bluuebunny/crossref_metadata_2025 huggingface dataset:
Reproducibility of core temperature threshold for sweating onset in humans
Authors: Brengelmann G. L. , Savage M. V. , Avery D. H.
Published: December 2017

The control of sweating in humans has been described quantitatively in terms of skin and core temperatures (Tsk and Tcore, respectively). However, the precision with which features of the relationship between sweat rate and Tcore at a given Tsk can be reproduced in the short term is not known. We focused on the threshold Tcore. We held Tsk at 38 degrees C until sweating began for two periods separated by a period of cooling with Tsk at 32 degrees C in six men and three women. The esophageal temperature (Tes) at which sweating began was invariably lower in the second period of heating (average difference 0.09 degree C; maximum 0.17 degree C). Also, the rate of rise in Tes was invariably higher (average 148%) during the second period of heating. Thus, although a threshold cannot be reproduced within the error of Tes measurement, the consistency and small magnitude of the downward shift recommend our protocol as a practical method for evaluating other influences on thermoregulation, provided that the effects are big enough to be seen against a background of an expected small decrease. From the fundamental point of view, the consistency of the downward displacement has provocative implications, e.g., the rate of change in Tcore influences sweating or thermosensitive units in slow-responding thermal compartments contribute to the Tcore input signal.
PMN cell counts and phagocytic activity of highly trained athletes depend on training period
Authors: Hack V. , Strobel G. , Weiss M. , Weicker H.
Published: December 2017

We tested the hypothesis that polymorphonuclear leukocyte (PMN) cell counts and phagocytic activity determined by latex ingestion and superoxide anion production are influenced by different training periods. We investigated long-distance runners before and up to 24 h after a graded exercise test to exhaustion during moderate training (MT) and intense training (IT) and compared them with untrained (control) subjects. Cell counts and phagocytic activity at rest and after exercise did not differ significantly between MT and control. On the contrary, IT showed a significant (P < or = 0.05) decrease in PMN cell count at rest (2.55 +/- 0.3 cells/nl) compared with MT (3.63 +/- 0.2 cells/nl) and control (3.41 +/- 0.8 cells/nl). Furthermore, phagocytic activity was significantly reduced (P < or = 0.05) in IT at rest and after exercise compared with MT and control. A strong inverse correlation (r = -0.75; P < or = 0.01) between epinephrine and superoxide anion production was found. These results provide evidence that the phagocytic activity depends on the training period and indicate impaired PMN functions during IT, which might lead to increased susceptibility to infection.
Muscle energetics and pulmonary oxygen uptake kinetics during moderate exercise
Authors: Barstow T. J. , Buchthal S. , Zanconato S. , Cooper D. M.
Published: December 2017

The present study tested whether, during moderate exercise, 1) the dynamic responses of ADP and changes in free energy of ATP hydrolysis (delta GATP) were similar to those of phosphocreatine [PCr; as would be expected for a simple controller of muscle respiration (QO2)] and 2) the rise in pulmonary O2 uptake (VO2) during cycle exercise would reflect the rise in muscle QO2 indicated by the calf PCr kinetics. The responses of PCr, Pi, ADP, and delta GATP were measured from the calf in five subjects during supine treadle exercise using 31P-magnetic resonance spectroscopy and compared with those for VO2, measured breath by breath during upright cycle exercise. The time constants for delta GATP [24.2 +/- 14.2 (SE) s] were not significantly different from those for PCr (26.3 +/- 17.3 s) and Pi (30.7 +/- 22.5 s) (P > 0.05). The time constants for phase 2 VO2 (29.9 +/- 16.8 s) were also similar to those of PCr. In contrast, the dynamics of ADP were distorted from those of PCr due to dynamic changes in pH. These results are consistent with mechanisms of respiratory control that feature substrate control by PCr or thermodynamic control through changes in delta GATP. However, these results are not consistent with substrate control by ADP in a simple fashion. Furthermore, the similarity of time constants for phase 2 VO2 and muscle PCr suggests that phase 2 VO2 kinetics reflect those of muscle QO2 in healthy subjects during moderate exercise.
Anatomy of membranous bronchioles in normal, senile and emphysematous human lungs
Authors: Verbeken E. K. , Cauberghs M. , Lauweryns J. M. , van de Woestijne K. P.
Published: December 2017

Serial reconstructions of the membranous bronchioles (MB) were performed in randomly selected tissue blocks cut parallel to the pleural surface in fixated human lungs. Two to four normal, senile, and emphysematous lungs were examined. Three (2 in senile lungs) orders of MB were observed with a dichotomous branching pattern. Emphysematous lungs are characterized by an overall decrease in airway diameter with localized stenoses. Comparison with mean airway diameter (d) and density [n (no. of MBs per cm2 of lung tissue)] of MBs obtained using standard morphometric techniques (random sections approximately 1 cm from the pleura) showed that the values of d and n are biased because of the inclusion in the measurements of a number of respiratory bronchioles and bronchi. When these misclassifications are corrected for, it appears that d corresponds quite well to the mean diameter of the terminal bronchioles (TB) and n to approximately twice the density of TBs. After correction, n is not significantly reduced in emphysematous lungs (the grossly destroyed areas being excluded) compared with normal lungs. The estimate of the number of TBs obtained from the present data is markedly less than that calculated by Weibel (Morphometry of the Human Lung. Berlin: Springer-Verlag, 1963), which suggests that the number of bronchi was overestimated by Weibel by at least one generation. Finally, values of peripheral airway resistance computed from the present anatomic data correspond quite well to direct measurement performed on the same lungs before fixation (Verbeken et al., J. Appl. Physiol. 72:2343–2353, 1992).
Effect of arterial blood pressure and ventilation gases on cardiac depression induced by coronary air embolism
Authors: van Blankenstein J. H. , Slager C. J. , Soei L. K. , Boersma H. , Verdouw P. D.
Published: December 2017

