bluuebunny/crossref_metadata_2025 huggingface dataset:
Muscle glycogen storage after prolonged exercise: effect of the glycemic index of carbohydrate feedings
Authors: Burke L. M. , Collier G. R. , Hargreaves M.
Published: December 2017

The effect of the glycemic index (GI) of postexercise carbohydrate intake on muscle glycogen storage was investigated. Five well-trained cyclists undertook an exercise trial to deplete muscle glycogen (2 h at 75% of maximal O2 uptake followed by four 30-s sprints) on two occasions, 1 wk apart. For 24 h after each trial, subjects rested and consumed a diet composed exclusively of high-carbohydrate foods, with one trial providing foods with a high GI (HI GI) and the other providing foods with a low GI (LO GI). Total carbohydrate intake over the 24 h was 10 g/kg of body mass, evenly distributed between meals eaten 0, 4, 8, and 21 h postexercise. Blood samples were drawn before exercise, immediately after exercise, immediately before each meal, and 30, 60, and 90 min post-prandially. Muscle biopsies were taken from the vastus lateralis immediately after exercise and after 24 h. When the effects of the immediate postexercise meal were excluded, the totals of the incremental glucose and insulin areas after each meal were greater (P < or = 0.05) for the HI GI meals than for the LO GI meals. The increase in muscle glycogen content after 24 h of recovery was greater (P = 0.02) with the HI GI diet (106 +/- 11.7 mmol/kg wet wt) than with the LO GI diet (71.5 +/- 6.5 mmol/kg). The results suggest that the most rapid increase in muscle glycogen content during the first 24 h of recovery is achieved by consuming foods with a high GI.
Costal diaphragm curvature in the dog
Authors: Boriek A. M. , Liu S. , Rodarte J. R.
Published: December 2017

The curvature of the midcostal region of the diaphragm in seven dogs was determined at functional residual capacity (FRC) and end inspiration during spontaneous breathing and mechanical ventilation and at total lung capacity in the prone and supine positions. Metallic markers were attached to muscle fibers on the abdominal surface of the diaphragm, and the dog was allowed to recover from surgery. The three-dimensional positions of the markers were determined by biplane videofluoroscopy. A quadratic surface was fit to the bead positions. The principal axes of the quadratic surface lie nearly along and perpendicular to the muscle fibers. In both the supine and prone positions, the values of the principal curvatures were similar at FRC and end inspiration during spontaneous breathing, when muscle tension and transdiaphragmatic pressure both increase with increasing lung volume, and during mechanical ventilation and passive inflation to total lung capacity, when both decrease relative to their magnitude at FRC. No abrupt change of curvature, which might be expected at the edge of the zone of apposition, was apparent. The curvature along the muscle fiber was 0.35 +/- 0.07 cm-1; the curvature perpendicular to the muscle fiber was much smaller, 0.06 +/- 0.01 cm-1. The costal region of the diaphragm displaces and shortens as lung volume increases, but its shape, as described by its curvatures, does not change substantially.
Phases of metabolism during progressive exercise to fatigue in human skeletal muscle
Authors: Kent-Braun J. A. , Miller R. G. , Weiner M. W.
Published: December 2017

The purpose of this study was to assess noninvasively both the "oxidative potential" and the sequence of metabolic events that occur during the transition from rest to fatigue in an isometrically exercising muscle. 31P-magnetic resonance spectroscopy was used to obtain continuous measures of intracellular phosphocreatine (PCr), inorganic phosphate (Pi), and proton concentration ([H+]) in the tibialis anterior muscle of eight healthy human volunteers during a progressive isometric exercise protocol. The exercise protocol consisted of 2-min stages, with a duty cycle consisting of 4 s of contraction and 6 s of relaxation, beginning at 10% of the force from an initial maximal voluntary contraction (MVC) and increasing by 10% to a final load of 80% MVC. An MVC was performed at the beginning of each stage; a decrease in MVC indicated fatigue. The initial linear slope of the relationship between force and Pi/PCr was used as an index of oxidative potential for the muscle. This initial slope ranged from 85 to 167% MVC/(Pi/PCr), indicating substantial variability of oxidative potential in these subjects. The changes in Pi/PCr and [H+] over time were best described with a bilinear fit of the individual data. The inflection point for each fit was defined as the point at which the slopes intersected. The Pi/PCr inflection point occurred at a similar value of Pi/PCr in all subjects [0.47 +/- 0.04 (SE)]. The Pi/PCr inflection point occurred significantly earlier (7.8 +/- 0.7 min) than the [H+] inflection point (9.3 +/- 0.4 min, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Limitation of airway smooth muscle shortening by cartilage stiffness and lung elastic recoil in rabbits
Authors: Moreno R. H. , Lisboa C. , Hogg J. C. , Pare P. D.
Published: December 2017

Airway smooth muscle can contract to 20% of its starting length when stimulated maximally and allowed to contract isotonically in vitro. In vivo airway smooth muscle contraction of this degree would result in widespread airway closure. We hypothesized that elastic loads related to cartilage stiffness and lung parenchyma-airway interdependence limit in vivo airway smooth muscle shortening. We measured pulmonary resistance in anesthetized tracheostomized New Zealand White rabbits before and after intravenous treatment with papain in a concentration that produced generalized cartilage softening. Papain treatment caused a significant increase in pulmonary resistance that was completely reversed by application of 4 cmH2O positive end-expiratory pressure and that was partially reversed by vagotomy. Papain pretreatment also resulted in a substantial alteration in the pulmonary resistance-dose relationship to intravenously administered acetylcholine. In addition, maximal resistance after the highest concentration of acetylcholine was greater in papain-treated animals than in the control animals, but the position of the dose-response relationship was not shifted (i.e., there was no change in the effective dose causing 50% maximal response). Application of 4 cmH2O positive end-expiratory pressure in untreated animals resulted in a marked decrease in the bronchoconstriction produced by an effective dose of acetylcholine causing 50% of maximal response, whereas application of 4 cmH2O negative end-expiratory pressure resulted in a marked enhancement of the bronchoconstrictor response to the same intravenous dose of acetylcholine. We conclude that cartilage elasticity and lung recoil are important determinants of the ability of airway smooth muscle to shorten and produce airway narrowing in vivo.
Persistent effects of exercise on skeletal muscle glucose transport across the life-span of rats
Authors: Cartee G. D. , Briggs-Tung C. , Kietzke E. W.
Published: December 2017

