bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic intermittent hypoxia increases sympathetic responsiveness to hypoxia and hypercapnia
Authors: Greenberg Harly E. , Sica Anthony , Batson Deirdre , Scharf Steven M.
Published: December 2017

We sought to determine whether chronic exposure to intermittent hypoxia (CIH) increases sympathetic responsiveness to subsequent chemoreflex stimulation. Sprague-Dawley rats were exposed to 30 days of CIH: exposure chamber %O2 [fractional concentration of chamber O2([Formula: see text])] nadir 6.5–7% with return to 21% each minute for 8 h/day during the diurnal sleep period (Exp group). Sham controls (SC group) were similarly handled but kept at 21%[Formula: see text] and compared with unhandled controls (UC group). Rats were then anesthetized with urethan, and preganglionic cervical sympathetic activity (CSA), diaphragm electromyogram, arterial pressure, and electrocardiogram were recorded while the rats were spontaneously breathing 100% O2, room air, 10% O2, 12% CO2, and 10% O2-12% CO2. CSA and heart rate were also recorded during phenylephrine infusion to assess baroreceptor function. Mean arterial pressure was significantly greater in Exp than in SC and UC rats during all conditions ( P < 0.05). A vasopressor response to 10% O2-12% CO2 was observed only in Exp rats. CSA was greater in Exp than in SC and UC rats during 10% O2, 12% CO2, and 10% O2-12% CO2 but not during room-air exposure. A significant increase in CSA compared with room air was noted during 10% O2, 12% CO2, and 10% O2-12% CO2 in Exp but not in SC or UC rats. No differences in baroreceptor function were observed among groups. We conclude that CIH leads to increased sympathetic responsiveness to chemoreflex stimulation.
Substrate and enzyme profile of fast and slow skeletal muscle fibers in rhesus monkeys
Authors: Grichko Varvara P. , Gettelman Gwen J. , Widrick Jeffrey J. , Fitts Robert H.
Published: December 2017

Results from the Russian Cosmos program suggest that the rhesus monkey is an excellent model for studying weightlessness-induced changes in muscle function. Consequently, the purpose of this investigation was to establish the resting levels of selected substrate and enzymes in individual slow- and fast-twitch muscle fibers of the rhesus monkey. A second objective was to determine the effect of an 18-day sit in the Spacelab experiment-support primate facility [Experimental System for the Orbiting Primate (ESOP)]. Muscle biopsies of the soleus and medial gastrocnemius muscles were obtained 1 mo before and immediately after an 18-day ESOP sit. The biopsies were freeze-dried, and individual fibers were isolated and assayed for the substrates glycogen and lactate and for the high-energy phosphates ATP and phosphocreatine. Fiber enzyme activity was also determined for the glycolytic enzymes phosphofructokinase and lactate dehydrogenase (LDH) and for the oxidative markers 3-hydroxyacyl-CoA dehydrogenase (β-OAC) and citrate synthase. Consistent with other species, the fast type II fibers contained higher glycogen content than did the slow type I fibers. The ESOP sit had no significant effects on the metabolic profile of the slow fibers of either muscle or the fast fibers of the soleus. However, the fast gastrocnemius fibers showed a significant decline in phosphocreatine and an increase in lactate. Also, similar to other species, the fast fibers contained significantly higher LDH activities and lower 3-hydroxyacyl-CoA dehydrogenase activities. For the muscle enzymes, the quantitatively most important effect of the ESOP sit occurred with LDH where activities increased in all fiber types postsit except the slow type I fiber of the medial gastrocnemius.
Bolus dispersal through the lungs in surfactant replacement therapy
Authors: Espinosa F. F. , Kamm R. D.
Published: December 2017

A model is presented of surfactant replacement therapy. An instilled bolus is pushed into the lungs on the first inspiration, coating the airways with a layer of surfactant and depositing some in the alveoli. Layer thickness depends on the capillary number (μ U/γ, where μ, U, and γ are bolus viscosity, advancing meniscus velocity, and surface tension, respectively). Larger capillary number leads to thicker layers, reducing alveolar delivery. Subsequently, surface tension gradients sweep surfactant into alveoli not receiving surfactant during the first inspiration. The effects on spreading of sorption kinetics, bolus viscosity, initial layer thickness, initial penetration of surfactant, gravity, and shear stress are examined. Sorption nearly eliminates surface tension gradients in central airways but produces a sharp transition at the leading edge of the exogenous layer. Local thinning of the liquid layer results, trapping 95% of the surfactant in the airways. Gravity and ventilation augment transport somewhat. Transport to the periphery takes 4–170 s for the leading edge but considerably longer for the bulk of the surfactant. The model demonstrates how the various physical parameters governing surfactant distribution might alter the response to surfactant replacement therapy.
Mechanical effects of pharyngeal constrictor activation on pharyngeal airway function
Authors: Kuna Samuel T. , Vanoye Christi R.
Published: December 2017