In this study the time course of cardiac depression after selective intracoronary injection of air bubbles was investigated in six anesthetized pigs (30 +/- 2 kg) with different mixtures of ventilation gases and different mean arterial blood pressures (MAP). Air bubbles of 150 microns diam were injected into the left anterior descending coronary artery (LADCA) in a volume of 2 microliters/kg body wt. In each animal an injection of air bubbles was applied during ventilation with N2-O2 and a MAP of 77 +/- 3 mmHg (N2-O2/low pressure) or 111 +/- 3 mmHg (N2-O2/high pressure) and during ventilation with pure O2 and a MAP of 77 +/- 3 mmHg (O2/low pressure) or 110 +/- 3 mmHg (O2/high pressure). Systemic hemodynamic variables such as left ventricular pressure, its peak first derivatives, and MAP changed < 10% after injection of air bubbles. During N2-O2/low pressure, systolic segment length shortening in the LADCA region (SS-LADCA) decreased from baseline and did not return to baseline within the 10 min after injection of air bubbles. During N2-O2/high pressure and O2/low pressure, SS-LADCA was decreased between 60 and 120 s, whereas for O2/high pressure this period was from 60 to 90 s. By calculating the time integral of the deviation from baseline of SS-LADCA, it could be demonstrated that the depression of regional myocardial function was less severe during O2/high pressure and O2/low pressure than during N2-O2/low pressure. We conclude that, when coronary air embolism occurs during hypertension and during ventilation with pure O2 instead of a normal N2-O2 mixture, the resulting depression of regional myocardial function is reduced.
Contractile and cellular remodeling in rabbit skeletal muscle after cyclic eccentric contractions
Authors: Lieber R. L. , Schmitz M. C. , Mishra D. K. , Friden J.
Published: December 2017

The time course of muscle contractile and cellular properties was studied in rabbit ankle flexor muscles after injury produced by eccentric exercise. Cyclic eccentric exercise was produced by increasing the tibiotarsal angle of the rabbit while activating the peroneal nerve by use of transcutaneous electrodes. Muscle properties were measured 1, 2, 3, 7, 14, and 28 days after exercise to define the time course of muscle changes after injury. A control group receiving only isometric contraction was used to study the effect of cyclic activation itself. The magnitude of the torque decline after 1 day was the same with use of isometric or eccentric exercise, but eccentric exercise resulted in a further decrease in torque after 2 days, at which time isometrically exercised muscles had fully recovered. The most prominent morphological changes in the injured muscle fibers were the loss of antibody staining for the desmin cytoskeletal protein and deposition of intracellular fibronectin, even when the injured muscle fibers retained their normal complement of contractile and enzymatic proteins. The presence of fibronectin inside the myofibers indicated a loss of cellular integrity. Invasion by inflammatory cells was apparent on the basis of localization of embryonic myosin. Thus eccentric exercise initiates a series of events that results in disruption of the cytoskeletal network and an inflammatory response that could be the mechanism for further deterioration of the contractile response.
Structural composition of lung parenchymal strip and mechanical behavior during sinusoidal oscillation
Authors: Ludwig M. S. , Dallaire M. J.
Published: December 2017

The lung parenchymal strip is comprised of many different anatomic elements, including small vessels, small airways, and alveolar walls. We questioned whether the relative amounts of these different structures are important in determining the mechanical behavior of this preparation during dynamic oscillations. We studied 16 parenchymal strips (10 x 2 x 2 mm) from 12 Sprague-Dawley rats. The strips were suspended in an organ bath filled with Krebs solution, bubbled with 95% O2–5% CO2, and maintained at 37 degrees C. One end of the strip was attached to a force transducer, and the other end was attached to a lever system that effected length (L) changes. We oscillated the strips at various resting tensions (T) (0.9 and 1.5 g), frequencies (0.1, 0.3, 0.6, and 1.0 Hz), and amplitudes (1.1, 2.4, and 5.3% of optimal L). We obtained T vs. L curves and calculated the resistance, elastance, and hysteresivity (ratio of energy dissipated to energy stored) of the tissue. At the end of the experiment, the strips were fixed in Formalin at T = 1 g. Histological sections were examined, and the amounts of airway, blood vessel, and alveolar wall were quantified using point counting techniques. We found that whereas resistance varied significantly with frequency and T, elastance and hysteresivity varied with only T. The fractional areas of alveolar, blood vessel, and bronchial wall were 86.3 +/- 0.5 (SE), 8.4 +/- 0.3, and 5.3 +/- 0.4%. Only hysteresivity and the fractional area of alveolar wall were significantly correlated at the lower resting tension (r = -0.76, P = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
Electrically evoked myoelectric signals in back muscles: effect of side dominance
Authors: Merletti R. , De Luca C. J. , Sathyan D.
Published: December 2017