Very young rats (< 2 mo) have a persistent increase in insulin-stimulated glucose transport rate in skeletal muscle for several hours after completing a bout of exercise. We studied the effect of exercise on the glucose transport activity of isolated epitrochlearis muscles from male Fischer 344/Brown Norway F1 hybrid rats across a wide range of the life-span (at 3.5, 13, and 25 mo). The stimulation of 3-O-methylglucose (3-MG) accumulation by a submaximally effective insulin concentration (100 microU/ml) was enhanced (50–75%) 4 h after exercise, regardless of age. In contrast, the 3-MG transport rate with 20,000 microU/ml insulin was enhanced after exercise only in the youngest rats (35%), and this increased responsiveness occurred despite no changes in muscle total GLUT-4 levels. In addition, epitrochlearis GLUT-4 levels were reduced by 29% between 3.5 and 13 mo of age in sedentary rats but did not decline further between 13 and 25 mo of age. GLUT-4 levels were moderately but significantly (P < 0.05) related (r = 0.554) to epitrochlearis muscle capacity for insulin-stimulated 3-MG transport.
Forearm vascular responses to baroreceptor unloading at the onset of dynamic exercise
Authors: Nishiyasu T. , Shi X. , Mack G. W. , Nadel E. R.
Published: December 2017

To determine the extent to which reflexes accompanying muscular exercise (associated with central command) interact with cardiopulmonary (CP) baroreceptor-mediated reflexes controlling forearm vascular resistance (FVR), we examined the forearm vasoconstrictor response at the onset of dynamic exercise, with and without CP baroreflex unloading, in 10 physically active men. CP baroreceptors were unloaded by application of lower body negative pressure (LBNP) at rest and during five 4-min bouts of supine exercise at 25 and 32 degrees C. Exercise intensities were 10 (essentially no load) and 100 W, and LBNP was applied at -10, -20, -30, and -40 mmHg during rest and at -20 and -40 mmHg during exercise. Resting FVR was 33.0 +/- 3.2 and 14.0 +/- 2.7 resistance units, and cardiac stroke volume (SV) was 117 +/- 7 and 126 +/- 9 ml/beat at 25 and 32 degrees C, respectively. We found a linear relationship between the increase in FVR and decrease in SV during LBNP; the slope of the relationship was significantly lower at 32 degrees C (FVR = 51.7–0.29SV) than at 25 degrees C (FVR = 123–0.79SV). At the onset of 100-W exercise without LBNP, FVR increased significantly to 50.2 +/- 9.0 and 21.2 +/- 3.2 units at 25 and 32 degrees C, respectively, whereas SV was unchanged. Application of -40-mmHg LBNP reduced SV significantly to 68 +/- 5 and 71 +/- 6 ml/beat and increased FVR significantly to 89.0 +/- 11.3 and 36.3 +/- 7.6 units at 25 and 32 degrees C, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of dehydration on thermoregulatory responses of horses during low-intensity exercise
Authors: Naylor J. R. , Bayly W. M. , Gollnick P. D. , Brengelmann G. L. , Hodgson D. R.
Published: December 2017

Effects of dehydration on thermoregulatory and metabolic responses were studied in six horses during 40 min of exercise eliciting approximately 40% of maximal O2 consumption and for 30 min after exercise. Horses were exercised while euhydrated (C), 4 h after administration of furosemide (FDH; 1.0 mg/kg i.v.) to induce isotonic dehydration, and after 30 h without water (DDH) to induce hypertonic dehydration. Cardiac output was significantly lower in FDH (144.1 +/- 8.0 l/min) and in DDH (156.6 +/- 6.9 l/min) than in C (173.1 +/- 6.2 l/min) after 30 min of exercise. When DDH, FDH, and C values were compared, dehydration resulted in higher temperatures in the middle gluteal muscle (41.9 +/- 0.3, 41.1 +/- 0.2, and 40.6 +/- 0.2 degrees C, respectively) and pulmonary artery (40.8 +/- 0.3, 40.1 +/- 0.2, and 39.7 +/- 0.2 degrees C, respectively). Temperatures in the superficial thoracic vein and subcutaneous sites on the neck and back and peak sweating rates on the neck and back were not significantly different in DDH and C. In view of higher core temperatures during exercise after dehydration and decrease in cardiac output without concomitant increases in peripheral temperatures or reduced sweating rates, we conclude that the impairment of thermoregulation was primarily due to decreased transfer of heat from core to periphery.
Carotid chemoreceptors and respiratory adaptations to dead space loading during incremental exercise
Authors: Syabbalo N. C. , Zintel T. , Watts R. , Gallagher C. G.
Published: December 2017

