bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in cardiovascular adaptations to endurance exercise training between older men and women
Authors: Spina R. J. , Ogawa T. , Kohrt W. M. , Martin W. H. , Holloszy J. O. , Ehsani A. A.
Published: December 2017

Recent studies have shown that people in their seventh decade are able to adapt to exercise training with an increase in maximal O2 uptake (VO2max) similar in relative magnitude to that observed in young people. The purpose of this study was to determine the relative contributions of increases in stroke volume and O2 extraction to the training-induced increase in VO2max in older men and women. Fifteen men [63 +/- 3 (SE) yr] and 16 women (64 +/- 3 yr), in good health, participated in 9–12 mo of endurance exercise training at 70 to 85% of maximal heart rate for 45 min/day, 4 days/wk. VO2max increased 19% (2.35 +/- 0.1 to 2.8 +/- 0.1 l/min; P < 0.01) in the men and 22% (1.36 +/- 0.1 to 1.66 +/- 0.1 l/min; P < 0.01) in the women in response to training. In the men, stroke volume during maximal exercise was 15% higher after training, and this increase accounted for 66% of the increase in VO2max. The remainder of the increase in VO2max was accounted for by a 7% greater arteriovenous O2 content difference during maximal exercise. In contrast, training resulted in no change in stroke volume in women, in whom the entire increase in VO2max was accounted for by a greater arteriovenous O2 content difference (12.2 +/- 0.4 before vs. 14.4 +/- 0.4 ml O2/100 ml blood after; P < 0.01) during maximal exercise. There were no changes in these variables in the control subjects. The mechanisms responsible for the training-induced increase in VO2max in the older men were similar to those found in young people.(ABSTRACT TRUNCATED AT 250 WORDS)
Cholinergic and opioid involvement in release of growth hormone during exercise and recovery
Authors: Thompson D. L. , Weltman J. Y. , Rogol A. D. , Metzger D. L. , Veldhuis J. D. , Weltman A.
Published: December 2017

Cholinergic and opioid pathways have been implicated as mediators of the increased growth hormone (GH) release observed during exercise. This study compared the GH responses induced by a moderate-intensity exercise bout during treatment with placebo (Plac), the opioid receptor antagonist naltrexone (Nalt), the indirect cholinergic agonist pyridostigmine (PD), or a combination of the two drugs (P + N). Ten active males served as subjects (age, 25.1 +/- 0.6 yr; wt, 79.7 +/- 2.5 kg; % body fat, 14.9 +/- 1.4; peak oxygen consumption, 46.2 +/- 2.7 ml.kg-1 x min-1). Blood samples were drawn at 5-min intervals during the 4.5-h testing period to determine the GH concentration. The testing period was divided as follows: 0600–700 h = baseline, 0700–0800 h = preexercise, 0800–0830 h = exercise, and 0830–1030 h = recovery. Drugs were administered 1 h before exercise (at 0700 h). Exercise consisted of 30 min of cycling at an individualized work load previously found to elicit a blood lactate concentration of 2.5 mM. Heart rate, oxygen consumption, blood lactate, and blood glucose were measured throughout the exercise period. Results indicated that neither the resting GH concentration nor the metabolic parameters during exercise were altered by the treatments. Peak serum GH concentration was not significantly altered by the treatments (range 7.3 +/- 2.0 to 12.6 +/- 4.4 micrograms/l).(ABSTRACT TRUNCATED AT 250 WORDS)
Carbonic anhydrases in cytosol, nucleus, and membranes of rat liver
Authors: Dodgson S. J. , Quistorff B. , Ridderstrale Y.
Published: December 2017

The relative contribution of each functional carbonic anhydrase (CA) isozyme to liver CA activity of fed or starved adult male rats has been determined. The functional isozymes are CA II, CA III, CA IV, and CA V. Total CA, CA III, CA II, CA IV, and CA V activities (in mumol CO2 converted.min-1.liver-1), as measured by mass spectrometric assay using NaHC18O16O in aqueous solution at pH 7.4 and 37 degrees C, were 94,867, 38,621, 37,000, 14,515, and < 5,000 in fed rats and 40,630, 10,498, 9,137, 18,338, and < 2,600 in starved rats, respectively. CA II was unevenly distributed throughout the liver. In perivenous and periportal cytosols, as determined by the digitonin-pulse perfusion technique, CA II activity was (in mg cytosolic protein-1) 325 and 69 in fed rats and 167 and 33 in starved rats, respectively. CA III was more evenly distributed and less affected by starvation: CA III activity in perivenous and periportal cytosols was (in mg cytosolic protein-1) 84 and 55 in fed rats and 113 and 52 in starved rats, respectively. Evidence that CA III was concentrated in the nucleus was obtained histochemically by the Ridderstrale cobalt-precipitation technique in 2-microns-thick glutaraldehyde-fixed sections from adult fed rats. Liver CA activity was higher in the perivenous hepatocytes in cytosols and nuclei, whereas CA IV was homogeneously distributed. Incubation of the 2-microns sections with 1 microM acetazolamide resulted in inhibition of all membrane-associated CA, 50% of cytosolic CA, and no nuclear CA.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of prolonged alveolar hypoxia on pulmonary arterial pressure and segmental vascular resistance
Authors: Welling K. L. , Sanchez R. , Ravn J. B. , Larsen B. , Amtorp O.
Published: December 2017