The mechanical effects of pharyngeal constrictor (PC) muscle activation on pharyngeal airway function were determined in 20 decerebrate, tracheotomized cats. In 10 cats, a high-compliance balloon attached to a pressure transducer was partially inflated to just occlude the pharyngeal airway. During progressive hyperoxic hypercapnia, changes in pharyngeal balloon pressure were directly related to phasic expiratory hyopharyngeus (middle PC) activity. In two separate protocols in 10 additional cats, the following measurements were obtained with and without bilateral electrical stimulation (0.2-ms duration, threshold voltage) of the distal cut end of the vagus nerve’s pharyngeal branch supplying PC motor output: 1) pressure-volume relationships in an isolated, sealed upper airway at a stimulation frequency of 30 Hz and 2) rostrally directed axial force over a stimulation frequency range of 0–40 Hz. Airway compliance determined from the pressure-volume relationships decreased with PC stimulation at and below resting airway volume. Compared with the unstimulated condition, PC stimulation increased airway pressure at airway volumes at and above resting volume. This constrictor effect progressively diminished as airway volume was brought below resting volume. At relatively low airway volumes below resting volume, PC stimulation decreased airway pressure compared with that without stimulation. PC stimulation generated a rostrally directed axial force that was directly related to stimulation frequency. The results indicate that PC activation stiffens the pharyngeal airway, exerting both radial and axial effects. The radial effects are dependent on airway volume: constriction of the airway at relatively high airway volumes, and dilation of the airway at relatively low airway volumes. The results imply that, under certain conditions, PC muscle activation may promote pharyngeal airway patency.
Estimating respiratory mechanics in the presence of flow limitation
Authors: Bijaoui Eve , Tuck Stephanie A. , Remmers John E. , Bates Jason H. T.
Published: December 2017

Dynamic collapse of the pulmonary airways, leading to flow limitation, is a significant event in a number of respiratory pathologies, including obstructive sleep apnea syndrome and chronic obstructive pulmonary disease. Quantitative evaluation of the mechanical status of the respiratory system in these conditions provides useful insights into airway caliber and tissue stiffness, which are hallmarks of such abnormalities. However, assessing respiratory mechanics in the presence of flow limitation is problematic because the single-compartment linear model on which most assessment methods are based is not valid over the entire breath. Indeed, even deciding which parts of a breath are flow limited from measurement of mouth flow and pleural pressure often proves to be difficult. In this study, we investigated the use of two approaches to assessing the overall mechanical properties of the respiratory system in the presence of inspiratory flow limitation. The first method is an adaptation of the classic Mead-Whittenberger method, and the second method is based on information-weighted histograms obtained from recursively estimated signals of respiratory resistance and elastance. We tested the methods on data simulated by using a computer model of the respiratory system and on data collected from obese sleeping pigs. We found that the information-weighted histograms provided the more robust overall estimates of respiratory mechanics.
Influence of intercellular tissue connections on airway muscle mechanics
Authors: Meiss R. A.
Published: December 2017

Contraction of smooth muscle in visceral organs is modified by structures external to the muscle. Within muscle tissue itself, connective tissue plays an important role in force transference among the contractile cells. Connections arranged radially can affect contractile mechanics by limiting tissue expansion at short lengths. Previous work suggests that increased stiffness at extreme shortening is due to such radial constraints. Two approaches to further study of these effects are reported. To increase radial constraints, very thin Silastic bands were placed loosely about strips of canine trachealis muscle at rest length. The strips were allowed to shorten under light afterloads, expanding until restrained by the bands. Subsequent removal of the bands allowed increased shortening, with less increase in stiffness at short lengths. Related isometric effects were observed. To reduce constraints, muscle strips were partially digested with collagenase. Compared with control conditions, this treatment permitted further shortening, with less increase in stiffness at short lengths. These results emphasize the role of extracellular structures in determining mechanical function of smooth muscle.
Influence of group B streptococci on piglet pulmonary artery response to bradykinin
Authors: Whitehurst Richard M. , Laskey Rachel , Goldberg Ronald N. , Herbert Donald , Van Breemen Cornelius
Published: December 2017

To study whether a sepsis-induced increase in des-Arg9-bradykinin (des-Arg9-BK) and bradykinin (BK) B1-receptor activity participates in the observed increase in pulmonary vascular resistance in neonatal group B streptococcal sepsis (GBS), isometric force bioassays of pulmonary artery (PA) rings were studied, after 4-h exposure to either Krebs or GBS, by using the following protocols: 1) BK dose-response curve, 2) vascular response to BK with NG-nitro-l-arginine methyl ester (l-NAME), and 3) response to des-Arg9-BK (BK metabolite and B1agonist). PA rings exposed to BK resulted in contraction in the GBS group and a decrease in resting tension in the Control group ( P = 0.034) at a concentration of 10−5M. GBS-treated PA rings contracted more to des-Arg9-BK than did Controls ( P < 0.001). BK (10−6M) relaxed preconstricted PA rings incubated in GBS less than BK relaxed Controls ( P < 0.001), and preincubation withl-NAME decreased relaxation in both. These results suggest that GBS decreased endothelium-dependent BK relaxation and increased contractile response to des-Arg9-BK. We speculate that this occurs secondary to upregulation of B1receptors reflected by B1-agonist-mediated PA contraction.
Vasomotor responses of soleus feed arteries from sedentary and exercise-trained rats
Authors: Jasperse Jeffrey L. , Laughlin M. Harold
Published: December 2017

Our goals were to determine the nature of endothelium-dependent and -independent vascular responses in isolated soleus feed arteries (SFA) and to test the hypothesis that these responses would be altered by exercise training. Exercise-trained rats ran 30 m/min, up a 15% grade, 1 h/day, 5 days/wk for 10–12 wk, while sedentary control rats were confined to normal cage activity. SFA were isolated, cannulated, and pressurized at 90 cmH2O. After a 1-h equilibration period, the dose-response relationships to constrictors, endothelium-dependent dilators, and endothelium-independent dilators were examined. SFA developed spontaneous tone, demonstrated myogenic reactivity by maintaining vessel diameter in the face of large changes in intraluminal pressure, and constricted in a dose-dependent manner to norepinephrine and potassium chloride. SFA dilated in a dose-dependent manner to the endothelium-dependent dilators acetylcholine and increased flow and to the endothelium-independent dilator sodium nitroprusside. SFA did not dilate to the putative endothelium-dependent dilators bradykinin, substance P, and clonidine or to adenosine. Dilation to acetylcholine was attenuated markedly by arginine analogs and less by 20 mM KCl, but it was unaltered by indomethacin. These results indicate that SFA respond to a number of vasoactive substances, consistent with the hypothesis that SFA participate in the control of vascular resistance. However, exercise training does not appear to elicit a stimulus adequate to alter vasomotor responses in SFA.
Mechanical properties of lung parenchyma during bronchoconstriction
Authors: Okazawa Mitsushi , D’Yachkova Yulia , Paré Peter D.
Published: December 2017