Dead space (VD) loading has been shown to cause an increase in tidal volume and a decrease in respiratory frequency at moderate to high levels of ventilation (VI) during exercise (J. Appl. Physiol. 70: 55–62, 1991). This study examined the role of carotid chemoreceptors (CC) in the breathing pattern response to added VD during maximal incremental exercise; we used hyperoxia to silence the CC. Nine healthy subjects exercised on a bicycle ergometer on 4 different days while inspiring air with VD (AVD) and without VD [air control (AC)] and while inspiring 100% O2 with VD (O2VD) and without VD (O2C). Equipment resistance for VD and control studies was identical, and the exercise tests were done in a randomized order. At a matched level of VI equivalent to 75% VI at the end of the AC experiments (102 l/min), the breathing pattern in the AVD and O2VD tests was significantly deeper and slower (P < 0.05) than that in the AC and O2C tests. The difference in tidal volume between AVD and AC tests (delta = 0.26 +/- 0.16 liter) was not significantly different from that between O2VD and O2C tests (delta = 0.23 +/- 0.23 liter). The breathing pattern was the same in the AC and O2C tests. It is concluded that the altered breathing pattern with VD loading is not mediated by the CC.
Influence of active muscle size on sympathetic nerve discharge during isometric contractions in humans
Authors: Seals D. R.
Published: December 2017

We tested the hypothesis that sympathetic nerve discharge to nonactive skeletal muscle (MSNA) is influenced by active muscle size during isometric contractions performed at a constant submaximal force in humans. In six subjects, MSNA (peroneal microneurography), arterial pressure, heart rate, and ratings of perceived effort were recorded before (resting control) and during isometric contractions of either a small hand muscle [1st dorsal interosseus (FDI); 2 trials (FDI1 and FDI2)] or the fore- and upper arm muscles (handgrip; 1 trial) sustained to the point of exhaustion and normalized to endurance time (te). There were no differences in resting control levels. MSNA, heart rate, arterial pressure, and perceived effort all increased similarly during the two FDI contractions. During handgrip, the rates of rise and peak increases MSNA, heart rate, and arterial pressure were much greater than during FDI (all P < 0.05), but peak levels of perceived effort were not different. These findings indicate that during voluntary isometric efforts sustained to the same performance and perceptual end points the rates of increase and final levels of MSNA, heart rate, and arterial pressure are greater during contraction of a larger muscle mass and that these responses appear to be similar during successive trials of a task when normalized to te. Thus, active muscle size can be an important factor in the regulation of sympathetic nervous system discharge and cardiovascular function during isometric muscle activity in the human.
Geometric hysteresis in pulmonary surface-to-volume ratio during tidal breathing
Authors: Miki H. , Butler J. P. , Rogers R. A. , Lehr J. L.
Published: December 2017

We investigated the dynamic history dependence of lung surface area-to-volume ratio (S/V) during tidal breathing in live rabbits with use of our recently developed technique of diffuse optical scattering. We also examined the effect of methacholine (continuous intravenous infusion, 1#x2013;10 micrograms.kg-1.min-1) on lung micromechanics with the same technique. Animals were anesthetized, tracheostomized, and mechanically ventilated, and the left lung was exposed through a thoracotomy. An optical fiber delivering light from a He-Ne laser was attached normal to the pleural surface, producing a circular light pattern on the pleural surface from diffusively scattered light within the parenchyma. The pattern of light intensities was measured using a CCD video camera connected to a computer. S/V during tidal breathing changed in a manner qualitatively consistent with geometric similarity. There was a small but significant hysteresis in S/V vs. volume, with S/V inspiration greater than S/V expiration at the same volume. However, during methacholine challenge, the sense of hysteresis reversed; S/V inspiration was less than S/V expiration at isovolume points. Moreover, S/V during methacholine challenge systematically decreased at all lung volumes compared with control. These findings suggest that 1) during normal tidal breathing, stress hysteresis in ductal tissue is larger than septal stress hysteresis (septal tissue plus surface tension) and 2) the effect of methacholine on tissue in the septa is greater than the corresponding effect in ductal tissue.
Neurohumoral regulation of the pulmonary circulation during circulatory hypotension in conscious dogs
Authors: Peterson W. P. , Trempy G. A. , Nishiwaki K. , Nyhan D. P. , Murray P. A.
Published: December 2017

We investigated the effects of circulatory hypotension (HYPO) on the left pulmonary vascular pressure-flow relationship in chronically instrumented conscious dogs and the role of five neurohumoral mechanisms in either mediating or modulating the response to this stimulus. HYPO was induced by acute (approximately 15-min) inflation of a hydraulic occluder implanted around the thoracic inferior vena cava, which decreased systemic arterial pressure to approximately 55 mmHg. HYPO resulted in active pulmonary vasoconstriction (53–66%; P < 0.01) in intact conscious dogs. Sympathetic alpha 1-adrenoreceptor block reduced (P < 0.01) the magnitude of HYPO-induced pulmonary vasoconstriction by 91–99%. Neither sympathetic beta-adrenoreceptor block nor cholinergic muscarinic receptor block had any significant effect on the magnitude of HYPO-induced pulmonary vasoconstriction. Surprisingly, angiotensin II receptor block increased (P < 0.05) HYPO-induced pulmonary vasoconstriction by 69–91%. In contrast, arginine vasopressin V1-receptor block reduced (P < 0.05) HYPO-induced pulmonary vasoconstriction by 34–41%. These results indicate that the pulmonary circulation of intact conscious dogs is actively regulated by three distinct neurohumoral mechanisms during HYPO. Sympathetic alpha 1-adrenoreceptor activation is the primary mediator of HYPO-induced pulmonary vasoconstriction. Angiotensin II and arginine vasopressin exert opposing pulmonary vasodilator and vasoconstrictor effects during HYPO, whereas sympathetic beta-adrenoreceptor and cholinergic muscarinic receptor activation do not appear to modulate the pulmonary vascular response to HYPO.
Lactate turnover at rest and during submaximal exercise in patients with heart failure
Authors: Katz S. D. , Bleiberg B. , Wexler J. , Bhargava K. , Steinberg J. J. , LeJemtel T. H.
Published: December 2017