This work had two goals, to study the effect of hand dominance on myoelectric signal variables and fatigue indexes in back muscles and to assess the repeatability of the estimates of such variables. Myoelectric manifestations of muscle fatigue were studied in the right and left longissimus dorsi muscles of five right-handed and five left-handed normal male subjects. Myoelectric signals (M waves), evoked by stimulation applied to a muscle's motor point, were detected with surface electrodes. Each test consisted of eliciting a tetanic contraction of 30 s duration with supramaximal stimulation at 25 Hz and was repeated five times on 5 different days for each subject. The mean and median frequencies of the resulting power spectra of the M waves were plotted vs. time, and fatigue indexes were obtained from the time course of these variables. Only two-thirds of the elicited contractions provided signals of sufficiently good quality to obtain reliable estimates of the mean and median frequencies. Criteria for acceptability are described. Analysis of variance and paired comparisons showed a statistically significant effect of side dominance on fatigue indexes in the right-handed subjects but not in the left-handed subjects. Normalized initial slope and other fatigue indexes based on spectral variables demonstrated myoelectric manifestations of fatigue that were greater on the dominant side. We surmise that the differences are related to the fiber type modifications associated with the unilateral usage of the upper limbs and the consequent activation of the nondominant side of the back.
Age-related differences in diaphragm muscle injury after lengthening activations
Authors: Watchko J. F. , Johnson B. D. , Gosselin L. E. , Prakash Y. S. , Sieck G. C.
Published: December 2017

The susceptibility of postnatal day 15 and adult rat diaphragms (DIAs) to acute injury after repetitive isovelocity lengthening activations was examined in vitro. Forces were measured during two phases of each stimulation protocol: 1) isometric phase: during the first 300 ms of each 500-ms train, DIA length was not changed; and 2) isovelocity lengthening phase: during the remaining 200 ms of each stimulus train, DIA was lengthened at a constant velocity from 90 to 110% of optimal length. At maximal activation (75 Hz and a lengthening velocity of 1.0 optimal length per second), the maximum force measured during the isometric phase and that measured during the isovelocity lengthening phase were both greater in adult DIAs than in day 15 DIAs but both declined to a greater extent in adults with repetitive activation. Ultrastructural analysis showed that after lengthening activations muscle fiber injury was very evident in adult but much less prevalent in day 15 DIAs. This difference in susceptibility between the adult and day 15 DIAs did not depend on differences in peak force or absolute velocity of lengthening. We conclude that lengthening activations result in DIA injury and that the adult is more susceptible than its younger counterpart.
Sex differences in surface EMG interference pattern power spectrum
Authors: Cioni R. , Giannini F. , Paradiso C. , Battistini N. , Navona C. , Starita A.
Published: December 2017

Sex differences in the spectral parameters of the surface electromyogram (EMG) power spectrum were studied during voluntary muscle contractions of different strength with rest in between. The influence of two different types of leads (unipolar and bipolar) on the values of the spectral parameters was also investigated under the same experimental conditions. The subjects were 15 healthy female and 15 healthy male volunteers. The relationship between the amplitude (root mean square) of the EMG and the force developed was not linear. The mean values of the median power frequency were lower in women than in men. With both types of lead, the increase in force was accompanied by a progressive increase in median power frequency in male and female subjects. The significant differences in spectral parameters observed in the two sexes are probably correlated with anatomic differences.
Effect of exercise on cold tolerance and metabolic heat production in adult and aged C57BL/6J mice
Authors: Shechtman O. , Talan M. I.
Published: December 2017

Two groups of adult (12-mo-old) and two groups of aged (24-mo-old) C57BL/6J male mice were subjected to a standardized cold stress test (3-h partial restraint at 6 degrees C). One group from each age group was tested in the morning, and the other was tested in the afternoon. Half of the mice were subjected to running exercise on a treadmill during 1 h before the cold stress test. The other half were placed on a nonoperational treadmill for 1 h before the cold stress test. One hour of exercise resulted in improvement of cold tolerance during the subsequent cold exposure in both age groups but only during afternoon testing. Improvement in cold tolerance was not accompanied by an elevation of cold-induced metabolic heat production in adult mice. Metabolic heat production in aged mice showed only modest elevation. The discrepancy between improvement in cold tolerance and lack of elevation of metabolic heat production suggests that the primary mechanism for augmentation of cold tolerance after exercise in the afternoon is an improvement in cold-induced vasoconstriction of skin vessels, which is probably normally compromised in the afternoon.
Absent peripheral chemosensitivity in Prader-Willi syndrome
Authors: Gozal D. , Arens R. , Omlin K. J. , Ward S. L. , Keens T. G.
Published: December 2017

Abnormalities in ventilatory control during wakefulness and sleep have been observed in patients with Prader-Willi syndrome (PWS). The role of peripheral chemoreceptors in the pathophysiology of abnormal ventilatory responses in PWS is unknown. We studied peripheral chemoreceptor function during wakefulness in 17 genetically confirmed PWS patients [age 27.0 +/- 2.5 (SE) yr; 7 males, 10 females; body mass index 31.1 +/- 1.4 kg/m2] and compared their responses with 17 control subjects matched for age, sex, and body mass index. All PWS and control subjects had normal resting end-tidal PCO2 and arterial O2 saturation while awake. Peripheral chemoreceptor function was assessed by the ventilatory responses to 100% O2 breathing, five tidal breaths of 100% N2, and vital capacity breaths of 15% CO2 in O2. Control subjects decreased minute ventilation (VE) by 15.5 +/- 3.6% during hyperoxia. However, PWS patients increased VE by 17.6 +/- 3.3%, indicating a paradoxical response to hyperoxia (P < 0.00001). After CO2 vital capacity breaths, PWS patients showed no significant change and control subjects showed a marked increase (P < 0.0001) in VE. During N2 breathing, again PWS patients showed no change and control subjects exhibited a marked increase (P < 0.00005) in VE. We conclude that PWS patients have absent peripheral chemoreceptor ventilatory responses. We speculate that the lack of ventilatory responses is due to primary peripheral chemoreceptor dysfunction and/or defective afferent pathways to central controllers.
Respiratory muscle pressure analysis in pressure-support ventilation
Authors: Yamada Y. , Shigeta M. , Suwa K. , Hanaoka K.
Published: December 2017

