. , Sebille Alain
Published: December 2017

Dystrophin-deficient skeletal muscles of mdx mice undergo their first rounds of degeneration-regeneration at the age of 14–28 days. This feature is thought to result from an increase in motor activity at weaning. In this study, we hypothesize that if the muscle is prevented from contracting, it will avoid the degenerative changes that normally occur. For this purpose, we developed a procedure of mechanical hindlimb immobilization in 3-wk-old mice to restrain soleus (Sol) and extensor digitorum longus (EDL) muscles in the stretched or shortened position. After a 14-day period of immobilization, the striking feature was the low percentage of regenerated (centronucleated) myofibers in Sol and EDL muscles, regardless of the length at which they were fixed, compared with those on the contralateral side (stretched Sol: 8.4 ± 6.5 vs. 46.6 ± 10.3%, P = 0.0008; shortened Sol: 1.2 ± 1.6 vs. 50.4 ± 16.4%, P = 0.0008; stretched EDL: 05 ± 0.5 vs. 32.9 ± 17.5%, P = 0.002; shortened EDL: 3.3 ± 3.1 vs. 34.7 ± 11.1%, P = 0.002). Total numbers of myofibers did not change with immobilization. This study shows that limb immobilization prevents the occurrence of the first round of myofiber necrosis in mdx mice and suggests that muscle contractions play a role in the skeletal muscle degeneration of dystrophin-deficient mdx mouse muscles.
α-Lipoic acid supplementation: tissue glutathione homeostasis at rest and after exercise
Authors: Khanna Savita , Atalay Mustafa , Laaksonen David E. , Gul Mustafa , Roy Sashwati , Sen Chandan K.
Published: December 2017

Antioxidant nutrients have demonstrated potential in protecting against exercise-induced oxidative stress. α-Lipoic acid (LA) is a proglutathione dietary supplement that is known to strengthen the antioxidant network. We studied the effect of intragastric LA supplementation (150 mg/kg, 8 wk) on tissue LA levels, glutathione metabolism, and lipid peroxidation in rats at rest and after exhaustive treadmill exercise. LA supplementation increased the level of free LA in the red gastrocnemius muscle and increased total glutathione levels in the liver and blood. The exercise-induced decrease in heart glutathione S-transferase activity was prevented by LA supplementation. Exhaustive exercise significantly increased thiobarbituric acid-reactive substance levels in the liver and red gastrocnemius muscle. LA supplementation protected against oxidative lipid damage in the heart, liver, and red gastrocnemius muscle. This study reports that orally supplemented LA is able to favorably influence tissue antioxidant defenses and counteract lipid peroxidation at rest and in response to exercise.
Effect of a single bout of acute exercise on plasma human immunodeficiency virus RNA levels
Authors: Roubenoff Ronenn , Skolnik Paul R. , Shevitz Abby , Snydman Laura , Wang Alicia , Melanson Suzanne , Gorbach Sherwood
Published: December 2017

Acute exercise is known to activate the immune system and thus could lead to increased human immunodeficiency virus (HIV) replication. We sought to determine whether a single acute bout of exercise, similar to what people experience when starting an intensive exercise program, has a detrimental effect on plasma HIV RNA levels. Twenty-five patients with HIV infection performed one 15-min bout of acute exercise. Absolute neutrophil counts, serum creatine phosphokinase, and 72-h urinary 3-methylhistidine (a marker of muscle protein breakdown) were measured before and after the exercise, along with plasma HIV RNA levels. There were increases in neutrophil counts ( P < 0.06), serum creatine phosphokinase ( P < 0.01), and urinary 3-methylhistidine ( P < 0.01) in response to exercise, indicating a mild acute-phase response with muscle proteolysis. However, mean HIV RNA, which was elevated at baseline in 22 of the 25 subjects (mean of 4 × 105 ± 0.7 × 105 copies/ml), did not increase during the week after exercise ( P = 0.12). Small changes in RNA were seen in the three subjects with initially undetectable HIV RNA, but the significance of these changes is unclear. Acute exercise does not have a deleterious effect on HIV replication in adults with high viral loads. Because regular exercise training has not been shown to activate the acute-phase response, the lack of increased viral loads in response to an acute exercise intervention suggests that exercise training is safe in people with HIV infection.
Hyperosmolar saline induces reflex nasal secretions, evincing neural hyperresponsiveness in allergic rhinitis
Authors: Sanico Alvin M. , Philip George , Lai Gordon K. , Togias Alkis
Published: December 2017