The time course of hypoxic pulmonary vasoconstriction and its segmental distribution were studied during prolonged (150 min) alveolar hypoxia in in vivo dog lungs at constant-flow perfusion. With the pulmonary and the systemic circulations separated by two extracorporeal circuits, adequate systemic oxygenation was achieved throughout the experiments. The pulmonary circulation exhibited a time-related biphasic hypoxic vasoconstrictor response: an initial rapid contraction [79 +/- 11% (SE) above control level] was followed by a partial relaxation when a second slow and sustained vasoconstriction (92 +/- 13% above control level) superseded. We partitioned the pulmonary circulation into two segments by arterial occlusion: an upstream arterial segment and a downstream segment consisting of a middle and a venous segment. Measurements were performed at baseline and during the late sustained vasoconstrictor response. Prolonged alveolar hypoxia increased pulmonary capillary pressure by 90 +/- 18%, the site of pulmonary vasomotion being the arterial upstream and downstream middle and venous segments.
Progressive stretch overload of skeletal muscle results in hypertrophy before hyperplasia
Authors: Antonio J. , Gonyea W. J.
Published: December 2017

Intermittent stretch of the anterior latissimus dorsi (ALD) muscle produces fiber hypertrophy without fiber hyperplasia (J. Appl. Physiol. 74: 1893–1898, 1993). This study was undertaken to determine if a progressive increase in load and duration of stretch would induce extremely large muscle fiber areas or if the fibers would reach a critical size before the onset of fiber hyperplasia. Weights ranging from 10 to 35% of the bird's mass were attached to the right wing of 26 adult quail while the left wing served as the intra-animal control. The stretch protocol was as follows: day 1 (10% wt), days 2 and 3 (rest), day 4 (15% wt), days 5–7 (rest), day 8 (20% wt), days 9 and 10 (rest), days 11–14 (25% wt), days 15 and 16 (rest), and days 17–38 (35% wt). Birds were killed after 12, 16, 20, 24, and 28 days of stretch not including rest days. Muscle mass increased 174% (12 days), 196% (16 days), 225% (20 days), 264% (24 days), and 318% (28 days). Muscle length increased 60% (12 days), 34% (16 days), 59% (20 days), 50% (24 days), and 51% (28 days). Mean fiber area increased 111% (12 days), 142% (16 days), 75% (20 days), 90% (24 days), and 39% (28 days). Fiber number, which was measured histologically, increased significantly by 82% only in the 28 days of stretch group. The percentage of slow tonic fibers did not change for any of the time points examined.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of inspired CO2 on ventilation and perfusion heterogeneity in hyperventilated dogs
Authors: Domino K. B. , Swenson E. R. , Polissar N. L. , Lu Y. , Eisenstein B. L. , Hlastala M. P.
Published: December 2017

We studied the effect of inspired CO2 on ventilation-perfusion (VA/Q) heterogeneity in dogs hyperventilated under two different tidal volume (VT) and respiratory rate conditions with the use of the multiple inert gas elimination technique. Dogs anesthetized with pentobarbital sodium were hyperventilated with an inspired fraction of O2 of 0.21 by using an increased VT (VT = 30 ml/kg at 18 breaths/min) or an increased respiratory rate (VT = 18 ml/kg at 35 breaths/min). The arterial CO2 tension (PaCO2) was varied to three levels (20, 35, and 52 Torr) by altering the inspired PCO2. The orders of type of ventilation and PaCO2 level were randomized. Compared with normocapnia, VA/Q heterogeneity was increased during hypocapnia induced by increased respiratory rate ventilation, which was indicated by an increase in dispersion indexes and arterial-alveolar inert gas partial pressure difference areas (P < 0.01). In contrast, VA/Q heterogeneity was not affected by hypocapnia when a large VT ventilation was used. Under the conditions of our study, hypercapnia did not result in statistically significant changes in VA/Q heterogeneity with either type of ventilation. Increased VT ventilation reduced dead space at all PaCO2 levels (P < 0.01) and reduced the log standard deviation of the ventilation distribution during normocapnia (P < 0.05) and hypocapnia (P < 0.01). We conclude that hypocapnia increased VA/Q heterogeneity when hyperventilation was achieved with a rapid respiratory rate. Therefore, a lack of improvement in VA/Q matching with inhaled CO2 may be associated with the use of a large VT. These data suggest that hypocapnic bronchoconstriction may be important in mediating hypocapnia-induced VA/Q inequality in dogs.
Effects of detraining on endurance capacity and metabolic changes during prolonged exhaustive exercise
Authors: Madsen K. , Pedersen P. K. , Djurhuus M. S. , Klitgaard N. A.
Published: December 2017

The effects of 4 wk of detraining on maximal O2 uptake (VO2max) and on endurance capacity defined as the maximal time to exhaustion at 75% of VO2max were studied in nine well-trained endurance athletes. Detraining consisted of one short 35-min high-intensity bout per week as opposed to the normal 6–10 h/wk. Detraining had no effect on VO2max (4.57 +/- 0.10 vs. 4.54 +/- 0.08 l/min), but endurance capacity decreased by 21% from 79 +/- 4 to 62 +/- 4 min (P < 0.001). Endurance exercise respiratory exchange ratio was higher in the detrained than in the trained state (0.91 +/- 0.01 vs. 0.89 +/- 0.01; P < 0.01). Muscle [K+] values were unchanged during exercise and were similar in the trained and detrained states. Muscle [Mg2+] values were similar at rest and at minute 40 (30.3 +/- 0.9 vs. 30.8 +/- 0.6 mmol/kg dry wt) but increased significantly at exhaustion to 33.8 +/- 1.0 mmol/kg dry wt in the trained state and to 33.9 +/- 0.9 mmol/kg dry wt in the detrained state. The elevated muscle [Mg2+] at exhaustion could contribute to fatigue in prolonged exercise through an inhibition of Ca2+ release from sarcoplasmic reticulum. It is concluded that the endurance capacity can vary considerably during detraining without changes in VO2max. Altered substrate utilization or changes in electrolyte regulation may account for the reduced endurance capacity.
Control of bronchomotor tone during perinatal development in sheep
Authors: Perez Fontan J. J. , Kinloch L. P.
Published: December 2017