Systemic and lower limb skeletal muscle lactate metabolism was studied in 10 men with congestive heart failure by use of a primed continuous intravenous infusion of L-(+)-[U-14C]lactate. Arterial and deep femoral venous blood samples were obtained at rest and during 30 min of submaximal exercise. Systemic lactate metabolic turnover rate (Rd) was determined using Steele's isotopic steady-state equation (Rd = isotopic infusion rate/arterial specific activity). Plasma lactate concentrations in the artery and deep femoral vein did not change significantly from resting values during exercise (1.11 +/- 0.13 vs. 1.26 +/- 0.12 and 1.27 +/- 0.12 vs. 1.30 +/- 0.12 mM, respectively), whereas Rd increased from 22.5 +/- 1.8 to 41.6 +/- 4.8 mumol.kg-1.min-1 (P < 0.005). Rd did not significantly correlate with arterial lactate concentration during rest or exercise. Because of simultaneous uptake and release of lactate in skeletal muscle, arterial and deep femoral venous lactate concentrations are not closely related to either systemic or lower limb skeletal muscle lactate metabolism in patients with congestive heart failure.
Pulmonary microvascular injury after intestinal ischemia-reperfusion: role of P-selectin
Authors: Carden D. L. , Young J. A. , Granger D. N.
Published: December 2017

The objective of this study was to determine whether pulmonary endothelial expression of the adhesive glycoprotein P-selectin contributes to the lung injury and leukostasis observed after intestinal ischemia-reperfusion (I/R). The pulmonary capillary filtration coefficient and lung myeloperoxidase activity were determined in rat lungs isolated after 120 min of superior mesenteric artery occlusion and 90 min of reperfusion. Intestinal I/R resulted in a marked increase in the pulmonary capillary filtration coefficient compared with control and sham-operated rats. The increase in pulmonary microvascular permeability elicited by intestinal I/R was effectively prevented by pretreatment with a P-selectin monoclonal antibody (MAb; MAb PB1.3) but was unaffected by a control MAb. The intestinal I/R-induced increase in pulmonary microvascular permeability was accompanied by a dramatic sequestration of granulocytes in the lung compared with control and sham-operated rats; however, neither the P-selectin nor the control MAbs affected this event. These results indicate that P-selectin contributes to the pulmonary microvascular dysfunction observed after intestinal I/R. The inhibition of intestinal I/R-induced lung injury by immunoneutralization of P-selectin appears to be unrelated to the accompanying lung leukosequestration.
Ventilatory and metabolic responses to cold and CO2 in intact and carotid body-denervated awake rats
Authors: Gautier H. , Bonora M. , Trinh H. C.
Published: December 2017

We investigated in conscious rats the characteristics and modes of action of CO2 on thermoregulation and ventilatory control during cold stress. In a group of 10 rats studied intact and after carotid body denervation, measurements of metabolic rate (VO2), ventilation (V), shivering, and colonic temperature (Tc) were made at controlled ambient temperatures (Ta) of 25, 20, 15, 10, and 5 degrees C. Animals were exposed on different days to 1) normoxia, 2) normoxia and 4% CO2, 3) 12% hypoxia, or 4) 10.8% hypoxia and 4% CO2. The following results were obtained. 1) During CO2 exposure in normoxia or hypoxia, VO2 is increased at Ta of 25 degrees C and decreased for lower Ta. These effects are partly mediated by carotid body afferents. 2) Shivering and nonshivering thermogenesis and therefore Tc regulation are affected by CO2 exposure as shown by relationships between VO2-Tc and VO2-shivering intensity. 3) V is controlled by PO2 and PCO2 directly through their peripheral and central actions but also indirectly through their effects on VO2. Our conclusions are as follows. 1) Control of Tc is markedly dependent on PCO2 level. Carotid body afferents play a role, but direct central effects acting on the different sources of thermogenesis and possibly on thermolysis are most prominent. 2) As far as control of V is concerned, during hypercapnia in normoxia or hypoxia, several analogies may be formed between exposure to cold and muscular exercise, both of which increase VO2 and V, suggesting common integrative mechanisms at the central nervous system level.
Respiratory effect of the intercostal muscles in the dog
Authors: Wilson T. A. , De Troyer A.
Published: December 2017

In a previous paper (J. Appl. Physiol. 73: 2283–2288, 1992), respiratory effect was defined as the change in airway pressure produced by active tension in a muscle with the airway closed, mechanical advantage was defined as the respiratory effect per unit mass per unit active stress, and it was shown that mechanical advantage is proportional to muscle shortening during the relaxation maneuver. Here, we report values of mechanical advantage and maximum respiratory effect of the intercostal muscles of the dog. Orientations of the intercostal muscles in the third and sixth interspaces were measured. Mechanical advantages of the muscles in these interspaces were computed by computing their shortening from these data and data in the literature on rib displacement. We found that parasternal internal intercostals and dorsal external intercostals of the upper interspace have large inspiratory mechanical advantages and that dorsal internal intercostals of the lower interspace and triangularis sterni have large expiratory mechanical advantages. Mass distributions in the two interspaces were also measured, and maximum respiratory effects of the muscles were calculated from their mass, mechanical advantage, and the value for maximum stress in skeletal muscle. Estimated maximum respiratory effects of the inspiratory and expiratory muscle groups of the entire rib cage were tested by measuring the maximum inspiratory pressures that were generated by the parasternal and external intercostals acting alone. Measured pressures, -13 cmH2O for the parasternals and -11 cmH2O for the external intercostals, agreed well with the computed values.
Effects of cocaine on incremental treadmill exercise in horses
Authors: McKeever K. H. , Hinchcliff K. W. , Gerken D. F. , Sams R. A.
Published: December 2017