Interdependence between airways and the lung parenchyma is thought to be a major mechanism preventing excessive airway narrowing during bronchoconstriction. Because the elastance of the lung increases during bronchoconstriction, the lung’s tethering force could also increase, further attenuating bronchoconstriction. We hypothesized that the bulk (κ) and shear moduli (μ) of the lung increase similarly during bronchoconstriction. To test this hypothesis, we excised rabbit lungs and measured the lung volume, pulmonary elastance, κ, and μ at transpulmonary pressures of 4, 6, 8, 12, and 16 cmH2O using pressure-volume curves, slow oscillations of the lung, and an indentation test. Bronchoconstriction was induced by nebulizing carbachol by using small tidal-volume ventilation to prevent hyperinflation. The measurement of κ and μ was repeated after carbachol treatment. After carbachol treatment, the increase in κ was significantly greater than that in μ. The estimated value for μ was ∼0.5 × transpulmonary pressureboth before and after carbachol treatment. These data suggest that the tethering effect of the lung parenchyma, which serves to attenuate bronchoconstriction, is not significantly increased during carbachol administration unless there is hyperinflation.
Effects of acetaminophen and ibuprofen on renal function in the stressed kidney
Authors: Farquhar W. B. , Morgan A. L. , Zambraski E. J. , Kenney W. L.
Published: December 2017

Exercise, salt restriction, and/or dehydration causes transient reductions in renal function that may be buffered by vasodilatory prostaglandins (PGs). Over-the-counter (OTC) analgesics have the potential to alter renal hemodynamics by inhibiting renal PGs. Therefore, we tested the renal effects of the maximal recommended dose of acetaminophen (Acet, 4 g/day) and ibuprofen (Ibu, 1.2 g/day) vs. a placebo (Pl) in humans subjected to progressive renal stresses. After baseline measurements, 12 fit young (25 ± 1 yr) men and women underwent 3 days of a low (10 meq/day)-sodium diet while taking one of the drugs or Pl (crossover design). Day 4 involved dehydration (−1.6% body wt) followed by 45 min of treadmill exercise (65% maximal O2uptake) in the heat (36°C). These combined stressors caused dramatic decreases in effective renal plasma flow, glomerular filtration rate (GFR), and sodium excretion. Baseline GFR (range: 118–123 ml/min) decreased to 78 ± 4, 73 ± 5, and 82 ± 5 ml/min postexercise in the Acet, Ibu, and Pl trials, respectively, with a significantly greater decrease in GFR in the Ibu trial ( P < 0.05 vs. Pl). OTC Ibu has small but statistically significant effects on GFR during exercise in a sodium- and volume-depleted state; OTC Acet was associated with no such effects.
Cerebral vasomotor reactivity at high altitude in humans
Authors: Jansen Gerard F. A. , Krins Anne , Basnyat Buddha
Published: December 2017

The purpose of this study was twofold: 1) to determine whether at high altitude cerebral blood flow (CBF) as assessed during CO2 inhalation and during hyperventilation in subjects with acute mountain sickness (AMS) was different from that in subjects without AMS and 2) to compare the CBF as assessed under similar conditions in Sherpas at high altitude and in subjects at sea level. Resting control values of blood flow velocity in the middle cerebral artery ( V MCA), pulse oxygen saturation ([Formula: see text]), and transcutaneous [Formula: see text] were measured at 4,243 m in 43 subjects without AMS, 17 subjects with AMS, 20 Sherpas, and 13 subjects at sea level. Responses of CO2 inhalation and hyperventilation on V MCA,[Formula: see text], and transcutaneous[Formula: see text] were measured, and the cerebral vasomotor reactivity (VMR = Δ V MCA/[Formula: see text]) was calculated as the fractional change of V MCA per Torr change of [Formula: see text], yielding a hypercapnic VMR and a hypocapnic VMR. AMS subjects showed a significantly higher resting control V MCA than did no-AMS subjects (74 ± 22 and 56 ± 14 cm/s, respectively; P < 0.001), and[Formula: see text] was significantly lower (80 ± 8 and 88 ± 3%, respectively; P < 0.001). Resting control V MCA values in the sea-level group (60 ± 15 cm/s), in the no-AMS group, and in Sherpas (59 ± 13 cm/s) were not different. Hypercapnic VMR values in AMS subjects were 4.0 ± 4.4, in no-AMS subjects were 5.5 ± 4.3, in Sherpas were 5.6 ± 4.1, and in sea-level subjects were 5.6 ± 2.5 (not significant). Hypocapnic VMR values were significantly higher in AMS subjects (5.9 ± 1.5) compared with no-AMS subjects (4.8 ± 1.4; P < 0.005) but were not significantly different between Sherpas (3.8 ± 1.1) and the sea-level group (2.8 ± 0.7). We conclude that AMS subjects have greater cerebral hemodynamic responses to hyperventilation, higher V MCAresting control values, and lower[Formula: see text] compared with no-AMS subjects. Sherpas showed a cerebral hemodynamic pattern similar to that of normal subjects at sea level.
Characteristics of the muscle mechanoreflex during quadriceps contractions in humans
Authors: Herr Michael D. , Imadojemu Virginia , Kunselman Allen R. , Sinoway Lawrence I.
Published: December 2017