The extent to which respiratory muscles are exerted during partially supported ventilation is difficult to differentiate, because these muscles and the ventilator work simultaneously to produce ventilation. We have developed a new method for determining the pressure developed by the respiratory muscles in partially supported ventilation. In seven patients on pressure-support ventilation (PSV), pressure, flow, and lung volume change were measured at the airway opening. Various PSV levels (0–15 cmH2O) were applied to each patient in random order. By utilizing a model of respiratory mechanics, we calculated the pressure developed by the respiratory muscles and the inspiratory work performed by the muscles from the measured parameters by use of the resistance and elastance of the respiratory system obtained during controlled ventilation. Increasing PSV from 0 to 15 cmH2O modulated the resultant breathing pattern, i.e., increasing tidal volume and decreasing respiratory rate. The respiratory muscle pressure, although less negative, had a shape that corresponded to the shape of airway occlusion pressure at each PSV level, and both pressures decreased concomitantly with increasing PSV. The respiratory muscle work progressively decreased with increasing PSV. This analysis enabled clear and continuous quantifications of the respiratory muscle force generation and inspiratory work during partially supported ventilation.
Systemic hemorrhage augments local O2 extraction in canine intestine
Authors: Samsel R. W. , Schumacker P. T.
Published: December 2017

When O2 delivery (QO2) to a tissue is reduced, microvascular adjustments facilitate increases in O2 extraction, thereby delaying the onset of O2 supply-limited metabolism until a critically low QO2 is reached. The present study investigated the contribution of the autonomic nervous system to these adjustments by measuring O2 extraction in isolated intestine. In anesthetized dogs, a 30- to 50-g segment of intestine was vascularly isolated and its QO2 was decreased in stages by reducing the speed of an occlusive pump. In a normovolemic group (n = 11), blood volume was maintained to minimize sympathetic tone while flow to the intestine was reduced. In a hypovolemic group (n = 7), blood volume was removed in stages to augment sympathetic tone as flow to the intestinal segment was simultaneously reduced. A hypovolemic alpha-adrenergic-blocked (alpha-blocked) group (n = 6) was identical to the corresponding alpha-adrenergic intact (alpha-intact) group except that alpha-adrenergic effects were inhibited with phenoxybenzamine (3 mg/kg). The systemic critical O2 extraction ratio in the alpha-blocked group (69 +/- 6%) was less than that in the alpha-intact group (77 +/- 7%; P = 0.05). In the intestine, the critical O2 extraction ratio was significantly poorer in the normovolemic (45 +/- 11%) group than in either hypovolemic group (alpha-intact: 69 +/- 3%, P < 0.00005; alpha-blocked: 62 +/- 9%, P < 0.005). These findings demonstrate that systemic hemorrhage significantly augments critical O2 extraction in intestine during progressive local stagnant hypoxia and suggest that nonadrenergic vasoconstrictor mechanisms may play an important role.
Effects of maximal exercise and venous occlusion on fibrinolytic activity in physically active and inactive men
Authors: Szymanski L. M. , Pate R. R. , Durstine J. L.
Published: December 2017

The purposes of this study were to 1) characterize changes in fibrinolytic activity in response to maximal exercise and 5-min venous occlusion and 2) compare responses in men of various habitual physical activity levels. Tissue plasminogen activator (TPA) activity and plasminogen activator inhibitor 1 (PAI-1) activity were measured in 15 inactive, 15 regularly active, and 15 highly active men. Data were analyzed using a three-way analysis of variance with repeated measures. Pretest TPA activity was similar among groups. TPA activity increased postexercise with higher values seen in the active groups (P < 0.001). The highly active group also significantly increased TPA activity postvenous occlusion (P < 0.01). Pretest PAI-1 activity was different among groups, with the inactive group showing the highest activity and the highly active group the lowest (P < 0.05). PAI-1 activity decreased with exercise (P < 0.01) but did not change with venous occlusion. In conclusion, active men exhibited greater changes in fibrinolytic activity with maximal exercise and venous occlusion than inactive men. This enhanced fibrinolytic activity may be an important mechanism mediating the cardioprotective effect provided by regular physical activity.
Metabolic and work capacity of skeletal muscle of PFK-deficient dogs studied in situ
Authors: Brechue W. F. , Gropp K. E. , Ameredes B. T. , O'Drobinak D. M. , Stainsby W. N. , Harvey J. W.
Published: December 2017

Mechanical and metabolic relationships of muscle lacking phosphofructokinase (PFKD) activity were compared with muscle having normal phosphofructokinase (NORM) activity by using the gastrocnemius-plantaris muscle group with isolated circulation in situ. Muscle contractile properties were similar in both groups. Initial power output (W) during repetitive tetanic (200 ms, 50 impulses/s) isotonic contractions was similar in both groups; however, W declined significantly more (30–80%) in PFKD than in NORM muscle over time, with a constant O2 uptake (VO2)/W. Despite similar O2 and substrate delivery, PFKD muscle had a lower VO2 (42–55%), less glucose uptake, similar free fatty acid uptake, and lactic acid uptake rather than output, during contractions. Muscle venous H+ concentration, strong ion difference, and PCO2 increased during contractions, the magnitude of change being smaller in PFKD muscle. Elevating arterial lactate concentration before contractions in PFKD muscle resulted in significant improvements in W and VO2 without altering the acid-base exchange at the muscle. Increasing O2 delivery by increasing arterial O2 concentration in PFKD dogs did not improve W or VO2. We conclude that, despite no inherent mechanical or contractile differences, PFKD muscle has a severely limited oxidative capacity and exaggerated fatigue and blood flow responses to contractions due to limited substrate metabolism resulting from the inability to utilize glycogen and/or glucose.
Regulation of bioenergetics in O2-limited isolated rat hearts
Authors: Samaja M. , Casalini S. , Allibardi S. , Corno A. , Chierchia S. L.
Published: December 2017