To characterize the perinatal maturation of the cholinergic control of the airways, we compared the effects of bilateral cervical vagotomy and supramaximal vagal stimulation on the airway resistances of 7 premature (130–133 days of gestation), 11 term newborn, and 9 9-wk-old lambs anesthetized with pentobarbital. Resistances were partitioned between central and peripheral airways with catheters placed retrogradely into peripheral bronchi and capsules attached to the pleural surface in communication with subpleural air spaces. The central and peripheral airway resistances of premature and term newborn lambs and the peripheral resistance of 9-wk-old lambs decreased after vagotomy but only when the lungs were ventilated with small tidal volumes at mean transpulmonary pressures < or = 7.5 cmH2O. Vagotomy caused smaller absolute changes in central airway resistance than vagal stimulation. In contrast, both vagotomy and vagal stimulation produced similar absolute changes in peripheral airway resistance, indicating that resting cholinergic outflow is preferentially distributed to the peripheral airways even at the earlier ages. The effects of vagal stimulation on airway resistance were prevented by atropine. Our results prove that a resting bronchomotor tone can be present in both central and peripheral airways before the term of gestation in sheep. This tone depends on the activity of cholinergic fibers in the vagus and can be regionally controlled.
Upper airway muscle activity during sustained hypoxia in awake humans
Authors: Okabe S. , Hida W. , Kikuchi Y. , Kurosawa H. , Midorikawa J. , Chonan T. , Takishima T. , Shirato K.
Published: December 2017

To examine the effects of sustained hypoxia on upper airway and chest wall muscle activity in humans, we measured genioglossus muscle (GG) activity, inspiratory intercostal muscle (IIM) activity, and ventilation during sustained hypoxia in 17 normal subjects and 17 patients with obstructive sleep apnea (OSA). The trial of sustained hypoxia was performed as follows: after an equilibration period of 3 min, isocapnic hypoxia (arterial O2 saturation = 80 +/- 2%) was maintained for 20 min. GG EMG was measured with a fine-wire electrode inserted percutaneously, and IIM EMG was measured with surface electrodes. Ventilatory response to sustained hypoxia was initially increased and subsequently decreased. Stable phasic GG activity during spontaneous tidal breathing was observed in 6 normal subjects and 10 patients with OSA. Responses of GG and IIM activities to sustained hypoxia showed a biphasic response qualitatively similar to the ventilatory response in these 16 subjects. The absolute value of the subsequent decline in GG activity was similar to that of the initial increase, whereas the subsequent decline in IIM activity was smaller than that of the initial increase. Percent GG activity was significantly lower than both percent IIM activity and percent minute ventilation during the decline and plateau phases. There were no significant differences in ventilatory and EMG responses between the normal subjects and the patients with OSA. We conclude that, during wakefulness, upper airway muscle activity declined to a greater extent than inspiratory pump muscle activity during sustained hypoxia.
Anaerobic energy release in working muscle during 30 s to 3 min of exhausting bicycling
Authors: Medbo J. I. , Tabata I.
Published: December 2017

To examine the anaerobic energy release during intense exercise, 16 healthy young men cycled as long as possible at constant powers chosen to exhaust the subjects in approximately 30 s, 1 min, or 2#x2013;3 min. Muscle biopsies were taken before and approximately 10 s after exercise and analyzed for lactate, phosphocreatine (PCr), and other metabolites. O2 uptake was measured for determination of the accumulated O2 deficit (a whole body measure of the anaerobic energy release), and this indirect measure of the anaerobic energy release was compared with a direct value obtained from measured muscle metabolites. Muscle lactate concentration rose by 30.0 +/- 1.2 mmol/kg and muscle PCr concentration fell by 12.4 +/- 0.9 mmol/kg during the 2#x2013;3 min of exhausting exercise. The anaerobic ATP production was consequently 58 +/- 2 mmol/kg wet muscle mass, which may be the maximum anaerobic energy release for human muscle during bicycling. Because the anaerobic ATP production was 6 and 32% less for 1 min and 30 s of exercise, respectively, than for 2 min of exercise (P < 0.03), 2 min of exhausting exercise may be required for maximal use of anaerobic sources. Lactate production provided three times more ATP than PCr breakdown for all three exercise durations. There was a close linear relationship between the rates of anaerobic ATP production in muscle and the value estimated for the whole body by the O2 deficit (r = 0.94). This suggests that the accumulated O2 deficit is a valid measure of the anaerobic energy release during bicycling.
Effect of hypercapnia and hypoxia on arytenoideus muscle activity in normal adult humans
Authors: Kuna S. T. , Insalaco G. , Villeponteaux D. R. , Vanoye C. R. , Smickley J. S.
Published: December 2017

The electrical activity of the arytenoideus muscle, a vocal cord adductor, was measured in 14 normal adult humans during progressive isocapnic hypoxia and progressive hyperoxic hypercapnia. Electromyograms of the arytenoideus were obtained with intramuscular hooked-wire electrodes implanted by means of a fiber-optic nasopharyngoscope. Correct placement of the electrodes was confirmed by discharge patterns during voluntary maneuvers. In three of the subjects, respiratory-related arytenoideus activity was not present during quiet breathing or chemical stimulation. During quiet breathing in the 11 other subjects, the arytenoideus exhibited phasic activity during expiration and usually tonic activity throughout the respiratory cycle. Phasic and tonic arytenoideus activity decreased under hypoxic and hypercapnic conditions. At higher levels of chemical stimulation in many subjects, short abrupt bursts of activity were frequently present at the transitions between inspiration and expiration. To determine the mechanical effect of the latter electromyographic findings, arytenoideus activity and fiber-optic images of the glottic aperture were simultaneously recorded in nine additional normal adult human subjects during progressive hyperoxic hypercapnia. The short abrupt bursts of arytenoideus activity were usually associated with a decrease in glottic aperture, although no change and an increase in glottic aperture were observed in individual subjects. The results suggest that the arytenoideus muscle may have an important role in the control of ventilation in normal human subjects.
Demonstration of pulmonary vascular perfusion by electron and light microscopy
Authors: Konig M. F. , Lucocq J. M. , Weibel E. R.
Published: December 2017