We examined muscle sympathetic nerve activity (MSNA) in the nonexercising lower limb during repetitive static quadriceps contraction paradigm at 25% maximal voluntary contraction in eight men. Subjects performed 20-s contractions with 5-s rest periods for up to 12 contractions. Although the workload was constant, we found that MSNA amplitude rose as a function of contraction number [0.6 ln (amplitude/min)/contraction]; this suggests chemical sensitization of the muscle reflex response. We employed signal-averaging techniques and then integrated the data to examine the onset latency of the MSNA response as a function of the 25-s contraction-rest period. We observed an onset latency of ∼4–6 s. Moreover, although the onset latency did not appear to vary as a function of contraction number, the rate of MSNA increase took approximately four contractions to reach a steady-state rate of rise; this suggests contraction-induced sensitization. The onset latency reported here is similar to findings in recent animal studies, but it is at odds with latencies determined in prior human handgrip contraction studies. We believe our data suggest that 1) mechanically sensitive afferents contribute importantly to the MSNA response to the paradigm employed and 2) these afferents may be sensitized by the chemical products of muscle contraction.
Influence of body temperature on the development of fatigue during prolonged exercise in the heat
Authors: González-Alonso José , Teller Christina , Andersen Signe L. , Jensen Frank B. , Hyldig Tino , Nielsen Bodil
Published: December 2017

We investigated whether fatigue during prolonged exercise in uncompensable hot environments occurred at the same critical level of hyperthermia when the initial value and the rate of increase in body temperature are altered. To examine the effect of initial body temperature [esophageal temperature (Tes) = 35.9 ± 0.2, 37.4 ± 0.1, or 38.2 ± 0.1 (SE) °C induced by 30 min of water immersion], seven cyclists (maximal O2 uptake = 5.1 ± 0.1 l/min) performed three randomly assigned bouts of cycle ergometer exercise (60% maximal O2 uptake) in the heat (40°C) until volitional exhaustion. To determine the influence of rate of heat storage (0.10 vs. 0.05°C/min induced by a water-perfused jacket), four cyclists performed two additional exercise bouts, starting with Tes of 37.0°C. Despite different initial temperatures, all subjects fatigued at an identical level of hyperthermia (Tes = 40.1–40.2°C, muscle temperature = 40.7–40.9°C, skin temperature = 37.0–37.2°C) and cardiovascular strain (heart rate = 196–198 beats/min, cardiac output = 19.9–20.8 l/min). Time to exhaustion was inversely related to the initial body temperature: 63 ± 3, 46 ± 3, and 28 ± 2 min with initial Tes of ∼36, 37, and 38°C, respectively (all P < 0.05). Similarly, with different rates of heat storage, all subjects reached exhaustion at similar Tes and muscle temperature (40.1–40.3 and 40.7–40.9°C, respectively), but with significantly different skin temperature (38.4 ± 0.4 vs. 35.6 ± 0.2°C during high vs. low rate of heat storage, respectively, P < 0.05). Time to exhaustion was significantly shorter at the high than at the lower rate of heat storage (31 ± 4 vs. 56 ± 11 min, respectively, P < 0.05). Increases in heart rate and reductions in stroke volume paralleled the rise in core temperature (36–40°C), with skin blood flow plateauing at Tes of ∼38°C. These results demonstrate that high internal body temperature per se causes fatigue in trained subjects during prolonged exercise in uncompensable hot environments. Furthermore, time to exhaustion in hot environments is inversely related to the initial temperature and directly related to the rate of heat storage.
Alterations of heart function and Na+-K+-ATPase activity by etomoxir in diabetic rats
Authors: Kato Kiminori , Chapman Donald C. , Rupp Heinz , Lukas Anton , Dhalla Naranjan S.
Published: December 2017

To examine the role of changes in myocardial metabolism in cardiac dysfunction in diabetes mellitus, rats were injected with streptozotocin (65 mg/kg body wt) to induce diabetes and were treated 2 wk later with the carnitine palmitoyltransferase inhibitor (carnitine palmitoyltransferase I) etomoxir (8 mg/kg body wt) for 4 wk. Untreated diabetic rats exhibited a reduction in heart rate, left ventricular systolic pressure, and positive and negative rate of pressure development and an increase in end-diastolic pressure. The sarcolemmal Na+-K+-ATPase activity was depressed and was associated with a decrease in maximal density of binding sites (Bmax) value for high-affinity sites for [3H]ouabain, whereas Bmaxfor low-affinity sites was unaffected. Treatment of diabetic animals with etomoxir partially reversed the depressed cardiac function with the exception of heart rate. The high serum triglyceride and free fatty acid levels were reduced, whereas the levels of glucose, insulin, and 3,3′,-5-triiodo-l-thyronine were not affected by etomoxir in diabetic animals. The activity of Na+-K+-ATPase expressed per gram heart weight, but not per milligram sarcolemmal protein, was increased by etomoxir in diabetic animals. Furthermore, Bmax(per g heart wt) for both low-affinity and high-affinity binding sites in control and diabetic animals was increased by etomoxir treatment. Etomoxir treatment also increased the depressed left ventricular weight of diabetic rats and appeared to increase the density of the sarcolemma and transverse tubular system to normalize Na+-K+-ATPase activity. Therefore, a shift in myocardial substrate utilization may represent an important signal for improving the depressed cardiac function and Na+-K+-ATPase activity in diabetic rat hearts with impaired glucose utilization.
Lactate kinetics at rest and during exercise in lambs with aortopulmonary shunts
Authors: Beaufort-Krol Gertie C. M. , Zijlstra Willem G. , Takens Janny , Molenkamp Marieke C. , Meuzelaar Koos J. , Smid Gioia B. , Kuipers Jaap R. G.
Published: December 2017