Four mature horses were used to test the effects of two doses (50 and 200 mg) of intravenously administered cocaine on hemodynamics and selected indexes of performance [maximal heart rate (HRmax), treadmill velocity at HRmax, treadmill velocity needed to produce a blood lactate concentration of 4 mmol/l, maximal mixed venous blood lactate concentration, maximal treadmill work intensity, and test duration] measured during an incremental treadmill test. Both doses of cocaine increased HRmax approximately 7% (P < 0.05). Mean arterial pressure was 30 mmHg greater (P < 0.05) during the 4- to 7-m/s steps of the exercise test in the 200-mg trial. Neither dose of cocaine had an effect on the responses to exertion of right atrial pressure, right ventricular pressure, or maximal change in right ventricular pressure over time. Maximal mixed venous blood lactate concentration increased 41% (P < 0.05) with the 50-mg dose and 75% (P < 0.05) with the 200-mg dose during exercise. Administration of cocaine resulted in decreases (P < 0.05) in the treadmill velocity needed to produce a blood lactate concentration of 4 mmol/l from 6.9 +/- 0.5 and 6.8 +/- 0.9 m/s during the control trials to 4.4 +/- 0.1 m/s during the 200-mg cocaine trial. Cocaine did not alter maximal treadmill work intensity (P > 0.05); however, time to exhaustion increased by approximately 92 s (15%; P < 0.05) during the 200-mg trial.(ABSTRACT TRUNCATED AT 250 WORDS)
Respiratory and cardiovascular responses to static handgrip exercise in humans
Authors: Fontana G. A. , Pantaleo T. , Bongianni F. , Cresci F. , Manconi R. , Panuccio P.
Published: December 2017

We studied the time course of respiratory and cardiovascular responses by evaluating changes in the breathing pattern, mean blood pressure (MBP), and heart rate elicited by 3 min of static handgrip at 15, 25, and 30% of the maximum voluntary contraction (MVC) in 15 healthy volunteers. Muscle tension and integrated electromyographic activity remained fairly constant during each trial. During 15% MVC bouts, initially only mean inspiratory flow increased; then, tidal volume and minute ventilation (VI) also rose progressively. No significant changes in MBP and heart rate were observed. During 25 and 30% MVC bouts, not only did mean inspiratory flow, VT, and VI increase but MBP and heart rate increased as well. A slight and delayed rise in respiratory rate was also observed. Unlike 15 and 25% MVC handgrip, 30% MVC handgrip caused a small decrease in end-tidal PCO2. Changes in the pattern of breathing occurred more promptly than those in cardiovascular variables in the majority of subjects. Furthermore, we found a positive correlation between changes in VI and those in cardiovascular variables at the end of 25 and 30% MVC trials. This study indicates that respiratory and cardiovascular responses to static handgrip exercise are controlled independently.
Human muscle glycogen resynthesis after exercise: insulin-dependent and -independent phases
Authors: Price T. B. , Rothman D. L. , Taylor R. , Avison M. J. , Shulman G. I. , Shulman R. G.
Published: December 2017

To study the effects of glycogen depletion and insulin concentration on glycogen synthesis, gastrocnemius glycogen was measured with 13C-nuclear magnetic resonance at 4.7 T after exercise. Subjects performed single-leg toe raises to deplete gastrocnemius glycogen to 75, 50, or 25% of resting concentration (protocol I). Insulin dependence of glycogen synthesis was assessed after depletion to 25% with (protocol II) and without (protocol III) infusion of somatostatin to inhibit insulin secretion. After depletion to 75 and 50%, glycogen resynthesis rates were similar (2.4 +/- 0.7 and 2.8 +/- 0.6 mM/h, respectively). When glycogen was depleted to 25% (< 30 mM), the resynthesis rate was significantly higher (P < 0.02) at 33 +/- 7 mM/h, and it declined to 3.5 +/- 0.9 mM/h at > 35 mM glycogen. At < 35 mM glycogen, synthesis was not affected by low insulin (24 +/- 4 mM/h, protocol vs. 19 +/- 3 mM/h, protocol III), whereas at > 35 mM glycogen, synthesis ceased without insulin (-0.07 +/- 0.19 mM/h, protocol II). After depletion to 25% (protocol III), plasma lactate transiently increased (0.81 mM at rest, 1.82 mM 0 h after exercise, and 0.76 mM 2 h after exercise), whereas other plasma constituents did not significantly change. We conclude that after depletion to < 30 mM initial glycogen resynthesis is insulin independent and glycogen dependent, which suggests local control.
Liposome-entrapped PGE1 posttreatment decreases IL-1 alpha-induced neutrophil accumulation and lung leak in rats
Authors: Leff J. A. , Baer J. W. , Kirkman J. M. , Bodman M. E. , Shanley P. F. , Cho O. J. , Ostro M. J. , Repine J. E.
Published: December 2017