Assessing the role of O2 supply in the regulation of cardiac function in O2-limited hearts is crucial to understanding myocardial ischemic preconditioning and adaptation to hypoxia. We exposed isolated Langendorff-perfused rat hearts to either ischemia (low coronary flow) or hypoxemia (low PO2 in the perfusing medium) with matched O2 supply (10% of baseline). Myocardial contractile work and ATP turnover were greater in hypoxemic than in ischemic hearts (P < 0.05; n = 12). Thus, the energy demand was higher during hypoxemia than during ischemia, suggesting that ischemic hearts are more downregulated than hypoxemic hearts. Venous PO2 was 12 +/- 2 and 120 +/- 15 Torr (P < 0.0001) for ischemic and hypoxemic hearts, respectively, but O2 uptake was the same. Lactate release was higher during hypoxemia than during ischemia (9.7 +/- 0.9 vs. 1.4 +/- 0.2 mumol/min, respectively; P < 0.0001). Electrical stimulation (300 min-1; to increase energy demand) increased performance in ischemic (P < 0.005) but not in hypoxemic hearts without changes in venous PO2 or O2 uptake. However, venous lactate concentration and lactate release increased in ischemic (P < 0.002) but not in hypoxemic hearts, suggesting that anaerobic glycolysis provides the energy necessary to meet the increased energy demand in ischemic hearts only. We conclude that high intracellular lactate or H+ concentration during ischemia plays a major role as a downregulating factor. Downregulation disappears in hypoxemic hearts secondary to enhanced washout of lactate or H+.
Ca2+ and lipolysis in adipocytes from exercise-trained rats
Authors: Izawa T. , Komabayashi T.
Published: December 2017

The effects of Ca2+ on lipolysis and protein kinase activity in adipocytes from exercise-trained rats were investigated. Chronic exercise significantly increased lipolytic responses to norepinephrine and dibutyryl adenosine 3′,5′-cyclic monophosphate (cAMP). The inhibitory effects of N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7), a calumodulin inhibitor, on norepinephrine- and dibutyryl cAMP-stimulated lipolysis were significantly greater in trained than in sedentary rats. Training did not alter cAMP-dependent protein kinase activity. However, the inhibitory effect of W-7 on cAMP-dependent protein kinase activity was much greater in trained than in sedentary rats. The basal intracellular free Ca2+ concentration ([Ca2+]i) was significantly higher in trained than in sedentary rats. The rapid and transient increases in [Ca2+]i due to adrenocorticotropic hormone and phenylephrine from basal levels were significantly lower in trained than in sedentary rats. However, the higher basal [Ca2+]i level in trained rats led to increases in sustained [Ca2+]i levels after stimulation. We concluded that in trained rats the regulation of protein kinase activity by cAMP depends to a greater degree on Ca(2+)-calmodulin complex than it does in sedentary rats and that training alters adipocyte intracellular Ca2+ homeostasis, including [Ca2+]i responsiveness to hormones.
Preload release increases blood flow and decreases fatigue during repetitive isotonic muscle contractions
Authors: Ameredes B. T. , Brechue W. F. , Stainsby W. N.
Published: December 2017

The effects of preload on blood flow (Q), O2 uptake (VO2), and fatigue were investigated in the canine gastrocnemius-plantaris muscle in situ. Repetitive (1 contraction/s, 200 ms duration) afterloaded (0.25–0.3 maximal active isometric tension) isotonic tetanic contractions were performed in high-preload (HP; 69 g/g, n = 5), low-preload (LP; 35 g/g, n = 6), and preload-release (PR; 0 g/g, n = 5) experiments. Maximal Q values (1.0, 1.6, and 2.1 ml.min-1.g-1, P < 0.05 for all comparisons) and Q2 delivery (8, 13, and 17 mumol.min-1.g-1, P < 0.05 for all comparisons) increased significantly with decreasing preload. The maximal VO2 of HP was 7.2 mumol.min-1.g-1, which is significantly lower than both LP (10.5 mumol.min-1.g-1, P < 0.05) and PR values (11.4 mumol.min-1.g-1, P < 0.05); these differences were sustained through 20 min of contractions. Fatigue, measured as a loss of power production, was 63, 37, and 23% at 20 min of contractions in HP, LP, and PR, respectively, indicating significantly less fatigue with decreasing preload (P < 0.05 for all comparisons). These data demonstrate that the preload, present as the level of passive tension maintained between contractions, can influence Q, VO2, and fatigue during repetitive isotonic tetanic contractions of muscle in situ by a mechanically determined metabolic modulation of dynamic muscle performance.
Dextran sulfate activates contact system and mediates arterial hypotension via B2 kinin receptors
Authors: Siebeck M. , Cheronis J. C. , Fink E. , Kohl J. , Spies B. , Spannagl M. , Jochum M. , Fritz H.
Published: December 2017