To estimate the fraction of dense pulmonary capillary network that is perfused under physiological conditions, we developed a new method for the demonstration of in vivo capillary perfusion by light and electron microscopy. Blood plasma was labeled by 8-nm colloidal gold particles coated with rabbit serum albumin. In anesthetized rabbits, 4#x2013;5 ml of this tracer were injected into the right atrium. Two and 15 min later, the circulation was interrupted by a snare around the heart, and the lung was fixed by instillation with glutaraldehyde. Gold particles were found in the plasma space of alveolar capillaries as well as in other organs. A random sample of thin sections studied by electron microscopy revealed that the entire capillary bed of the lung was perfused at least with plasma within 2 min after tracer infusion. Light microscopy of silver-enhanced sections showed areas with different staining intensities but no obviously unperfused capillaries. The concept of capillary recruitment, which would require a significant fraction of capillaries unperfused at rest, may have to be reassessed to consider time factors as well as the two-phase nature of blood; red blood cells and plasma may take different paths.
Growth of airways and air spaces in teenagers is related to sex but not to symptoms
Authors: Merkus P. J. , Borsboom G. J. , Van Pelt W. , Schrader P. C. , Van Houwelingen H. C. , Kerrebijn K. F. , Quanjer P. H.
Published: December 2017

To determine growth patterns of the lung and airways in adolescents, we analyzed maximal expiratory flow-volume curves, closing capacity, and residual volume. They were obtained every 6 mo for up to 7 yr in 430 boys and 125 girls (11–19 yr), of whom 143 boys and 36 girls were classified as symptomatic; symptoms were most often minor and limited to childhood. Development of flows vs. volumes was used to investigate growth of the airways relative to lung size. A model of isotropic growth of the airways and air spaces (J. Appl. Physiol. 65: 822–828, 1988) was modified for increasing elastic recoil pressure with growth. Growth of airways relative to volume occurred faster in teenage boys than in teenage girls and was compatible with isotropic growth in 92% of asymptomatic boys and in 44% of asymptomatic girls: dysanaptic growth in teenage girls seems to be a normal phenomenon and not a unique characteristic of symptomatic subjects. Subjects with respiratory symptoms in childhood and/or adolescence have lower flows for a given lung size and airway closure at a greater lung volume when they enter adulthood. However, no difference in patterns of lung growth was observed in association with the presence of respiratory symptoms.
Tracheal and neck position influence upper airway airflow dynamics by altering airway length
Authors: Thut D. C. , Schwartz A. R. , Roach D. , Wise R. A. , Permutt S. , Smith P. L.
Published: December 2017

Upper airway obstruction during sleep is characterized by inspiratory airflow limitation and reductions in maximal inspiratory airflow (VImax). To determine how mechanical factors modulate VImax, we analyzed pressure-flow relationships obtained in the isolated upper airway of paralyzed cats. VImax and its determinants, the pharyngeal critical pressure (Pcrit) and the nasal resistance (Rn) upstream to the flow-limiting site (FLS), were measured as caudal tracheal displacement, neck position, and airway length were systematically varied. As the proximal tracheal stump was displaced caudally, graded increases in VImax from 145.3 +/- 90.8 (SD) to 285.9 +/- 117.5 ml/s (P < 0.02) and decreases in Pcrit from -3.0 +/- 3.0 to -9.5 +/- 3.4 cmH2O (P < 0.002) were seen without any significant change in Rn. During neck flexion, significant decreases in VImax from 192.1 +/- 68.5 to 87.2 +/- 48.4 ml/s (P = 0.001), increases in Pcrit from -5.3 +/- 2.03 cmH2O to -1.6 +/- 1.4 cmH2O (P < 0.001), and decreases in Rn from 29.7 +/- 12.2 cmH2O.l-1.s to 16.2 +/- 8.9 cmH2O.l-1.s (P < 0.001) were noted compared with the neutral or extended neck position. Relative to the neutral airway length, upper airway length was found to decrease by 1.15 +/- 0.14 cm during neck flexion and to lengthen by 0.45 +/- 0.12 cm during neck extension. When tracheal displacement and neck position were altered, VImax and Rn correlated directly and Pcrit correlated inversely with airway length (P < 0.001). We conclude that alterations in airflow mechanics with caudal tracheal displacement and changes in neck positions are primarily due to alterations in airway length.
Effect of ischemia-reperfusion on diaphragm strength and fatigability
Authors: Supinski G. , Stofan D. , DiMarco A.
Published: December 2017

Although episodes of prolonged limb skeletal muscle ischemia followed by periods of reperfusion and reoxygenation are known to elicit free radical-mediated injury, the susceptibility of the diaphragm to this form of injury is not known. The purpose of the present study was to determine the effects of a period of severe partial ischemia, followed by reperfusion, on diaphragm contractile function. We also examined the effect of administration of a free radical scavenger, dimethyl sulfoxide (DMSO), on the diaphragmatic response to ischemia-reperfusion. Experiments were performed on three groups of anesthetized dogs in which a vascularly isolated strip of diaphragm was dissected in situ: 1) a control group in which the diaphragm was perfused at the ambient systemic pressure, 2) a group in which the diaphragm was made ischemic for 3 h and reperfused for 1 h, and 3) a group given DMSO before periods of ischemia and reperfusion. In all groups, we measured diaphragm strip strength and fatigability; we also assessed diaphragm blood flow at several levels of contractile activity. Periods of ischemia, followed by reperfusion, were found to produce a downward shift of the diaphragm force-frequency relationship and also to markedly increase diaphragm fatigability. Diaphragm blood flow at rest and at low levels of contractile activity was unaffected by ischemia-reperfusion, but the flow achieved during fatiguing contractions was appreciably lower than that in nonischemic control animals. DMSO administration protected the diaphragm from the effects of ischemia-reperfusion, preventing alterations in fatigability and strength. Diaphragm flow in DMSO-treated animals was similar to that in controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Reflex bronchial vasodilation in dogs evoked by injection of a small volume of water into a bronchus
Authors: Pisarri T. E. , Coleridge H. M. , Coleridge J. C.
Published: December 2017