In a previous study [G. C. M. Beaufort-Krol, J. Takens, M. C. Molenkamp, G. B. Smid, J. J. Meuzelaar, W. G. Zijlstra, and J. R. G. Kuipers. Am. J. Physiol. 275 ( Heart Circ. Physiol. 44): H1503–H1512, 1998], a lower systemic O2 supply was found in lambs with aortopulmonary left-to-right shunts. To determine whether the lower systemic O2 supply results in increased anaerobic metabolism, we used [1-13C]lactate to investigate lactate kinetics in eight 7-wk-old lambs with shunts and eight control lambs, at rest and during moderate exercise [treadmill; 50% of peak O2consumption (V˙o 2)]. The mean left-to-right shunt fraction in the shunt lambs was 55 ± 3% of pulmonary blood flow. Arterial lactate concentrations and the rate of appearance (Ra) and disappearance (Rd) of lactate were similar in shunt and control lambs, both at rest (lactate: 1,201 ± 76 vs. 1,214 ± 151 μmol/l; Ra = Rd: 12.97 ± 1.71 vs. 12.55 ± 1.25 μmol ⋅ min−1 ⋅ kg−1) and during a similar relative workload. We found a positive correlation between Ra and systemic blood flow, O2 supply, andV˙o 2 in both groups of lambs. In conclusion, shunt lambs have similar lactate kinetics as do control lambs, both at rest and during moderate exercise at a similar fraction of their peak V˙o 2, despite a lower systemic O2supply.
Shortening of muscle relaxation time after creatine loading
Authors: van Leemputte M. , Vandenberghe K. , Hespel P.
Published: December 2017

The effect of creatine (Cr) supplementation on muscle isometric torque generation and relaxation was investigated in healthy male volunteers. Maximal torque (Tmax), contraction time (CT) from 0.25 to 0.75 of Tmax, and relaxation time (RT) from 0.75 to 0.25 of Tmax were measured during 12 maximal isometric 3-s elbow flexions interspersed by 10-s rest intervals. Between the pretest and the posttest, subjects ingested Cr monohydrate (4 × 5 g/day; n = 8) or placebo ( n = 8) for 5 days. Pretest Tmax, CT, and RT were similar in Cr and placebo groups. Also in the posttest, Tmax and CT were similar between groups. However, posttest RT was decreased consistently by ∼20% ( P < 0.05) in the Cr group from the first to the last of the 12 contractions. In addition, the mean decrease in RT after Cr loading was positively correlated with pretest RT ( r = 0.82). It is concluded that Cr loading facilitates the rate of muscle relaxation during brief isometric muscle contractions without affecting torque production.
Effect of acute normovolemic hemodilution on distribution of blood flow and tissue oxygenation in dog skeletal muscle
Authors: Hutter Jörg , Habler Oliver , Kleen Martin , Tiede Matthias , Podtschaske Armin , Kemming Gregor , Corso Carlos , Batra Sanjay , Keipert Peter , Faithfull Simon , Messmer Konrad
Published: December 2017

Acute normovolemic hemodilution (ANH) is efficient in reducing allogenic blood transfusion needs during elective surgery. Tissue oxygenation is maintained by increased cardiac output and oxygen extraction and, presumably, a more homogeneous tissue perfusion. The aim of this study was to investigate blood flow distribution and oxygenation of skeletal muscle. ANH from hematocrit of 36 ± 3 to 20 ± 1% was performed in 22 splenectomized, anesthetized beagles (17 analyzed) ventilated with room air. Normovolemia was confirmed by measurement of blood volume. Distribution of perfusion within skeletal muscle was determined by using radioactive microspheres. Tissue oxygen partial pressure was assessed with a polarographic platinum surface electrode. Cardiac index (3.69 ± 0.79 vs. 4.79 ± 0.73 l ⋅ min−1 ⋅ m−2) and muscle perfusion (4.07 ± 0.44 vs. 5.18 ± 0.36 ml ⋅ 100 g−1 ⋅ min−1) were increased at hematocrit of 20%. Oxygen delivery to skeletal muscle was reduced to 74% of baseline values (0.64 ± 0.06 vs. 0.48 ± 0.03 ml O2 ⋅ 100 g−1 ⋅ min−1). Nevertheless, tissue [Formula: see text] was preserved (27.4 ± 1.3 vs. 29.9 ± 1.4 Torr). Heterogeneity of muscle perfusion (relative dispersion) was reduced after ANH (20.0 ± 2.2 vs. 13.9 ± 1.5%). We conclude that a more homogeneous distribution of perfusion is one mechanism for the preservation of tissue oxygenation after moderate ANH, despite reduced oxygen delivery.
The physiological strain index applied to heat-stressed rats
Authors: Moran D. S. , Horowitz M. , Meiri U. , Laor A. , Pandolf K. B.
Published: December 2017