To define some of the mechanisms underlying dextran sulfate (DXS)-induced hypotension, we investigated the effects of either the plasma kallikrein inhibitor des-Pro2-[Arg15] aprotinin (BAY x 4620) or the specific bradykinin B2-receptor antagonist Hoe-140 on the hypotensive response to DXS. In the first study, anesthetized miniature pigs were given DXS alone, DXS plus BAY x 4620 in various doses, or saline. As expected, DXS alone produced a profound but transient systemic arterial hypotension with a concomitant reduction in kininogen. Circulating kinin levels, complement fragment des-Arg-C3a, and fibrin monomer were all increased. Treatment with BAY x 4620 produced a dose-dependent attenuation of these effects with complete blockade of the hypotension as well as the observed biochemical changes at the highest dose (360 mg). In a second study, two groups of pigs were given either DXS alone or DXS plus Hoe-140. DXS-induced hypotension was completely blocked by Hoe-140 pretreatment; however, kininogen was again depleted. We conclude, therefore, that DXS-induced hypotension is produced by activation of plasma kallikrein that results in the production of bradykinin and that liberation of bradykinin and its action on B2 receptors in the vasculature are both necessary and sufficient to produce the observed effects on circulatory pressure.
Enhancement of parasympathetic cardiac activity during activation of muscle metaboreflex in humans
Authors: Nishiyasu T. , Tan N. , Morimoto K. , Nishiyasu M. , Yamaguchi Y. , Murakami N.
Published: December 2017

We measured the changes in heart rate (HR) variability estimated from the standard deviation of the R-R intervals to evaluate cardiac parasympathetic tone noninvasively before and during activation of muscle metaboreflex induced by postexercise muscle ischemia. Eight healthy male subjects performed sustained handgrip at 50% maximal voluntary contraction followed by forearm occlusion. Mean arterial pressure, cardiac stroke volume, and ratio of cardiac preejection period to left ventricular ejection time (PEP/LVET) were also measured. During the 2-min occlusion after 60 s of handgrip with voluntary respiration, HR variability and mean arterial pressure were significantly increased from baseline (54.4 +/- 6.1 to 80.1 +/- 12.8 ms and 81 +/- 1 to 99 +/- 3 mmHg, respectively) and PEP/LVET was decreased from resting level of 0.404 +/- 0.022 to 0.363 +/- 0.036. During occlusion and recovery, HR did not change from baseline level in any experiment. There was no influence of occlusion itself or of cessation of exercise per se on any parameters. Although overall enhanced HR variability was seen, probably due to lower breathing frequency and larger tidal volume, similar results were also obtained from an experiment with controlled respiration, showing that the increase in HR variability was not due to the changes in tidal volume or breathing frequency during occlusion. In conclusion, the HR variability is increased during activation of the muscle metaboreflex induced by postexercise muscle ischemia in humans. This finding shows that the parasympathetic cardiac tone is enhanced during activation of the muscle metaboreflex in humans and balances enhanced cardiac sympathetic activity to result in an unchanged HR.(ABSTRACT TRUNCATED AT 250 WORDS)
Influence of site of tracheal pressure measurement on in situ estimation of endotracheal tube resistance
Authors: Navalesi P. , Hernandez P. , Laporta D. , Landry J. S. , Maltais F. , Navajas D. , Gottfried S. B.
Published: December 2017

In situ measurement of distal tracheal pressure (Ptr) via an intraluminal side-hole catheter (IC) has been used to determine endotracheal tube (Rett) and intrinsic patient (Rpt) resistances in intubated subjects. Because of differences in cross-sectional area between the endotracheal tube (ETT) and trachea, fluid dynamic principles predict that IC position should critically influence these results. Accordingly, the aim of this study was to determine the effect of IC position on Rett. Ptr was recorded in vitro through an IC from 2 cm inside, at the tip of, or 2 cm outside an ETT (7, 8, and 9 mm ID) situated within an artificial trachea (13, 18, and 22 mm ID). A reference value of Rett was also obtained. Results were unaffected by IC position during inspiration, overestimating Rett by 7.9 +/- 0.7% (SE). In contrast, during expiration, Rett fell as IC position changed from outside to inside the ETT and was underestimated by 41.3 +/- 3.6% with Ptr recorded inside the ETT. Varying ETT or tracheal size had little effect on the relative error in Rett. The IC itself did increase Rett due to a reduction in effective cross-sectional area, the change varying directly with IC size and inversely with ETT caliber. In vivo values in 11 intubated patients were comparable to in vitro results. In summary, IC position and size can have important consequences on in situ measurements of Ptr and should be considered when clinically monitoring Rett or Rpt.
Excess oxygen delivery during muscle contractions in spontaneously hypertensive rats
Authors: Lash J. M. , Bohlen H. G.
Published: December 2017

These experiments determined whether a deficit in oxygen supply relative to demand could account for the sustained decrease in tissue PO2 observed during contractions of the spinotrapezius muscle in spontaneously hypertensive rats (SHR). Relative changes in blood flow were determined from measurements of vessel diameter and red blood cell velocity. Venular hemoglobin oxygen saturation measurements were performed by using in vivo spectrophotometric techniques. The relative dilation [times control (xCT)] of arteriolar vessels during contractions was as large or greater in SHR than in normotensive rats (Wistar-Kyoto), as were the increases in blood flow (2 Hz, 3.50 +/- 0.69 vs. 3.00 +/- 1.05 xCT; 4 Hz, 10.20 +/- 3.06 vs. 9.00 +/- 1.48 xCT; 8 Hz, 16.40 +/- 3.95 vs. 10.70 +/- 2.48 xCT). Venular hemoglobin oxygen saturation was lower in the resting muscle of SHR than of Wistar-Kyoto rats (31.0 +/= 3.0 vs. 43.0 +/- 1.9%) but was higher in SHR after 4- and 8-Hz contractions (4 Hz, 52.0 +/- 4.8 vs. 43.0 +/- 3.6%; 8 Hz, 51.0 +/- 4.6 vs. 41.0 +/- 3.6%). Therefore, an excess in oxygen delivery occurs relative to oxygen use during muscle contractions in SHR. The previous and current results can be reconciled by considering the possibility that oxygen exchange is limited in SHR by a decrease in anatomic or perfused capillary density, arteriovenular shunting of blood, or decreased transit time of red blood cells through exchange vessels.
Adaptations in muscle metabolism to prolonged voluntary exercise and training
Authors: Green H. J. , Jones S. , Ball-Burnett M. , Farrance B. , Ranney D.
Published: December 2017