Injection of water into a lobar bronchus stimulates airway C-fibers and rapidly adapting receptors and evokes airway defense reflexes. To determine whether this stimulus also evokes a reflex increase in bronchial blood flow (Qbr), we injected 1–2 ml of water into a lobar bronchus in anesthetized dogs. Injection decreased arterial pressure but increased Qbr from 9 +/- 1 to 21 +/- 3 ml/min. The increase had a latency of 6–8 s and reached a peak after approximately 20 s; Qbr returned to control after 60–90 s. Airway mucosal blood flow, measured by colored microspheres, increased in proportion to Qbr. In contrast, flow in an adjacent intercostal artery that did not supply the airway decreased slightly. Injection of isosmotic saline had little effect. In 13 of 16 dogs, the water-induced increase in Qbr was abolished by cutting or cooling the cervical vagus nerves and hence was entirely dependent on centrally mediated vagal pathways. When the vagus nerves were intact, about one-third of the vasodilator response remained after pharmacological blockade of muscarinic and adrenergic receptors. We conclude that in dogs the defense response to water in the lower airways includes a large increase in Qbr that is partly due to activation of nonadrenergic noncholinergic autonomic pathways.
Effects of age at cordotomy and subsequent exercise on contraction times of motor units in the cat
Authors: Smith L. A. , Eldred E. , Edgerton V. R.
Published: December 2017

The contraction times (CTs) of functionally isolated motor units (MUs) in the soleus (SOL) and medial gastrocnemius (MG) muscles were determined in cats that had been spinalized at ages 2 (n = 15) or 12 (n = 9) wk and then either subjected to exercise on a treadmill or simply given manipulative care of the hindlimbs. The MUs were tested approximately 12 wk after the low-thoracic cordotomy, and comparisons were made with data from control animals. The CT of 50.9 ms obtained for SOL units (n = 163) in the spinal cats was 22% shorter than the mean of 65.0 ms for MUs (n = 57) from control cats (n = 4). Contrary to expectation, the CT in animals spinalized at 12 wk was significantly shorter than that in the 2-wk group. The CT for MG units (n = 105) in spinal cats was also significantly shorter (11%) than that in controls cats (n = 66, 6 cats), and those units identified by their high fatigue index as being of slow or fatigue-resistant type had a shorter CT than units with a low index. No distinction in CT of exercised and nonexercised groups was detected for either muscle. These findings are discussed in relation to the bearing influences of supraspinal and segmental origin have on CT duration in SOL and MG muscles during growth of the kitten. A slight, significant decrease (6%) in the fatigue index of SOL MUs (n = 144) was detected, but the values remained high (mean 0.87).
Role of endogenous adenosine in hypoxic ventilatory response in humans: a study with dipyridamole
Authors: Yamamoto M. , Nishimura M. , Kobayashi S. , Akiyama Y. , Miyamoto K. , Kawakami Y.
Published: December 2017

To examine the role of endogenous adenosine in hypoxic ventilatory response, we measured, in nine normal young adults, ventilatory responses to isocapnic progressive hypoxia and subsequent sustained hypoxia [arterial O2 saturation (SaO2); 80%, 20 min] with and without pretreatment with dipyridamole in a double-blind crossover fashion. Dipyridamole, an adenosine uptake blocker, was expected to enhance the effect of endogenous adenosine. Pretreatment with dipyridamole (0.5 mg/kg) significantly augmented the slope of the ventilatory response to isocapnic progressive hypoxia from 0.35 +/- 0.13 (SE) to 0.70 +/- 0.25 l.min-1.%fall of SaO2(-1) (P < 0.01), although there were no significant changes in resting ventilation. On the other hand, minute ventilation, when expressed as a percentage of peak ventilation, declined to 68.4 +/- 4.3% with dipyridamole at the 9–11th min of sustained hypoxia, which was significantly lower than the 90.2 +/- 8.3% with a placebo (P < 0.05), and finally reached 56.1 +/- 7.2% with dipyridamole and 78.7 +/- 9.2% with the placebo (P < 0.1) at the 18–20th min of sustained hypoxia. In an attempt to more specifically examine the role of adenosine, aminophylline (5 mg/kg), an adenosine receptor antagonist, was injected before pretreatment with dipyridamole in four subjects. Aminophylline infusion abolished or at least attenuated the effect of dipyridamole in all four subjects. These data suggest that endogenous adenosine has a modulatory role in hypoxic ventilatory response in adult humans.
Dynamic response of cochlear blood flow to occlusion of anterior inferior cerebellar artery in guinea pigs
Authors: Ren T. , Avinash G. B. , Nuttall A. L. , Miller J. M. , Laurikainen E. A. , Quirk W. S.
Published: December 2017

In this study we investigated the autoregulation and hemodynamics of cochlear blood flow (CBF) as measured by laser-Doppler flowmetry. When the anterior inferior cerebellar artery was clamped, CBF decreased approximately 40% (not to “biological zero”), followed by a gradual increase. When the clamp was released, CBF quickly increased to as much as 167% of the baseline level and then slowly returned to baseline. We assume that the dynamic CBF response to anterior inferior cerebellar artery clamping reflects primarily a combination of passive elastic properties of the cochlear vessels and active autoregulatory mechanisms. The decrease portion of the negative phase and the increase portion of the positive phase reflect mainly passive behavior, static compliance, and resistance of vessels, whereas the slow exponential negative and positive changes indicate an active response of vessels: an autoregulatory mechanism based on compensatory vascular dilation and constriction. Our preliminary data show a very strong CBF autoregulatory response to a change in intravascular pressure. Sympathetic stimulation can enhance this autoregulation, and CO2 inhalation promotes compensatory dilation and inhibits compensatory vascular constriction.
A modified force-velocity equation for smooth muscle contraction
Authors: Wang J. , Jiang H. , Stephens N. L.
Published: December 2017