We investigated whether hyperosmolar saline (HS), applied via paper disk onto the septum of one nostril, induces a nasal secretory response. Furthermore, we examined whether this response is accentuated in patients with active allergic rhinitis (AR) compared with healthy volunteers. Unilateral HS produced significant nasal secretions both ipsilateral and contralateral to the site of challenge in the AR group and only ipsilaterally in the healthy group. The HS-induced nasal secretions were significantly greater in the AR vs. the healthy subjects. In a separate study, we ascertained that the nasal response to HS is neurally mediated and found that ipsilateral nerve blockade with lidocaine significantly attenuates the HS-induced secretions bilaterally. In another group of AR subjects, we determined whether nociceptive fibers were involved in this response and found that sensory nerve desensitization with repeated application of capsaicin attenuated the HS-induced nasal secretions. Finally, we determined whether the secretory hyperresponsiveness in AR is attributable to increased reactivity of submucosal glands rather than of nerves. We found that the dose response to methacholine, which directly stimulates the glands, was identical among AR and healthy subjects. We conclude that, in AR, nasal challenge with HS induces significantly greater reflex secretions involving capsaicin-sensitive nerve fibers, consistent with the notion of neural hyperresponsiveness in this disease.
Vagal esophageal receptors in anesthetized dogs: mechanical and chemical responsiveness
Authors: Sekizawa S.-I. , Ishikawa T. , Sant’Ambrogio F. B. , Sant’Ambrogio G.
Published: December 2017

This study was performed to evaluate the characteristics of esophageal receptors in anesthetized and artificially ventilated dogs. The electrical activity of the esophageal afferents was recorded from the peripheral cut end of the cervical vagus nerve. A cuffed catheter was inserted into the esophagus at the level of the third tracheal ring and was used to establish the esophageal location of the endings. Most of the receptors were localized in the intrathoracic portion of the esophagus. The majority of the receptors studied (36 of 43) showed a slow adaptation to a maintained stretch of the esophageal wall. Vagal cooling blocked receptor activity at temperatures ranging from 3.5 to 25°C. Twenty-eight of 43 receptors, including 4 rapidly adapting endings (RAR), were challenged with saline, HCl + pepsin (HCl-P; pH 1) and distilled water (8 ml, 37°C). HCl-P solutions specifically stimulated only three receptors; saline or water did not. Five slowly adapting receptors and two RARs were also challenged with topically applied capsaicin; only one RAR was stimulated. To ascertain a possible effect of smooth muscle contraction, 17 receptors were tested with intravenous injections of ACh and/or asphyxia; only 4 were stimulated. These characteristics do not support an important reflexogenic role of the esophagus in response to chemical stimuli.
Enhanced activity of carotid body chemoreceptors in rabbits with heart failure: role of nitric oxide
Authors: Sun Shu-Yu , Wang W. , Zucker I. H. , Schultz H. D.
Published: December 2017

An enhanced peripheral chemoreflex has been documented in patients with chronic heart failure (CHF). This study aimed to examine the characteristics of carotid body (CB) chemoreceptors in response to isocapnic hypoxia in a rabbit model of pacing-induced CHF and to evaluate the possible role that nitric oxide (NO) plays in the altered characteristics. The chemosensitive characteristics of the CB were evaluated by recording single-unit activity from the carotid sinus nerve in both an intact and a vascularly isolated preparation. It was found that the baseline discharge under normoxia (intact preparation: arterial [Formula: see text] 90–95 Torr; isolated preparation: [Formula: see text]100–110 Torr) and the chemosensitivity in response to graded hypoxia ([Formula: see text] 40–70 Torr) were enhanced in CHF vs. sham rabbits. These alterations were independent of the CB preparations (intact vs. isolated). NO synthase inhibition by N ω-nitro-l-arginine increased the baseline discharge and the chemosensitivity in the intact preparation, whereas l-arginine (10−5 M) inhibited the baseline discharge and the chemosensitivity in the isolated preparation in sham but not in CHF rabbits. S-nitroso- N-acetylpenicillamine, an NO donor, inhibited the baseline discharge and the chemosensitivity in both CB preparations in CHF rabbits but only in the isolated preparation in sham rabbits. The amount of NO produced in vitro by the CB under normoxia was less in CHF rabbits than in sham rabbits ( P < 0.05). NO synthase-positive varicosities of nerve fibers within the CB were less in CHF rabbits than in sham rabbits ( P < 0.05). These data indicate that an enhanced input from CB occurs in the rabbit model of pacing-induced CHF and that an impairment of NO production may contribute to this alteration.