We found that treatment with liposome-entrapped prostaglandin E1 (Lip-PGE1), but not with empty liposomes and/or free PGE1, decreased the leak of intravascularly administered 125I-labeled albumin into lungs of rats given interleukin-1 alpha (IL-1 alpha) intratracheally. Lip-PGE1 treatment also decreased lung myeloperoxidase activity, lung lavage neutrophil increases, and lung histological abnormalities found in rats given IL-1 alpha intratracheally. Interestingly, decreased lung leak and lung neutrophil accumulation occurred when Lip-PGE1 was given intravenously 2.5 h after, but not immediately before, intratracheal IL-1 alpha administration. When Lip-PGE1 treatment was given both before and 2.5 h after IL-1 alpha administration, lung leak was decreased to baseline levels. Lip-PGE1 treatment given 2.5 h after IL-1 alpha administration also decreased lung oxidized glutathione levels, which increased in rats given IL-1 alpha intratracheally. We conclude that postinsult treatment with Lip-PGE1 decreases lung leak, neutrophil recruitment, and oxidative responses in lungs of rats given IL-1 alpha intratracheally.
Influence of suspension on the oxidative burst by rat neutrophils
Authors: Miller E. S. , Koebel D. A. , Davis S. A. , Klein J. B. , McLeish K. R. , Goldwater D. , Sonnenfeld G.
Published: December 2017

The influence of spaceflight on the oxidative burst of neutrophils is not known. The present study was designed to evaluate the influence of antiorthostatic suspension, a ground-based modeling system designed to simulate certain aspects of weightlessness that occur after spaceflight, on the capacity of rat neutrophils to express the oxidative burst, an important host defense mechanism against microbial pathogens. Rats were suspended in whole body harnesses in the antiorthostatic orientation for a 3- or 7-day period. Control rats were suspended orthostatically or allowed to remain in vivarium cages without the attachment of any suspension materials. After suspension, peripheral blood was harvested and neutrophils were isolated by density gradient centrifugation. The enriched neutrophil preparations were stimulated with N-formyl-methionyl-leucine-phenylalanine and phorbol myristic acid to induce the oxidative burst. It was found that neutrophils isolated from suspended animals released the same levels of superoxide anion as did vivarium control animals that were not suspended, indicating that whole body suspension did not alter this aspect of rat neutrophil function.
Measurement of plasma volume in rats with use of fluorescent-labeled albumin molecules
Authors: Gillen C. M. , Takamata A. , Mack G. W. , Nadel E. R.
Published: December 2017

We describe a method for measuring plasma volume (PV) in small animals that allows small sample sizes but does not require the use of radioisotopes and thus is a convenient approach for making repeated measurements. Texas Red covalently bound to albumin (TR-A) was used in a typical indicator-dilution technique to measure PV. The relative fluorescent intensity of TR-A is linear to its concentration (up to 0.15 mg/ml) at an excitation lambda of 590 nm and an emission lambda of 610 nm. Catheters were inserted through the right jugular vein of anesthetized rats and threaded into the vena cava. A 0.5-ml control blood sample was taken, a measured quantity of TR-A was injected, and the catheter was flushed with saline. A 0.5-ml postinjection sample was taken 5 min after TR-A injection. PV was calculated by comparing the difference between the relative fluorescent intensity of control and postinjection plasma samples to a standard. The PV of 22 rats [362 +/- 14 (SE) g] was 14.1 +/- 0.4 ml (39.6 +/- 0.9 ml/kg body wt) measured by the TR-A method and 12.8 +/- 0.4 ml (35.9 +/- 1.0 ml/kg body wt) measured by a standard radioiodinated albumin method. There was a strong correlation between PV measured by both methods in the same rat (r = 0.90, P < 0.01). Infusion experiments indicated that the TR-A method can detect acute changes in PV, and repeated measurements of PV made on a chronically instrumented rat demonstrated that the method can reliably measure PV on consecutive days.
Stress protein induction in skeletal muscle: comparison of laboratory models to naturally occurring hypertrophy
Authors: Kilgore J. L. , Timson B. F. , Saunders D. K. , Kraemer R. R. , Klemm R. D. , Ross C. R.
Published: December 2017

The purpose of the study was to compare stress protein [heat shock protein (HSP) 72] response in laboratory models of hypertrophy to naturally occurring work-induced hypertrophy. Two laboratory models of hypertrophy inducement, namely, compensatory hypertrophy and stretch hypertrophy, were compared with hypertrophy resulting from migratory flight in the blue-winged teal. We hypothesized that HSP 72 would be expressed more strongly in hypertrophied muscle than in control muscle. Furthermore, we hypothesized that changes occurring in laboratory models would also occur in work-induced enlargement. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analyses were used to assess HSP 72 levels in control and hypertrophied muscle. Laboratory models elicited similar responses, with increased HSP 72 content in hypertrophied muscle. Work-induced hypertrophy or disuse atrophy did not change the degree of HSP 72 expression in the blue-winged teal. The presence of HSP 72 in these conditions may indicate that stressors eliciting changes in muscle protein expression, including the loss of muscle mass, may elicit HSP 72 synthesis.
Tonic respiratory drive in the absence of rhythm generation in the conscious dog
Authors: Horner R. L. , Kozar L. F. , Phillipson E. A.
Published: December 2017

This study was designed to determine whether a chemoreceptor-mediated tonic respiratory drive exists below the apneic threshold. Expiratory (triangularis sterni) and inspiratory (diaphragm and parasternal intercostal) electromyographic activities were recorded in three awake relaxed dogs breathing through an endotracheal tube inserted into a permanent tracheostomy. The cervical vagus nerves were cold blocked to avoid the complicating effects of vagal inputs on respiratory activity. During hypocapnia produced by mechanical hyperventilation, expiratory muscle activity converted from rhythmic to tonic discharge when inspiratory muscle activity and spontaneous breathing movements were abolished. In hypocapnia, changes in arterial PCO2 (in hyperoxia) were produced by changing the ventilator rate for steady-state (> 6 min) CO2 stimuli and by disconnecting the ventilator for transient CO2 stimuli. By use of either method, a CO2-mediated drive to the expiratory muscle was consistently observed during hypocapnic apnea. At a constant level of hypocapnia, inhalation of 5% O2 consistently caused the onset of spontaneous breathing; the onset of phasic inspiratory activity was associated with reciprocal inhibition of the tonic expiratory activity. However, inhalation of 10 and 15% O2 caused an inhibition of the tonic expiratory activity, even without the onset of breathing. These results suggest that the response threshold of the respiratory chemoreceptors is lower than the apneic threshold and that a chemoreceptor-mediated tonic respiratory drive persists during apnea.
Effect of hypoxia on neuromuscular transmission in the developing diaphragm
Authors: Bazzy A. R.
Published: December 2017