A physiological strain index (PSI) based on heart rate (HR) and rectal temperature (Tre) was recently suggested to evaluate exercise-heat stress in humans. The purpose of this study was to adjust PSI for rats and to evaluate this index at different levels of heat acclimation and training. The corrections of HR and Treto modify the index for rats are as follows: PSI = 5 (Tret− Tre 0) ⋅ (41.5 − Tre 0)−1+ 5 (HRt− HR0) ⋅ (550 − HR0)−1, where HRtand Tretare simultaneous measurements taken at any time during the exposure and HR0and Tre 0are the initial measurements. The adjusted PSI was applied to five groups ( n = 11–14 per group) of acclimated rats (control and 2, 5, 10, and 30 days) exposed for 70 min to a hot climate [40°C, 20% relative humidity (RH)]. A separate database representing two groups of acclimated or trained rats was also used and involved 20 min of low-intensity exercise (O2consumption ∼50 ml ⋅ min−1⋅ kg−1) at three different climates: normothermic (24°C, 40% RH), hot-wet (35°C, 70% RH), and hot-dry (40°C, 20% RH). In normothermia, rats also performed moderate exercise (O2consumption ∼60 ml ⋅ min−1⋅ kg−1). The adjusted PSI differentiated among acclimation levels and significantly discriminated among all exposures during low-intensity exercise ( P < 0.05). Furthermore, this index was able to assess the individual roles played by heat acclimation and exercise training.
Larynx vs. esophagus as reflexogenic sites for acid-induced bronchoconstriction in dogs
Authors: Ishikawa Teruhiko , Sekizawa Shin-Ichi , Sant’Ambrogio Franca B. , Sant’Ambrogio Giuseppe
Published: December 2017

Bronchoconstriction in asthmatic patients is frequently associated with gastroesophageal reflux. However, it is still unclear whether bronchoconstriction originates from the esophagus or from aspiration of the refluxate into the larynx and larger airway. We compared the effect of repeated esophageal and laryngeal instillations of HCl-pepsin (pH 1.0) on tracheal smooth muscle activity in eight anesthetized and artificially ventilated dogs. Saline was used as control. We used pressure in the cuff of an endotracheal tube (Pcuff) as a direct index of smooth muscle activity at the level of the larger airways controlled by vagal efferents. The Pcuff values of the first 60 s after instillations were averaged, and the difference from the baseline values was evaluated. Changes in Pcuff were significantly greater with laryngeal than with esophageal instillations ( P = 0.0166). HCl-pepsin instillation into the larynx evoked greater responses than did saline ( P = 0.00543), whereas no differences were detected with esophageal instillations. Repeated laryngeal exposure enhanced the responsiveness significantly ( P < 0.001). Our data indicate that the larynx is more important than the esophagus as a reflexogenic site for the elicitation of reflex bronchoconstriction in response to acidic solutions.
Altered reflex sensitivity after repeated and prolonged passive muscle stretching
Authors: Avela Janne , Kyröläinen Heikki , Komi Paavo V.
Published: December 2017

Experiments were carried out to test the effect of prolonged and repeated passive stretching (RPS) of the triceps surae muscle on reflex sensitivity. The results demonstrated a clear deterioration of muscle function immediately after RPS. Maximal voluntary contraction, average electromyographic activity of the gastrocnemius and soleus muscles, and zero crossing rate of the soleus muscle (recorded from 50% maximal voluntary contraction) decreased on average by 23.2, 19.9, 16.5, and 12.2%, respectively. These changes were associated with a clear immediate reduction in the reflex sensitivity; stretch reflex peak-to-peak amplitude decreased by 84.8%, and the ratio of the electrically induced maximal Hoffmann reflex to the maximal mass compound action potential decreased by 43.8%. Interestingly, a significant ( P < 0.01) reduction in the stretch-resisting force of the measured muscles was observed. Serum creatine kinase activity stayed unaltered. This study presents evidence that the mechanism that decreases the sensitivity of short-latency reflexes can be activated because of RPS. The origin of this system seems to be a reduction in the activity of the large-diameter afferents, resulting from the reduced sensitivity of the muscle spindles to repeated stretch.
Evaluation of pulmonary resistance and maximal expiratory flow measurements during exercise in humans
Authors: Beck Kenneth C. , Hyatt Robert E. , Mpougas Panagiotis , Scanlon Paul D.
Published: December 2017

To evaluate methods used to document changes in airway function during and after exercise, we studied nine subjects with exercise-induced asthma and five subjects without asthma. Airway function was assessed from measurements of pulmonary resistance (Rl) and forced expiratory vital capacity maneuvers. In the asthmatic subjects, forced expiratory volume in 1 s (FEV1) fell 24 ± 14% and Rl increased 176 ± 153% after exercise, whereas normal subjects experienced no change in airway function (Rl−3 ± 8% and FEV1−4 ± 5%). During exercise, there was a tendency for FEV1 to increase in the asthmatic subjects but not in the normal subjects. Rl, however, showed a slight increase during exercise in both groups. Changes in lung volumes encountered during exercise were small and had no consistent effect on Rl. The small increases in Rl during exercise could be explained by the nonlinearity of the pressure-flow relationship and the increased tidal breathing flows associated with exercise. In the asthmatic subjects, a deep inspiration (DI) caused a small, significant, transient decrease in Rl 15 min after exercise. There was no change in Rl in response to DI during exercise in either asthmatic or nonasthmatic subjects. When percent changes in Rl and FEV1 during and after exercise were compared, there was close agreement between the two measurements of change in airway function. In the groups of normal and mildly asthmatic subjects, we conclude that changes in lung volume and DIs had no influence on Rl during exercise. Increases in tidal breathing flows had only minor influence on measurements of Rl during exercise. Furthermore, changes in Rl and in FEV1 produce equivalent indexes of the variations in airway function during and after exercise.
Effect of upper airway negative pressure on proprioceptive afferents from the tongue
Authors: Brancatisano A. , Davis P. , van der Touw T. , Wheatley J. R.
Published: December 2017