It has been suggested that in skeletal muscle the force-velocity relationship may not be a simple hyperbolic one, as defined by Hill's equation. To determine whether smooth muscle demonstrated the same properties, quick-release force-velocity curves were obtained from canine tracheal smooth muscle. The results showed that the observed data points for tracheal smooth muscle systematically deviated from a hyperbola. Such deviation occurred at values of force (P) approaching maximum isometric force (Po) for curves elicited by quick release at 2 and 10 s in the course of isometric contractions. Shortening velocities under a given afterload were overestimated at the high-force end (P > 75% Po) by Hill's equation; this implied that a relationship more complex than a simple hyperbola was involved at high loads. We next focused on finding an equation to also fit those directly measured data points that did not conform to a hyperbola. Our rationale in developing the equation was that a plot of the linearized transform of Hill's equation should yield a straight line over the entire range of loads at which velocities were measured. The plot demonstrated that, in the low-load high-velocity portion of the curve, a peak value was reached at 70–80% Po, which decreased as load increased in the high-load low-velocity portion.(ABSTRACT TRUNCATED AT 250 WORDS)
Respiratory-related activity of soft palate muscles: augmentation by negative upper airway pressure
Authors: Van der Touw T. , O'Neill N. , Brancatisano A. , Amis T. , Wheatley J. , Engel L. A.
Published: December 2017

We studied respiratory-related activity of the soft palate muscles in 10 anesthetized tracheostomized supine dogs. Moving time average (MTA) electromyographic (EMG) activity was measured in the palatinus (PAL), levator veli palatini (LP), and tensor veli palatini (TP) with bipolar fine-wire electrodes and in the diaphragm with bipolar hook electrodes. Measurements were made during tracheostomy breathing and nasal breathing with the mouth sealed (NB). During tracheostomy breathing, all soft palate muscles displayed respiratory-related phasic inspiratory and expiratory as well as tonic EMG activity. During NB, peak inspiratory EMG activity increased in PAL, LP, and TP because of an increase in both phasic inspiratory and tonic MTA activity. In contrast, phasic expiratory activity did not change. A constant negative pressure equal to peak inspiratory tracheal pressure during NB was applied to the caudal end of the isolated upper airway with the nose occluded. This was associated with soft palate muscle responses qualitatively similar to the responses during NB but accounted for only 39, 25, and 32% of the magnitude of the peak inspiratory MTA EMG responses to NB in PAL, LP, and TP, respectively. Our results demonstrate that the soft palate muscles exhibit respiratory-related activity in common with other upper airway muscles. Furthermore, such activity is augmented in each soft palate muscle during NB, and negative upper airway pressure makes a substantial contribution to the recruitment of soft palate muscle activity.
Athletic heart syndrome in dogs competing in a long-distance sled race
Authors: Constable P. D. , Hinchcliff K. W. , Olson J. , Hamlin R. L.
Published: December 2017

The cardiac effects of endurance training were evaluated by cardiac auscultation and electrocardiographic examination of 48 heavily trained sled dogs (3,000–5,000 km of training), 18 lightly trained sled dogs (300–800 km of training), 19 untrained sled dogs, and 14 mongrel dogs. A grade I-II/VI early- to midsystolic cardiac murmur was auscultated with increasing frequency as training level increased. The QRS duration (66.1 +/- 7.4 ms) and QT interval (236 +/- 20 ms) were significantly (P < 0.05) longer in heavily trained sled dogs than in mongrel dogs (QRS, 60.6 +/- 4.6; QT, 219 +/- 11 ms). A long QT interval (> 250 ms) was observed in 8 (16.7%) heavily trained dogs but not in the other groups. A significant rightward shift in the mean electrical axis of ventricular depolarization in the frontal plane was observed in heavily trained sled dogs. The auscultatory and electrocardiographic findings in heavily trained sled dogs were remarkably similar to those reported in elite human endurance athletes, suggesting that endurance-trained sled dogs provide a naturally occurring model for the athletic heart syndrome.
Changes in lung lipid during spontaneous labor in fetal sheep
Authors: Chapman D. L. , Carlton D. P. , Nielson D. W. , Cummings J. J. , Poulain F. R. , Bland R. D.
Published: December 2017

The goals of this study were 1) to examine changes in lung liquid formation and composition during spontaneous labor in fetal lambs and 2) to determine the importance of beta-adrenergic stimulation and transepithelial Na+ flux in removing liquid from the lung lumen near birth. We measured net production of lung liquid (Jv), lung liquid composition, and transpulmonary electrical potential difference (PD) before and during labor in fetal sheep with chronically implanted tracheal and vascular catheters. We determined Jv by measuring rate of change in lung liquid concentration of 125I-albumin, an impermeant tracer that was mixed in lung liquid at the start of each study. In 17 paired experiments, Jv decreased from 11 +/- 2 ml/h (Jv > 0 = secretion) before labor to -1 +/- 2 ml/h (Jv < 0 = absorption) during labor; in 5 paired experiments, PD changed from -7 +/- 1 mV (lumen negative) before labor to -12 +/- 1 mV during labor. To determine whether absorption of lung liquid during labor is the result of beta-adrenergic stimulation, we studied the effect of propranolol on Jv during labor. When propranolol (40 microM) was added to lung liquid during active labor, Jv decreased from -2 +/- 2 to -8 +/- 3 ml/h (n = 9). Thus, propranolol did not inhibit lung liquid absorption during labor. To determine whether transepithelial Na+ movement provides the driving force for lung liquid clearance during labor, we tested the effects of amiloride, an Na+ transport inhibitor, on Jv and PD.(ABSTRACT TRUNCATED AT 250 WORDS)
Dependence of surfactant function on extracellular pH: mechanisms and modifications
Authors: Haddad I. Y. , Holm B. A. , Hlavaty L. , Matalon S.
Published: December 2017