To study the effects of hypoxia on neuromuscular transmission in the developing diaphragm, phrenic nerve-hemidiaphragm preparations were obtained from newborn (4–9 days) and older (22–30 days) rats. Diaphragms were stimulated directly or indirectly (via the nerve) for 1 s at frequencies of 10–80 Hz. Force generated in response to stimulation was measured during perfusion of oxygenated Ringer solution (control) and Ringer solution bubbled with 95% N2–5% CO2 (hypoxia). After 45 min of hypoxia, the force response of the older diaphragms to direct stimulation had decreased to approximately 50% of control at > or = 40 Hz; however, when stimulation occurred via the nerve at these frequencies only 15–20% of control force was generated. In the newborn diaphragms, the force decrement after similar or longer periods of hypoxia (< or = 90 min) was 30– 40% irrespective of the route or frequency of stimulation. After 15 min of reoxygenation, the force response to both muscle and nerve stimulation recovered completely in the older diaphragms but only partially in the newborn diaphragms (range 77% of control at 50 Hz to 95% of control at 10 Hz). These data suggest that in the newborn diaphragm 1) neuromuscular transmission is more resistant to the effects of hypoxia than the older diaphragm and 2) the predominant effect of hypoxia is peripheral in the diaphragm muscle fibers, whereas in the older diaphragm the effect is before or at the neuromuscular junction.
Basis for the selective reduction of pulmonary vascular resistance in humans during infusion of adenosine
Authors: Utterback D. B. , Staples E. D. , White S. E. , Hill J. A. , Belardinelli L.
Published: December 2017

The objective of this study was to demonstrate the basis for the selective reduction of pulmonary vascular resistance by intravenous infusion of adenosine. Secondary objectives of the study were to determine the rate of central infusion of adenosine at which the nucleoside appears in the systemic circulation and to relate this to hemodynamic events. Plasma concentrations of adenosine in the right and left atria were measured during peripheral (5 patients) and central (12 patients) infusions of adenosine in adults with normal pulmonary arterial pressures undergoing coronary artery bypass surgery. The hemodynamic effects of central (right ventricle) infusion of adenosine were also examined. The extraction of adenosine across the pulmonary vascular bed was found to be 73.6 +/- 4.8%. The mean maximal decrease in pulmonary vascular resistance index, 48.8 +/- 9.6%, occurred at an adenosine infusion rate of 30 micrograms.kg-1.min-1, whereas the systemic vascular resistance index remained unchanged. Thus, adenosine, administered centrally in anesthetized patients with normal pulmonary vascular resistances, selectively lower pulmonary vascular resistance. The basis for this selective effect is the substantial extraction of adenosine during passage through the pulmonary vascular bed.
Cardiovascular and respiratory effects of adenosine in humans after pulmonary denervation
Authors: Morgan-Hughes N. J. , Corris P. A. , Healey M. D. , Dark J. H. , McComb J. M.
Published: December 2017

Adenosine infusion causes tachycardia in normal subjects. A proposed mechanism is secondary pulmonary stretch receptor activation due to hyperventilation, induced by direct stimulation of carotid body chemoreceptors by adenosine. We examined responses to adenosine (incremental doses given by intravenous infusion, 5 min each rate) in six normal volunteers and six lung-transplant recipients with pulmonary denervation. Adenosine caused chemoreceptor stimulation in both groups with minute ventilation increasing from 5.8 +/- 0.4 to 10.7 +/- 1.3 l/min (P < 0.05) in the volunteers and from 4.8 +/- 0.4 to 9.2 +/- 0.8 l/min (P < 0.001) in the lung-transplant recipients. There was no difference in the magnitude of the ventilatory increase between the two groups (P = NS at all infusion rates). Adenosine produced tachycardia in both groups, with heart rate increasing from 66 +/- 5 to 84 +/- 3 beats/min (P < 0.01) in the volunteers and from 82 +/- 6 to 110 +/- 6 beats/min (P < 0.05) in the lung-transplant recipients. There was no difference in the magnitude of the heart rate response between the two groups (P = NS at all infusion rates). These data suggest, contrary to previous thinking, that pulmonary stretch receptor activation does not contribute to adenosine-induced tachycardia in humans.
Gut and muscle tissue PO2 in endotoxemic dogs during shock and resuscitation
Authors: Vallet B. , Lund N. , Curtis S. E. , Kelly D. , Cain S. M.
Published: December 2017