We examined whether receptors in the tongue muscle respond to negative upper airway pressure (NUAP). In six cats, one hypoglossal nerve was cut and its distal end was prepared for single-fiber recording. Twelve afferent fibers were selected for study on the basis of their sensitivity to passive stretch (PS) of the tongue. Fiber discharge frequency was measured during PS of the tongue and after the rapid onset of constant NUAP. During PS of 1–3 cm, firing frequency increased from 17 ± 7 to 40 ± 11 (SE) Hz ( P < 0.01). In addition, 8 of the 12 fibers responded to NUAP (−10 to −30 cmH2O), with firing frequency increasing from 23 ± 9 to 41 ± 9 Hz ( P < 0.001). In two fibers tested, the increase in firing frequency in response to NUAP was not altered by topical anesthesia (10% lignocaine) applied liberally to the entire upper airway mucosa. Our results demonstrate that afferent discharges from the hypoglossal nerve are elicited by 1) stretching of the tongue and 2) NUAP before and after upper airway anesthesia. We speculate that activation of proprioceptive mechanoreceptors in the cat’s tongue provides an additional pathway for the reflex activation of upper airway dilator muscles in response to NUAP, independent of superficially located mucosal mechanoreceptors.
Short-term potentiation of ventilation after different levels of hypoxia
Authors: Menendez Astryd A. , Nuckton Thomas J. , Torres José E. , Gozal David
Published: December 2017

Short-term potentiation of ventilation (VSTP) may be observed in healthy subjects on sudden termination of an hypoxic stimulus. We hypothesized that the level of hypoxia preceding normoxia would modify the duration and magnitude of the ensuing ventilatory decay. Ten healthy adults were studied on two different occasions, during which they were randomly exposed to isocapnic 6 or 10% O2for 60 s and then switched to an isocapnic normoxic gas mixture. Both hypoxic gases induced significant ventilatory responses, and mean peak minute ventilation before the isocapnic normoxic switch was higher in 6% O2( P < 0.001). The fast time constant of the two-exponential equation representing the best fit for ventilatory decay was unaffected by the magnitude of the hypoxic stimulus. However, the slow time constant, which is considered to represent VSTP, was markedly prolonged in 6% compared with 10% O2 [106.7 ± 11.3 vs. 38.2 ± 6.1 (SD) s, respectively; P< 0.0001]. This result indicates that VSTP is stimulus dependent. We conclude that the magnitude of hypoxia preceding a normoxic transient modifies VSTP characteristics. We speculate that the interdependence function of ventilatory stimulus and short-term potentiation is crucial for preservation of system stability during transitions from high to low ventilatory drives.
Explosive-strength training improves 5-km running time by improving running economy and muscle power
Authors: Paavolainen Leena , Häkkinen Keijo , Hämäläinen Ismo , Nummela Ari , Rusko Heikki
Published: December 2017

To investigate the effects of simultaneous explosive-strength and endurance training on physical performance characteristics, 10 experimental (E) and 8 control (C) endurance athletes trained for 9 wk. The total training volume was kept the same in both groups, but 32% of training in E and 3% in C was replaced by explosive-type strength training. A 5-km time trial (5K), running economy (RE), maximal 20-m speed ( V 20 m), and 5-jump (5J) tests were measured on a track. Maximal anaerobic (MART) and aerobic treadmill running tests were used to determine maximal velocity in the MART ( V MART) and maximal oxygen uptake (V˙o 2 max). The 5K time, RE, and V MART improved ( P < 0.05) in E, but no changes were observed in C. V 20 m and 5J increased in E ( P < 0.01) and decreased in C ( P < 0.05).V˙o 2 max increased in C ( P < 0.05), but no changes were observed in E. In the pooled data, the changes in the 5K velocity during 9 wk of training correlated ( P< 0.05) with the changes in RE [O2 uptake ( r = −0.54)] and V MART( r = 0.55). In conclusion, the present simultaneous explosive-strength and endurance training improved the 5K time in well-trained endurance athletes without changes in theirV˙o 2 max. This improvement was due to improved neuromuscular characteristics that were transferred into improved V MART and running economy.
Helium and sulfur hexafluoride bolus washin in short-term microgravity
Authors: Dutrieue Brigitte , Lauzon Anne-Marie , Verbanck Sylvia , Elliott Ann R. , West John B. , Paiva Manuel , Prisk G. Kim
Published: December 2017

We performed single-breath washout (SBW) tests in which He and sulfur hexafluoride (SF6) were inspired throughout the vital capacity inspirations or were inhaled as discrete boluses at different points in the inspiration. Tests were performed in normal gravity (1 G) and in up to 27 s of microgravity (μG) during parabolic flight. The phase III slope of the SBW could be accurately reconstructed from individual bolus tests when allowance for airways closure was made. Bolus tests showed that most of the SBW phase III slope results from events during inspiration at lung volumes below closing capacity and near total lung capacity, as does the SF6-He phase III slope difference. Similarly, the difference between 1 G and μG in phase III slopes for both gases was entirely accounted for by gravity-dependent events at high and low lung volumes. Phase IV height was always larger for SF6 than for He, suggesting at least some airway closure in close proximity to airways that remain open at residual volume. These results help explain previous studies in μG, which show large changes in gas mixing in vital capacity maneuvers but only small effects in tidal volume breaths.
Splanchnic glucagon kinetics in exercising alloxan-diabetic dogs
Authors: Coker Robert H. , Lacy D. Brooks , Krishna Mahesh G. , Wasserman David H.
Published: December 2017