We investigated alterations in pH on the surface properties of natural lung surfactant and the calf lung surfactant extract (CLSE), suspended in 10 mM N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid, using a pulsating bubble surfactometer. Increasing the pH value of the medium to > 7.4 decreased the ability of CLSE, but not of natural lung surfactant mixtures (2 mg phospholipid/ml), to achieve a low minimum surface tension during dynamic compression and enhanced their sensitivity to albumin inactivation. These detrimental effects on surface tension were reversed by addition of surfactant protein A (SP-A; 3% by weight) or by increasing the lipid concentration to 4 mg/ml. SP-A-induced lipid aggregation at pH 10 was not different than at pH 7.4. Alkalinization impaired the ability of CLSE to restore normal lung mechanics in excised surfactant-deficient rats lungs. These results indicate that cooperation between SP-A and the hydrophobic surfactant proteins has an important role in achieving low minimum surface tension at pH > or = 7.6.
Increased endothelium-derived NO in hypertensive pulmonary circulation of chronically hypoxic rats
Authors: Isaacson T. C. , Hampl V. , Weir E. K. , Nelson D. P. , Archer S. L.
Published: December 2017

The hypothesis that the endothelium-derived relaxing factor/nitric oxide (EDNO) activity is elevated in chronic hypoxic pulmonary hypertension (CH-PHT) was tested using isolated Krebs-albumin-perfused rat lungs. Concentration of the EDNO decomposition products (NOx) in the lungs′ effluent was measured by a modified chemiluminescence assay. The functional significance of basal EDNO production was studied by measuring the vasoconstrictor response to an EDNO synthesis inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME). Reactivity to the endothelium-dependent vasodilator substance P and to exogenous NO was also studied. More NOx was found in effluent from CH-PHT (22.3 +/- 9.8 nM) than control (0.4 +/- 3.9 nM) lungs. The L-NAME-induced vasoconstriction was greater in CH-PHT than in control rats. The sensitivity, but not the maximal vasodilation, to exogenous NO was elevated in CH-PHT. The substance P-induced vasodilation was potentiated in CH-PHT compared with control rats and blocked by L-NAME in both groups. We conclude that basal and agonist-stimulated pulmonary EDNO activity is enhanced in this model of CH-PHT. The EDNO synthesis may play a counterregulatory role in CH-PHT.
Effects of acute caffeine withdrawal on habituated male runners
Authors: Hetzler R. K. , Warhaftig-Glynn N. , Thompson D. L. , Dowling E. , Weltman A.
Published: December 2017

This study investigated the effects of caffeine withdrawal on six trained caffeine-habituated male runners: age 29.8 +/- 5.8 (SD) yr, height 180.4 +/- 5.4 cm, weight 77.3 +/- 6.7 kg, maximal O2 uptake 63.0 +/- 5.4 ml.kg-1.min-1, and daily caffeine intake 674 +/- 128 mg. The subjects received a loading dose (5 mg/kg body wt) of caffeine 48 h before each testing session. They were then given (using a repeated-measures double-blind design) additional doses of caffeine (5 mg/kg body wt) or a placebo 36, 24, 12, and 2 h before testing. They ran at a velocity corresponding to their lactate threshold for 60 min in a caffeine withdrawal or caffeinated condition. Caffeine withdrawal resulted in no significant differences in absolute O2 uptake, O2 uptake relative to maximal O2 uptake, respiratory exchange ratios, or free fatty acid concentrations. Glycerol concentrations were significantly attenuated in the withdrawal condition. No significant differences were revealed in calculated substrate utilization. It was concluded that caffeine withdrawal significantly affects lipolysis but not substrate utilization during prolonged running.
Sympathetic nerve activity during prolonged rhythmic forearm exercise
Authors: Batman B. A. , Hardy J. C. , Leuenberger U. A. , Smith M. B. , Yang Q. X. , Sinoway L. I.
Published: December 2017

Exercise is a potent stimulus to activate the sympathetic nervous system. Previous work suggests that metabolite-sensitive muscle afferents are activated near the point of fatigue, and, when activated, they determine the muscle sympathetic nerve activity (MSNA) response to isometric forearm exercise. Yet, studies using a more prolonged rhythmic exercise paradigm suggest that the sympathetic nervous system can be activated in a more graded fashion. The purpose of this study was to determine whether metaboreceptor stimulation would also be responsible for MSNA responses to prolonged rhythmic isotonic forearm exercise. Subjects (n = 16) performed rhythmic isotonic forearm exercise at 25% maximal voluntary contraction for 30 min as we measured MSNA (microneurography). We observed progressive increases in MSNA with a peak increase of 161 units from a baseline value of 180 units. We also performed posthandgrip circulatory arrest (PHG-CA) in nine of these subjects. This maneuver isolates the metaboreceptor contribution to MSNA. During PHG-CA, delta MSNA values were not different from those observed during a freely perfused recovery period (n = 7). We also compared MSNA responses during the rhythmic paradigm with those seen during a static protocol at 40% of maximal voluntary contraction in five subjects. The two types of exercise caused similar increases in MSNA, but only the static paradigm was associated with a sustained MSNA response during PHG-CA. Finally, 31P-nuclear magnetic resonance was used to evaluate muscle metabolic responses during rhythmic and static forearm exercise (n = 6). Static exercise caused muscle acidosis and an increase in H2PO4-, whereas rhythmic exercise had no effect on muscle metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)
Ontogeny of dry gas hyperpnea-induced bronchoconstriction in guinea pigs
Authors: Murphy T. M. , Ray D. W. , Alger L. E. , Phillips I. J. , Roach J. C. , Leff A. R. , Solway J.
Published: December 2017