There is indirect evidence that tissue hypoxia occurs in human sepsis and surface measures of muscle tissue PO2 (PtiO2) in hypodynamic endotoxic animals are decreased. This study assessed systemic and regional tissue oxygenation in a more relevant model of hyperdynamic endotoxicosis. We isolated venous outflow from the left hindlimb and a segment of ileum in six anesthetized dogs to measure muscle and gut O2 delivery and uptake (VO2) and lactate flux, gut intramucosal pH (pHi) by tonometry, and PtiO2 by multi-point surface electrodes placed on mucosal and serosal surfaces of gut and on muscle. We then infused Escherichia coli lipopolysaccharide (LPS; 2 mg/kg) over 1 h followed by a 2-h infusion of dextran (0.5 ml.kg-1.min-1). LPS infusion significantly decreased systemic and gut VO2, cardiac output (Q), and blood pressure and increased arterial lactate and gut lactate flux. Resuscitation increased Q to above baseline and restored systemic VO2. In response to LPS and then resuscitation, muscle PtiO2 distribution did not change, suggesting little microcirculatory disturbance, although mean PtiO2 first decreased and then increased. In contrast, gut VO2 and pHi remained low and lactate output remained high, despite restoration of gut blood flow. Gut VO2, lactate flux, pHi, and PtiO2 histograms were consistent with a marked redistribution of blood flow within the gut wall, away from the mucosa and toward the muscularis. These data show that, in hyperdynamic acute endotoxemia, skeletal muscle PtiO2 and VO2 are well maintained, but blood flow within the gut is significantly disturbed with mucosal hypoxia.
Functional and biochemical assessment of postpreservation lung viability in a rat model
Authors: DeCampos K. N. , Waddell T. K. , Slutsky A. S. , Wang Y. , Wang X. , Post M. , Patterson G. A.
Published: December 2017

We examined the relationship between DNA synthesis and postpreservation lung hemodynamics and gas exchange. Adult male Wistar rats (n = 168) were randomly allocated into seven groups (n = 24) according to the pulmonary vascular flush used [EuroCollins (EC), saline, or no flush] and to the temperature of flush and storage (4, 21, or 37 degrees C). In each group, lungs were stored for four different time periods (0–24 h). After storage, incorporation of [3H]-thymidine into DNA was measured in the right lung, and in 72 rats the left lung was reperfused for 1 h with venous blood in an ex vivo paracorporeal rat lung system. Autoradiography of EC lungs revealed that alveolar macrophages and epithelial cells were the two major cell types synthesizing DNA during ischemia. Gas exchange after preservation with EC was universally poor. In unflushed and saline-flushed lungs, a critical threshold for viability was detected beyond which DNA synthesis and lung effluent PO2 decreased more rapidly at higher storage temperatures. A positive correlation was found between the final lung effluent PO2 and [3H]thymidine uptake (R2 = 0.62; P < 0.0001). In this model, deoxyribonucleic acid synthesis was a good index of postpreservation hemodynamics and gas exchange function.
Airway and tissue behavior during induced constriction in rats: intravenous vs. aerosol administration
Authors: Nagase T. , Moretto A. , Ludwig M. S.
Published: December 2017

The distribution of contractile agonist during intravenous (i.v.) or aerosol (AR) administration is likely to be different. We questioned whether the different pattern of distribution would result in different effects on lung tissue response. We measured tracheal and alveolar pressure in open-chest mechanically ventilated [frequency 1 Hz, tidal volume 8 ml/kg, positive end-expiratory pressure (PEEP) 3 cmH2O] rats under control conditions and after i.v. or AR administration of saline or methacholine (MCh; i.v., 50 micrograms.kg-1.min-1; AR, 256 mg/ml). We calculated lung elastance and resistances of lung, tissue, and airway by fitting the equation of motion to changes in tracheal and alveolar pressure. Lungs were then frozen in situ with liquid nitrogen (PEEP=3 cmH2O) and processed via freeze substitution. Airway constriction was assessed by measuring the ratio of airway lumen to ideally relaxed area. Tissue distortion was assessed by measuring mean linear intercept between alveolar walls (Lm), atelectasis index (ATI) derived by calculating ratio of tissue to air space, and SD of Lm and ATI. I.v. and AR MCh increased lung resistance to a similar degree. However, changes in tissue resistance and lung elastance after AR MCh were significantly greater than those after i.v. MCh, whereas the change in airway resistance was significantly less. After i.v. MCh, airway constriction was prominent and evenly distributed. After AR MCh, airway constriction was less prominent and decreased as airway size decreased. Tissue distortion, i.e., SD of Lm and ATI, was significantly greater after AR than i.v. MCh.(ABSTRACT TRUNCATED AT 250 WORDS)
Muscle fructose-2,6-bisphosphate and glucose-1,6-bisphosphate during insulin-induced hypoglycemia
Authors: Winder W. W. , Carling J. M. , Duan C. , Jones J. P. , Palmer S. L. , Walker M. C.
Published: December 2017

Glucose production during insulin-induced hypoglycemia in the fasted state is heavily dependent on the process of hepatic gluconeogenesis. Skeletal muscle glycogen is one possible source of lactate for hepatic gluconeogenesis. Fructose 2,6-bisphosphate (F-2,6-P2) and glucose 1,6-bisphosphate (G-1,6-P2) are two allosteric activators of muscle glycolysis. To investigate their putative role in the control of muscle lactate production during hypoglycemia, fasted rats were infused via jugular catheters with insulin in 0.9% NaCl or with 0.9% NaCl alone for 60 or 120 min. Muscles were removed and clamp frozen in liquid nitrogen. The insulin infusion produced plasma insulin values of 97 +/- 13 microU/ml after 1 h and 100 +/- 9 microU/ml after 2 h. Blood glucose in the saline-infused rats was 4.6 +/- 0.2 mM after 1 h and 5.1 +/- 0.1 mM after 2 h compared with 1.5 +/- 0.01 and 1.0 +/- 0.1 mM after 1 and 2 h, respectively, in the insulin-infused rats. The hypoglycemic rats had significantly elevated plasma epinephrine and blood lactate levels compared with the saline-infused rats. F-2,6-P2 and G-1,6-P2 were increased two- to five-fold in white quadriceps of hypoglycemic rats compared with that of saline-infused rats. The results are consistent with F-2,6-P2 and G-1,6-P2 playing a role in stimulating muscle lactate production as a source of gluconeogenic substrate during insulin-induced hypoglycemia.