In previous research we established using a short-term (5–7 days) training model that increases in muscle oxidative potential are not a prerequisite for the characteristic energy metabolic adaptations (lower lactate, glycogen depletion, and phosphocreatine hydrolysis) observed during prolonged exercise. To investigate whether increased muscle aerobic potential further potentiates the metabolic adaptive response, seven healthy male volunteers [maximal O2 uptake (VO2max) = 45.1 +/- 1.1 (SE) ml.kg-1.min-1] engaged in an 8-wk training program consisting of 2 h of cycle exercise at 62% of pretraining VO2max 5–6 times/wk. Analysis of tissue samples obtained from the vastus lateralis after 60 min of exercise revealed that by 4 wk of training muscle lactate concentration, phosphocreatine hydrolysis, and glycogen depletion were depressed (all P < 0.05). Further training for 4 wk had no additional effect (P < 0.05). The ratio of fructose 6-phosphate to fructose 1,6-phosphate, an index of phosphofructokinase activity, was not altered with training. Muscle oxidative potential as estimated from the maximal activity of succinic dehydrogenase increased by 31% by 4 wk of training (P <0.05) before plateauing during the final 4 wk of training. The increase in VO2max of 15.6% (P < 0.05) noted with training was also primarily expressed during the initial 4 wk. O2 uptake during submaximal exercise was unchanged. Because the metabolic response was similar in magnitude to that previously observed with short-term training, we conclude that, at least for the conditions of this study, the development of increased muscle aerobic potential is of minimal consequence on the magnitude of the energy metabolic adaptations examined.
Rat retrotrapezoid nucleus iono- and metabotropic glutamate receptors and the control of breathing
Authors: Nattie E. E. , Li A.
Published: December 2017

We injected 10 nl (unilateral) of glutamate receptor antagonists or agonists into the region of the retrotrapezoid nucleus and measured the phrenic nerve and blood pressure responses. The rats were chloralose-urethan anesthetized, paralyzed, vagotomized, and ventilated, and each injection location was verified anatomically. Integrated phrenic amplitude was most reliably affected. The N-methyl-D-aspartic acid (NMDA) antagonists 2-amino-5-phosphonopentanoic acid and 6-cyano-7-nitroquinoxaline-2,3-dione (which affects both NMDA and non-NMDA receptors) both decreased baseline eucapnic phrenic amplitude and the CO2 response. Glutamate increased phrenic amplitude in a dose-dependent manner, an effect blocked by prior injection of the NMDA and non-NMDA antagonists at the same site. The response duration depended on the duration of the glutamate injection: responses to 3-s injections lasted a few minutes, and responses to 60-s injections lasted for > 30 min. The long-lasting effect was reproduced by injection of the metabotropic agonist 1(S),3(R)-aminocyclopentanedicarboxylic acid at 0.01–0.02 times the glutamate dose. We conclude that the rat retrotrapezoid nucleus has an endogenous source of glutamate that maintains eucapnic phrenic output and allows expression of the CO2 response. NMDA and possibly non-NMDA receptors are involved. Their stimulation increases phrenic output via ionotropic and metabotropic receptor processes with the latter resulting in long-lasting phrenic stimulation.
Effect of aging on beta 2-adrenergic receptor-stimulated flux of K+, PO4, FFA, and glycerol in human forearms
Authors: Ford G. A. , Dachman W. D. , Blaschke T. F. , Hoffman B. B.
Published: December 2017

beta-Adrenergic responses have been shown to decline with aging, particularly in the cardiovascular system. We infused terbutaline, a selective beta 2-adrenoceptor agonist, into the brachial artery of 10 young (mean age 25 yr, range 22–31 yr) and 9 elderly (mean age 73 yr, range 68–81 yr) healthy subjects to examine its effects on nutrient flux. Forearm K+, PO4, free fatty acid (FFA), and glycerol uptake were determined by measurement of forearm blood flow (using dye dilution) and brachial arterial and deep venous plasma substrate concentrations. Elderly subjects were less sensitive to terbutaline-mediated increases in forearm blood flow, net fluxes of K+, and glycerol but not net fluxes of FFA or PO4. The mean fitted slopes of each parameter vs. the log of the terbutaline concentration, a measure of forearm beta-adrenergic sensitivity, for young and elderly groups were 4.9 +/- 1.7 (SD) vs. 2.4 +/- 2.3 for forearm blood flow (P <O 0.05), 0.84 +/- 0.46 vs. 0.43 +/- 0.37 for K+ net flux (P < 0.05), -157 +/- 113 vs. -26 +/- 26 for glycerol net flux (P < 0.01), -336 +/- 429 vs. -44 +/- 457 for FFA net flux (P = 0.11), and 0.31 +/- 0.24 vs. 0.18 +/- 0.16 for PO4 net flux (P = 0.14). Terbutaline promoted net uptake of K+ into skeletal muscle less well in the elderly, although net PO4 flux was similar in the two groups. Terbutaline-stimulated vasodilation and net glycerol efflux but not FFA efflux were impaired with aging. These data demonstrate that heterogeneous changes in beta-adrenergic responses occur with aging.
Heart rate and blood pressure variabilities during graded head-up tilt
Authors: Mukai S. , Hayano J.
Published: December 2017