The purpose of this study was to define the relationship between arterial immunoreactive glucagon (IRG) and IRG that perfuses the liver via the portal vein during exercise in the diabetic state. Dogs underwent surgery >16 days before the experiment, at which time flow probes were implanted in the portal vein and the hepatic artery, and Silastic catheters were inserted in the carotid artery, portal vein, and hepatic vein for sampling. Dogs were made diabetic with alloxan injected intravenously ∼3 wk before study (AD) or were studied in the nondiabetic state (ND). Each study consisted of a 30-min basal period and a 150-min moderate-exercise period on a treadmill. The findings from these studies indicate that the exercise-induced increment in portal vein IRG can be substantially greater in AD compared with ND, even when arterial and hepatic vein increments are not different. The larger IRG gradient from the portal vein to the systemic circulation in AD dogs is a function of a twofold greater increase in nonhepatic splanchnic IRG release and a fivefold greater hepatic fractional IRG extraction during exercise. In conclusion, during exercise, arterial IRG concentrations greatly underestimate the IRG levels to which the liver is exposed in ND, and this underestimation is considerably greater in dogs with poorly controlled diabetes.
Differential expression of stress proteins in rat myocardium after free wheel or treadmill run training
Authors: Noble Earl G. , Moraska Albert , Mazzeo Robert S. , Roth David A. , Olsson M. Charlotte , Moore Russell L. , Fleshner Monika
Published: December 2017

High-intensity treadmill exercise increases the expression of a cardioprotective, inducible 72-kDa stress protein (SP72) in cardiac muscle. This investigation examined whether voluntary free wheel exercise training would be sufficient to confer a similar response. Male Sprague-Dawley rats were randomly assigned to either treadmill (TM-Tr) or free wheel (FW-Tr) training groups. By the end of the 8-wk training period, TM-Tr animals ran 1 h/day, 5 days/wk up a 10% grade, covering a distance of 8,282 m/wk. FW-Tr rats ran, on average, 5,300 m/wk, with one-third of the animals covering distances similar to those for the TM-Tr group. At the time of death, hearts of trained and caged sedentary control (Sed) animals were divided into left (LV) and right (RV) ventricles. Citrate synthase activity and the relative immunoblot contents of SP72, SP73 (the constitutive isoform of the SP70 family), and a 75-kDa mitochondrial chaperone (SP75) were subsequently determined. LV and RV did not differ on any measure, and SP73, SP75, and citrate synthase were not affected by training. Cardiac SP72 levels were elevated over fourfold in both ventricles of TM-Tr compared with RV of FW-Sed rats. Despite the animals having run a similar total distance, cardiac SP72 content in FW-Tr rats was not different from that in Sed animals. These data indicate that voluntary exercise training is insufficient to elicit an elevation of SP72 in rat heart and suggest that exercise intensity may be a critical factor in evoking the cardioprotective SP72 response.
cGMP and cAMP cause pulmonary vasoconstriction in the presence of hemolysate
Authors: Voelkel Norbert F. , Allard Jenny D. , Anderson Steven M. , Burke Thomas J.
Published: December 2017

We recently reported that addition of a small amount of hemolysate to the salt solution that perfused isolated rat lungs hypersensitized the vasculature to subsequent additions of ANG II or exposure to hypoxia, and addition of NO gas (⋅ NO) to the perfusate that contained hemolysate caused a strong vasoconstrictor rather than a vasodilator response. In the present study, we demonstrate that CO and the secondary messengers cGMP and cAMP (usually associated with vasodilation) exert similar effects in hemolysate-perfused lungs. Analogs of the cyclic nucleotides cGMP or cAMP (8-bromo-cGMP and dibutyryl-cAMP, respectively) caused profound vasoconstriction in the isolated rat lung perfused with a salt solution that contained hemolysate. The cGMP- or cAMP-analog-induced vasoconstriction was inhibited by chemically dissimilar Ca2+antagonists, by the protein phosphatase inhibitor okadaic acid, and, to a lesser degree, by protein kinase inhibitor H-7. Antiphosphothreonine immunoblotting demonstrated that lungs perfused with hemolysate exhibit increased phosphorylation of several proteins. These data indicate that, in the presence of hemolysate, pulmonary vasculature responds to nominally vasodilatory stimuli, including analogs of cGMP and cAMP, with vasoconstriction rather than vasodilation. The importance of our finding is the paradoxical nature of the response to (analogs of) cyclic nucleotides because, to our knowledge, cyclic nucleotide-induced vasoconstriction has not been previously reported.
SRF protein is upregulated during stretch-induced hypertrophy of rooster ALD muscle
Authors: Flück Martin , Carson James A. , Schwartz Robert J. , Booth Frank W.
Published: December 2017

Serum response element 1 has previously been reported to be necessary and sufficient for activation of the skeletal α-actin promoter during hypertrophy of the anterior latissimus dorsi (ALD) muscle of roosters [J. A. Carson, R. J. Schwartz, and F. W. Booth. Am. J. Physiol. 270 ( Cell Physiol. 39): C1624–C1633, 1996]. Serum response factor (SRF) protein is the transcription factor that binds as a homodimer to serum response element 1 and activates the skeletal α-actin promoter. An increased expression of exogenous SRF protein in replicating C2C12myoblasts induced a three- to fourfold activation of the skeletal α-actin promoter (L. Wei, W. Zhou, J. D. Croissant, F.-E. Johansen, R. Prywes, A. Balasubramamyan, and R. J. Schwartz. J. Biol. Chem. 273: 30287–30294, 1998). Thus we hypothesized that SRF protein concentration would be increased during hypertrophy of skeletal muscle. In the present study, 10% of the rooster’s body weight was attached to the left wing to induce enlargement of the ALD muscle compared with the contralateral muscle. With Western analysis, a significant increase in SRF protein per gram of wet weight of the ALD muscle was noted at 7 and 13 days of hypertrophy. Furthermore, the increase in SRF protein occurred in both crude nuclear protein and cytoplasmic fractions in 7-day stretched ALD muscles. This is the first report showing increased protein concentration for a transcription factor whose regulatory element in the skeletal α-actin promoter has previously been shown to be required for the transduction of a hypertrophy signal in overloaded skeletal muscle of an animal.