Adolescent guinea pigs (AGPs) demonstrate dry gas hyperpnea-induced bronchoconstriction (HIB) that shares key features with HIB in humans with asthma. The airways of immature animals exhibit enhanced reactivity to diverse types of stimulation. We tested whether dry gas HIB is also increased in newborn guinea pigs (NGPs). We quantified HIB as the fractional increase of respiratory system resistance (Rrs) over baseline (BL) in five 4- to 7-day-old NGPs after 10 min of hyperpnea, as well as changes in Rrs elicited by intravenous methacholine or capsaicin, and compared these responses with those of AGPs. During hyperpnea, analogous stimuli were delivered by mechanically imposing hyperpnea at 3.0, 4.5, and 6.0 times quiet eucapnic minute ventilation (VE). In AGPs, hyperpnea caused significant bronchoconstriction that increased with VE; peak fractional increase of Rrs was 7.6 +/- 2.0 times BL. In contrast, hyperpnea caused insignificant bronchoconstriction in NGPs (1.4 +/- 0.2 times BL after the largest VE; P < 0.05 vs. AGP). Responses elicited by methacholine (10(-10)-10(-7) mol/kg) or capsaicin (0.01–10.0 microgram/kg) were similar in NGPs and AGPs. In AGPs, hyperpnea suppressed HIB until posthyperpnea. To determine whether the reduced HIB of NGPs was caused by enhanced suppression, NGPs and AGPs were administered acetylcholine (10(-10)-10(-7) mol/kg i.v.) during BL eucapnic ventilation and during eucapnic hyperpnea with warm humidified gas. Responses to acetylcholine were suppressed in AGPs and NGPs to a similar degree. We conclude that HIB is markedly diminished shortly after birth in guinea pigs and that it increases substantially during maturation.(ABSTRACT TRUNCATED AT 250 WORDS)
Human lung impedance from spontaneous breathing frequencies to 32 Hz
Authors: Farre R. , Peslin R. , Rotger M. , Navajas D.
Published: December 2017

Lung impedance (ZL) was measured from 0.1875 to 32 Hz in spontaneously breathing healthy subjects by spectral analysis of the pressure and flow signals generated simultaneously by the muscular generator of breathing and by a forced oscillation system. This method did not require cooperation from the subject to perform panting or special ventilatory maneuvers and therefore allowed us to analyze the frequency dependence of lung resistance, reactance, and elastance (-2 pi.frequency.reactance) at the physiological conditions of normal breathing. Resistance and elastance parameters were also computed by multiple linear regression of the time-domain pressure and flow data on a simple resistance-elastance model. Resistances and elastances computed at the breathing frequency by spectral analysis and by multiple linear regression were similar (nonsignificant differences < 4 and 10%, respectively). The results obtained when comparing ZL from the breathing component (0.1875–0.75 Hz) of the recorded signals and from the forced oscillation component (2–32 Hz) were fairly consistent. ZL (0.1875–10 Hz) was interpreted in terms of a model consisting of an airway compartment, including a resistance and an inertance, in series with a viscoelastic tissue compartment (J. Hildebrandt. J. Appl. Physiol. 28: 365–372, 1970) characterized by two parameters. The model analysis provided parameter values (resistance 2.49 +/- 0.58 hPa.l-1.s, inertance 1.70 +/- 0.29 Pa.l-1.s2, Hildebrandt parameters 4.87 +/- 2.28 and 0.73 +/- 0.99 hPa/l) consistent with the hypothesis that lung tissue in healthy humans during spontaneous breathing behaves as a viscoelastic structure with a hysteresivity of approximately 0.10.
Hypoxic vasodilation does not require nitric oxide (EDRF/NO) synthesis
Authors: Vallet B. , Curtis S. E. , Winn M. J. , King C. E. , Chapler C. K. , Cain S. M.
Published: December 2017

Our question was whether inhibition of nitric oxide [endothelium-derived relaxing factor (EDRF)/NO] production in an in situ vascularly isolated but innervated canine hindlimb would prevent hypoxic vasodilation or interfere with O2 extraction during ischemic (IH) or hypoxic hypoxia (HH). After a control period, we gave NG-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg i.v.) to two of four groups of six dogs before a 30-min period of IH or HH. In IH, arterial inflow from a pump-membrane oxygenator system was lowered from 65 to 35 ml.min-1.kg-1 with PO2 maintained at approximately 110 Torr. In HH, PO2 was lowered from 107 to 28 Torr with flow at 78 ml.min-1.kg-1. Total O2 delivery was lowered to approximately 5 ml.min-1.kg-1 in all groups during hypoxia. Hindlimb vascular resistance (LVR) increased from 1.11 +/- 0.09 to 2.21 +/- 0.25 peripheral resistance units (PRU; P < 0.05) after L-NAME infusion and hindlimb O2 uptake increased from 3.9 +/- 0.2 to 4.5 +/- 0.3 ml.min-1.kg-1 (P < 0.05). In controls, LVR decreased from 1.10 +/- 0.06 to 0.63 +/- 0.04 PRU with HH (P < 0.05) and from 1.03 +/- 0.06 to 0.82 +/- 0.02 PRU (P = NS) with IH. In L-NAME-treated dogs, LVR decreased from 2.38 +/- 0.37 to 1.07 +/- 0.13 PRU with HH (P < 0.05) and from 2.04 +/- 0.29 to 1.41 +/- 0.13 PRU (P = NS) with IH. There were no differences in O2 extraction ratio (0.72) or in O2 uptake between groups during hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)