We investigated the responses of the frequency components of heart rate (HR) and blood pressure (BP) variabilities to progressive changes in autonomic activity induced by the graded head-up tilt technique in 12 normal subjects (age 19–27 yr) under the condition of frequency-controlled respiration (0.25 Hz). During low-level tilt (0–30 degrees), the R-R interval was unchanged and the amplitude of the high-frequency (HF; 0.25 Hz) component of HR variability showed only a slight insignificant decrease. The amplitude of the low-frequency (LF; 0.04–0.15 Hz) component of HR variability increased progressively as the angle increased (P < 0.05). During high-level tilt (30–90 degrees), the R-R interval and the HF amplitude of HR variability decreased progressively with tilt angle (P < 0.001 for both). The LF amplitude of HR variability peaked at a tilt angle of 30 degrees. The LF-to-HF ratio of HR variability and the LF amplitude of systolic and diastolic BP variabilities increased progressively as the tilt angle increased from 0 to 60 degrees (P < 0.001), although systolic and diastolic BPs were unchanged. These results suggest that mixed autonomic responses to orthostatic stress, which are thought to be mediated by both cardiopulmonary and arterial baroreflex mechanisms, can be distinguished by changes in the frequency components of HR and BP variabilities.
Unidirectional sodium and potassium flux in myogenic L6 cells: mechanisms and volume-dependent regulation
Authors: Sen C. K. , Hanninen O. , Orlov S. N.
Published: December 2017

To clarify the relative participation of particular ion transport systems in net univalent cation fluxes under basal conditions and altered volume of skeletal muscle-derived cells, the effect of inhibitors of the Na(+)-K+ pump (ouabain), univalent ion cotransporters [bumetanide, furosemide, and (dihydroindenyl)oxy alkanoic acid], and N+/H+ exchanger (ethylisopropylamiloride) on 86Rb and 22Na fluxes has been studied in L6 myoblasts incubated in isosmotic (320 mosmol/kg) and anisosmotic media. Under the isosmotic condition, the relative contribution of ouabain-inhibited and ouabain-insensitive bumetanide-inhibited component of 86Rb influx was approximately 15–20 and 60%, respectively. 22Na influx was inhibited by bumetanide and ethylisopropylamiloride by 25 and 15%, respectively. Under isosmotic conditions, an increase of L6 cell volume was observed after addition of extracellular acetylcholine, extracellular K(+)-induced depolarization, or lowering of the pH of the incubation medium. High extracellular glutathione (150 microM) did not affect the cell volume of the muscle-derived cells bathed in isosmotic medium. Results of this study suggest that the bumetanide-inhibited component of K+ influx plays a key role in the adjustment of transmembrane K+ gradient in L6 myoblasts. The Na+/H+ exchanger appears to be important in regulatory volume increase.
How mode of stimulus affects the relative contribution of elastance and hysteresivity to changes in lung tissue resistance
Authors: Salerno F. G. , Moretto A. , Dallaire M. , Ludwig M. S.
Published: December 2017

Challenges with high concentrations of constrictor agonist delivered by intravenous vs. aerosol result in different modifications of the mechanical properties of lung tissues. We questioned whether low doses of a smooth muscle agonist administered via different routes (aerosol, i.v. bolus, i.v. continuous infusion) or an increase in positive end-expiratory pressure (PEEP) would result in different mechanical perturbations of lung tissues. Tracheal and alveolar pressures and flow were measured in open-chest mechanically ventilated (frequency 1 Hz, tidal volume 10 ml/kg, PEEP 4 cmH2O) rats under baseline conditions and after administration of low doses of methacholine or after increases in PEEP. We calculated lung elastance (EL), lung resistance, and tissue resistance (Rti) by fitting the equation of motion to changes in tracheal and alveolar pressures. Airway resistance and hysteresivity (eta) were derived from the above measurements. For comparable increases in Rti, the aerosol and PEEP groups showed large increases in EL with a decrease in eta, whereas the two intravenous groups showed large increases in eta with smaller increases in EL. The largest contribution of eta to the overall increase in Rti was seen in the intravenous bolus group. When induced changes in EL vs. induced changes in eta were plotted, different relationships were found for the four groups. We conclude that despite similar increases in Rti a different kind of mechanical perturbation occurred in the lung tissues that depended on the nature of the stimulus.
Hypothermic effect of melatonin and nocturnal core body temperature decline are reduced in aged women
Authors: Cagnacci A. , Soldani R. , Yen S. S.
Published: December 2017

In young humans, the nocturnal rise of the hypothermic hormone melatonin generates 40–50% of the circadian core body temperature (Tc) decline. The nocturnal Tc decline is reduced with aging in men. In this study we investigated whether a similar attenuation occurs in women and whether it is associated with a reduced serum concentration and/or action of melatonin. The circadian rhythms of melatonin and Tc (measured in the vagina) and the responses of both Tc (measured into the auricolar canal) and finger skin temperature to melatonin administration (100 mg at 0800) were investigated in two experiments involving young (22–32 yr) and aged (54–62 yr) women. In aged women, the nocturnal onset of the melatonin rise was phase advanced and Tc decline and Tc rhythm amplitude were reduced (P < 0.0005). The serum melatonin concentrations in aged women were similar to those of young women, but the melatonin capability to reduce Tc and increase skin temperature was markedly impaired. Our data show that, in women, an aging-associated reduction of temperature responses to melatonin is probably involved in inducing an attenuation of the nocturnal Tc decline and circadian Tc rhythm amplitude.